A TEXT-BOOK 
OF 
PATHOLOGY 
With a Final Section on 
POST-MORTEM EXAMINATIONS AND THE METHODS OF 
PRESERVING AND EXAMINING DISEASED TISSUES 
BT / 
FRANCIS DELAFIELD, M. D., LL. D. 
•nr 
SOMETIME PROFESSOR OF THE PRACTICE OF MEDICINE, COLLEGE OF PHYSICIANS AND SURGEONS, 
COLUMBIA UNIVERSITY, NEW YORK 
AND 
T. MITCHELL PRUDDEN, M. D., LL. D. 
EMERITUS PROFESSOR OF PATHOLOGY, COLLEGE OF PHYSICIANS AND SURGEONS, COLUMBIA 
UNIVERSITY, NEW YORK 
Uwelttb JEbition 
REVISED BY 
FRANCIS CARTER WOOD, M. D. 
DIRECTOR OF THE PATHOLOGICAL DEPARTMENT, ST. LUKE'S HOSPITAL, NEW YORK 
DIRECTOR OF THE INSTITUTE OF CANCER RESEARCH, COLUMBIA UNIVERSITY, 
NEW YORK 
WITH SEVENTEEN FULL-PAGE PLATES AND "EIGHT HUNDRED AND NINE 
'ILLUSTRATIONS'IN THE TEXT IN BLACK AND COLORS 
NEW YORK 
WILLIAM WOOD AND COMPANY 
MDCCCCXXII Copyright, 1922 \ 
By WILLIAM WOOD & COMPANY 
THE MAPLE PRESS - YORK PA PREFACE TO THE TWELFTH EDITION 
In the revision of this volume for its twelfth edition, many detailed 
textual changes have been made and new illustrations inserted. The 
bulk of such alterations will be found in the chapters on tumors, on the 
liver, and in the portion devoted to the nervous system. Of late years, 
the whole subject of neuro-pathology has been studied with great energy 
and many contributions have been made to our knowledge. Much of 
this work happily originates in this country and is therefore easily acces- 
sible to the student. For this reason the references have been greatly 
amplified in this portion of the book. In the matter of the insertion of 
the references, which have grown to fill a very considerable portion of the 
text, the author has been guided by the fact, obvious to all teachers of 
medicine, that despite the announcement that the average student pos- 
sesses a reading knowledge of French and German upon entrance, the 
actual amount of such knowledge when put to the test of practice often 
resembles most closely one of those imaginary quantities so current in 
the recent physical theories of time and space. But despite this fact 
the medical student during his course is being encouraged to read a great 
deal more than he was a few years ago and to facilitate this excellent prac- 
tice many of the older German and French references have been substi- 
tuted by corresponding ones in English. For after all a reference is of 
little use unless it is going to be used. Fortunately, the development of 
the study of pathology in this country, hampered though it is by our 
medieval laws and attitudes governing post-mortem examination of the 
body, has been considerable of late so that the student who may be 
without access to an extensive library of foreign scientific literature, may 
still inform himself more or less completely on the question in hand. 
I wish to acknowledge here the kindly interest of many of my col- 
leagues in pathology who have made suggestions and helpful criticism 
of the last edition of this book. Many of these suggestions have been 
most useful and as far as possible have been embodied in the present 
text. The author is under special obligations to Dr. I. J. Sands who was 
kind enough to read the chapter on the nervous system and made many 
valuable suggestions for its improvement. 
Francis Carter Wood. 
August 1, 1922. 
III CONTENTS. 
PART FIRST. 
Introduction 3 
CHAPTER I. 
The Conditions of Disease 8 
CHAPTER II. 
Changes in the Circulation of the Blood 22 
CHAPTER III. 
Regressive Tissue Changes 44 
CHAPTER IV. 
Progressive Tissue Changes 73 
CHAPTER V. 
Inflammation 97 
CHAPTER VI. 
Animal Parasites 130 
CHAPTER VII. 
Plant Parasites 158 
CHAPTER VIII. 
The Relations of Micro-organisms to Disease-Infection and Immunity, 175 
CHAPTER IX. 
The Infectious Diseases 226 
CHAPTER X. 
Malformations 355 
CHAPTER XI. 
Tumors 372 
CHAPTER XII. 
The Lesions Induced by- Poisons 469 
CHAPTER XIII. 
General Diseases 485 
CHAPTER XIV. 
The Lesions in Certain Forms of Death from Violence 503 
GENERAL PATHOLOGY. 
V VI 
CONTENTS 
PART SECOND. 
General Considerations 513 
CHAPTER I. 
The Blood and the Blood-forming Organs 514 
CHAPTER II. 
The Lymph-Nodes 546 
CHAPTER III 
The Spleen and Thymus 566 
CHAPTER IV. 
The Thyroid and Adrenals - . . . . 583 
CHAPTER V. 
The Circulatory System 595 
CHAPTER VI. 
The Respiratory System 661 
CHAPTER VII. 
The Digestive System 730 
CHAPTER VIII. 
The Liver 808 
CHAPTER IX. 
The Urinary Organs 849 
CHAPTER X. 
The Reproductive Organs of the Female 909 
CHAPTER XI. 
The Reproductive Organs of the Male 1011 
CHAPTER XII. 
Voluntary Muscle 1031 
CHAPTER XIII. 
The Bones and Joints 1042 
CHAPTER XIV. 
The Nervous System 1089 
SPECIAL PATHOLOGY. 
PART THIRD. 
THE METHOD OF MAKING POST-MORTEM EXAMINATIONS AND THE 
METHODS OF PRESERVING AND EXAMINING 
PATHOLOGICAL TISSUES. 
CHAPTER I. 
The Method of Making Post-mortem Examinations 1185 
CHAPTER IL 
General Methods of Preserving Pathological Specimens and Prepar- 
ing them for Study 1227 PART I. 
GENERAL PATHOLOGY. INTRODUCTION. 
The successful pursuit of pathology-the science which treats of 
disease-depends largely upon the clearness and accuracy of the student's 
knowledge of the fundamentals of both gross and microscopic anatomy, 
of embryology, of biological chemistry, and of physiology. The posses- 
sion of such knowledge by the reader is necessarily assumed in this 
epitomized presentation of a large and rapidly extending field of observa- 
tion and research. 
The Nature of the Living Body.-Leaving aside an accurate definition 
of life, as not indispensable, and at present not attainable, it is impor- 
tant constantly to realize that the normal living body is a complex 
and delicate mechanism incapable of creating new forces, but able, by 
means of its cellular and molecular organization, to accumulate or store 
energy derived from without, releasing this under fixed and definite 
conditions. This storing of energy is possible by means of the capacity of 
living body-cells to build up complex molecular combinations from 
simpler forms. The energy so stored in the cells may later be released 
by the fracturing of the complex molecules into forms of simpler type. 
Both the storing and the releasing of energy are largely bound up with 
the activities of the catalyzers or ferments present in the cell. This 
process it is which makes possible all expression of life. 
The Chemistry of Life.-The complex molecular combinations through 
which energy is stored and released by cells during the processes of life 
are especially characterized by their content of carbon, nitrogen, hydrogen, 
oxygen, and sulphur. Iron and phosphorus are found in some of them 
while numerous other elementary substances often share in their composi- 
tion. Such molecular combinations are called proteins. There is reason 
to believe that the protein molecule is of great size and complexity, that 
during life it is capable of entering upon an exceedingly great variety of 
combinations and readjustments of its structure conditioned upon 
heredity and environment. The simpler types, equally valuable as 
sources of energy, are the fats and carbohydrates, more or less abundant 
constituents of all cells. 
This adjustment takes place, not continuously, but at intervals, for 
one of the most interesting phases of the metabolic manifestations of 
many organisms, both of the lower type and of the more complex, is 
a rhythm of function which expresses itself in successive periods of ac- 
tivity and rest. The most striking is the periodic release of ferments, 
which furnish the body the means, not only of breaking down ingested 
material, but also of synthesizing the same in other portions of the body. 
It is inevitable that the proteins and their performances while sharing 
in the processes of life, and the various influences which determine these 
performances, should fix the storm center of research into the nature of 
life and offer the highest promise of light upon the ultimate and funda- 
3 4 
INTRODUCTION 
mental problems of biology. But we must be patient and not too eager 
to carry the formulae and the working hypotheses of the chemists, with- 
out due reserve, over into the domain of living things, whose story and 
performances, and whose limitations, also, we are only just beginning to 
spell out. 
The details of the chemistry of the life processes, so far as they are 
known, and their relationship to protein substances and protein metabo- 
lism in general, and to the highly specific enzymes, and a consideration 
of the successes, the hopes, and the dreams of the chemists within this 
borderland of living matter, belong in those studies in physiological and 
physical chemistry which naturally precede the consideration of the 
problems of pathology, and should be sought in special treatises.1 
The Characters of Disease.-Many of the earlier views concerning life 
and death and health and disease, which have long since given way to 
more accurate conceptions, still hold a certain sway among the thought- 
less, perpetuated by traditional forms of speech. One of these is that 
disease is an entity, something foreign to the body which may enter from 
without, and with which the body may struggle and fight, which it may 
conquer or to whose ravages it may succumb. It will be wise for the 
student constantly to remember that disease is not a thing, but a process. 
It is an abnormal activity of certain of the physiological functions of the 
body in response to an injury. This may or may not be associated with 
appreciable morphological alterations of the body structure. It is those 
agencies and conditions to which the body has not adapted itself, which, 
swaying its normal capacities now one way and now another, induce the 
functional aberrations and structural alterations by which disease is 
manifested. 
It follows from this that the functional abnormalities and the struc- 
tural alterations which make up the signs, symptoms, and lesions of dis- 
ease involve the expression of no new functional capacities which the 
normal body does not possess. These may be diminished or exalted; 
they may be perverted or abolished; or the cells may now and then re- 
vert to forms and to phases of activity which the body has long since 
outgrown or largely suppressed in its slow adaptation to conditions of 
life which now constitute the normal. But the body in disease manifests 
no new functions, develops no new forms of energy, reveals no new 
capacities. 
The Significance of Cells in Pathology.-If pathology is to be for the 
student or the practitioner anything but a mass of more or less useful facts 
he must learn to correlate its data with the facts and laws of normal 
morphology and normal physiology. While he should be conscious 
always, on the one hand, of the invisible molecular changes which under- 
1 See, for example, Mathews, A. P., Physiological Chemistry, 2d edition, New York, 1917; Hammer- 
sten, Lehrb. d. physiologischen Chemie, Wiesbaden, 1914; Lusk, G., Science of Nutrition, Philadelphia, 
1917; Hober, R., Physikalische Chemie d. Zelle u. d. Gewebe, Leipzig, 1906; Bayliss, W. M., Principles 
of General Physiology, London, 1915; McClendon, J. F., Physical Chemistry of Vital Phenomena, 
Princeton, 1917; Wells, H. G., Chemical Pathology, 3d edition, Philadelphia, 1918; Robertson, Physical 
Chemistry of the Proteids, 1918; Bechhold, H., Die Kolloide in Biologie und Medizin, Dresden, 1912; 
Abderhalden, E„ Lehrbuch d. physiol. Chemie, 3d edition, Berlin, 1914, and Abwehrfermente, 4th 
edition, Berlin, 1914; v. FUrth, 0., Probleme d. physiol, u. path. Chemie, Leipzig, 1912. INTRODUCTION 
5 
lie the manifestations of energy, and, on the other, will not ignore the 
details of gross morphology, his attention will be most constantly drawn 
to the cells as the life units upon which ultimately both the form and 
function of living things depend. He will realize that as the cells of the 
normal body are w'hat they are in form and in function because of the 
conditions under which they have been slowly evolved, and are at the 
moment placed; so when the conditions change and become abnormal, 
it is to the cells that he must look for an understanding of the aber- 
rations and disturbances by which we recognize disease. 
In normal physiology attention is most keenly centered to-day upon 
the structure and performances of cells as the field richest in the promise 
of significant revelations. So, also, in pathology, by similar methods 
and with equal persistence, must the structure and performances of cells 
under abnormal conditions be studied if we are to hope with reason for 
a clearer comprehension of disease. This has long been recognized, and 
to the conception of the pathological processes as essentially cellular 
processes are due the great advances which this phase of biological science 
has made during the past few decades. But the newer knowledge of the 
cell, not as a membranous bag nor as a mere lump of protoplasm, but as 
a complex machine whose various structural features are of the utmost 
significance, has greatly widened the field of cellular pathology. 
Manifestations of heredity which are displayed in the body as a 
whole have long been known. To-day we may and must take account 
of the marks of heredity in individual cell life. Not a few of what we 
call the aberrances of cells in disease are but the expression of cell traits 
and capacities latent in the environment which has become the usual and 
therefore the normal, but finding expression as the sway of the body- 
organism is released under disturbances of its equilibrium. Thus cells 
thrown out of function may in a measure revert in character to types of 
a simpler structure, and cells long comparatively quiescent may, under 
varying stimuli, assume capacities and forms which they seemed to have 
outgrown. 
Of course, in the pursuit of pathological morphology it is the dead 
body and dead tissues with which we are most often engaged. But these 
are of special interest only as they reveal structures or indicate processes 
which were maintained during life. So that he who can most closely 
correlate the knowledge of the living cells with his observations upon 
those which are dead will gain most from his morphological studies. 
The Interrelationship of Cells and of Organs.-While the pathology of 
to-day is essentially a cellular pathology, while it is illuminating and con- 
venient to consider the cells as physiological and structural units, main- 
taining a certain independence of existence and function, it is neverthe- 
less true that beyond their mere juxtaposition in the body, beyond a close 
mutual dependence upon the common blood supply and nerve control, 
there is a subtle and as yet little understood transmission of physiological 
impulses from cell to cell. Whether this is often by protoplasmic con- 
tinuity, by electrical or chemical1 impulses carried by the nerves, or largely 
1 Tashiro, Am. Jour. Physiol., 1913, xxxii, 107. 6 
INTRODUCTION 
by special agents or hormones present in the circulating fluids of the body, 
we do not know. But it should not be left out of the account in some of 
the more complex and subtle problems which, in health as in disease, the 
life of the cell and the life of the body present. 
The interrelationship of organs, and the innervation and circulation 
which they share in common, have most important bearings upon both 
the morphology and physiology of disease. This relationship will be 
considered briefly in the later chapters of this book, but should receive 
especial attention in the study of clinical pathology. 
The Excitants of Disease.-When we study the so-called causes of 
disease, we should remember always that, underlying the manifestations 
of disease, as well as sustaining the correlated processes which we name 
health, are the complex and ceaseless chemical transformations which in 
both health and disease alike supply the energy which sustains all ex- 
pression of life. So that what we are wont to call the causes, whether 
external or internal, of disease are really not primary or efficient causes, 
but liberating impulses or excitants which sway and modify the orderly 
transformations of energy constituting health, with those manifestations 
of perturbed function or altered structure, or both, on which our con- 
ceptions of disease are framed. 
Phases and Classifications of Pathology.-Pathology, then, deals with 
the disturbances of function and the alterations in structure in living 
beings, induced by unusual agencies and conditions. The functional 
disturbances thus induced are embraced as symptoms of disease in 
physiological or, far better, f unctional pathology, which so largely domi- 
nates the scientific activities of the physician and forms the basis for the 
practice of his art. The phenomena of pathological physiology are in no 
sense opposed to those of normal physiology, but are their inevitable 
correlatives when the living body is placed under sufficiently abnormal 
conditions. Morphological pathology is concerned with the structural 
alterations of the organism which may result from abnormal conditions. 
Morphological pathology deals with both the gross and the micro- 
scopic alterations of structure, and hence embraces both pathological 
anatomy and pathological histology. 
But alterations in structure are so closely associated with disturbances 
in function, and both are so constantly dependent upon the inciting fac- 
tors in disease, that an intelligent study of morphology necessitates a 
constant consideration of etiology and of certain phases of pathological 
physiology. 
It is customary and convenient in the study of pathology to consider 
together the general or elementary abnormal processes and conditions 
and the etiological factors in disease without reference to their special 
manifestations in particular organs or parts of the body. This division 
of the subject is called General Pathology. Special Pathology deals with 
the forms and details of lesions in individual organs or parts of 
the body. 
Correlated Sciences.-The human body is so complex in its organiza- 
tion that the student of pathology, like the student of normal morphology INTRODUCTION 
7 
and physiology, is under the constant necessity of seeking light through 
the study of simpler organisms. In our extremely differentiated and 
intimately coordinated cells, many features fundamentally simple are 
veiled or modified; so that we can understand them only when we inter- 
pret them in the light of less advanced forms. In other words, the 
results of this differentiation, by which we mean the formation and 
localization of many different kinds of substances out of the relatively 
simple structures of the primitive cell, are so complex that we must turn 
to simpler types with less highly organized structure and more constant 
environment than exist in the mammalia. For this reason many of the 
most important discoveries concerning fertilization have been made on 
the free-swimming sexual cells of the sea urchin and other similar marine 
forms. 
Thus it is that in the lore of the zoologist and the botanist we may 
find the key to obscure and important manifestations of aberrant cell 
life. It is, in truth, through the pursuit of comparative pathology that 
some of our greatest advances in the conceptions of disease have been 
won, and in it lies much promise for the future. With the help of 
embryology, many obscure pathological conditions may be better under- 
stood. The highly developed technical methods of physiology and 
pharmacology, also, have been most valuable by placing in the hands of 
the experimental worker in pathology apparatus already perfected for 
purposes but slightly different from his own. 
But it is to chemistry, both of the cell and of the organism, in health 
and in disease, that the scientific physician looks most eagerly for the 
solution of the manifold problems of medicine which each day become 
more numerous and urgent. 
It is not, however, only the biological form of chemistry which holds 
out promises for the future; its youthful cousin, the physical, is daily 
extending its interest in many aspects of medicine. For we are realizing 
more clearly that in those complex and subtle processes which we are 
wont to call vital, such physical factors as molecular constitution, surface 
tension, conditions of dispersion, osmosis and diffusion, electrical equi- 
librium, elasticity, and pressure, are of the highest significance and in 
our studies cannot be wisely ignored. 
It is well to remember, however, lest any undue optimism lead to the 
notion that but little remains to be done, that biological chemistry is 
not yet directly concerned with the composition and intracellular trans- 
formations of living cells, but only with their decomposition products 
and the exchanges which go on between the cell and its environment. 
It is still, therefore, engaged with the interpretation of living processes 
in the terms of dead protoplasm or its dead products. Life still, as ever, 
escapes analysis.1 
1 For a discussion of these and cognate problems as related to pathology, see Marchand and Krehl, 
Handbuch d. allg. Pathologie, Leipzig, 1912; and Bouchard and Roger, Pathologic g6n6rale, Paris, 1912. 
For interesting studies on the general biological methods of attack, using the lower animals, see 
Child, C. M., Individuality in Organisms, Chicago, 1915; and Senescence and Rejuvenation, Chicago, 
1915. CHAPTER I. 
THE CONDITIONS OF DISEASE. 
Adaptation in Health and Disease.-The human body, like other 
living organisms, has acquired its present form and its varied functions 
through gradual adaptation to its environment. 
The maintenance of the normal life of the body involves a normal 
mechanism and impulse to start with, and a constant and successful 
adjustment to the conditions under which it is placed. While the 
continuance of the state which we call health depends upon the approxi- 
mate maintenance of the external conditions to which the body has 
become adapted, it should be borne in mind that the adaptive capacity 
of the body is in many ways so effective that it can maintain its normal 
structure and functions in spite of unusual surroundings and adverse 
influences. Thus, for example, the body can adapt itself, within the 
limits of what we call health, to alterations, deficiencies, or excesses of 
nutrient material; to varying extremes of heat or cold, moisture or dry- 
ness; to electrical tension; to animal and vegetable parasites; and to 
various poisons, both those which come from without and those which 
result from faulty metabolism. Beyond certain rather ill-defined limits, 
however, the adaptive capacity cannot go, and disease results. 
Disposition to Disease.-The adaptive capacity may vary greatly in 
different individuals, depending upon age, sex, race, etc., so that adverse 
conditions which one individual can sustain without marked functional 
disturbance or structural damage may induce in another more or less 
serious disease. There is thus disposition and relative immunity to dis- 
ease. For example, children are in general much more disposed to cer- 
tain diseases than are adults; and the negro is more prone to develop 
keloid tumors than is the white race. This disposition to disease is not, 
however, always fixed, but may give way to immunity under conditions 
which we shall study especially in the acute infections. 
Disposition to disease may be inherited and find expression through 
obvious structural abnormalities or through subtle functional defects, 
difficult or impossible to define or detect. 
Classes of Disease Conditions.-The harmful conditions to which the 
body may be subjected and which incite disease may be divided into two 
classes, external and internal. We may thus speak of external and inter- 
nal conditions of disease. 
It does not fall within the scope of this book to enter upon a dis- 
cussion of the many and varied conditions under which disease occurs, 
nor to place in array the many and wearisome phases of classification 
which have been more or less imposing or useful in the earlier days of 
8 CONDITIONS OF DISEASE 
9 
pathology and medical practice. We shall consider here only some of 
the more general conditions of disease, referring for a study of the de- 
tails of the specific excitants to later chapters. 
External Conditions of Disease. 
Disturbances of Nutrition.-The body may suffer through excessive 
or deficient nourishment. Too much food may in certain, though not 
in all, persons lead to an abnormal accumulation of fat. Too much food 
or unsuitable food may lead to disorders of the digestive apparatus 
or it may lead to the production within the body of metabolic sub- 
stances which seriously damage important organs.1 There is much 
reason for believing that through such faulty metabolism forms of 
autointoxication may arise which damage the parenchyma of the 
liver and kidney, for example, so that structural as well as functional 
disorders arise. 
On the other hand, through insufficient nutriment the fat may 
disappear,, the voluntary muscle substance diminish, and the blood 
deteriorate.2 Inanition may, however, occur in persons whose food 
supply is both abundant and suitable; for example, in structural or 
functional disorders of the digestive organs, in the insane, etc. Nutri- 
tion may suffer also in the absence of a sufficient amount of water or of 
proteins or of inorganic salts in the food.3 
Air Supply.-Through the function of respiration a supply of oxygen is 
furnished to the blood in the recesses of the lungs, and excretory prod- 
ucts are carried off. The failure of this function may be due to a lack 
of air bearing the oxygen or to some interference with the respiratory 
channels or mechanism. The failure of oxygen to reach the lungs in 
proper condition and quantity is followed by forcible respiratory efforts 
which mark dyspnea. A fatal suppression of respiration by the ex- 
clusion of air is called suffocation or strangulation. Asphyxia is a con- 
dition in which respiration is suspended, but the heart continues to beat. 
This condition is of frequent occurrence in the new-born, and is associ- 
ated with many forms of disease of the respiratory organs. (For a more 
detailed consideration of asphyxia, suffocation, and strangulation see 
page 503.) 
Occupation.-Many diseases are closely dependent in origin upon 
unsanitary conditions associated with occupation. The dusty air 
prevalent in many stores, factories, theatres, court-rooms, prisons, 
schools, etc., may damage the lungs directly and render them more 
vulnerable in the presence of pathogenic microorganisms. The high 
temperature and foul air common in many places of work or assembly 
may be serious predisponents to disease. Finally, the abuse of alco- 
1 For interesting studies in the effect of deficient dietaries, see Mendel, L. B., Jour. Am. Med. Assn., 
1915, ixiv, 1539; and numerous papers by Osborne and Mendel, Jour. Biol. Chern., 1912, xii, 473; 1915, 
xx, 351; 1915, xxiii, 439; 1916, xxv, 1; 1916, xxvi, 1. 
2 Benedict, F. G., The Influence of Inanition on Metabolism, Carnegie Inst., Washington, Bull. 77, 
1907; Meyers, Jour. Med. Research, 1917, N. S. xxxi, 51. 
3 Consult for details, Lusk, Science of Nutrition, Philadelphia, 3d edition, 1917; and Wells, Chemical 
Pathology, 3d edition, Philadelphia, 1918. 10 
CONDITIONS OF DISEASE 
holic drinks and tobacco may be cited among many common excesses 
as agencies through which the conditions of disease are fulfilled. 
Damage from Excessive or Deficient Heat.-Through the heat-regu- 
lating mechanism of the body a remarkable adaptation to moderate 
elevations of temperature is possible.1 But the maintenance of life is 
incompatible with very high temperatures. 
Local exposure to both extreme heat and extreme cold induces necro- 
sis and various phases of inflammation of the tissues. 
Death may be caused by the inspiration of smoke and flame; by the 
drinking of hot fluids; by the direct contact of flame or hot substances 
with the external surface of the body. It may be due to the direct efiect 
of the agents, to secondary affections of the viscera, or to the exhaustion 
produced by long-continued inflammation and suppuration. Sudden 
death may occur after extensive burnings of the skin.2 
It is usual to divide burns into four degrees: 1, erythema of the skin; 2, formation 
of vesicles; 3, formation of an eschar; and 4, charring of the tissue. In the erythema- 
tous stage, the only lesions are a reddening of the skin due to the widening of the 
capillaries under the influence of the irritation, edema of the subcutaneous tissue, and, 
later, separation of the upper layer of the epidermis in the form of scales. The second 
degree burn, in which vesicles are formed, shows on examination only large or small 
collections of serum which lie in the upper layers of the skin and push up the epidermis. 
The basal layers of cells may remain attached to the corium in mild cases. If the 
fluid is drained off, repair takes place in a short time with covering of the granulation 
tissue of the corium by new epithelium, and a return to normal conditions if the burn 
has not been too deep; otherwise the hair, sweat, and sebaceous follicles may not 
regenerate and the epidermis may remain thin and smooth, without the rugae which are 
usually present in the normal skin. The section of such a scar shows that the normal 
papillary downgrowth of the epithelium into the corium has not been regenerated, but 
that the layer of epidermis is very thin, smooth, and of even thickness. Extensive 
changes of this type are noted only after suppuration has occurred, and not when the 
serum is absorbed aseptically. 
In a third degree burn, that in which an eschar is formed, the upper layers of the 
skin are actually destroyed by contact with the burning agent, whatever it may be. 
The microscopic examination of such skin shows on the surface a mass of dead tissue, 
either brownish or blackish, and thrombosed vessels, with great injection of those of 
the deeper tissues. A very considerable edema separates the connective-tissue 
fibers of the corium. The area about the eschar usually shows burns of the first and 
second degree. When the necrotic area separates from the healthy tissue, suppura- 
tion is likely to take place with local and general sepsis, and the final results may be a 
deep ulcer with erosion of the larger vessels, thrombosis, and a consequent embolus of 
the various organs, and, at a later stage, amyloid degeneration of the internal viscera 
through the suppuration. As soon as the eschar has separated, the wound granulates 
and forms a dense scar, which may or may not be covered up with epithelium. 
Whether this occurs or not depends upon the size of the burned area, for the ingrow- 
ing epithelium will extend just a certain distance. The scar tissue in the skin causes 
contractures of various types, even in superficial burns. In every deep burn there is 
always a tendency for the tissue to break down and form ulcers later, even after com- 
plete epidermization has taken place. Very rarely a squamous-cell epithelioma or a 
sarcoma may develop in the scar. 
The lesions of burns of the fourth degree do not differ essentially from those of the 
third. The surface of the skin is deeply charred; the lesions extend into the corium 
or the subcutaneous fatty tissue; and in-consequence, the ulceration and scarring, if 
1 Lee, F. S., Am. Jour. Pub. Health, 1912, ii, 863 (bibl.); Jour. Am. Med. Assn., 1914, Ixiii, 1625, 
(bibl.); Science, 1916, xliv, 183. 
2 For a study of sudden death following severe burns, consult Silbermann, Virchows Arch., 1890, 
cix, 488 (bibl.). CONDITIONS OF DISEASE 
11 
the subject survive the injury, is much more severe. Recovery depends very largely 
on the area of the skin involved; where more than half the body is burned, even to a 
very slight degree, death is almost certain to occur. It is not possible to produce the 
appearance of a burn by heat applied to the skin after death. 
After death from severe burns there is apt to be congestion of the brain and the 
thoracic and abdominal viscera. The lymph-nodes and the lymphatic tissues through- 
out the body may be swollen and the seat of endothelial-cell proliferation and necrosis. 
There is usually albuminous degeneration of the liver and kidneys; the spleen is 
swollen, and the seat of focal necrosis. Focal necrosis in the bone-marrow has been 
noted. There may be capillary thromboses, interstitial hemorrhages in the kidney, 
hemoglobinuria, and leucocytosis. These lesions indicate the presence of toxic sub- 
stances in the body fluids, and thus the general condition may be regarded as an in- 
stance of autointoxication.1 
Secondary lesions are not infrequent after severe burns. There may be edema of 
the glottis, pseudomembranous inflammation of the larynx and trachea, pneumonia, 
ulceration of the duodenum,2 and pyemia with infarctions in the lungs, liver, spleen, 
and kidneys, and lesions in the suprarenal capsules. 
The action of cold on the body causes both general and local changes, which 
resemble to a certain extent those caused by heat, although the internal changes are 
much less extensive. Locally, three degrees of injury by cold may be described: 
1, an erythema of the skin; 2, a vesicular stage; and 3, an actual necrosis due to frost. 
The skin and subcutaneous tissue will bear a considerable degree of freezing if thaw- 
ing takes place promptly, as is known to all who have used cold as a local anesthetic; 
if, however, the freezing has lasted beyond a certain stage, the tissues, when they thaw 
out, show the first degree of frost-bite. The skin, after the reaction sets in, is very 
much reddened and swollen. Microscopically, the vessels are dilated, and the tissues 
are edematous. After a few days, repair usually takes place, but the tissues remain 
sensitive for a considerable period, and fresh freezing generally results in a more severe 
lesion. This condition is what is known clinically as chilblain. These are chronically 
inflamed, usually sharply localized, swellings of the skin, which are caused by paralysis 
of the vessels, serous exudation, and inflammatory hyperplasia of the skin and corium. 
They are most commonly seen on the hands and feet, especially on the extensor 
surface of the joint or outer part of the foot, less frequently on the face, and are usually 
due to repeated light chillings of the skin, especially in wet weather. They occur 
most often in young people, especially anemic and poorly nourished individuals. If 
they are improperly cared for, ulceration may occur, but if well treated they usually 
heal spontaneously. The chief reason for the interest which they excite is their 
extreme painfulness on pressure. 
In the second degree of frost-bite, the skin is violet or deep red, and is covered with 
vesicles, and there is stasis in the smaller arteries, which leads to exudation of plasma, 
to edema, and to the formation of the vesicles. The contents of the vesicles are usu- 
ally colored with blood, rarely purely serous. Such a lesion may heal without serious 
alteration of the tissue, but if infection takes place, it may dry up and form the so- 
called mummified slough, with, later, demarcation from the sound tissue. Such 
gangrene occurs even if the temperature to which the tissues are exposed is not below 
freezing. It is due, as stated, to circulatory disturbances. If the cold is much greater 
the gangrene is due to actual killing of the tissues by freezing. 
While exposure of the entire body to cold may cause death there is nothing char- 
acteristic in the post-mortem findings. The symptoms as reported by arctic travellers 
point to a general reduction of the activity of the body functions and cerebral ischemia 
with slowed respiration, low blood pressure and pulse rate, great somnolence, and, 
ultimately, coma. Recovery has been observed after the body temperature had 
fallen as low as 24°C. 
1 For a study of the visceral changes following extensive burns, consult Bardeen, Jour. Exper. Med., 
1897, ii, 501 (bibl.); McCrae, Trans. Assn. Am. Phys., 1901, xvi, 153; and Locke, Boston Med. and 
Surg. Jour., 1902, cxlvii, 480 (bibl.). For additional bibl. on the effects of heat and cold, see Krehl 
and Marchand, Handb. d. allg. Path., vol. i, Leipzig, 1908. 
2 This phenomenon is extremely rare and by many is considered to be merely an accidental concur- 
rence of ulcers of the duodenum with death from burns. For report of an undoubted case and discus- 
sion, see Busse, Otto, Verhandl. d. deutsch path. Gesellsch., 1914, xvii, 290. 12 
CONDITIONS OF DISEASE 
Electricity.-Lightning.-A large proporti'on of the persons who are 
struck by lightning die instantly; but those who survive the immediate 
effect may recover quickly without serious injury. The more seriously 
injured may continue comatose or delirious for several hours, and then 
either die or recover; or they may die after some time from the effects of 
the burns and injuries received. 
The post-mortem appearances are very variable. Sometimes there 
are no marks of external violence or internal lesions. Sometimes the 
clothes are burnt and torn, while the skin beneath them is unchanged. 
Usually there are marks of contusion and laceration, or ecchymoses, 
or lacerated, punctured wounds, or fractures of the bones, or super- 
ficial or deep burns. The track of the electric current may sometimes 
be marked by dark red arborescent streaks on the skin. Fractures 
are rare. 
The internal viscera may be lacerated and disorganized from lightning. 
Artificial Electrical Currents.-In death from powerful artificial elec- 
trical currents, either by accident, as in linemen and others, or in elec- 
trical executions, there may be local burnings of varying degree where 
the wires or electrodes come in contact with the skin. The clothes may 
be pierced with holes at the point of exit of the current. Internally 
there appear to be no marked or characteristic lesions, either gross or 
microscopical, in this form of death. Observations have been made of 
the occasional, not constant, occurrence on the floor of the fourth ven- 
tricle of small hemorrhages, the significance of which is doubtful. Other 
petechial spots have been noted beneath the serous surfaces of the endo- 
cardium, pericardium, and pleura, and on the spleen.1 Some days after 
injury from high voltage alternating currents, gangrene may occur in a 
limb through which the current has passed. The phenomenon is due to 
an extensive endarteritis involving the endothelium and subendothelial 
tissues of the large arteries and resulting in the formation of extensive 
thrombi. The localization of the changes points to the vessels as being 
the best conductors of the current, for the surrounding tissue is spared. 
Roentgen Rays and Radium.2-Since it has been shown that Roentgen 
rays and the gamma rays of radium are light rays of very short wave 
lengths, the finer mechanism of their action has been much studied. 
Apparently such light rays have the capacity to break up the atom in 
their passage through it and to set free ionic particles with a considerable 
velocity.3 It is these negatively charged particles, and not the rays 
themselves, which act upon the tissues and induce destructive processes. 
The effect is primarily upon the nucleus without immediate interference 
with the life of the cell. Threshhold exposures stimulate division of the 
nucleus; large ones slow such division; still larger exposures kill the 
> Cunningham, New York Med. Jour., 1899, Ixx, 581, 615; Jelliffe, Peterson and Haines, Text- 
book of Legal Medicine, Philadelphia, 1904, i, 245. 
2 For general information on z-rays and radium, see Rutherford, E., Radioactive Substances and Their 
Radiations, Cambridge, 1913; Kaye, G. W. C., X-rays, 2d edition, London, 1917; Colwell, H. A., and 
Russ, S., Radium, X-rays and the Living Cell, London, 1913; Janeway, H. H., Barringer, B. S., and 
Failla, G., Radium Therapy in Cancer, New York, 1917. 
3 See, for methods of photographing these ions as they are given off, Wilson, C. R. T., Proc. Roy. 
Soe., Ser. A, 1911, Ixxxv, 285. CONDITIONS OF DISEASE 
13 
nucleus, but do not act lethally upon the cytoplasm.1 In ascaris, the 
dividing cell is at least eight times as vulnerable to radiation as that in 
the resting phase, the increased vulnerability being most evident in the 
metaphase.2 Thus, it has been shown that embryonic chicken heart 
muscle growing in vitro will continue to beat for days after the nucleus 
has been killed by exposure to a lethal dose of radium.3 The same is 
true also of trypanosomes,4 which retain their motility, but cannot divide. 
Hertwig,5 in a series of experiments on frogs' ova, demonstrated that with 
radium it is possible so to damage the nucleus of the ovum or spermato- 
zoon that it cannot functionate with the nucleus of an untreated cell of 
the other sex, although the sperm still possesses the power of initiating 
the maturation division of the ovum or, if untreated, to cause division of 
the radiated egg and supply a male nucleus. In such cases the larva 
which develops is either male or female, depending upon whether the 
nucleus of the ovum or of the spermatozoon has been killed. 
In mammalian tissues the cells of the blood-forming and lymphoid 
apparatus are the most sensitive to radiation. Other tissues and organs 
show varying degrees of susceptibility; next to the spleen and bone- 
marrow, the gonads are most easily influenced; the thymus, also, is very 
sensitive. The muscles, connective tissues, cartilage, bone, salivary and 
thyroid glands, and especially the brain are quite insensitive to any but 
very extreme and repeated exposures. Touch corpuscles and other 
terminal apparatus of the nerves seem easily killed. 
The milder lesions produced by radium or Roentgen rays are most 
easily studied in the skin. Moderate exposures produce, after about 
ten days, an erythema with dilatation of the vessels, perivascular collec- 
tions of leucocytes, and swelling of the capillary endothelium. The 
Malpighian layer of the skin is edematous, the cell nuclei are pycnotic 
and stain poorly, and later the cells may fuse to form syncytial groups. 
The sweat glands and hair follicles are edematous and surrounded by 
leucocytic infiltration. Restoration to normal takes place rapidly. If 
the burn is more severe, thrombosis of the vessels may occur with areas 
of hemorrhage. The cellular changes are more extensive, with great 
edema of the connective tissue. After severe burns complete restitution 
may not take place, but the epidermis may remain thin, the corium 
dense, with few vessels, and the hair, sweat, and sebaceous glands atrophic. 
A network of dilated vessels may persist under the skin. These areas of 
altered skin are very sensitive to further radiation, and are very apt to 
break down and ulcerate without apparent cause. 
After excessive exposures to Roentgen rays or radium, there is very 
little tendency to heal; even skin grafts do not take well on the devitalized 
surface, the reason being chiefly the condition of the blood-vessels. The 
surface of such a burn is covered with a layer of granulation tissue, 
1 Packard, C., Jour. Exper. Zool., 1915, xix, 323; 1916, xxi, 199. 
2 Mottram, J. C., Arch. Middlesex Hosp., 1913, xxx, 98. 
3 Prime, F., Proc. New York Path. Soc., 1916, xvi, 56. See, also, v. Wassermann, Deutsch, med. 
Wchnschr., 1914, xl, 524. 
4 Halberstaedter, Berl. klin. Wchnschr., 1914, li, 252. 
6 Hertwig, O., Handbuch d. Radium-Biologie und -Therapie (Lazarus), Wiesbaden, 1913, p. 163. 14 
CONDITIONS OF DISEASE 
which may be fairly firm and usually is infiltrated with large numbers of 
plasma or lymphoid cells. In the connective tissue are often found large 
cells with irregular nuclei in fairly close connection with similar strands 
of cells which extend down from the epidermis and lead to the suspicion 
that these cells are epithelial in origin. In general, however, they lie 
close to the surface. Occasionally, below the ulcerated area the tissue 
loses its inflammatory infiltration, except for occasional collections of 
lymphocytes and plasma cells, and assumes a very firm consistence. 
Fat areas may remain of normal appearance; nerve trunks show atrophy 
of the nerve fibers with the production of a large amount of connective 
tissue in the bundles. There may be scattered areas of phagocyted 
blood pigment from old hemorrhages. The connective-tissue sclerosis 
may reach an extraordinary degree; areas may be found where only a 
half dozen nuclei are visible in the field of a low power lens. The nuclei 
are also abnormal, with a small amount of chromatin either distributed 
throughout the entire nucleus or gathered in pycnotic masses; the 
latter is observed especially if the burn has been recently treated with 
x-ray with the idea of stimulating it to heal. But it is in the blood- 
vessels that the most striking lesions occur. There is an extraordinary 
thickening of all the vessel coats, leading in some places to complete 
obliteration of the lumen, while in others a small space may still remain 
patent. The hypertrophy seems to be chiefly in the subendothelial 
layers, the circular bundles remaining fairly well defined. The endo- 
thelial lining usually persists. The elastic lamina does not show' at all 
clearly in those vessels which have undergone extensive alterations, but 
is broken up into small particles. Not every vessel is affected and, as a 
rule, the veins are less damaged than the smaller arteries. The devitali- 
zation of the tissue is due, therefore, to the diminution in the blood 
supply. These tissues, when incised, bleed continuously, as the vessels 
have lost their contractility.1 
If epidermization does occur, the skin is thin and very apt to break 
down at intervals, even years after the burning has occurred. Carcin- 
omata may develop in these scars, but are much more apt to follow 
repeated, non-burning exposures over a long period. The skin under 
these circumstances loses its flexibility and becomes thickened, with the 
formation of keratotic areas. These may appear and undergo spontane- 
ous healing, only to reappear again. Ultimately, when the victim has 
reached the cancer age, malignant changes may develop in these kera- 
toses, which, even before they alter their character, very closely resemble 
epitheliomata. Fortunately, with increased knowledge of the dangers 
of x-rays and radium, greater care is taken to protect the workers and 
patients, and severe burns or chronic irritation of the skin or sterility due 
to gonad destruction is a thing of the past.2 
The changes in the morphology of irradiated tumors are much the 
same as those described as occurring in the skin. 
1 For a study of chronic x-ray dermatitis, see Wolbach, S. B., Jour. Med. Research, 1909, N. S. 
xvi, 415. 
2 Hesse, O., Symptoinatologie, Pathogenese u. Therapie d. Rontgenkarzinoms, Leipzig, 1911; 
Pfahler, G. E., Jour. Am. Med. Assn., 1914, Ixii, 189; Ordway, T., ibid., 1916, Ixvi, 1. CONDITIONS OF DISEASE 
15 
The mechanism seems to be threefold: 1, the direct lethal action of 
the rays on the tumor cells; 2, the obliterating effect on the capillaries 
producing ischemic necrosis of portions of the tumor; and 3, the blocking 
effect of the late connective-tissue sclerosis. Whether other factors 
enter it is premature to say. The production of an active immunity by 
stimulation of certain cells such as the lymphocytes, as claimed by 
Murphy,1 is contrary to our experience in artificial immunity experi- 
mentally induced against the implantation of animal tumors, and seems 
not to be successful in the case of human neoplasms. 
Fig. 1.-Phagocytosis of Squamous Epithelium in Case of Radiated Epithelioma. 
Similar pictures may be seen in untreated tumors which are undergoing spontaneous regression. 
The tumor cells show pycnosis and chromatolysis of the nuclei and 
tend to form syncytial aggregations. The latter are presumably due to 
paralysis of the mitotic apparatus with continued vegetative functioning 
of the cytoplasm. Occasionally, tumor cells can be seen undergoing 
phagocytosis (Fig. 1) after their injury by radiation, but they are also 
unquestionably dissolved under the influence of the autolytic ferments and 
removed through the usual channels of the blood and lymph streams. 
Sudden shrinkage soon after treatment is often seen in very vascular 
1 Murphy, J. B., and Morton, J. J., Jour. Exper. Med., 1915, xxii, 204; Loeb, L., Jour. Am. Med 
Assn., 1915, Ixiv, 726. 16 
CONDITIONS OF DISEASE 
tumors and is due to thrombosis of the vessels with consequent necrosis 
of large areas of the tumor and absorption of the necrotic mass. At the 
periphery, where the tumor cells receive nutrition from the well-formed 
capillaries of the healthy connective tissue, survival of isolated areas of 
tumor is the rule, unless the exposure was sufficient to destroy the normal 
tissue also. As healthy granulation tissue is just as susceptible to the 
action of the rays as are growing cancer cells, there is probably no essen- 
tial sensitiveness of the cancer cell over the multiplying normal cell of 
the same type. Practically the same degree of sensitiveness is observed 
in radiated tissue cultures of carcinoma, sarcoma, normal connective 
tissue, and epithelial cells. These facts point to the limitations of radio- 
therapy, for the successful destruction of a highly malignant neoplasm 
implies the serious damage of the surrounding normal tissues.1 With 
Fig. 2.-Basal-cell Epithelioma of the Nose Showing Small Area of Squamous Cells. 
The tumor was removed surgically after failure to cure with radium. The squamous cells resist 
the rays, while the basal cells do not-an evidence of difference in radiation sensitiveness even in tumor 
cells. 
tumors of low virulence, such as the basal-cell epitheliomata of the face, 
the tumor cells may disappear before the healthy tissues are much dam- 
aged. The same is true of certain tumors, such as those of the uterus, 
where the remainder of the body is protected by the thick walls of the 
organ and large doses of radium can be given without excessive destruc- 
tion of vital tissue. Similarly, the tumors composed of lymphoid cells 
(lymphosarcomata) are in some instances curable, as the lymphocyte is 
very much more sensitive to radiation than is the connective-tissue cell. 
A similar sensitiveness has enabled striking results to be obtained in the 
treatment of the chronic myelogenous type of leukemia, in which radia- 
tion of the spleen and bone-marrow may bring the circulating blood to 
normal and unquestionably greatly prolong the life of the patient. The 
lymphatic forms of leukemia and the acute types do not respond so well. 
After exposure of tumors or leukemic masses to radiation, the nitrogen, 
i Wood, F. C., Trans. Assn. Am. Phys., 1914, xxix, 430; Wood, F. C., and Prime, F., Ann. Surg., 
1915, Ixii, 751; Prime, F., Proc. New York Path. Soc., 1916, xvi, 56; Jour. Cancer Research, 1917, 
ii, 107. 17 
CONDITIONS OF DISEASE 
and uric and phosphoric acids of the urine are increased owing to the 
excretion of cell constituents. 
Ultraviolet Light.-Light1 of ordinary wave length has but little 
destructive effect on the skin or subcutaneous tissues, merely producing 
pigmentation, even though it is capable of passing through a consider- 
able thickness of tissue, as is shown by the possibility of demonstrating 
the spectrum of sulphemoglobin through the palm of the hand when 
the latter is illuminated by sunlight. But if the tissues are sensitized 
by the injection of substances which very intensely absorb the rays of 
ordinary light, remarkable physiological effects may be produced. For 
example, if mice into which small quantities of hematoporphyrin have 
been injected are kept in a dark place, they remain in perfect health until 
the pigment is excreted in the urine; but if placed in the sunshine they 
die in convulsions in a few minutes.2 Patients in whom a pathological 
amount of hematoporphyrin is formed have been noticed to suffer from 
skin lesions (hydroa oestivale) and even to show necrotic areas in the 
portion of the body exposed to light.3 
These phenomena are based upon the well-known physical law that 
the chemical activity of the absorbed light is dependent upon the presence 
of absorption bands for a given wave length.4 Thus, a photographic 
plate not ordinarily sensitive to green, becomes, when stained with 
erythrosine, a dye which has a strong absorption in the green portion of 
the spectrum, extremely sensitive to light of approximately the same 
region.5 
As was first shown by Finsen,6 ultraviolet light is very active in pro- 
ducing changes in the skin, though it penetrates only about 0.5 mm., but 
if the tissues are rendered bloodless by pressure, the same light pene- 
trates nearly 5 mm. of skin, inducing inflammatory reactions at this 
depth. The protecting influence of the blood is due to its great absorp- 
tive power for ultraviolet light. The nature of the action on the tissue 
proteins is coagulative;7 and the effect is not due to an alteration in the 
activity of the intracellular enzymes.8 The susceptibility of the color- 
less cellular protoplasm or proteins in general to ultraviolet light seems to 
be conditioned upon the selective absorption of the rays by the aromatic 
amino acid radicals of the proteins. Such absorption bands were demon- 
strated forty years ago by Soret,9 and recently Kober10 has shown that 
tyrosin and phenylalanin have absorption bands in the ultraviolet; 
1 For a general review of the effect of light on the organism see Jesionek, A., Lichtbiologie u. Licht- 
pathologie, Wiesbaden, 1912; Bering, FLubarsch-Ostertag, Ergebn. d. allg. Path., 1914, xvii1, 790 
(bibl.)j Clark, J. H., Physiological Reviews, 1922, ii, 277 (bibl.). 
2 Hausmann, W., Uber optische sensibilisatoren in Tier- u. Pflanzenreiche, Fortschr. d. Natur- 
wissenschaft Forsch. (Abderhalden), 1912, vi, 243. 
3 Ehrmann, S., Arch. f. Dermat. u. Syph., 1909, xcvii, 83; Konigstein, H., and Hess, L., Dermat. 
Ztschr., 1910, xvii, 911; Linser, Arch. f. Dermat. u. Syph., 1906, Ixxix, 251. 
4 See v. Tappeiner, H., and Jodbauer, A., Die sensibillisierende Wirkung fluorescierender Substanzen, 
Leipzig, 1907; Flexner, Jour. Exper. Med., 1906, viii, 1; Mathews, Physiological Chemistry, New York, 
1917, p. 44. 
6 See Eder, Handb. d. Photographic, Halle a. S., 1902, vol. ii, part 2. 
8 Finsen, N„ Mitt. a. Finsens med. Lysinst., 1900, vol. i to x. 
7 Burge, W. E., Am. Jour. Physiol., 1917, xliii, 429. 
8 For histological details see Moller, Bibliotheca Medica, 1900, Heft 8. 
' Soret, Arch. d. sc. phys. et nat., Geneve, 1878, p. 322, 359. 
10 Kober, P. A., Jour. Biol. Chem., 1915, xxii, 433. 18 
CONDITIONS OF DISEASE 
hence, the filtration of ultraviolet rays through solutions of these sub- 
stances inhibits the toxic action of the rays upon living cells.1 
The effects produced by ultraviolet light are familiar in the form of 
sunburn. More serious erythema and even deeper lesions are produced 
by exposure to naked electric arcs, especially those with magnetite 
poles (iron giving a spectrum rich in ultraviolet rays), to quartz mercury 
vapor lamps, and to other powerful illuminants which are used commer- 
cially. Fortunately, as has been stated, ultraviolet light does not pene- 
trate well vascularized tissue for more than about 0.5 mm., and while the 
cornea is transparent, the lens of the eye protects the retina so that 
resulting burns are superficial and of little practical importance, especially 
as a thin layer of ordinary glass completely absorbs the ultraviolet light. 
The general effect of ultraviolet light on the organism is to increase 
metabolism and, secondarily, to stimulate the blood-forming organs 
and general resistance to infection; hence, notwithstanding the slight 
penetration of sunlight, the exposure of the bodies of tuberculous persons 
to direct action of the sun's rays at high altitudes has produced extra- 
ordinary improvement in the lesions, and in many cases caused rapid 
restoration to health.2 
Trauma.-The various forms of mechanical injury which the body 
may suffer need not be considered here in detail. The significance to 
life and health depends upon the extent of the injury and the part of 
the body affected. Thus, a concussion of the brain, even without 
obvious structural lesion, may be immediately fatal, while extensive 
laceration or crushing of a limb or muscle may be readily recovered 
from. 
Foreign Bodies.-We shall see later how the presence of lifeless 
foreign bodies, or of animal and vegetable parasites-bacteria, pro- 
tozoa, etc.-may be harmful to the organism, and the adaptive measures 
by which in favorable cases protection is secured. 
Poisons.-Certain forms of poisons are to be reckoned among the 
external agents harmful to the body. These will be considered in a 
later section. 
Increased Atmospheric Pressure (Caisson Disease).3-An extreme in- 
crease in atmospheric pressure, such as is often nowadays maintained 
in tunnels, caissons, and other construction works, is sometimes the 
occasion of death, especially when the pressure is relieved by a too sud- 
den return to normal conditions, that is, in what is technically called 
decompression. The danger seems to lie, apart from individual sus- 
ceptibility, in the rapidity of the decompression. 
When the pressure is relieved, susceptible individuals may breathe with difficulty, 
be cyanosed, and bleed from the nose, ears, eyes, and other mucous membranes. There 
may be pain in the joints, muscles, and abdomen. There may be paralyses, especially 
of the lower extremities. The bodies of the victims are often contorted from the 
1 Harris, F. I. and Hoyt, H. S., Science, 1917, N. S. xlvi, 318. 
2 Rollier, La cure de soleil, Paris, 1914; Mayer, E., Am. Rev. Tuberc., 1918, i, 698; 1921, v, 75; Hyde 
andLo Brasso, New York Med. Jour., 1917, cv, 11. 
3 Brooks, H., Proc. New York Path. Soc., 1907, vii, 58; Boycott, Damant, and Haldane, Jour. Hyg., 
London, 1908, viii, 342; Keays, F. L., Researches of Med. Dept., Cornell Univ., New York, 1909, vol. ii; 
Hill, Caisson Sickness and the Physiology of Work in Compressed Air, London, 1912. CONDITIONS OF DISEASE 
19 
muscular contraction, hence the common name of the condition, "the bends." All of 
these symptoms may be promptly relieved by recompression. On the other hand, 
susceptible persons may succumb within a few hours to the disorder.1 
The lesions in fatal cases are quite variable. During compression the blood ab- 
sorbs an abnormal quantity of the gases from the air. This is due to the fact that the 
nitrogen is not specifically held in the blood, but dissolves in that fluid in proportion 
to the pressure, while the reserve oxygen capacity of the hemoglobin keeps this gas 
in solution. In decompression the oxygen is held but the nitrogen escapes, and 
to this "frothing" of the blood in too rapid decompression the symptoms and lesions 
of caisson disease are, in part at least, due. On external inspection no lesion may be 
evident; or there may be marked cyanosis of the face and mucous membranes of the 
mouth, nose, etc Crepitation of the skin may be elicited on light pressure, even 
Fig. 3.-Caisson Disease. 
Air in the vessels of the pia mater on the surface of the brain. 
though the skin be not obviously puffed up. The internal lesions are also variable. 
Of these, general venous congestion and frothy blood in the veins and capillaries are 
the most constant and characteristic. The gas in the vessels may be best seen in 
the pia mater cerebralis (Fig. 3) and in the omentum. Petechial hemorrhages may 
be found in the brain and cord. The gas sometimes accumulates in small blebs in 
the nerve tissue. 
In cases which recover from the primary effects of the pressure there may be 
secondary degenerations in the nervous system, paralysis, emaciation, trophic ulcers, 
etc. 
Internal Conditions of Disease. 
In distinction to those external agencies which lead to disease, there 
are many conditions of the body itself which are incompatible with the 
maintenance of health. There are a|so general conditions, due to dis- 
turbances of metabolism, such as diabetes and gout, which we shall con- 
sider separately later, in which abnormal amounts of sugar and uric acid 
are present, leading to many local and general disturbances. 
iFor acute effects of caisson disease, see Erdman, Am. Jour. Med. Sc., 1913, cxlv, 520. 20 
CONDITIONS OF DISEASE 
The powerful influence of the emotions on the bodily functions has 
recently had many experimental demonstrations.1 The relationship 
between excessive mental activity and some of the diseases of the nervous 
system, the heart, and the arteries, has long been suspected, if not 
proved, but there is no question as to the relationship of severe shock 
to the production of diabetes. 
But by far the more common internal conditions associated with dis- 
ease are the structural and functional alterations of the various organs of 
the body, which may lead directly or indirectly to the most complex 
departures from the normal. Some of these will be considered more in 
detail in later sections of this book. We may note here, however, as 
examples, a few of these complex relationships between local lesions 
and the general welfare of the organism. 
Lesions of the heart valves lead to disturbances of the circulation of 
the blood in various parts of the body, so that, as we shall see later, 
both functional and structural changes harmful to the individual may 
occur in important viscera, for example, in the lungs, kidneys, liver, 
blood-vessels, etc., and secondarily in the walls of the heart itself. 
In the gastrointestinal canal defective innervation, or trauma, or 
tumors, or constrictions may lead to the accumulation of ingested material, 
to innutrition, to intoxication through decomposition of the albuminous 
or other ingredients of the retained material. 
So in the liver, an insufficient production of bile or an occlusion of 
the gall-ducts may lead to digestive disturbances, to a deposition of 
bile pigment in various parts of the body-icterus; to the accumulation 
of bile in the blood-cholemia. On the other hand, an overproduction 
of bile may take place in the destruction of abnormal quantities of red 
blood-cells, leading to icterus.2 Furthermore, through disturbances in 
the glycogenic function of the liver, sugar may accumulate in the blood. 
These examples of the bearing of functional disturbances and struc- 
tural lesions of individual organs upon each other, and upon the welfare 
of the body as a whole, must suffice, since the scope of this book does 
not permit us to enter upon this wide field of pathological physiology, 
for the adequate consideration of which we must refer to systematic 
treatises on the practice of medicine. 
Race.-Examples of racial disposition to disease are not uncommon. 
Thus African negroes are less susceptible than are the whites to malaria. 
On the other hand, in this country the negro is especially vulnerable 
to tuberculosis. 
Age is an important factor in the liability to disease, though the 
reason for this is in very few instances at all clear. In childhood, for 
example, diseases of the digestive system are readily induced by un- 
suitable food. In advanced life, the vascular system is a vulnerable 
part of the body. This apparent predisposition of age may, however, 
be referred to the wearing out of the vascular mechanism. 
Sex appears to be a definite factor in disease disposition, for such 
1 Cannon, Bodily Changes in Pain, Hunger, Fear, and Rage, New York, 1915. 
2 Hooper, C. W., and Whipple, G. H., Jour. Exper. Med., 1916, xxiii. 137. 21 
CONDITIONS OF DISEASE 
maladies as diabetes, gout, general paralysis, tabes, etc., are more 
common in males than in females. But here, as in the age factor, many 
obvious external conditions, such as occupation, food, excesses in food 
and drink, syphilis, etc., may be invoked as elements of determining 
importance but not inherent in the condition of sex. The conditions 
incident to child-bearing, however, favor the occurrence of many more 
or less serious abnormalities of structure and function peculiar to th 
female. 
Heredity.-The relations of heredity to disease are extremely com- 
plex and subtle, and our knowledge of the subject is still too meager to 
permit of a profitable exposition within the limits which this book im- 
poses. In certain infectious diseases, syphilis, for example, the in- 
fective agent may be transmitted from the parents to the offspring. 
This, however, is not the conveyance of physiological or. structural 
peculiarities, but only of an external disease excitant. 
For the sake of clearness of thought and correctness of observation it 
is well for the student and physician to remember that those features and 
capacities of the organism which are inherited, are those and those alone 
derived from the maternal and paternal germ plasm, or through the reac- 
tion of these upon each other. The many and varied external influences 
brought to bear upon the fetus during intrauterine life, may induce 
marked departures from the normal, but these abnormalities are not in a 
proper sense inherited. They are more correctly designated congenital.1 
A curious example of such external influence is the production of monsters 
occasionally delivered after exposure of the pregnant uterus to large 
amounts of x-ray with therapeutic intent, such as the reduction in size 
of a fibromyoma. 
Susceptibility to disease may be inherited, to tuberculosis, for 
example; though we are unable to define clearly either structural or 
functional traits to which this vulnerability may be attributed. 
There are numerous examples of hereditary anomalies or dispositions 
to disease. We cannot consider them here in detail, but we may men- 
tion as examples, hemophilia, color-blindness, nyctalopia, myopia, 
neuroses of various types, angioneurotic edema,2 obesity, gout, and dia- 
betes.3 The inheritance of a chemical anomaly is seen in the cystinurics4 
and alkaptonurics. 
1 Many interesting examples of heredity in man have been collected by Bateson, W., Mendel's Prin- 
ciples of Heredity, Cambridge, 1913; and by Davenport, C. E., Heredity in Relation to Eugenics, New- 
York, 1911. See, also, Morgan, T. H., Heredity and Sex, New York, 1913; and Castle, W. E., Heredity, 
New York, 1913. For an interesting study of Mendelian heredity, as exemplified in a crossing between 
the white and black races, see Fischer, E., Die Rehobother Bastards, Jena, 1913. 
2 Crowder and Crowder, Arch. Int. Med., 1917, xx, 840. 
3 For a full discussion of these anomalies, see Pearson, K., Treasury of Human Inheritance, Galton 
Eugenics Laboratory, London, 1912. 
* Garrod, A. E., Inborn Errors of Metabolism, London, 1909. For a fuller exposition of the subjects 
considered in this chapter, consult Adami, J. G., Principles of Pathology, vol. i, Philadelphia, 1908; 
Thoma, R., Lehrb. d. pathologischen Anatomie, Stuttgart, 1894; Bouchard, Ch., and Roger, G. H., 
Pathologie g6n6rale, Paris, 1912-14. CHAPTER II. 
CHANGES IN THE CIRCULATION OF THE BLOOD. 
General Conditions. 
The circulation of the blood in the body is maintained by a very 
efficient and delicate mechanism capable of prompt and effective ad- 
justment to changes in the local and general conditions under which 
the body is placed. 
The factors especially concerned in the maintenance of the normal 
circulation and in its adaptability to new and unfavorable conditions 
are the contractile heart with its valves, the elastic arteries, the innerva- 
tion of the heart and vessels, gravitation, and the various phases of 
pressure and suction upon the veins from external sources, direct mus- 
cular action, respiratory movements, etc., which promote the passage of 
the blood upon its rounds. Finally, the character of the blood itself may 
have an important bearing upon the efficiency of the circulatory mechan- 
ism. Alterations in any of these factors may involve disturbances of 
the circulation.1 
We may glance briefly at some of these factors in the circulation, and 
first at the heart itself. The energy sustaining the circulation is primarily 
derived from the contractile heart, so that the condition of its muscle 
and innervation are of the first significance. Should the heart muscle 
be enfeebled, through lack of proper nutriment or innervation or by 
degeneration of the muscle, for example, the circulation suffers in manner 
and degree depending upon the part of the heart involved. Thus if 
the muscle of the right ventricle is enfeebled, blood is not properly 
drawn into the ventricle and is not sent with sufficient force into the 
lungs. The venous system then becomes overfilled with blood. If the 
muscle of the left ventricle be enfeebled, too little blood is sent into the 
arterial system and the pulmonary vessels are not properly emptied. 
Changes in the valvular openings of the heart or in the valves them- 
selves lead to disturbances of the circulation. Thus if the openings are 
narrowed, too little blood passes them; or if the valves fail to close 
properly, some of the blood flows backward through them. In this 
way both the pulmonary and the systemic veins become overfilled. 
The circulation may also suffer through alterations in the walls of 
the blood-vessels. The elasticity and contractility of the arterial walls 
are important factors in the maintenance of a normal circulation, since 
they sustain and reinforce the heart pressure on the blood and convert 
the pulsating movement imparted by that organ into a continuous, 
uniform flow through the capillaries and veins. If the arterial walls 
become stiffened and less elastic, or if their lumen becomes narrowed, 
1 See, for details concerning the physiology and pathology of the circulation, Wiggers, Circulation 
in Health and Disease, Philadelphia, 1915 (bibl.). 
22 CHANGES IN THE CIRCULATION OF THE BLOOD 
23 
more work is thrown upon the heart muscle. Thus the peripheral cir- 
culation is impaired unless, in a manner which we shall presently con- 
sider, the power of the heart muscle is increased by hypertrophy. Ob- 
struction of the veins may induce similar disturbances in the heart and an 
impaired local or general circulation. 
The circulation of the blood being controlled by the nervous system 
through the distribution of nerves to both the heart and the vessels, 
alterations in the central nervous system affecting the vagus or the 
sympatheticus, or severe traumatic injuries to the body involving re- 
flex disturbances, may induce serious local or general interference with 
the circulation of the blood. 
The respiratory movements of expiration and inspiration favor the 
circulation of the blood, so that interference with these may be of con- 
siderable importance. Thus pleuritic effusions, severe spasms of cough- 
ing, etc., may induce changes in the pulmonary circulation and the 
right heart as well as in the systemic circulation. 
The movements of the muscles of the trunk and extremities acting 
together with the valves of the veins contribute to the forces carrying 
the blood forward in circulation. Severe spasm of the muscle, as in 
epilepsy, tetanus, strychnine poisoning, etc., may induce stagnation of 
the blood in the veins of the trunk and the viscera so that it does not 
return properly to the heart. 
These are some of the more important of the changes which the 
general circulation suffers in conditions which interfere with the cir- 
culatory mechanism. 
The means by which the heart and the blood-vessels adapt themselves 
to various disturbing conditions through compensatory alterations will be 
considered in the chapters in " Special Pathology" dealing with these 
organs. 
We shall now consider in more detail the local effects of a disturbed 
circulation. 
Hyperemia and Anemia. 
Within physiological limits the amount of blood in a part may vary 
considerably under vasomotor control according to the functional necessi- 
ties of the part or vascular territory. Under a great variety of abnormal 
conditions the blood content suffers changes so excessive and so lasting as 
to be pathological. It is the latter alone which we are to consider here. 
A part of the body may contain an excess of blood, a condition called 
hyperemia (congestion). This is distinguished from plethora, which signi- 
fies a general excess of blood in the body. On the other hand, there may 
be too little blood in a part of the body, a condition which is called 
anemia. 
HYPEREMIA. 
Hyperemia may occur either through increased arterial supply, 
active hyperemia (acute congestion), or through some hindrance to the 
venous outflow of the part, passive hyperemia (venous congestion). 24 
CHANGES IN THE CIRCULATION OF THE BLOOD 
Active Hyperemia.-This may occur through dilatation of the 
arteries by the action of various physical and chemical agents directly 
upon their muscular coats, or through the vasomotor nerves, or from 
the reduction of pressure upon the vessels from without. 
Thus, injuries or stimulation of the vasomotor nerves, heat, the 
sudden evacuation of large exudates, trauma, and the action on the 
vessels of a great variety of chemical irritants may lead to a dilatation 
Fig. 4.-Hyperemia of the Blood-vessels near a Bronchus. 
In chronic bronchitis. 
of the vessels, and, as friction is diminished with the dilatation of the 
lumen, to a more rapid flow of the blood. 
Under these conditions the affected region becomes redder, warmer, 
and may be more or less swollen, and under certain conditions the 
arterial characters of the blood and pulsation of the vessels may be 
extended into the venous trunks. 
Passive Hyperemia (venous congestion).-In passive hyperemia 
due to obstruction to the outflow of blood from a part, there is an over- 
filling of the veins and capillaries (Fig. 4). The hindrance to the CHANGES IN THE CIRCULATION OF THE BLOOD 
25 
outflow of blood may be due to compression of the vessels from without, 
as from tumor, aneurysm, ligature, displacement, or from new interstitial 
tissues in various organs. It is frequently the result of thrombosis. 
One of the most fruitful determining causes of passive hyperemia is 
the lesions of the heart which interfere with the regular entrance and 
exit of the blood from that organ. Thus, in incompetence or stenosis 
of the mitral valve the pulmonary vessels become congested; the right 
ventricle does not properly empty itself. So the systemic veins in vary- 
ing degrees suffer engorgement, and the viscera become involved in the 
secondary alterations due to chronic hyperemia. 
The effect of venous obstruction varies greatly, depending upon its 
degree, upon the rapidity of its occurrence, and upon the structure and 
functional importance of the part involved. If, as in most instances 
is the case, venous anastomoses exist between the partially or wholly 
Fig. 5.-Diagram Illustrating the Establishment of Collateral Circulation in Obstruc- 
tion of a Vein-After Ribbert. 
The veins a and b at A are connected by a slender trunk, c. If a in B is occluded, as by a throm- 
bus, the blood cannot all pass out of the territory drained by a, so that the vessels here are dilated- 
congestion. If, however, the small anastomosing trunk widens as at C, the congestion is relieved by 
the conveyance away of the blood through the vein b. 
occluded and other vessels, these may enlarge, and with the establish- 
ment of this collateral circulation a more or less complete adaptation 
to the changed conditions is secured (see Fig. 5). The collateral veins 
and even capillaries in the involved region widen and their walls thicken; 
and thus while for a time hyperemia of varying intensity may exist, this 
gradually resolves. 
The possibilities of adaptation to venous obstruction are sometimes 
very great even when large trunks are concerned. Thus, a ligature of 
the femoral vein or a blocking of the inferior or superior vena cava may 
be compensated by the establishment of abundant collateral channels. 
On the other hand, after the blocking of the renal or splenic or of a main 
trunk of the portal vein, the circulation is re-established with difficulty. 
If a collateral circulation be not at once and readily established, 
and often even if this be the case, local venous obstruction leads to 
certain well-defined changes in the hyperemic region. If the obstruction 
be partial, the flow of blood is slower than normal; the vessels are dilated; 
more or less fluid may transude into the surrounding tissues; and dia- 
pedesis (see page 102) of the red blood-cells may occur. On the other 
hand, if the obstruction be complete in a large venous trunk, the capil- 
laries and veins in the involved region dilate; the axial stream of ery- 26 
CHANGES IN THE CIRCULATION OF THE BLOOD 
throcytes in the veins disappears; the entire lumen is crowded with 
them; the blood pressure rises; the current wavers, slows, and stops. 
Then the red cells become packed into a homogeneous mass in the dilated 
vessel-this is stasis. Diapedesis and transudation now occur in the 
capillaries and veins of the involved region. Finally, if the circulation 
be not re-established, hemorrhagic infarction (see page 36) or death 
of the tissue-necrosis-may follow. 
If the venous obstruction be removed, as may be done experimentally 
in the tongue or mesentery of the frog (see page 127), one may observe 
under the microscope the disappearance of the stasis and the re-establish- 
ment of the circulation. The homogeneous blood mass resolves itself 
into its component corpuscles; the blood moves at first fitfully and 
irregularly, then the current is established; the distention diminishes, 
and, after a longer or shorter time, if the lesion have not been too ex- 
treme, the part assumes its normal appearance. 
In passive hyperemia the tissue involved is more or less dark red in 
color-cyanotic-owing to the accumulation in the vessels of unaerated 
blood; the temperature may be lowered when the area concerned is 
extensive; it may also be swollen in part from the distention of the 
vessels, in part from the extravasation of fluid; finally, there may be 
pulsation and increased pressure in the veins. 
If the hyperemic condition be long continued-chronic congestion- 
the walls of the involved vessels may become thickened; there may be 
interstitial fibrous hyperplasia in the affected region; or there may be 
varying degrees of cell degeneration or of atrophy. Thus function may 
be interfered with or suspended. 
In many instances of diminished heart power or when for any reason 
the blood circulates with difficulty under favorable conditions, the effect 
of gravity may manifest itself in dependent portions of the body or of 
the organs, so that these become hyperemic. This condition is called 
hypostatic congestion. The most marked example of this condition is in 
the lungs of debilitated persons, the dependent portions of which fre- 
quently become engorged with blood. This is often associated with 
edema, atelectasis, and more or less cellular exudate in the air spaces. 
ANEMIA. 
The word anemia is used not only to denote the lack of blood in a 
part, but also to indicate a reduction or alteration in various constituents 
of the blood itself, a condition familiarly called "poverty" of the blood. 
General anemia due to impoverishment of the blood will be considered 
in the chapter on the Special Pathology of the Blood and the Blood- 
forming Organs. We are here concerned only with local anemia- 
ischemia. 
Local anemia may be due to the cutting off of the blood supply by 
the occlusion of the arteries in thrombosis and embolism; by ligatures; 
by the narrowing of the lumen through pathological processes in the 
wall of the vessel; by tumors, exudates, etc.; by contraction of the 
vessels from nerve lesions as in Raynaud's disease; by the action upon the CHANGES IN THE CIRCULATION OF THE BLOOD 
27 
vessel of physical agents-cold-or by chemical substances or drugs 
which induce marked constriction-suprarenal extract and ergot. Fur- 
thermore, mechanical pressure upon the vessel from without or compres- 
sion of an entire organ or part may induce various grades of anemia. 
The affected part or organ in anemia becomes paler than normal, 
often with a yellowish tinge; the temperature is lowered; and the vol- 
ume may be diminished; finally, if the absence of blood persist, the 
function and nutrition of the involved part suffer, and atrophy, fatty 
degeneration, and death of tissue may occur. 
If, however, the anemia be only partial or if it be of short duration, 
in some organs the nutrition may not suffer in marked degree; in others, 
however, the brain, for example, extreme damage may follow even a 
temporary anemia. 
The degree, duration, and results of local anemia are largely dependent 
upon the cause of the shutting off of the blood supply, and the possi- 
bility of its restoration directly or through the establishment of a collat- 
eral circulation. Thus, for example, anemia from compression as 
from an arterial ligature may at once resolve if the determining cause be 
removed. But even though an artery remain blocked, circulation may 
be in a measure restored by the dilatation of anastomosing capillaries or 
by the backflow of venous blood into the region deprived of its vascular 
pressure from the closed arteries. While a certain amount of fresh 
blood may reach the affected region in these ways, it is only when anas- 
tomoses exist between the branches of the closed and neighboring arterial 
trunks that a fairly complete collateral circulation can be established. 
For a further consideration of this subject see Embolism (page 35). 
Hemorrhage and Transudation. 
HEMORRHAGE. 
Hemorrhage is an escape of blood from the heart or vessels. It 
may occur from a rupture of the walls of the vessels, and is then called 
hemorrhage by rhexis. The rupture may be occasioned by injury, by 
lesions of the walls of the vessels which render them too weak to resist 
the blood pressure from within, or it may occur from the blood pressure 
in the thin and incompletely developed walls of new-formed vessels as in 
granulation tissue, tumors, etc. The arrest of hemorrhage may take 
place through the contraction of the wall of the vessel or by the forma- 
tion of a clot. 
Under other conditions, without recognizable changes in the vessels, 
all the elements of the blood may become extravasated by passing, with- 
out rupture, through their walls. This is called hemorrhage by diape- 
desis. Such hemorrhages are usually small, but may be very extensive. 
They occur in the smaller veins and capillaries, the cells and fluids of the 
blood passing out through the cement substance between the endothelial 
cells. Although no marked morphological changes have as yet been 
detected which explain this extravasation, it is probable that some 
change in the nutrition of the walls does occur which renders them more 28 
CHANGES IN THE CIRCULATION OF THE BLOOD 
permeable. Hemorrhage by diapedesis is apt to occur as a result of 
venous congestion, or when the flow of blood in the smaller vessels has 
been suspended for some time; or it may result from the action of some 
poison, or from an injury not leading to rupture; or it may occur in incom- 
pletely developed blood-vessels in tumors and other new-formed tissues. 
In the extravasation of blood by diapedesis the white blood-cells may 
pass through the walls of the vessels, partly at least in virtue of their 
ameboid movements; the red cells, on the other hand, having no power 
of spontaneous movement, are, according to Arnold, carried passively 
through the walls by minute currents of fluid which, under the changed 
condition, stream in increased force and volume through the endothelial 
cement substance into the tissue spaces outside. 
The altered condition of the blood-vessels leading to hemorrhage may 
be local or general, and in the latter case it may either be congenital, as 
in some cases of the hemorrhagic diathesis, or it may be the result of 
a general disease, such as scurvy, purpura, etc. The presence of bacteria 
in the vessels, or of bacterial or other poisons in the blood, as in malig- 
nant endocarditis and in hemophilia neonatorum, may induce changes in 
the walls of the vessels, leading to extravasation. 
Forms of Hemorrhage.-Very small hemorrhages are called petechia, 
larger, diffuse accumulations of blood in the interstices of the tissues 
are commonly called ecchymoses or suggillations. A complete infiltra- 
tion of a circumscribed portion of tissue with blood is called a hemor- 
rhagic infarction. A collection of blood in a tumor-like mass is called a 
hematoma. Special names are given to hemorrhage in different parts of 
the body; thus, bleeding in the lungs is called hemoptysis; vomiting 
blood from the stomach, hematemesis; nosebleed, epistaxis; hemorrhage 
from the uterus, metrorrhagia; certain forms of brain hemorrhage, 
apoplexy. In the so-called hematuria the blood may be derived from 
either the kidney or the bladder. Sometimes the elements of the tissue 
into which the blood escapes are simply crowded apart; sometimes, as 
in the brain, they are broken down. 
The extravasated blood in the tissues usually soon coagulates, al- 
though exceptionally it remains fluid for a long time. A certain num- 
ber of the white blood-cells may wander into adjacent lymph-vessels, or 
they may remain entangled with the red cells in the meshes of the fibrin. 
The fluid is usually soon absorbed; the fibrin and a portion of the white 
blood-cells disintegrate and are absorbed (see page 71). The red blood- 
cells soon give up their hemoglobin, which decomposes and may be 
carried away or be deposited either in cells or in the intercellular sub- 
stance at or near the seat of the hemorrhage, either in the form of yellow 
or brown granules or as crystals of hematoidin (see page 64). Some- 
times all trace of extravasations of blood in the tissues disappears, but 
frequently their seat is indicated for a long time by a greater or less 
amount of pigment or by new-formed connective tissue. Occasionally 
the blood mass, in a more or less degenerated condition, becomes en- 
capsulated by connective tissue, forming a cyst. 
The action of phagocytes (see page 115) in the disposal of dead ma- CHANGES IN THE CIRCULATION OF THE BLOOD 
29 
terial is here, as it is under a great variety of conditions, an impor- 
tant factor in the restoration of the body, after lesion, to its normal 
conditions. 
Hemorrhages in the New-born. 
Hemorrhages, sometimes extensive, in various parts of the body- 
gastrointestinal canal, mouth, nose, navel, or the viscera-are not infre- 
quent in the first few days of life. Aside from the occasional discovery 
of ulcers in the gastrointestinal walls, the reason for these hemorrhages 
is not evident at autopsy.1 This condition has been called morbus 
maculosus neonatorum. Hemorrhages from the skin, mucous membranes, 
or navel may take place in the syphilitic new-born. Hemoglobinuria 
may occur in epidemic form in young children. 
Hemophilia {Hemorrhagic Diathesis'). 
This abnormal condition consists in a liability to persistent hemor- 
rhage on the slightest provocation, and is dependent upon some consti- 
tutional peculiarity which is unknown to us. It is usually hereditary, 
being transmitted only through the female line and manifested in the 
males; it appears in females only when the parents are a hemophilious 
male and a female carrying hemophilia. The condition is, therefore, 
sex-limited.2 An uncommon thinness of the intima of the arteries has 
been noticed in some cases of "bleeders," and other changes have been 
described; but there are no constant lesions associated with the hemor- 
rhages, as yet discovered, which would satisfactorily account for their 
occurrence. The hemorrhages may be traumatic in origin, or they may 
occur spontaneously from the mucous membranes. 
Transudation is the passage, through the walls of the blood-vessels 
into the interstitial spaces outside, of fluid from the blood, with little or 
no admixture of its cellular elements. This occurs constantly, to a cer- 
tain extent, under normal conditions, and forms the commencement of 
the lymph circulation. But when the amount of fluid passing through 
the walls of the blood-vessels is increased, or its outflow into the larger 
lymph-trunks is hindered so that it accumulates in undue quantity in 
the interstices and lymph-channels of the tissues, the condition is 
pathological.3 
An accumulation of transuded fluid in the interstices of the tissues 
is called edema; in the serous cavities, dropsy. Extensive edematous 
infiltration of the subcutaneous tissue is called anasarca. If the transu- 
date accumulates in the pleural cavity the condition is called hydro- 
thorax; in the pericardium, hydropericardium; in the ventricles of the 
brain, hydrocephalus. In similar fashion various other names are in 
TRANSUDATION. 
1 For a study of hemorrhagic diseases of the new-born, with bibl., see Graham, Jour. Exper. Med., 
1912, xv, 307. 
2 For a discussion of this and other anomalies of heredity, see, Pearson, K., Treasury of Human 
Inheritance, London, 1912. 
3 For a study of edema see Meltzer, Harrington Lectures, Univ, of Buffalo, Am. Med., 1904, viii, 19; 
also Pearce, Arch. Int. Med., 1909, iii, 422. 30 
CHANGES IN THE CIRCULATION OF THE BLOOD 
common use for the accumulation of transudates in the body cavities; 
as hydroperitoneum (ascites), hydrarthrosis, hydrocele, etc. 
Its occurrence may depend upon some hindrance to the venous circu- 
lation or increase of capillary pressure, especially when associated with 
alterations in the walls of the blood-vessels, or upon changes in osmotic 
pressure induced by a reduction in the nutrient efficiency of the blood, 
by injuries, or in other ways which may affect the processes of filtration 
and osmosis, by which chiefly, it is believed, the normal transudation of 
fluids occurs. There is, furthermore, strong and increasing evidence that 
the endothelial cells of the capillaries possess active secretory or other 
functional capacities which should be taken account of in the attempt to 
comprehend transudation as well as many other pathological phenomena 
and lesions. A simple interference with the outflow of lymph does not 
usually alone suffice to induce transudation, although it may favor its 
occurrence. Edema may depend upon little understood abnormalities 
of the nervous system, as in the so-called neuropathic edemas. 
In addition, Widal and his pupils1 have called attention to the nature 
of the edema in chronic nephritis due to the retention of sodium chloride 
by the excretory failure of the kidneys. This type of edema is apparently 
caused by the necessity for a fixed chloride content of the blood, so that 
when chloride is retained water is retained also in the interstices of the 
tissues. If dropsical patients are put for a few days upon a salt-free 
diet, they may lose large quantities of water, even as much as fifteen 
kilos; but if after this period ten grammes of salt are added to the diet, 
edema, with re-accumulation of water, occurs. 
The transuded fluid, called transudate, is usually transparent and 
colorless or yellowish; it contains the same salts as the blood plasma, 
but less albumin. It may contain fat, mucin, urea, biliary acids, color- 
ing-matter of the bile; fibrinogen is usually present in variable quantity, 
and, rarely, fibrin. It may contain endothelial cells from the lymph- 
spaces or lining cells from the serous cavities, and a variable number of 
red and white blood-cells. The amount of fluid which may accumulate 
in the tissue varies greatly, depending upon whether they are loose or 
dense in texture. The fibers and cells of loose tissues may be crowded 
widely apart; the cells are apt to be more granular than normal, they 
may contain droplets of fluid, or they may be atrophied. Transudates 
occurring in inflammation usually contain a considerable number of 
white blood-cells and more or less fibrin, and differ in this from the non- 
inflammatory transudations; but in some cases there is no sharp dis- 
tinction between them. The inflammatory transudates are often called 
exudations or exudates. 
Resorption and Absorption. 
Under many conditions, both normal and abnormal, fluids and solid 
particles are taken into the recesses of the tissues from without, or are 
gathered from one place in the tissues to be carried in the blood or 
lymph-currents or by cells to other parts or to places of excretion. Thus 
1 Widal, Ambard, and Weill, Sem. m6d., 1913, xxxiii, 370. CHANGES IN THE CIRCULATION OF THE BLOOD 
31 
from the intestinal contents both liquid substances and small solid 
particles, such as fat droplets, bacteria, etc., may be taken into the body 
fluids. In exudative inflammations, such as pleurisy or pneumonia, 
large quantities of fibrin, red and white blood-cells, and fluids may 
accumulate in the cavities, to be presently removed. So also dead 
tissue, blood clots, etc., and foreign bodies may be removed through 
various processes of resorption. 
The absorption of fluid substances or the resorption of those which 
are rendered soluble takes place through the lymph-channels, as we 
have seen, whence they may be eliminated through the excretory organs. 
Solid material, .such as fibrin, dead cells, etc., may be removed either 
through the action of fluids which render them soluble, lytic fluids 
(page 122), or through the intervention of living cells, phagocytes (page 
115). These processes will be considered in detail in a later section of 
this book. 
Thrombosis and Embolism. 
THROMBOSIS. 
Thrombosis is the coagulation of the blood or the agglomeration oi 
agglutination of the formed elements of the 
blood into a more or less coherent mass dur- 
ing life. The coagulum or mass is called a 
thrombus (Fig. 6). 
Thrombi may be composed of fibrin and of 
red and white blood-cells intermingled in about 
the same proportion as in an ordinary extravas- 
cular blood clot (Fig. 7). These are called red 
thrombi and usually occur from some sudden 
stoppage of the circulation. Other thrombi, 
usually such as form while the blood is in 
motion, may consist almost entirely of white 
blood-cells with a little fibrin, or of these in- 
termingled with blood-platelets; or they may 
consist almost entirely of blood-platelets; all 
of these forms are called white thrombi. Red 
thrombi, when decolorized by changes in the 
blood pigment, may somewhat resemble 
genuine white thrombi. Mixed thrombi are 
usually lamellated (Fig. 8) and contain vary- 
ing proportions of fibrin, red and white blood- 
cells, and platelets. The fibrin fibrils in 
thrombi, as elsewhere, often coalesce, forming 
hyaline masses. A similar change may take 
place in the blood-platelets. Thrombi may 
consist almost wholly of red blood-cells. 
Causes of Thrombosis.-Thrombi may 
occur as the result of an injury to the wall of 
Fig. 6.-Occluding Thkombus 
of the Iliac. 
The vessel is laid open, showing 
the lamellated clot- 32 
CHANGES IN THE CIRCULATION OF THE BLOOD 
a vessel, or may follow its compression or dilatation; they may result 
from some alteration of the wall of the vessel by disease, or by the re- 
tardation of the circulation as is well shown by the fact that thrombi 
are three times as frequent in the veins as in the arteries. So long as the 
endothelial lining of the vessel is intact, simple retardation of the circulation 
does not usually alone suffice to induce coagulation; but changes in the 
endothelium in a great variety of conditions, such as inflammation, de- 
generation, atheroma, calcification, and the presence of bacteria or their 
toxins, tumors, and foreign bodies, favor its occurrence, especially when 
associated with changes in the circulation or in the character and contents 
of the blood. Thrombi may develop from an embolus. Thrombosis is a 
not infrequent complication of the infectious diseases as well as of the 
cachectic conditions associated with various acute and chronic general 
diseases. 
One may conveniently class the various determining causes of 
thrombosis into: 1, those associated with a slowing of the blood-current; 
2, those relating to changes in the walls of the blood-channels; and 3, those 
involving such alterations in the blood itself as favor coagulation. These 
factors are frequently associated.1 
1. Disturbances of the circulation 
favoring thrombosis are frequently de- 
pendent upon enfeebled heart action, and 
thrombi may then form in the auricles 
behind the valves or among the trabeculae 
of the heart (Fig. 7), behind the valves 
of the veins, in the veins of the lower ex- 
tremities, in the great venous sinuses of 
the brain, or wherever by reason of ab- 
normal conditions the regular flow of the 
blood is interfered with-as in aneurysms, 
varices, etc. Such thrombi are sometimes 
called stagnation thrombi. When forming 
under marked asthenic conditions they 
are called marantic thrombi. In this class 
belong thrombi induced by pressure or 
ligature of the vessels. 
2. Thrombi associated with alterations in the walls of the blood- 
vessels may follow mechanical injuries to the vessels and may be con- 
servative in the control of hemorrhage. The action of various forms of 
cathogenic bacteria within or in the vicinity of blood-vessels inducing 
lesions of the walls is a fruitful determining factor in thrombosis. This 
is common in acute endocarditis, in septicemia, in various forms of phle- 
bitis, and in tuberculosis. In chronic lesions of the walls of the heart and 
blood-vessels, associated with degeneration and necrosis (atheroma, calci- 
fication, etc.), thrombi may form. The growth of tumors into the blood- 
channels affords favorable conditions for the development of thrombi. 
Fig. 7.-Portion of Red Thrombus. 
This shows red blood-cells, fibrin, and 
a few leucocytes. 
1 For a study of the conditions relating to the occurrence of thrombosis, such as changes in the 
coagulability of the blood, power of agglutination, local and general condition of the blood flow, and 
endothelial damage, see Aschoff, Cartwright Lecture, Arch. Int. Med., 1913, xii, 503. For full review, 
see, also, Hanser, R., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1921, xix2, 147 (bibl.). CHANGES IN THE CIRCULATION OF THE BLOOD 
33 
3. The alterations of the blood itself favoring thrombosis are obscure. 
Such are the impoverishment of the blood in anemia, the presence of 
bacterial toxins or of the bacteria themselves in various infectious 
diseases. Many of the so-called marantic thrombi are probably due to 
the presence of bacteria or of their toxins in the blood or in the walls 
of the vessels. Some cases of " white swelling" following parturition are 
probably of this nature. 
Among the less frequent alterations of the blood favoring thrombosis 
may be mentioned the presence of hemolytic substances, as in the 
transfusion of alien blood and the artificial introduction of certain 
animal and vegetable extracts. 
Forms of Thrombi.-Various forms of thrombi, aside from those 
already described, have received special names. Thus thrombi are 
called primary or propagated, depending upon whether they are con- 
Thia ia an occluding thrombua. At the right and alao above are maaaea of red blood-cella, while the 
remainder ia largely fibrin in layera, indicating succeaaive depoaits. 
Fig 8.-Lamellated Thrombus. 
fined to the original site of formation or extend for some distance from 
the point of origin. Sometimes such extension is marked by variations 
in the color, density, and structure of the extending thrombus. A 
secondary thrombus is one formed upon an embolus or a pre-existent 
thrombus. A thrombus may be obstructing or parietal; solid or canal- 
ized; simple or infective; it may be arterial or venous-all names whose 
significance is obvious. 
Agglutinative Thrombi.1-The recent studies on agglutination and 
hemolysis (page 197) have led to the belief that certain thrombi occur- 
1 Consult Flexner, Jour. Med. Research, 1902, N. S. iii, 316; Pearce, R. M., ibid., 1904, N. S. vii, 
329; and Pearce and Winne, Am. Jour. Med. Sc., 1904, cxxviii, 669 (bibl.). 34 
CHANGES IN THE CIRCULATION OF THE BLOOD 
ring in infectious diseases, as well as under other conditions, may arise 
from the development of agglutinative substances in the blood. Under 
the action of these substances the red blood-cells may, without the 
formation of fibrin, clump together, leading to thrombosis. Such 
thrombi are called agglutinative thrombi. They have been observed 
repeatedly in typhoid fever and other infections. In such masses of 
agglutinated red blood-cells the individual corpuscles may not be seen, 
the whole presenting a hyaline mass. Thus may be formed a variety of 
the so-called hyaline thrombi. Welch1 has suggested the probability that 
under similar conditions leucocytes also may form agglutinative thrombi. 
Hyaline Thrombi.-Under a variety of conditions, but especially in 
local and general infections and in intoxications, there is present in the 
capillaries and in the small arteries and veins a homogeneous, translu- 
cent, nearly colorless material, partially or wholly blocking the vessels. 
This hyaline material, whose origin is still in doubt, has in some in- 
stances a staining reaction similar to fibrin. In other cases hyaline 
thrombi are probably special forms of agglutinative thrombi (see above). 
Alterations in Thrombi.-After a certain amount of shrinkage by 
which the fluids are squeezed out and the thrombus becomes denser 
and drier, the changes which occur in it may be in the direction either 
of degeneration and absorption or of organization. The leucocytes, the 
fibrin, and the blood-plates may degenerate, forming a granular material 
which may become infiltrated with salts of lime, forming the so-called 
phleboliths, or vein stones. In other cases the thrombi may soften and 
disintegrate. This softening may be simple and the result of fatty or 
other form of tissue degeneration, resulting in a white or reddish or 
brown grumous mass, which may resemble, but is not, pus. Or, in many 
instances, softening probably occurs through the autolytic processes 
(page 122) initiated and sustained largely by leucocytes. On the other 
hand, softening of the thrombus may be associated with bacteria or 
other infectious material with general suppuration. In this "puru- 
lent" or "septic" softening of the thrombus the risk is great of a dis- 
tribution of the infectious material through the circulation. Finally, 
the thrombus may be replaced by a new formation of vascular con- 
nective tissue, itself disappearing by autolysis or phagocytosis as the 
new tissue is formed. This is called "organization of the thrombus," 
but in reality the new connective tissue is produced, not from the cells 
of the thrombus itself, but from the cells of the walls of the affected 
trunk, from whose vessels the new blood-vessels of the thrombus also 
arise (compare page 89). In this way the vessel may be completely 
and permanently occluded, or, more rarely, one or several channels may 
be established through the new connective-tissue mass (Fig. 9). 
Effects of Thrombosis.-The consequences of thrombosis vary 
greatly, depending upon the seat, size, and nature of the thrombus. 
They are of two classes: 1, those depending upon the direct disturbance 
of circulation from the occlusion of the lumen of the vessel; and, 2, 
those determined by the detachment of the thrombus or the separation of 
* IFeZcA, Huxley Lecture, Medical News, 1902, Ixxxi, 721. CHANGES IN THE CIRCULATION OF THE BLOOD 
35 
a part of it, and the distribution of these through the circulatory channels 
to various parts of the body. 
1. The occlusion of either arteries or veins may be compensated by 
the establishment of collateral circulation. The partial or total occlu- 
sion of an artery by a thrombus may lead to local anemia, degenera- 
tion, necrosis, or infarction (see page 37). The obstruction of a vein 
may lead to venous congestion and edema, and to various alterations 
already considered under the heading of Hyperemia. 
For a further consideration of thrombosis of the heart and separate 
vessels see sections dealing with these organs in Special Pathology. 
2. Whole thrombi or portions of these may be detached and carried 
forward by the blood-current, or, as the result of softening and disinte- 
This shows the vascular connective tissue which has replaced the clot, with five new channels through 
which the circulation is re-established. 
Fig. 9.-Organized Thrombus. 
gration, detritus, bacteria, etc., may be set free by unusual move- 
ment, by pressure, or without obvious special force. 
The performances and effects of such detached portions of thrombi 
will be considered in the next section, under embolism.1 
Thrombosis of Lymph-vessels. 
Thrombosis of the lymph-vessels is of occasional occurrence. The 
thrombus consists of fibrin and leucocytes. It may present forms and 
induce changes in the lymph-channels analogous with the forms and 
effects of thrombi in the blood-vessels. 
EMBOLISM. 
Embolism is the obstruction of a blood-vessel by the arrest in its 
lumen of some material carried along in the circulating blood. The 
mass causing the stoppage is called an embolus (Fig. 10). This may 
1 For a thorough and admirable consideration of the subject of thrombosis and embolism, with 
bibliography, consult Welch, Allbutt's System of Medicine, 1909, vi, pp. 691, et seq. 36 
CHANGES IN THE CIRCULATION OF THE BLOOD 
be composed of a great variety of substances. Ine most common emboli 
are detached portions of thrombi, especially from the heart valves, and 
these may have all the variety of structure which thrombi present. 
Masses of bacteria or other animal or vegetable parasites, fragments of the 
heart valves and of tumors, droplets of fat from the medulla of fractured 
bones (Fig. 11),parenchyma cells,1 masses of pigment, bubbles of air, etc., 
may form emboli. Embolism is, in a majority of cases, confined to the 
arteries and to the branches of the portal vein. Emboli after lodgment 
sometimes give rise to thrombosis, which may be very extensive. 
Effects of Embolism - Infarction.--'The 
changes which follow the more or less sudden 
and complete cutting off of the arterial blood 
from a part of the body by the lodgment of an 
embolus are so variable, depending upon the 
part of the body affected, the character of its 
vascular arrangement, and the possibilities of 
a collateral blood supply, that a concise com- 
prehensive description is difficult. 
When the arterial blood-current is cut off 
from the affected area, this does not at once 
become bloodless, because its vessels still con- 
tain the residual blood and a certain amount 
may enter at least the periphery through ad- 
jacent capillaries and small veins. Then if the 
involved region is not too large and the 
plugged vessels have sufficient anastomoses, 
the establishment of a collateral circulation 
may after a time be effected. On the other 
hand, if the plugged artery does not possess 
anastomosing trunks or is inadequately sup- 
plied with these-that is, belongs to those 
vessels which are called terminal arteries-end 
arteries-the effects are more marked and last- 
ing. There is stasis in the vessels; diapedesis of the red blood-cells 
may occur; and while a small amount of blood may enter the periphery 
of the involved region through the capillaries and veins so that the 
vessels here may be markedly congested, the tissues are not sufficiently 
nourished and they suffer varying degrees of degeneration; they may die 
and the whole central region become necrotic. This gradually developing 
process is called infarction, and the portion of involved tissue is called 
an infarct (Fig. 12). The area of infarction corresponding to the region 
supplied by the occluded vessel is usually more or less wedge-shaped. 
Infarcts in which the vessels are distended with blood, with interstitial 
Fig. 10.-An Embolus Lodged 
at the Point of Division of 
an Artery. 
This is a portion of clot which 
has been detached from a point 
above and swept along the blood 
current. It has increased in 
length by coagulation at its free 
extremities. 
1 The presence of liver-cell emboli in the lung capillaries and in the heart clots after traumatic 
rupture of the liver, and in infectious diseases involving local necroses of the liver, has been described 
by various observers. Emboli believed to be composed largely of placental cells or of cells from the 
bone-marrow are also described under various conditions. The facts relating to this subject of paren- 
chyma-cell emboli and its alleged significance may be found summarized by Lubarsch, Fortschr. d. Med., 
1893, xi, 805, 845; and by Aschoff, Virchows Arch., 1893, cxxxiv, 11. Consult also Warthin, Med. 
News, 1900, Ixvii, 405 (bibl.). CHANGES IN THE CIRCULATION OF THE BLOOD 
37 
hemorrhage by diapedesis and more or less necrosis of the involved area, 
are called hemorrhagic infarcts (Fig. 13). 
After a time the infarct becomes decolorized by diffusion of the dis- 
solved hemoglobin, inflammatory changes occur in its periphery, the 
blood-cells and involved tissues may undergo degeneration and be 
absorbed,1 and finally the seat of the 
infarction may be indicated only by a 
mass of cicatricial tissue, which fre- 
quently contains more or less pigment. 
In another class of cases, instead of 
an excessive distention of the vessels and 
an extravasation of blood in the affected 
region the tissue is simply deprived of 
nourishment and undergoes necrosis. 
The affected area then sooner or later 
becomes lighter in color from the diffu- 
sion of the hemoglobin, and is called 
an anemic or white infarct (Fig. 14). 
Inflammatory changes may occur in its periphery and a new connec- 
tive tissue capsule form around it, and the dead mass may thus persist 
for some time, or be gradually absorbed and replaced by cicatricial tissue. 
In certain instances it is believed that infarcts may be anemic from the 
beginning and not, as is apparently usually the case, 
as the result of changes in infarcts which are at first of 
the hemorrhagic type. 
The scope of this book does not permit us to con- 
sider the somewhat complicated and often obscure rea- 
sons why in one case there is hemorrhagic, in another 
white, infarction, as a result of embolus. 
If the embolic material consists of or contains infec- 
tive substances, such as some forms of bacteria, in ad- 
dition to the mechanical effects of simple emboli, we 
may have gangrene, suppuration, formation of abscesses, 
etc., as the result of the local action of the infectious 
material, even though this may be present in very small 
amount. 
The Location of Infarcts.-The organs in which em- 
bolic infarctions most frequently occur are the spleen, 
kidney, brain, lungs; less frequently the heart, retina, 
liver, and small intestines. 
Hemorrhagic infarction is not liable to occur in the 
liver from emboli in the branches of the portal vein, on 
account of the blood supply which may come to the 
affected region through the branches of the hepatic 
artery. On the other hand, embolic abscesses from infectious emboli are 
of not infrequent occurrence here. 
Fig. 11.-Fat Emboli in the Blood- 
vessels of the Lung. 
This followed bone fracture. 
Fig. 12.-Infarcts 
of the Spleen. 
1 For a study of the autolytic processes in the absorption of infarcts, see Wells, Jour. Med. Research, 
1906, N. S. x, 149. 38 
CHANGES IN THE CIRCULATION OF THE BLOOD 
The lung is supplied with blood through the pulmonary and the 
bronchial arteries; and the capillary network of the pulmonary tissue 
is so abundant that emboli in the pulmonary artery, although this is a 
terminal artery, do not readily lead to infarction in an otherwise healthy 
lung. When, however, the pulmonary circulation is disturbed, as in 
certain forms of heart disease, hemorrhagic infarction may follow em- 
bolism of the pulmonary artery. 
The arteries of the kidney and spleen are typical terminal arteries, 
and infarcts of these organs readily follow embolism. In the kidney 
the infarcts are most commonly anemic; in the spleen both hemor- 
rhagic and anemic infarcts are formed. Infarction in the heart may 
follow embolism, but is more commonly the result of thrombosis of 
branches of the coronary artery. Embolism of the cerebral arteries is 
Fig. 13.-Diagram Illustrating the Formation of a Hemorrhagic Infarct. 
The artery, A, plugged by an embolus, E, is a terminal artery, though it has abundant capillary 
anastomoses with the artery B, so that the territory deprived of blood is not sufficiently nourished and 
its tissues die; but from the abundant capillary anastomoses from the artery B, and from the vein C, 
a certain amount of blood enters the infarct area, which thus becomes hemorrhagic. 
seldom followed by extensive local collateral hyperemia and hemor- 
rhage, but is more apt to lead to cerebral softening. Hemorrhagic 
infarctions may occur exceptionally in regions not furnished with 
terminal arteries, as in the small intestines. Infarction does not follow 
embolism of single arterial trunks of the arms and legs because of the 
ready establishment of a collateral circulation. 
Pulmonary Embolism.-From the clinical aspect the most important 
form of pulmonary embolism is that type which does not give rise to 
infarction, but causes sudden death. This is seen after childbirth, after 
surgical operations, especially those on the lower portion of the abdomen, 
and in conditions in which the circulation of the lower extremities is inter- CHANGES IN THE CIRCULATION OF THE BLOOD 
39 
fered with, such as crushing wounds, when the muscles are lacerated 
and the vessels torn, prolonged rest in bed of persons with enfeebled cir- 
culation, etc. The thrombi, in these cases, form in the vessels of the calf 
and also in the femoral veins, as, for instance, where the limb comes in 
contact with the bed; and the circulation thus being slowed, deposition 
of blood-platelets occurs with the formation of the type of thrombus 
described by Aschoff.1 This thrombus gradually grows centrally into 
the blood-vessels and, finally, under some mechanical influence is set 
free in the circulation and passes to the right side of the heart, and then 
into one of the larger branches of the pulmonary artery, producing in 
many instances almost instantaneous death. Occasionally, however, 
Fig. 14.-Diagram Illustrating the Formation of an Anemic Infarct, 
The artery A is a terminal artery with a few capillary anastomoses with the neighboring artery B, 
so that when the embolus, E, cuts off the blood from the territory supplied by it, the involved region 
becomes anemic save in the peripheral zone of congestion. This is an anemic infarct. 
when the embolus is small, the patient may survive some hours in a 
condition of shock, deep cyanosis, and labored heart action before death 
comes. If the amount of lung occluded is still smaller, infarction may 
result and the patient survive. The condition is unusually serious be- 
cause it often occurs after relatively simple operations, and happens at 
the time the patient first gets out of bed, the movement being sufficient 
to dislodge the embolus. In making post-mortem examinations in the 
case of such suspicious deaths, it is important that both branches of 
the pulmonary artery be carefully opened while the heart and lungs are 
still undisturbed. If this is done, the embolus will frequently be found 
lying loose in a branch of the artery or even astride one of the bifurcations. 
1 Aschoff, L., Zieglers Beitr., 1912, lii, 205. 40 
CHANGES IN THE CIRCULATION OF THE BLOOD 
It is usually soft and red, and occasionally shows the marks of the valves 
of the veins with which it has been in contact. The frequency of such 
emboli varies considerably. While thrombosis occurs in about 1 per cent, 
of laparotomies for pelvic trouble, fatal embolism has been noted in 
different series of cases in from 0.1 to 0.2 per cent., though individual 
series may show considerably higher figures; for example, Zurhelle1 
reports that after myoma operations there were emboli in the lungs in 
1.5 per cent, of the cases. That infection has nothing to do with this 
type of thrombosis is shown by the fact that the introduction of aseptic 
technique has not diminished the number of fatal emboli.2 
The Sources of Emboli.-It should be remembered that as a rule 
emboli derived from a vein, and then most commonly detached from a 
venous thrombus, pass to the right side of the heart and are thence 
driven into the pulmonary artery, where, unless most minute, they are 
retained, since they cannot pass the pulmonary capillaries. Emboli 
in the left heart, the aorta, and the arterial system are derived from the 
pulmonary vein, the left heart, the aorta, or its branches (Fig. 15). 
Paradoxical Embolism.-While as a rule emboli follow the direction 
of the blood-current, one does sometimes find in the arterial system 
emboli of considerable size without being able to locate their source in the 
pulmonary vein, the left heart, or the aorta or its larger branches. 
Furthermore, under these circumstances one may discover an obvious 
source in the systemic veins. Since such emboli cannot pass the pulmon- 
ary capillaries they must have passed from the venous to the arterial 
system through an open foramen ovale into the left auricle, thence to be 
driven into the arteries (Fig. 15). This is called paradoxical embolism. 
It is of infrequent occurrence.3 
Retrograde Embolism.-Sometimes an embolus moves in a direction 
opposite to that of the blood-current, so that one may find in a small 
vein an embolus obviously derived from a larger vein or from the right 
heart. It has been assumed in explanation of this occurrence that 
under certain conditions in which the venous blood empties itself into 
the right heart with difficulty, as in the case of tricuspid incompetence, 
there might be an actual reversal of the venous current on which an 
embolus could be conveyed. It does not, however, appear that such a 
reflux of the venous blood is possible. Ribbert urges the view that 
while a complete reversal of the current is improbable in a congested 
vein, a pulsation wave may form with each heart-beat which could 
gradually force the embolus toward the periphery along the vessel 
wall. This retrograde transportation of an embolus is of rare occurrence 
in the large veins, especially in the inferior vena cava. 
The retrograde transportation of particles of tumor may give rise to 
very puzzling phases of metastasis. 
1 Zurhelle, E., Arch. f. Gynak., 1908, Ixxxiv, 443; Zieglers Beitr., 1910, xlvii, 539 (bibl.). 
2 For a full discussion of the question, see Aschoff, L., Beitrage zur Thrombosefrage, Leipzig, 1912; 
reprinted from Verhandl. d. Natursforsch. Gesellsch, 1911, p. 344; Rami, Arch. f. klin. Chir., 1918, 
Ixxxvii, 380; Cutler, E. C., and Morton, J. J., Surg., Gynec., and Obst., 1917, xxv, 621; Frdnkel, Arch, 
f. klin. Chir., 1908, Ixxxvi, 531; and Wilson, L. B., Ann. Surg., 1912, Ivi, 809. 
3 For details of unusual forms of embolism consult bibliography in Ziegler's General Pathology, 
English trans., 11th edition, New York, 1921. CHANGES IN THE CIRCULATION OF THE BLOOD 
41 
Fat Embolism.-After fracture of the long bones, fat from the 
marrow may find its way through opened veins into the right heart and 
into the pulmonary capillaries (Fig. 11). It may be found also in the 
capillaries of the kidneys. Fat embolism of the pulmonary capillaries 
Fig. 15.-Schematic Illustration oe Embolism-after Ribbert. 
The right lung, EL, and the left lung, LL, are connected with the heart through the pulmonary 
artery, PA, PA. The liver, L, and the right and left kidneys, EK, LK, are seen below with the aorta 
A and the vena cava, VC. The right ventricle, EV, and the left ventricle, LV, the right auricle, EA 
and the left auricle, LA, are exposed. From the thrombus T, a small portion, E, is detached and 
carried upward in the venous current through the vena cava to the heart. It turns into the pulmonary 
artery where it may lodge in the larger trunks in the lungs. Owing to its size it cannot pass the capil- 
lary system of the lungs, and hence cannot enter the general circulation. If, however, as is not infre- 
quently the case, an open foramen ovale exists, such an embolus could pass through the septum into 
the left heart, whence it could be sent through the aorta to the viscera, as is shown by the outlined 
embolus. A thrombus in the left heart, say on the mitral valve at M, if detached as is shown in the 
globular mass following the dotted line, may be sent into the aorta and thence into any of the small 
arterial trunks. In the diagram the embolus is lodged in the left kidney. 42 
CHANGES IN THE CIRCULATION OF THE BLOOD 
may be fatal, but in most cases does not appear to be of great signifi- 
cance. Fat embolism of the lungs is recorded following extensive 
fatty degeneration of the liver in phosphorus poisoning and severe kidney 
lesions.1 It is thought that there may be some correlation between 
shock due to severe injuries and fat embolism.2 
Emboli of Tumor Cells.-Clusters of tumor cells of considerable 
size may enter the vessels through erosion of their walls and may be 
transported in the blood-current as emboli (Fig. 202, p. 378). They may 
lodge in the trunks of large vessels, portal vein, pulmonary artery, etc., 
and in addition to the usual effects of embolism they may grow, forming 
metastatic tumors. Undoubtedly, only a small proportion of the tumor 
emboli which reach the organs ever develop into tumors. The majority 
are destroyed by encapsulation with fibrin and by the action of the fer- 
ments of the blood.3 
Air Embolism.-It rarely happens in surgical operations that a large 
quantity of air enters an opened vein and is aspirated to the right side 
of the heart. This may prove fatal. Air bubbles may be found mingled 
with the blood in the right heart, in the large veins leading to the heart, 
and in the pulmonary capillaries. Small quantities of air may enter the 
veins without having the slightest effect on the patient's condition; and 
the presence of a few air bubbles in the blood at autopsy is not an evi- 
dence that air had entered through a wounded vessel or that the patient's 
death was caused thereby. Researches on animals have showed that 
large quantities of air can be injected directly into the circulation without 
causing serious symptoms.4 The presence of gas in the vessels is common 
in caisson disease (page 18). In certain cases gas bubbles in the blood 
are due to infection with a gas-forming bacterium, the Bacillus aerogenes 
capsulatus (page 321). 
Experimental Study of Disturbances of the Circulation. 
One may observe many of the local disturbances of the circulation on the mesen- 
tery of the curarized5 frog. A loop of the intestine is drawn out through a lateral 
abdominal incision and laid over the glass window of a Thoma frog-plate (see Fig. 77). 
The part should be kept moist or irrigated with 0.6 per cent, salt solution. 
Under these conditions one may study various phases of hyperemia and stasis, 
hemorrhage by diapedesis and by slight injuries to the vessels, hemorrhage by rhexis 
and the formation of local thrombi by which it is controlled. By pressure on the 
vessels various disturbances of the circulation, thrombi, etc., can be secured.6 
1 For a study of fat embolism see Connell, Jour. Am. Med. Assn., 1905, xliv, 612; and Katase, A. 
Cor.-Bl. f. schweiz. Aerzte, 1917, xlvii, 545; for a study of fat emboli of the brain, see Naville and 
Fromberg, Arch, de m6d. exp6r., 1913, xxv, 405; and Grbndahl, N. B., Deutsch. Ztschr. f. Chir., 1911, cxi, 
56. 
2 Porter, W. T., New York Med. Jour., 1917, cvi, 894. 
3 Schmidt, M. B., Die Verbreitungswege des Karcinome, Jena, 1903. 
« See Goodridge, M., Am. Jour. Med. Sc., 1902, cxxiv, 461 (bibl.); Hare, H. A., ibid., p. 843; and 
v. Oppel, Deutsch. Ztschr. f. Chir., 1908, xcii, 437. 
6 The commercial curare is so variable in strength that it is best to make an aqueous solution of 
about 1:1,000 strength and test the effect, using just enough to secure immobility, and no more, since 
serious circulatory disturbances and death of the animal are readily induced with too liberal dosage. 
The solution-at first a few drops-is put beneath the skin in the dorsal lymph sac. It is well to give 
a preliminary dose a few hours before the use of the animal, bringing him partially under the influence 
of the drug, and to complete the effect just before the experiment. Under these conditions the second 
dose may be very small and thus untoward effects upon the circulation may be avoided. 
6 See for a further description of the method of studying the circulation in the living frog, p. 127. 43 
CHANGES IN THE CIRCULATION OF THE BLOOD 
By drawing forward the tongue of the curarized frog, fastening it in extension on 
the Thoma frog-plate designed for this purpose (Fig. 77), and ligating one of the large 
lateral veins, one can induce interesting phases of passive hyperemia and transudation. 
Embolism may be studied by the injection into the arteries of small particles- 
tobacco seed in the dog, begonia seed in the rabbit, or poppy seed-suspended in 
salt solution. These may be injected forcibly upward through the crural artery into 
the aorta. Embolism of the abdominal viscera, kidney, spleen, etc., with infarction 
may be thus induced. CHAPTER III. 
REGRESSIVE TISSUE CHANGES. 
General Considerations. 
There are three phases of activity in the transformations of energy 
which are characteristic of living cells. These are nutrition, reproduc- 
tion, and functional activity. But while these manifestations of energy 
are more or less distinct as properties of living matter, they are closely 
interdependent. It is the suitable balance of these activities fixed by 
prolonged environment which determines what we call health. When 
this balance is disturbed beyond the limits of physiological variation, the 
alterations which result may be manifest, either in the diminution or de- 
struction of tissue or in its increase or new formation. In other words, 
the cells of the body, when placed under conditions which seriously 
interfere with the orderly transformations of energy, may undergo 
alterations from the normal which are regressive on the one hand, or 
progressive on the other. 
We shall in this chapter consider the regressive processes and their 
effects; in the next those which are progressive. 
It is well to remember that the regressive as well as the progressive 
changes in the body are not limited to pathological conditions, but form 
a part of the normal processes through which growth is secured and 
function maintained.1 
The maintenance of the normal life and structure of the cell is closely 
dependent upon the conditions under which it is placed. If there is 
lack of sufficient or proper nutriment; if the waste products are not 
properly eliminated; if deleterious chemical substances either coming 
from without or formed by defective metabolism-poisons, toxins, etc. 
-are present; or if harmful physical agencies such as heat, cold, pressure, 
etc., are active; or, finally, if the innervation be defective, both the 
function and the structure of the cell may suffer. 
The functional changes of cells placed under unfavorable conditions 
are very variable and often very subtle owing to their complex and but 
little understood nature, and may be difficult of detection. These 
functional changes may or may not be associated with structural altera- 
tions which are obvious on microscopical observation. Cells may become 
larger than normal through increased functional activity, hypertrophy; 
they may become smaller, atrophy, under a variety of conditions pres- 
ently to be considered. Cells may swell through imbibition of fluid; they 
may be altered in shape from pressure. Finally, they may suffer various 
1 For a rSsumd of the relationship between normal and pathological regressive processes see 
Minot, Middleton Goldsmith Lecture on The Embryological Basis of Pathology, Science, 1901, 
xiii, 377, 481. 
44 REGRESSIVE TISSUE CHANGES 
45 
changes in internal structure. Various products of their metabolism 
or of degeneration of their cytoplasm may accumulate within them, or 
substances may enter from without-degeneration and infiltration. 
These and other changes due to an unfavorable environment may 
be recovered from, if not too extensive. But, on the other hand, if the 
damage be excessive the cell may die and suffer disintegration and 
absorption. This death of the cell, with subsequent physical and 
chemical changes, is called necrosis. 
It frequently happens, however, that the vitality of the cell is not 
at once extinguished, but that the processes of life and necrosis go on 
for a time together, ending in either its recovery or its death. This 
condition is called necrobiosis. 
Not all the cells of the body are equally sensitive to a deleterious 
environment. It is those which are more highly differentiated for the 
performance of special functions, or those which are more frequently 
exposed to harmful influences, which most often suffer. 
Atrophy. 
Atrophy is a diminution in the size of the body, of organs, or of tissue 
elements. It occurs as a physiological process in man as well as in cer- 
tain of the lower animals. Thus in man the thymus and the umbilical 
vessels undergo atrophy at an early period; while in old age, atrophy of 
the sexual organs and of the tissues in general is the usual mark of senil- 
This is atrophy from disuse of the striated muscle. Owing to the muscle pigment which has collected 
in the atrophied fibers this is called "pigment atrophy." 
Fig. 16.-Atrophy of Muscle. 
ity.1 On the other hand, as a pathological process, atrophy may occur 
in connection with disturbances of innervation or nutrition; from disuse 
or from pressure; or from the presence of poisons. Although it is con- 
venient to name these as phases of atrophy, they are not fundamentally 
distinct. In simple atrophy, under whatever conditions it may occur, the 
tissue elements become smaller without marked alterations in structure, 
1 For a study of the changes in the body in development and senility see the monographs of Muhl- 
mann, M., Uber die Ursache des Alters, Wiesbaden, 1900; Das Altern und der physiologische Tod, 
Jena, 1910 (bibl.); and Virchows Arch., 1914, ccxv, 1; Minot, C. S., The Problem of Age, Growth, and 
Death, New York, 1908; Chicd, C. M., Senescence and Rejuvenescence, Chicago, 1915. 46 
REGRESSIVE TISSUE CHANGES 
and may finally disappear altogether. In the majority of cases, how- 
ever, atrophy of cells or other tissue elements is not simple, but is asso- 
ciated with, and often determined by, various phases of degeneration- 
degenerative atrophy. The cytoplasm of atrophic cells is often more 
transparent than normal and may contain an undue proportion of 
pigment. 
An organ which is the seat of even extensive atrophy of some of its 
Fig. 17.-Atrophy and Distortion of the Liver from Tight Lacing-Female. 
The border of the organ is elongated and fibrous; the gall-bladder is long and distorted. 
cells is not necessarily diminished in size, but may even be much larger 
than normal. This is the case, for example, in amyloid degenerations of 
the liver. Sometimes the atrophy of parenchyma cells is accompanied 
by a new formation of connective tissue so extensive as to maintain, 
for a time at least, the size of the organ. 
Atrophy may be general or local and it has various phases which we 
shall briefly consider. REGRESSIVE TISSUE CHANGES 
47 
General Atrophy from Malnutrition affecting the body at large may 
occur as the result of deficient nutriment as in starvation, or a failure to 
assimilate food, and in various acute and chronic diseases. Under these 
conditions fatty and other forms of cell degeneration occur, with loss of 
the general adipose and reduction in size of muscle and other body cells. 
Senile Atrophy.-As the energies of life decline with the advance of 
years, the tissues and organs may undergo gradual and progressive atro- 
phy, but in varying degrees. The muscle cells of the heart are more 
slender, and brown pigment may accumulate within them-brown 
atrophy. The parenchyma cells of the liver, kidney, and generative 
Fig. 18.-Atrophy of Liver Cells. 
Pressure atrophy from amyloid degeneration of the blood-vessels. 
glands and the ganglion cells become smaller and may be more or less 
pigmented. Similarly the bones suffer atrophic changes, becoming 
more brittle, and the skin becomes wrinkled and dry. Senile atrophy 
may be associated with significant sclerotic changes in the blood-vessels 
and with atrophy of the lymph-nodes, spleen, and marrow. 
Atrophy from Suspension of Functional Activity-Atrophy from 
Disuse.-This is well exemplified in disused muscles or bones, as in vari- 
ous forms of paralysis. Voluntary muscles under these circumstances 
become more slender, lose their transverse striations, and become 
fibrillar. Brown pigment derived from the disappearing muscle sub- 
stance may gather in masses in the remaining fibers, and the nuclei of 
the sarcolemma may be increased in number (Fig. 16). The fibers may 
finally disappear and may be replaced by fat or fibrillar connective 
tissue. 
Pressure Atrophy.-This is seen under the ordinary conditions of 
modern life as the result of ill-adapted articles of dress, such as corsets, 
which frequently induce very marked atrophy with distortion of the 
liver (Fig. 17). But within the body itself pressure from a more vigor- 
ously growing tissue may induce atrophy of an adjacent part. Thus, 48 
REGRESSIVE TISSUE CHANGES 
tumors, cysts, accumulations of fluids in various cavities, aneurysms, 
degeneration of blood-vessels (Fig. 18), etc., may lead to local atrophy. 
Neurotic Atrophy.-While it is difficult to dissociate the direct tro- 
phic influence of the nerves upon tissues from the accompanying loss of 
function and interference with vascular supply, there appear to be 
cases of atrophy from neurotrophic influences. Atrophy of one side of 
the face in lesions of the trigeminus and in certain cerebral lesions, 
wasting of the associated muscles in destruction of the anterior cornua 
of the spinal cord, are examples. 
Degeneration. 
ALBUMINOUS DEGENERATION (Cloudy Swelling, Parenchymatous 
Degeneration, Acute Degeneration, Granular Degeneration). 
Under a variety of conditions in which there is a disturbance of cell 
metabolism, but especially often in infectious diseases and in intoxica- 
tions when poisonous substances come in contact with the tissues, the 
cells of the body show an accumulation in the cytoplasm of albuminous 
granules of various sizes and forms. While bacterial toxins are common 
excitants of this change, other vegetable toxins, such as abrin and ricin, 
or mineral poisons, as corrosive sublimate, may induce it. This is a type 
Fig. 19.-Albuminous Degeneration-Kidney. 
The lesion is moderate in degree and is most marked in the largest tubule above. 
of cell degeneration which is so often associated with infectious diseases 
and certain phases of inflammation that it is sometimes regarded as a 
part of the inflammatory process. The cells in this condition are 
usually swollen and are more opaque than normal, the nucleus being 
usually somewhat concealed in the granules when these are numerous 
(Fig. 19). The albuminous granules in the cells are soluble in dilute 
acetic acid, but not in ether, being thus distinguished from fat. 
While all the cells of the body are subject to this phase of proto- 
plasmic degeneration, it is most pronounced and frequent in the paren- REGRESSIVE TISSUE CHANGES 
49 
chyma cells of the liver and kidney, in muscle, and in epithelial cel of the 
mucous membranes. These are, it will be seen, cells which have a large 
amount of cytoplasm and in which metabolism is active and the exi- 
gencies of nutrition are imperative. The alterations in the ganglion 
cells of the central nervous system in infectious diseases and in various 
forms of intoxication are somewhat different from those occurring in 
other parenchyma cells and will be described in the section devoted to 
the Brain and Spinal Cord. 
Cells in a condition of albuminous degeneration may return to their 
normal state, they may become fatty, or they may die, become necrotic, 
and disintegrate. 
The liver, kidney, muscle, mucous membranes, etc., when in this con- 
dition, are often swollen and in gross appearance more opaque and gray 
than when normal. 
The exact chemical nature of this degenerative process is obscure 
and will doubtless remain so until we know much more than we now 
do of cell structure and cell metabolism.1 
Technique.-The microscopical study of this lesion is best made in fresh frozen 
sections of the tissue, by the rapid formalin method (page 1227), or in fresh tissue 
teased in 0.85 per cent, salt solution. 
FATTY DEGENERATION AND FATTY INFILTRATION. 
General Considerations. 
It should be remembered that besides the occurrence of fat cells in 
fat tissue and in the interstitial tissue of various organs, the accumulation 
of fat in certain epithelial cells is physiological, as in the functional 
processes of the mammary and sebaceous glands.2 In the involution 
of the uterus-also a physiological process-extensive fatty metamor- 
phosis of cell protoplasm occurs. 
It is customary and convenient, in considering the abnormal accu- 
mulation of fat in the tissues, to assume that in one set of cases-fatty 
degeneration-the fat is formed by a retrograde metamorphosis or degen- 
eration of the protein elements of protoplasm, a process by which the 
integrity and capacity of the cell are compromised, while in the other- 
fatty infiltration-it may be due to a simple accumulation in the cell of 
fat formed elsewhere-a condition of less significance. 
The validity of this assumption has of late been called in question. 
It involves in large measure the solution of the physiological problem 
whether normally the fat in the body is formed from proteins or from 
carbohydrates. Concerning this, many experiments and much argument 
have been made;3 but it appears not yet to be solved. The traditional 
1 For a study of albuminous degeneration see Albrecht, Verhandl. d. deutsch. path. Gesellsch., 1903, 
vi, 63. 
2 For chemistry of fats, see Mathews, Physiological Chemistry, 2d edition, New York, 1917, chap, 
iii; and Fischer and Hooker, Fats and Fatty Degeneration, New York, 1917. 
3 For a critical summary of this question see Taylor, Am. Jour. Med. Sc., 1899, cxvii, 569; and 
Albrecht, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1907, xi2, 1166. For a study of the role of soluble 
soaps in formation of fat in cells, see Klotz, Jour. Exper. Med., 1905, vii, 633; also Albrecht, foot-note 
above. For a study of myelinic substances in cells, see Albrecht, Verhandl. d. deutsch. path. Gesellsch., 
1903, vi, 95; and Adami, Jour. Am. Med. Assn., 1907, xlviii, 463. 50 
REGRESSIVE TISSUE CHANGES 
distinction between fatty degeneration and fatty infiltration will there- 
fore be made here, with such modifications and reserve as are fitting in 
view of our lack of knowledge. 
There is apparently a certain amount of fat or closely related sub- 
stances in the cytoplasm of many cells not demonstrable morphologically. 
Similarly there is fat in the blood which may be conveyed to cells. 
Under normal conditions these forms of fat enter into the metabolism of 
the cells and are used up. 
We might perhaps wisely adopt the conception of Ribbert that fatty 
degeneration is a condition in which the involved cells are so damaged 
through various harmful agencies that the fat which they may normally 
contain, but which is invisible in their cytoplasm, or fat taken into the 
cell from without, or fat formed in the cell metabolism, is not properly 
metamorphosed-burned-but accumulates in droplets in the cell 
body. The appearance of fat in connective-tissue cells growing in vitro 
affords support to this idea, as extracellular transport in this case is 
impossible. 
Fatty Degeneration. 
In fatty degeneration there is an accumulation of larger and smaller 
droplets of fat in the cell, sometimes so slight as to be scarcely visible, 
sometimes so great as largely to replace the protoplasm, crowding the 
nucleus to one side. These strongly refractile fat droplets are not 
changed by dilute acetic acid. They are soluble in ether, and when fresh 
Fig. 20.-Fatty Degeneration-Kidney. 
The fat droplets are stained black by osmic acid. 
are stained black by osmic acid (Fig. 20), red by Sudan III or Scharlach 
R. (Fig. 21), and red or blue by Nile blue sulphate (see technique below). 
Not infrequently, feathery clusters of delicate fat crystals are present in 
the cells. Cells in excessive fatty degeneration may disintegrate, form- 
ing an oily detritus in which, especially when much moisture is present, 
cholesterin crystals may form by decomposition of the lipoids. 
To the naked eye, organs in a condition of marked fatty degeneration 
are usually larger and softer than normal, have a grayish-yellow color or REGRESSIVE TISSUE CHANGES 
51 
are mottled with yellowish streaks or patches, and the normal markings 
of cut surfaces are more or less obscured. 
Fatty degeneration may be associated with or may follow albuminous 
degeneration and may occur under similar general conditions, as in 
infections, poisoning, etc. It is often associated with the processes of 
necrosis and disintegration in dead cells and dead tissue. It may be 
due to local or general disturbances of nutrition, from a great variety of 
causes-disturbances which either directly affect the life processes of 
Fig. 21.-Fatty Degeneration of Epithelium in the Kidney 
The fat droplets are stained with Scharlach R. 
the cells themselves or which produce alterations in their nutritive sup- 
ply. In addition to its local occurrence, as a result of local disturbances 
of circulation in the vicinity of inflammations or in tumors, etc., it is 
apt to occur in the liver, heart muscle, and kidney in chronic exhausting 
diseases and in conditions and diseases to which profound anemia is in- 
cident, in senility, or as the result of the action of certain poisons, such as 
phosphorus and arsenic. 
The function of the cell in fatty degeneration may be greatly impaired, 
as in fatty degeneration of the heart muscle. On the other hand, in the 
liver and kidney, the function of the organ may not apparently suffer even 
with marked degrees of the lesion. The cell may recover if the lesion 
be not too profound. 52 
REGRESSIVE TISSUE CHANGES 
Fatty Infiltration. 
This is of common occurrence under normal as well as pathological 
conditions. The fat is believed to originate outside of the cells, accumu- 
lating in them, and inducing a passive atrophy of the cytoplasm. Cells 
in a condition of abnormal fatty infiltration are scarcely to be distin- 
guished morphologically from those involved in fatty degeneration. 
The presence in the cells of large or small droplets of fat, without marks 
of degeneration in the remaining protoplasm, has been regarded as 
distinctive of infiltration. 
In some phases of fatty infiltration, as in the heart (Fig. 22) or the 
pancreas, for example, the fat accumulates in the cells of the interstitial 
The fat cells have accumulated between the muscle cells of the heart, and not within them as 
in fatty degeneration. 
Fig. 22.-Fatty Infiltration of the Heart. 
connective tissue in a manner identical with that in which the normal 
panniculus adiposus is formed. The heart muscles or the gland cells are 
under such conditions, affected secondarily through pressure atrophy 
from the accumulated fat. It should be remembered that fatty infiltra- 
tion and fatty degeneration may occur simultaneously. When fat pro- 
duction or fat storage is largely in excess of fat consumption from either 
local or general causes, the condition is called lipomatosis or liposis.1 
Lipoid Degeneration.-In the cortex of the adrenal and in the lutein 
cells of the ovary double refractive granules occur normally. Similar 
granules are found in atherosclerotic areas in the vessels, in some of the 
1 For a study of lipomatosis with bibl., see Lyon, Arch. Int. Med., 1910, vi, 10; and Matsuoka, 
Jour. Path, and Bacterio!., 1915, xx, 85. REGRESSIVE TISSUE CHANGES 
53 
nephritides, in the walls of old abscesses, and in the gall-bladder with 
biliary stasis, also in the so-called adrenal tumors of the kidney, in adeno- 
mata of the adrenal, and in xantho- 
mata of the skin. These granules 
are composed of a combination of 
cholesterin and fatty acid in the 
form of an ester (Fig. 23).1 
Technique.-Frozen sections should 
be made of fresh tissues, which may then 
be examined in 0.85 per cent, salt solu- 
tion with crossed Nicols for double re- 
fracting fat; or frozen sections of fresh 
tissue or that hardened in formalin can 
be stained for twenty minutes in a satu- 
rated solution of Sudan III or Scharlach 
R in equal parts of acetone and 70 per 
cent, alcohol, washed in 70 per cent, al- 
cohol, transferred to water, and mounted 
in glycerin or glycerin j elly. A saturated 
aqueous solution of Nile blue sulphate (Griibler) will also stain fat satisfactorily. 
With this stain the neutral fat is red, the nuclei blue, and the fatty acids dark blue. 
The granules which stain a purplish color are lipoids. It is an advantage, according 
to Schmorl, to wash the section in 1 per cent, acetic acid, and then in water, and 
embed in glycerin or glycerin jelly.2 
Fig. 23.-Lipoid Globules in Juice 
Expressed from Suprarenal. 
Viewed under crossed Nicols. 
GLYCOGEN INFILTRATION. 
Glycogen appears under abnormal conditions in the cells as hyaline, 
mostly globular masses of varying size (Fig. 24). It is soluble in water, 
is stained brownish-red by iodine, 
and does not, like amyloid, as- 
sume a greenish color by further 
addition of sulphuric acid. In 
diabetes it may occur in large 
quantities in the liver cells and 
in the epithelial cells of the 
uriniferous tubules, especially in 
those of Henle's loop, and in 
leucocytes. It may be found in 
fresh pus cells, in the cells of various forms of tumors, and in leucocytes 
in the blood in leukemia, in chronic diseases of the gastrointestinal tract 
in children, and in various acute and chronic diseases.3 
Technique.-If the tissue to be examined for glycogen be fresh, the iodine should 
be used in solution in glycerin (equal parts of Lugol's solution and glycerin), in order 
The droplets of glycogen are stained with iodine. 
Fig. 24.-Glycogen Infiltration of 
Epithelial Cells. 
1 Closely related to these esters, but differing from them by a lack of double refraction, are the so- 
called myelin bodies which appear in tissues undergoing autolysis or decay. They stain with neutral 
red. For a detailed study of certain of these lipoids see Bang, Chemie u. Biochem. der Lipoide, Berg- 
mann, 1911; Kawamura, Cholesterinesterverfettung, Jena, 1911; and MacLean, H., Lecithin and Allied 
Substances: The Lipins, London, 1918. 
2 For method of staining fat-acid crystals see Mallory and Wright's Pathological Technique, 6th 
edition, 1915, p. 406. For details of staining fat and lipoid substances see Schmorl, Pathologischen 
Unterchungsmethoden, 7th edition, Leipzig, 1914, p. 159. For recent improvements in the identi- 
fication of different types of fat, see Bell, E. T., Jour. Pa?th. and Bacteriol., 1914-15, xix, 105. 
3 For general review with bibl., see Gierke, E., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1907 
xi2, 871. 54 
REGRESSIVE TISSUE CHANGES 
to avoid its solution. If specimens are to be hardened, this should be done in absolute 
alcohol to avoid the solution of the glycogen. Sections of material hardened in alcohol 
are stained for 5 to 10 minutes in Lugol's solution; dehydrated in a mixture of absolute 
alcohol, 4 parts, and tincture of iodine, 1 part; cleared; and preserved in oil of origanum. 
The preferred method is that of Best (page 1239). 
Under many pathological conditions, cells, especially those of mucous 
membranes, glands, muscles, tumors, etc., contain one or more larger or 
smaller droplets of clear fluid (Fig. 25). The cell may thus be distended. 
These droplets are usually extranuclear and may crowd the nucleus to 
one side of the cell. The nature and source of this accumulated fluid are 
not definitely known. Its transparent appearance in the granular pro- 
toplasm has given rise to the term "vacuole." It may be associated 
with general tissue edema, with inflammatory and degenerative proc- 
esses, etc. 
SEROUS INFILTRATION OF CELLS (Hydropic Degeneration, Vacuolization). 
Mucous and Colloid Degeneration. 
There is a group of closely related translucent glycoprotein substances 
which it was formerly thought practicable to distinguish by simple 
chemical tests, especially relating to solubility. Among these are the so- 
called mucins and colloid. The simplicity of the earlier distinction has, 
Fig. 25.-Serous Infiltration 
of Epithelial Cells. 
Pig. 26.-Mucous Degeneration of Epithe- 
lial Cells. 
however, not been justified by more modern research, so that the separa- 
tion of mucous and colloid degeneration along the old lines does not 
express very definite chemical knowledge. It will, however, be con- 
venient, while awaiting light from the chemist, to maintain the old 
distinctions between mucous and colloid degeneration, unstable as are 
the foundations on which they rest. 
From a cystadenoma of the ovary. 
Mucous degeneration may occur in cells or in intercellular substance. 
When occurring in cells it consists, under pathological as under normal 
conditions, of the transformation of the protoplasm into a translucent, 
ropy, semifluid material, occupying more space than the unaltered pro- 
toplasm and hence causing a swelling of the cells (Fig. 26). The dis- 
tention of cylindrical epithelium by the accumulation of mucin-containing 
MUCOUS DEGENERATION. REGRESSIVE TISSUE CHANGES 
55 
substances in the outer portion of the cell, with the crowding of the nu- 
cleus and the remnant of the cytoplasm toward the base, often gives the 
cells the shape of a goblet or beaker (Fig. 27), hence the name "beaker 
cells," often applied to them. This appearance is especially well marked 
when the mucinogenous contents of the cell have been discharged from 
the free end. 
Mucins may collect in small transparent droplets within cells or may 
Formation of mucus in the epithelium of the small intestine. The mucus is stained with thionin. 
Fig. 27.-"Beakeb Cells." 
so distend them as to form a globular body with a scarcely visible rem- 
nant of nucleus or cytoplasm. The cells may be totally destroyed by 
the accumulation of the mucinous material within them. This new- 
formed material contains mucin in solution, which is precipitated by 
acetic acid and by alcohol. It swells up in water and is readily stained 
Fig. 28.-Mucous Degeneration of Fibrous Tissue of Mamma 
by thionin. It occurs under a variety of conditions, sometimes as an 
abnormal increase of a normal function of cells, as in many catarrhs, 
sometimes as an entirely abnormal transformation. 
In certain cases, as in many tumors, in cartilage, bone, and other 
tissues, the intercellular substance may undergo conversion into mucin- 56 
REGRESSIVE TISSUE CHANGES 
containing material, losing almost entirely its original structure (Fig. 
28). The cells in such cases may be affected only secondarily by the 
pressure which the new-formed material exerts upon them. 
Technique.-Tissues should be hardened in corrosive sublimate or formaldehyde 
followed by alcohol; the sections are stained with thionin, mucicarmine, or hematoxy- 
lin, which color the mucin-containing portions. 
COLLOID DEGENERATION. 
This is very closely allied, both in chemical and morphological char- 
acters, to mucous degeneration, and in many cases there is no definite 
microscopic distinction between them. But colloid material, which is 
normally present in the thyroid, is firmer and more consistent than 
mucinous, and does not yield a precipitate on addition of acetic acid or 
alcohol, and its formation is usually confined to cells, not involving 
intercellular substance, except by an atrophy which its accumulation 
sometimes induces. The cells may contain larger and smaller droplets 
of colloid material, or the latter may nearly or entirely replace the proto- 
plasm and accumulate to such an extent as to cause rupture and destruc- 
tion of the cell. In this way, and by the atrophy of intercellular sub- 
stance which its accumulation causes, cysts may be formed containing 
colloid material and cell detritus. Colloid material accumulates fre- 
quently in the thyroid gland. A material resembling, if not identical 
with, colloid is occasionally seen in the form of homogeneous globules 
in the tubules of kidneys which are the seat of other lesions, in the 
hypophysis, and in various tumors. 
Technique.-Tissues should be hardened in formaldehyde or Orth's fluid, and 
stained with picro-acid fuchsin. 
Hyaline Substances. 
Under a variety of conditions there are deposited in the tissues homo- 
geneous protein substances whose origin and nature are still obscure. 
Sometimes they are very abundant and seriously interfere with the 
function of the organs in which they occur. But frequently they are 
present in small amount and, with or without association with other 
processes, seem to be of slight importance. While some of these are 
characteristic in appearance and in the conditions under which they 
occur, and give definite gross and microchemical reactions, others seem 
at present to have no definite reactions and appearances, except the 
homogeneous character which they all share. 
One of these substances, amyloid, can be definitely differentiated by 
its appearance, color reactions, and the conditions under which it occurs. 
Another, hyaline substance, while less individualized than amyloid, is 
conveniently considered for the present as a definite material. The 
remainder of the homogeneous substances cannot be classified now and 
are probably of diverse origin and composition. REGRESSIVE TISSUE CHANGES 
57 
This is the transformation of tissues into a transparent, glassy sub- 
stance, much resembling amyloid in its morphological characters (Fig. 
29), but which does not give the microchemical reactions of amyloid, 
and appears under different conditions. 
Hyaline substance is resistant to the action of acids, and stains 
readily with acid fuchsin and eosin. It occurs especially in the walls of 
the smaller blood-vessels in various parts of the body, in voluntary 
muscle fibers, and sometimes involves interstitial tissue. It occurs in 
the thyroid, the brain, the reticular tissue of lymph-nodes, and in the 
HYALINE DEGENERATION. 
A. In the walls of small blood-vessels from a sarcoma. 
B. In muscle cells in infection of pregnant uterus. 
Fig. 29.-Hyaline Degeneration. 
ovaries; in the membrana propria of the tubules of the kidney and in 
Bowman's capsule; in the walls of aneurysms, in the lesions of diphtheria, 
tuberculosis, and syphilis; in the hyaloid membrane and vessels of the 
eye, and elsewhere. It occurs in the unstriated muscle fibers in infection 
of the uterus during pregnancy (Fig. 29). It is believed that fibrin, 
blood-plates, and leucocytes may undergo hyaline degeneration, and in 
the form of hyaline thrombi the altered material may block the capil- 
laries in many infectious diseases-typhoid fever, pneumonia, diphtheria, 
pyemia, etc.-and under other conditions (page 34). 
Hyaline substance is not uncommon in coarse trabeculae or in masses 
as an apparent modification of fibrin in inflammatory exudates and in 
thrombi. Hyaline casts are common in the kidney tubules.1 
Technique.-Hardening in alcohol, Orth's fluid, or formaldehyde. Staining by 
picro-acid fuchsin or by hematoxylin and eosin. 
AMYLOID DEGENERATION (Waxy or Lardaceous Degeneration). 
This is a process by which the basement substance of various forms 
of connective tissue, and especially the walls of the blood-vessels, become 
1 Consult for bibliography of studies on hyaline degeneration, Lubarsch, Lubarsch-Ostertag 
Ergebn. d. allg. Path., 1895, i2, 200; Davidsohn, ibid., 1908, xii, 424. 58 
REGRESSIVE TISSUE CHANGES 
swollen and thickened by their conversion into a translucent, firm, 
glassy, colorless material, albuminous in character. (For the micro- 
chemical reactions of amyloid substance see below under Technique.) 
This albuminous material may be present in the tissues in such small 
amount as to be recognizable only under the microscope, or it may be so 
abundant as to give a very characteristic appearance to the tissue. 
Parts in which the lesion is marked are usually enlarged, and some organs, 
the liver, for example, may reach a very large size. Affected parts 
contain less blood and feel harder than normal, and have a peculiar 
Fig. 30.-Amyloid Degeneration of Capillary Blood-vessels of a Glomerulus of the Kidney 
The waxy vessels are stained pink with methyl violet. 
shining and translucent appearance which varies in character, depending 
upon the extent and distribution of the degenerated areas and upon 
association with other lesions, such as fatty degeneration. It most 
frequently occurs in the smaller arteries and capillaries (Fig. 30), whose 
lumen is encroached upon by the thickening of the walls which the 
process involves. It is usually the media and intermediary layers of 
the intima which are earliest and most extensively affected. The change 
also often occurs in the interstitial connective tissue and membranae 
propriae of organs and in reticular connective tissue. It does not affect 
the parenchyma cells of organs. These, however, frequently undergo 
atrophy as the result of pressure from the swollen, degenerated tissue. 
It is not yet known whether amyloid degeneration is due to a direct REGRESSIVE TISSUE CHANGES 
59 
transformation of the tissue, or is an infiltration by some abnormal 
material formed elsewhere and brought to it, or is derived from the blood. 
Amyloid degeneration occurs most frequently and abundantly in 
the liver, spleen, kidneys, intestinal canal, and lymph-nodes; but it may 
occur, usually in a less marked degree, in other parts of the body: in 
the larger blood-vessels, in the interstitial tissue of the heart and mucous 
membranes of the air passages, and in the generative organs. It may 
occur locally or appear in various parts of the body at once. It most 
frequently occurs in connection with severe wasting diseases, particu- 
larly in those involving chronic suppuration and ulceration, especially of 
the bones. It is common in tuberculosis, syphilis, and the cachectic con- 
dition induced by malignant tumors, and is occasionally seen in severe 
malarial infection, dysentery, and leukemia.1 
Fig. 31.-Corpus Amylaceum in a Case of Carcinoma of the Prostate. 
The tissue is infiltrated with plasma cells due to the presence of a new growth. The central mass and 
the concentric deposition layers at the periphery of the body are well shown. X 600. 
Technique.-For microscopical examination, the tissue, either fresh or after pres- 
ervation, should be cut into thin sections, and these deeply stained with 1 per cent, 
aqueous solution of methyl violet; the sections are washed in water and mounted in 
glycerin. The differentiation between the amyloid and other parts is more distinct if, 
after staining, the specimen be dipped for an instant in HC1 and alcohol 1 : 100, and 
then carefully rinsed, before mounting in glycerin. The degenerated areas are thus 
stained rose-red, while the normal tissue elements have a bluish violet color. In 
some cases, for reasons which we do not know, the amyloid substance does not show 
a well-marked reaction with methyl violet. (For the detection of amyloid in fresh 
tissues by the iodine reaction see page 1213.) 
1 An extended study of amyloid degeneration may be found in a monograph by Wichmann, G. 
Zieglers Beitr., 1893, xiii, 487. See also Schilder, P., ibid., 1909, xlvi, 602 (bibl.); Davidsohn, W., Lubarsch- 
Ostertag, Ergebn. d. allg. Path., 1908, xii, 424; Hanssen, Biochem. Ztschr., 1908, xiii, 185; and Neuberg, 
Verhandl. d. deutsch. path. Gesellsch., 1904, vii, 19. 
A bibliography with a summary of experiments on the production of amyloid degeneration in 
animals will be found in an article by Maximow, A., Virchows Arch., 1898, cliii, 353. 60 
REGRESSIVE TISSUE CHANGES 
Corpora amylacea are small, spheroidal, homogeneous or lamellated 
bodies (Fig. 31) which occur in the acini of the prostate gland and in the 
ependyma of the brain and cord. In pathological conditions they are 
found in the lung (Fig. 32), in the brain and spinal cord, in extravasa- 
tions of blood, and in various other situations. In the brain and cord 
they may be very abundant, both in the membranes and in the substance 
and also in the glial and ganglion cells. They occur rarely in the pe- 
ripheral nerves. They may undergo calcification. When treated with 
aqueous iodine solution and dilute sulphuric acid, corpora amylacea 
assume a purplish color. With Best's method for staining glycogen they 
are colored a brilliant red, with Nile blue sulphate, a deep blue, and with 
Fig. 32.-Corpus Amylaceum in Case of Carcinoma of the Lung. 
neutral red, a deep red as are the fatty acids and soaps. It is probable, 
therefore, that they are composed of mixtures of some of the lipoids with 
glycogen or other carbohydrate material and traces of soaps and fatty 
acids. Corpora amylacea have no relation to amyloid degeneration.1 
There is in this condition a deposition, either in cells or in the inter- 
cellular substance, of larger and smaller granules composed chiefly of 
phosphate and carbonate of calcium (Fig. 33). These particles, when 
CALCAREOUS INFILTRATION. 
1 For a study of the relationship of corpora amylacea to amyloid substances, see OphUls, W., Jour. 
Exper. Med., 1900, v, 111 (bibl.). For a thorough study of corpora amylacea, especially those of 
the cerebrospinal axis, see St firmer, R., Nissl and Alzheimer, Histologische und histopathologische 
Arbeiten, Jena, 1913, v, 417 (biblj. REGRESSIVE TISSUE CHANGES 
61 
Fig. 33.-Calcification of Epithelial Cells of the Kidney. 
This is following sublimate poisoning. Some of the cells are converted into rounded, strongly 
refractile masses of lime salts. In others the lime is in the form of granules within the cells. The 
calcified parts are diffusely stained with hematoxylin. 
Fig. 34.-Calcification in Inflamed Omentum. 
The lime salts have been deposited in areas where the fibrous tissue has become necrotic. The omental 
fat has disappeared. 62 
REGRESSIVE TISSUE CHANGES 
abundant, give hardness, brittleness, and a whitish appearance to the 
affected tissue. Under the microscope they appear dark by transmitted, 
white and glistening by reflected, light. In hematoxylin-stained 
specimens, the tissue about the lime particles and masses is apt to be 
deeply and diffusely colored. Tissues may be nearly completely per- 
meated with salts, or the latter may be scattered in patches through 
them (Fig. 34). Sometimes large lamellated concretions are formed in 
tissues, usually at the seat of some old inflammatory process. Calcium 
salts may be deposited under abnormal conditions either in tissues or in 
the retained secretions and excretions of the body. In pathological 
calcifications they are retained, not in the diffuse state in which they 
Following sublimate poisoning. The calcium salts are deposited chiefly in the necrotic and fatty 
epithelium of the terminal portion of the convoluted tubules. 
Fiq. 35.-Calcareous Infiltration (Calcification) of the Kidney. 
exist in bone, but in particles or clumps, although the calcium compounds 
are essentially the same under both the normal and the pathological 
conditions. 
Calcification in tissues usually, if not always, occurs in parts which 
are dead or are in a condition of reduced vitality as a result of some 
antecedent abnormal process, as a rule of an inflammatory nature. 
Fatty degeneration of cells frequently precedes calcification. Among 
the most common and important examples of calcareous degeneration 
may be mentioned those which occui- in the valves of the heart in endo- 
carditis and the walls of the blood-vessels in chronic obliterative endar- 
teritis. It occurs in old thrombi, in old tuberculous areas, in old infarcts, 
in long-retained dead fetuses, in cartilage, in ganglion cells in old age REGRESSIVE TISSUE CHANGES 
63 
or after their death from any cause, and under many other conditions. 
Calcification of the epithelium and of casts in the kidney occurs after 
corrosive-sublimate poisoning in man (Fig. 35) and may be experiment- 
ally induced in animals. As examples of calcification of masses of secre- 
tion and excretion we may mention tonsillar calculi1 in which masses of 
epithelial cells, bacteria, etc., are infiltrated with calcium salts. Of simi- 
lar character are the preputial, bronchial, and intestinal calculi, and 
calculi in the ducts of various glands; and calcification in thrombi and 
other fibrinous structures. 
The calcium salts are derived from the blood and lymph in which 
they are held in solution. The rationale of their deposition in damaged 
cells and tissues is not yet clear, though much work and discussion have 
centered in the problem. The presence of phosphorus in the affected 
areas; the existence of fatty acids in cells and tissues-since fatty 
degeneration so frequently precedes calcification-with which the cal- 
cium may form insoluble soaps; and proteins capable of uniting with 
calcium, have all been urged as determining factors. We cannot enter 
here upon a discussion of this point.2 
Technique.-The carbonate of lime deposited in the tissues is dissolved by di- 
lute acids with evolution of carbonic-acid gas. This process may be observed under 
the microscope by running 5 per cent, hydrochloric acid under the cover-glass upon 
unstained sections; the gas bubbles are caught as they evolve beneath the coyer. 
If the salt is wholly calcium phosphate, the masses dissolve without gas production. 
If the fresh tissues are treated with silver nitrate solution, there is formed in the cal- 
cified areas a precioitate of silver phosphate which is blackened on exposure to light. 
Pigmentation. 
There is under normal conditions a cer- 
tain amount of pigment in the body-in the 
rete Malpighii of the skin, in the eye, in 
muscle, and in fat. This pigment is elabo- 
rated by the body-cells and may vary consid- 
erably in amount. 
The pigment which is formed under 
pathological conditions may be derived from 
the blood-hematogenous; from the bile- 
hepatogenous; or it may be elaborated by 
various cells after the analogy of the normal 
pigment-metabolic. Finally, pigment may 
be introduced into the body from without 
by drugs, in tattooing, or by inhalation- 
extraneous. The pigment in the body, of 
whatever origin, may be in yellow, brown, 
black, or reddish granules, or in crystalline 
form. It is often deposited in cells, but may lie free in the inter- 
Fig. 36.-Pigment Containing 
Iron within Epithelial Cells of 
the Air Vesicles of the Lungs. 
The iron pigment is colored blue. 
This specimen is from the lungs of an 
employe in the Subway in New York 
City. 
1 Calculi are masses of solid material of various composition precipitated from the body fluids. 
They will be considered under the separate organs in which they most frequently occur. 
2 Consult Wells, H. G., Jour. Med. Research, 1906, N. S. ix, 491 (bibl.); Arch. Int. Med., 1911, vn, 
721. Also, for a study of the role of diffusible soaps in the formation of cell fats and in calcareous degen- 
eration, see Klotz, 0., Jour. Exper. Med., 1905, vii, 633, and 1906, viii, 322. 64 
REGRESSIVE TISSUE CHANGES 
cellular substance. It is often transferred from place to place in 
the body.1 
Hematogenous Pigment.-Blood pigment may form by the de- 
composition of hemoglobin in thrombi, or in extravasated or the circulat- 
ing blood. Under these conditions the hemoglobin which is loosely 
associated with the plasma of the red blood-cells readily diffuses, leaving 
the cells-so-called "blood shadows"-pale and almost invisible and 
prone to disintegrate. This destruction of blood-cells is called hemolysis. 
Hemoglobin in solution in the body fluids2 undergoes various phases of 
decomposition which we cannot follow in detail here. One of the deriva- 
tives or groups of derivatives of the hemoglobin is called hemosiderin. 
Hemosiderin usually appears in the form of brown or black granules 
either in cells or free in the tissues. It is the usual form of blood pig- 
ment resulting from hemolysis. It gives the microchemical reaction for 
iron. For this test for iron in hemosiderin see foot-note below.3 
Fig. 37.-Hematogenous Pigment. Hematoidin Crystals and Masses Free and within 
Leucocytes. 
A further common decomposition product of hemoglobin is hema- 
toidin. Hematoidin is identical in chemical composition with the bile 
pigment, bilirubin. It may occur as red rhombic plates or acicular 
crystals or as granules (Fig. 37). It does not contain iron. This is 
the form of blood pigment which after a time is apt to form at the 
seat of old hemorrhages or in old blood-clots, thrombi, etc., where it 
may persist for a long time. 
Red blood-corpuscles may be taken up by various forms of phago- 
cytes, and within these cells the decomposition of the hemoglobin may 
lead to their pigmentation. Such cells are frequent in the pulmonary 
alveoli in chronic cardiac disease, as the so-called "heart failure cells." 
Hemolysis may take place in the circulating blood in many forms 
1 See Askanazy, M., Centralbl. f. allg. Path., 1906, xvii, 642. 
2 See page 519. 
3 To differentiate free iron and certain of the iron-containing pigments of the hemosiderin group, 
sections of the alcohol-hardened tissue are placed for an hour or longer in a 2 per cent, aqueous solution 
of ferrocyanide of potassium. Transfer to glycerin containing 0.5 per cent, hydrochloric acid. Under 
these conditions the iron will be stained blue or greenish-blue (Fig. 36). In order to secure a reaction 
for the ferrous as well as the ferric salts, use a mixture of 1 gram each of ferro- and ferricyanide of potas- 
sium in 100 c.c. of water. Transfer to acid glycerin as above. Contrast stains may be secured by alum 
carmine. 
There are, it should be remembered, certain iron compounds-the so-called "masked" iron- 
which are not demonstrable by the ordinary reaction. 
For a rSsumS of the microchemical reactions for iron, with bibl., see Tracy, M., Jour. Med. Research, 
1905, N. S. ix, 1; also, Mann, Physiological Histology, Oxford, 1912, p. 290. REGRESSIVE TISSUE CHANGES 
65 
of poisoning, in acute infections, notably in malaria, in pernicious ane- 
mia, in various cachexiae, etc. The hemoglobin thus set free in the 
body fluids may be eliminated through the urine, inducing hemo- 
globinuria; it may be used by the liver in the formation of bile; or it 
may undergo decomposition, and its derivatives may be deposited in 
the cells of various organs and in the tissues as pigment granules. 
A condition called hemochromatosis has been described, in which a 
brown pigment, probably derived from the hemoglobin of the blood, is 
deposited in various tissues of the body. The organs in this condition 
may appear notably pigmented on gross examination. The pigment 
particles which are found in the epithelial cells of glands, especially of 
the liver and pancreas, contain iron; while an iron-free pigment may be 
present in the smooth muscle cells of the gastrointestinal canal and of 
the blood- and lymph-vessels, and in connective-tissue cells. This pig- 
mentation is commonly associated with cirrhosis of the liver. Hemo- 
chromatosis may be associated with diabetes mellitus and cirrhosis of 
the liver, together with pigmentation of the skin-"bronze skin." 
The conditions leading to hemochromatosis are still obscure.1 
Fig. 38.-Anthracosis-Pigmentation of Connective-tissue Cells of the Lungs from Inhaled 
Coal Dust. 
Hepatogenous Pigment.-Pigmentation of tissues from the bile 
occurs under various conditions. The bile may enter the blood and tis- 
sue fluids in obstruction of the gall-ducts by inflammation, tumors, cal- 
culi, etc. In the condition called jaundice or icterus the tissues are 
stained yellowish or yellowish-green by bile pigment. Icterus, it should 
be remembered, may also occur in infectious diseases and in toxemia, 
under conditions which lead to destruction of red blood-cells within the 
vessels. Bile may still be formed when the portal blood is prevented 
from reaching the liver.2 Such transformation may take place, also, in 
the pleural and peritoneal cavities.3 Even an excessive carbohydrate 
diet will increase the formation of bilirubin.4 Bile pigment may be 
deposited in the liver, kidney, and elsewhere in the form of yellow or 
brown granules.5 
It consists largely of bilirubin, a substance identical with hema- 
1 For a careful study of hemochromatosis, see Opie, E. L., Jour. Exper. Med., 1899, iv, 279 (bibl.). 
2 Whipple, G. H., and Hooper, C. W., Jour. Exper. Med., 1913, xvii, 593, 612. 
3 Hooper, C. W., and Whipple, G. H., Jour. Exper. Med., 1916, xxiii, 137. 
• Hooper, C. W., and Whipple, G. H., Am. Jour. Physiol., 1916, xl, 332, 349 
5 Posselt, A., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1915, xvii2, 719. 66 
REGRESSIVE TISSUE CHANGES 
toidin, being derived from hemoglobin through the metabolism of the 
liver cells. 
Ochronosis.-Under conditions which are as yet little understood, 
minute, iron-free, gray or black granules of pigment which may be called 
melanotic are deposited especially in cartilage but also in other con- 
nective tissues. Melanuria may accompany this form of tissue pig- 
mentation. This condition has been called ochronosis.1 
The pigment may be seen lying in delicate strands in the connective tissue of the corium. 
Fig. 39.-Generalized Argyria Following Use of Argyrol. 
Metabolic Pigment.-Pigments called melanins,2 and probably 
derived from albumins, may be elaborated by various forms of cells, 
by processes apparently somewhat analogous with those concerned in 
normal pigmentation.3 This is exemplified in melanotic tumors (Plate 
1 For a study ot ochronosis see Pick, Berl. klin. Wchnschr., 1906, xliii, 478, 509, 556, 591; and Pou/sen' 
Zieglers Beitr., 1910, xlviii, 437 (bibl.l. 
2 Wieting and Hamdi, Zieglers Beitr., 1907, xlii, 23; Smith, D. T., Bull. Johns Hopkins Hosp., 1920, 
xxxi, 239. 
s For a study of the nature of skin pigment consult Abel, J. J., and Davis, W. S., Jour. Exper. Med., 
1896, i, 361; Chittenden and Albro, Am. Jour. Physiol., 1899, ii, 291; also Mann, Chemistry of the 
Proteids, New York, 1906, p. 580. 
For a general survey of such pigments, see Hueck, IT., Zieglers Beitr., 1912, liv, 68, and Oberndorfer, 
Lubarsch-Ostertag, Ergebn. d. allg. Path., 1921, xix2, 47 (bibl.). 67 
REGRESSIVE TISSUE CHANGES 
II), most frequently of the choroid and the skin, and possibly in the 
bronze skin of Addison's disease. 
Pigment whose nature is not very clearly defined may form in the 
smooth muscle tissue of the gastrointestinal walls, in various cachexise, 
in the heart muscle, in the so-called " brown atrophy," and, under certain 
conditions, in the liver. In old age pigment is frequent in the ganglion 
cells. It may occur in the cervical sympathetic ganglion cells in ex- 
ophthalmic goiter.1 
Extraneous Pigment.-As examples of pigment introduced into 
the body from without, we may mention the deposition of minute par- 
ticles of lead-lead line on the gums-or of silver from the use of silver salts 
-argyria; the coloring of the skin and lymph-nodes from tattooing; and 
especially the pigmentation of the lungs and bronchial glands from the 
inhalation of coal and other dust-pneumonokoniosis (Fig. 38). This 
is universally present under the conditions of indoor life which modern 
civilization imposes. Such pigment may be brown or black, and is 
usually in very small particles within cells or in the intercellular stroma. 
The pigment in argyria may result from the ingestion of inorganic 
salts of silver or from the continued use of local applications of the or- 
ganic compounds, such as argyrol. In the latter case, the subepithelial 
tissues of the entire body may contain enough pigment to give the patient 
a dusky bluish tint (Fig. 39). Local argyria is most often seen in the 
conjunctiva after the repeated employment of argyrol as an antiseptic.2 
Necrosis. 
Necrosis3 is the death of a circumscribed portion of tissue in the 
living body. It may be the result of insufficient nutrition from cutting 
off the blood supply, as by embolism, thrombosis, ligature, pressure, etc., 
or it may depend upon the action of destructive chemical agents, ex- 
treme degrees of temperature, the Roentgen rays, and radium. It may 
be due to bacterial toxins or to toxins formed by the animal tissues; 
to nerve lesions leading to trophic disturbances; or to mechanical injury. 
Defective nutrition of the body in various acute and chronic diseases 
disposes the individual to local necrosis when subjected to any of the 
direct agencies just enumerated. 
The general appearance of dead tissues varies greatly. In some cases 
there is a simple and gradual disintegration and softening of the tissue, 
resulting in a mass of degenerated cells and cell detritus, with more or 
less fluid and various chemical substances arising from decomposition. 
The softening of the brain in embolism is an example of simple necrotic 
softening-liquefaction necrosis. In some cases the dead tissues merely 
dry and shrivel gradually and become hard and dark-colored. 
In another class of cases the dead tissues are permeated by fluids 
which may be dark red in color, from the solution of coloring matter 
1 Wilson, L. B., Am, Jour. Med. Sc., 1916, clii, 809. 
2 Olsen, G. M., Jour. Am. Med. Assn., 1917, Ixix, 87. 
3 Albrecht, E., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1907, xi2, 1123 (bibl.). 68 
REGRESSIVE TISSUE CHANGES 
from the blood, and may contain bacteria which induce putrefaction, 
with the production of gases and various new chemical substances. The 
tissues become swollen and granular, and disintegrate; and finally the 
whole may form a mass of irregular granules, with fat droplets, tyrosin, 
leucin, and various forms of crystals, shreds of the more resistant kinds 
of tissue, and bacteria. 
The death of cells is marked by cessation of function and by certain 
morphological and chemical alterations of the body and the nucleus. 
As a rule the highly specialized cells, such as the functional cells of the 
brain, liver, and kidney, are most vulnerable in the presence of harmful 
conditions. 
There is at first no evident morphological difference between dead 
cells and living cells. But very soon in the former, changes occur. The 
cytoplasm may swell and become homogeneous from imbibition of fluids; 
or, on the other hand, it may become more coarsely granular. The 
nucleus stains less deeply or not at all with hematoxylin or other nuclear 
dyes (Fig. 40), owing to the disappearance of the chromatin which 
seems to dissolve in the tissue juices; this is called karyolysis. Some- 
times, however, the chromatin does not dissolve, or only partially dis- 
The cells in the lower portion of the cut are nearly normal; most of those above are more coarsely 
granular and have failed to take the nuclear stain, while at the top they are disintegrating. 
Fig. 40.-Necrosis of Epithelium in the Kidney. 
appears, the remainder breaking up into irregular, more or less deeply 
staining granules. This is called karyorrhexis. The nuclei of cells 
which are undergoing regressive processes or dying may become smaller 
and denser than normal and stain more deeply; this is called pycnosis. 
Presently the cell body may contain fat droplets, or without this it may 
disintegrate. 
Gangrene.-When death of a considerable mass of tissue occurs, and 
this either dries, as is possible on the surface of the body, or is associated 
with putrefaction in the tissue, the condition is called gangrene. The 
involved part, when on the surface of the body, may dry and become 69 
REGRESSIVE TISSUE CHANGES 
hard and brown or black-mummification, or dry gangrene1 (Fig. 41). 
On the other hand it may, when putrefactive bacteria are present, in 
addition to its discoloration, become soft and infiltrated with foul- 
Fig. 41.-Gangrene of the Foot. 
A sharp line separates the dead and gangrenous portion of the foot from the living tissues about the 
posterior part and the ankle. 
smelling gases-moist gangrene. If the affected part be comparatively 
bloodless, the discoloration, which is largely due to decomposition of the 
blood pigment, may be absent.2 
Focal Necrosis.-Necrosis involving a 
small circumscribed area of tissue, such as 
is frequent in toxemia, is called focal necrosis 
(page 232). Whether such focal necroses 
are due to destruction of the capillaries by 
the toxins in the blood, to a primary lesion 
of the parenchyma cells, or to minute 
thrombi, is as yet undetermined. 
Ulceration.-Necrosis with erosion 
involving the surface of the skin or of the 
mucous or serous membranes is called an 
ulcer. An ulcer may be necrotic in origin, 
from the cutting off of nutrition in a circum- 
scribed area, as in some forms of gastric 
ulcer. This may be associated with re- 
active inflammatory processes which tend 
to promote repair. On the other hand, 
the process may be inflammatory in origin, 
death of tissue following; a good example 
of this is the typhoid ulceration of the 
intestine which begins as an inflammatory process in the Peyer's patches. 
Coagulation Necrosis.-If dead areas of tissue (whether this con- 
dition be due to mechanical injury, to disturbances of nutrition, or to 
Fig. 42.-Coagulation Necrosis 
in Cells. 
The disappearance of the chromatin 
from the nuclei is indicated by their 
failure to stain, especially marked in 
the upper cells. 
1 For a study of senile gangrene, see Falta, Ztschr. f. Heilk., 1899, xx, 393 (bibl.). 
2 For more detailed studies of gangrene consult works on surgery. 70 
REGRESSIVE TISSUE CHANGES 
the local action of bacterial or other poisons) contain the substances 
necessary for the coagulation of their albuminous constituents, or if they 
are bathed with body fluids from adjacent parts in which the circula- 
tion is maintained, a characteristic coagulation of the necrotic elements 
is apt to occur. The composition of the cells of the tissue is altered, so 
that the cell bodies are shining and translucent, sometimes altered in 
shape; while the chromatin and 
finally the nuclei of the cells disap- 
pear (Fig. 42). The white infarc- 
tions of the spleen and kidneys, 
the areas of coagulation necrosis 
in tuberculosis, and the pellicle in 
croupous inflammation of the 
mucous membranes are the most 
common examples of this lesion. 
If, for example, in the spleen, 
one of the small arteries is plugged 
by an embolus, a corresponding 
portion of the spleen becomes 
anemic and appears as a white, 
wedge-shaped mass, sharply de- 
fined from the surrounding splenic 
tissue. If such a white infarction has existed but a short time, there is 
hardly any difference between the appearance of its anatomical elements 
and those of the surrounding spleen, except that they are differently 
affected by staining-fluids. If the infarction is older, the cells are small 
and shiny and their nuclei cannot be seen. 
In croupous inflammations of mucous membranes the epithelial cells 
become shiny, the nuclei disappear, 
and the shape of the cells is changed 
by the coagulation necrosis, so that 
a number of them together often 
look like a network of coagulated 
fibrin. 
Cheesy Degeneration (Caseation). 
-As commonly used, this term 
embraces the changes in the tissues 
which we have just considered 
under the more appropriate name 
of coagulation necrosis. But it is 
also applied to that form of degen- 
eration in which, under a variety 
of conditions, the dead tissue elements lose their normal structural 
features and become converted into an irregularly granular albuminous 
and fatty material (Fig. 43 and 44), which sometimes tends to disin- 
tegrate and soften, sometimes dries and becomes dense and firm, or 
may become infiltrated with salts of calcium. Thus cheesy degenera- 
tion may, and very often does, occur in tissues which are in the condi- 
Fig. 43.-Coagulation Necrosis. 
In tuberculous tissue. 
Fig. 44.-An Area of Cheesy Degenerator 
(Caseation) in a Miliary Tubercle in the 
Lungs. 71 
REGRESSIVE TISSUE CHANGES 
tion of coagulation necrosis; but it also occurs in tissues which are not 
the seat of coagulation necrosis, but which, for a variety of reasons 
and in a variety of ways, have lost their vitality. 
The terms "coagulation necrosis" and "cheesy degeneration," as 
commonly used, in part actually cover the same degenerative conditions. 
Bo.th are most frequently seen in connection with tuberculous infections. 
While their exact nature is as yet somewhat obscure, a step toward the 
understanding of the chemical processes underlying this type of necrosis 
has been made.1 The older theory was that caseation was produced 
by the anemia, the tissues being practically avascular. The more preva- 
lent view is, however, that the tubercle bacillus contains toxins which 
destroy the tissues, though an explanation for the persistence of the 
cheesy areas has been lacking. Recent work has shown, however, that 
the tubercle bacilli contain a ferment-inhibiting substance which seems 
to be of a fatty-acid nature and when saponified has the power of inhibit- 
ing the action of the autolytic, tryptic, and leucoproteic ferments; thus, 
the toxic substances of the tubercle bacilli have free play in causing necrosis 
of the tissues. This necrotic material is not removed by the ordinary 
process of autolysis or phagocytosis because of the inhibiting substances 
of the tubercle bacillus. The anemia caused by the occlusion of the 
blood-vessels also plays an important part as the cutting off of the 
fluid supply from the tissues prevents the dilution and subsequent 
absorption of the inhibiting substance. The reaction at the periphery 
of the cheesy area also prevents the entrance of fluids and thus the 
caseous area gradually increases in size, as the bacterial toxins cause the 
death of the surrounding tissues. The administration of iodides which 
saturate the fatty acids and prevent them from inhibiting the ferment 
often leads to breaking down of the cheesy areas in tuberculosis and even 
more strikingly in syphilitic gummata. 
Fat Necrosis.-This is a degenerative process most frequent in the 
subperitoneal fat and in and about the pancreas, and especially associated 
with lesions of that organ. We refer for details to the special section 
(page 803). 
The Disposal of Necrotic Tissues.-Necrotic tissues may be sepa- 
rated from the living body by inflammatory processes and wholly 
cast off, as in gangrene of a limb, or in bone, the dead portion in this case 
being called a sequestrum. 
Fragments of dead cells and tissues in the living body are in part 
disposed of by leucocytes or other mesoblastic cells which may be 
attracted to them, and may cause their solution by proteolytic enzymes 
which are set free or by the incorporation of particles of the dead tissue 
into their bodies where they are destroyed.2 
Furthermore, the absorption of necrotic tissues is in part due to 
proteolytic enzymes furnished by the dead and degenerating cells them- 
selves. The self-destruction of tissues in the ways indicated is called 
autolysis (page 122). To what extent the lytic substances through 
1 Jobling, J. W., and Petersen, W., Jour. Exper. Med., 1914, xix, 251, 383. 
2 See Phagocytes, p. 114. 72 
REGRESSIVE TISSUE CHANGES 
which dead tissues are softened may be derived directly from the blood 
plasma is not yet clear. At any rate, through chemotaxis, phagocytosis, 
and autolysis considerable masses of necrotic tissue may be finally re- 
moved.1 Dead bone is dissolved and disposed of by special forms of 
cells called osteoclasts2 (page 119). 
Recent studies relating to the adaptation of the body to various alien 
substances have led to new conceptions of the nature of the processes by 
which the body frees itself of useless or harmful material either devel- 
oped within it or introduced from without. (For a fuller consideration 
of these processes see cytolysis, page 197.) 
1 Wells, H. G., Jour. Med. Research, 1906, N. S. x, 149. 
2 Arey, L. B., Anat. Rec., 1917, xiii, 269. CHAPTER IV. 
PROGRESSIVE TISSUE CHANGES. 
Hypertrophy and Hyperplasia. 
Hypertrophy.-Under a variety of conditions, cells, parts of the 
body, or even organs become larger than normal. The structural change 
to which this enlargement is due may be a simple increase in size of the 
elementary structures of the part, the cells. This is called simple hyper- 
trophy. It is usually associated with some increased functional demand 
upon the cells and an increase in their functional capacity; as, for exam- 
ple, in the hypertrophy of the heart with lesions of the valves, or in the 
hypertrophy of one kidney, which in case of diminution or suspension 
of function in the other assumes the work of both-compensatory 
hypertrophy J 
Pathological hypertrophy in response to functional demand-func- 
tional hypertrophy-has its physiological prototype in the changes in the 
uterus and in the mammary gland during pregnancy. 
It should be borne in mind that the simple enlargement of a part or 
organ does not necessarily involve the hypertrophy of any of its structural 
elements. Thus there may be an increase of fat in a muscle causing 
its enlargement; waxy degeneration of the liver may determine great 
increase in the size of this organ. It is well to limit one's conception 
of hypertrophy to enlargement of specific structural elements of a part 
with maintenance or increase of functional capacity, and to consider 
other instances of enlargement, such as those just cited, as examples of 
pseudohypertrophy. 
Hyperplasia.-In many cases the increase in size of a part or 
organ is due not only, or not at all, to the increase in size of its element- 
ary structures, but to an increase in their number. This increase in 
number of the structural elements of a tissue or organ is called numer- 
ical hypertrophy, or hyperplasia.2 
Hyperplasia of connective tissue is of frequent occurrence in associa- 
tion with atrophy of the parenchyma of various organs, replacing the 
damaged cells as these diminish or disappear. This is called replace- 
ment hyperplasia. 
Hypertrophy and Hyperplasia in Special Organs.-In hypertrophy of 
the heart associated with the increased amount of work which it has to 
do in maintaining the circulation in various forms of valvular lesion, 
1 For bibliography of compensatory hypertrophy, see Aschoff, Lubarsch-Ostertag, Ergebn. d. allg. 
Path., 1898, v, 67. 
2 Consult for examples of hyperplasia and hypertrophy the following sections on Regeneration and 
Inflammation. 
73 74 
PROGRESSIVE TISSUE CHANGES 
pulmonary and vascular obstruction, or excessive bodily strain;1 in 
hypertrophy of the unstriated muscle such as may occur in the bladder 
in urethral stricture, calculi, etc., in the stomach in pyloric stenosis, in 
the arteries in chronic diffuse nephritis; as well as in the voluntary- 
muscle hypertrophy from athletic exercises, etc., the individual muscle 
cells and fibers are increased in length and in thickness. 
In hypertrophy of one kidney from the loss of the other or of part of 
its own substance by operation or lesion, there is enlargement of the 
epithelium, especially of the convoluted tubules and of the glomerular 
epithelium covering the tuft, the latter being also enlarged. Changes in 
the collecting tubes and in the interstitial tissue are less marked even in 
kidneys which are greatly increased in size. 
Compensatory hypertrophy of the liver following destruction of 
part of the parenchyma seems to be largely due to the new-formed 
liver cells, and to hyperplasia of the interstitial tissue, but the hyper- 
trophy of the old cells occurs. 
Compensatory hypertrophy of the thyroid2 and adrenals has been 
experimentally induced. Hypertrophy of one testicle occurs after the 
removal of the other, and the same is true of the mammary gland. Com- 
pensatory hypertrophy of the ovaries has not been observed. 
After destructive injury to the spleen its function may be in a 
measure assumed by the bone-marrow and lymphatic tissue which 
undergo compensatory hypertrophy. 
In most of these conditions hyperplasia of the interstitial tissue is 
associated with the hypertrophy of the specific parenchyma cells whose 
response to increased functional demands is marked by simple 
hypertrophy. 
Metaplasia. 
In the development of the body there is a constant and progressive 
differentiation of cells. When development is complete a certain speci- 
ficity exists, marked by functional and structural characters. These 
specific characters in cells are fairly permanent under normal conditions. 
Under a variety of abnormal conditions, however, they may undergo 
modification so that one type of cell or tissue may assume more or 
less completely the characters of another type. But the limitations 
of this change in type are strictly drawn, so that one type can assume 
only the characters of another which is closely related to it. This 
change of one form of tissue into another is called metaplasia. 
Thus, by a gradual change in the cells and stroma of fibrous tissue, 
this may be converted into bone, as mucous tissue may become fat tissue, 
and hyaline cartilage become fibrous. Metaplasia is a process involving 
active changes on the part of the living cells of the tissue, and should be 
clearly distinguished from certain degenerative and infiltrative processes, 
in the course of which one form of connective tissue may assume super- 
1 For conditions of cardiac hypertrophy see page 628. For a fuller consideration of the phases and 
conditions of hypertrophy see Adami, Principles of Pathology, Philadelphia, 1908, vol. i, 535. 
2 Such hypertrophy is not constant after removal of portions of the gland, and the conditions under 
which it may occur must be considered at present as not accurately determined. See for discussion 
oi the matter, Halsted, IF. 8., Am. Jour. Med. Sc., 1914, cxlvii, 56; and Hunnicutt, J. A., ibid., 1914, 
cxlviii, 207. 75 
PROGRESSIVE TISSUE CHANGES 
ficial resemblances to others of the group, as in calcareous and mucoid 
degeneration. 
The infiltration of the cells of fibrillar connective tissue with fat, 
and the reverse process in which the fat is lost, as in atrophy and emacia- 
tion, are not, strictly speaking, examples of metaplasia. 
While metaplasia is most common among the members of the con- 
nective-tissue group, it sometimes occurs in other tissues. Thus, for 
example, the epithelium of the nose, bronchi, urinary passages, corpus 
and cervix uteri, and gall-bladder may under a variety of conditions as- 
sume the characters of squamous epithelium of the skin type.1 
One should be critical in estimating the value of evidences of meta- 
plasia, which has apparently been assumed to occur more frequently 
than the facts justify. For example, many instances of alleged meta- 
plasia can be equally well accounted for on the assumption of defects 
of development in which a certain portion of tissue has failed to com- 
plete its differentiation, thus remaining in form and in situations which 
simulate the results of metaplasia. Or, cells of the differing types may 
have grown into the region from adjacent parts. 
When differentiation has advanced so that such distinct types of 
tissue have been formed as connective tissue, epithelium, muscle, nerve, 
these do not again merge through metaplasia. There is no evidence 
that mesoblastic tissues can be converted into those of the epiblastic or 
hypoblastic type or vice versa. 
Reversion. 
Under various conditions, but especially when highly differentiated 
cells have been thrown out of function, often as the result of inflammatory 
processes, they appear to assume the morphological characters which 
belong to an early stage in their development. This is called reversion, 
reversionary metamorphosis, or k at aplasia. Thus the flat epithelium of the 
air vesicles of the lungs or the cylindrical epithelium lining the bronchi 
or the stomach may become cuboidal. In the kidney the epithelium of 
the glomeruli and also of the convoluted tubules may become cuboidal. 
So in chronic peritonitis the mesothelium may become greatly thickened. 
Muscle fibers and connective-tissue cells may assume for a longer or 
shorter period distinctly embryonic forms. But here, as in metaplasia, 
one should accept the morphological evidence of reversion with due 
reserve, since in many instances the cells of the lower type in question 
may be the results of a reparative process not yet complete, and may 
have been derived from newly formed cells.2 Furthermore the shape of 
cells in general is so closely dependent upon nutrition, pressure, and 
mutual relationship that even slight departures from these may lead to 
changes in form quite as marked but not of such significance as those in- 
volved in reversion. 
1 For references to epithelial metaplasia, see Menetrier, Bouchard's Traite de pathologic g£n6rale, 
iii, pt. 2, p. 784. For a discussion of metaplasia, see Ribbert, HLehrbuch d. allg. Pathologic, 5th 
edition, Leipzig, 1915, p. 174; and Geschwulstlehre, 2d edition, Bonn, 1914; also Adami, J. G., Prin- 
ciples of Pathology, Philadelphia, 1908, vol. i, 586. 
2 See Ribbert, H., Geschwulstlehre, 2d edition, Bonn, 1914; also, for general review of reversion and 
growth in tissues, Adami, J. G., A. Jacobi Festschrift, 1900, p. 422; and Principles of Pathology, Phila- 
delphia, 1908, vol. i, 810. 76 
PROGRESSIVE TISSUE CHANGES 
Regeneration. 
General Considerations.-It is during the earlier periods of life that 
the new formation of cells in the body is most active. From the fertili- 
zation of the ovum until the tissues and organs have assumed the varied 
forms and functions which the physiological division of labor among the 
cells imposes, cell proliferation and cell adaptation to a changing envi- 
ronment are constant and important features of individual development. 
After this time, under normal conditions, new cell formation is largely 
limited to the replacement of worn-out cells or to the restitution of 
such cells as may be sacrificed in the performance of their physiological 
functions. 
The studies of Bizzozero have shown that, notwithstanding the great diversity in 
the capacity for physiological regeneration among tissues, they may be conveniently 
grouped into three classes, as follows: First, tissues whose cells are capable of multipli- 
cation throughout the life of the individual or for a considerable period after maturity, 
and so lead to a continual regeneration. These are tissues whose cells are labile and 
evanescent. In this class are the parenchyma cells of those glands or structures which 
produce formed elements, such as the spleen, lymph-nodes, bone-marrow, ovary, testi- 
cle; also the epithelium of the skin with its hair follicles and sebaceous glands, and of 
the mucous membranes of the respiratory, digestive, and genitourinary organs. Sec- 
ond, tissues whose elements increase by division up to the time of birth, or sometimes 
for a short period thereafter, when evidence of physiological regeneration ceases. 
These are tissues with permanent cells. In this class are the parenchyma cells of those 
glands which secrete fluid material, such as the liver, kidney, pancreas, salivary glands, 
etc., also members of the connective-tissue group, fibrous tissue, cartilage and bone, 
and the smooth muscle fibers. Third, striated muscle and nerve tissue. In these 
tissues, division by mitosis ceases at an early period and before the tissues have ac- 
quired their special characters. Here extensive regeneration does not occur. 
This grouping of tissues in accordance with their capacity for physiological regen- 
eration, while liable to modification under further research, affords a suggestive guide 
in our studies of regeneration under abnormal conditions. For beyond the regenera- 
tive capacity normally exercised by cells in response to the physiological wear and 
tear of life, they are frequently called upon to make good unusual losses, as the result 
of many forms of injury. 
Regeneration of injured tissues and new growths, as well as the 
hyperplasias above mentioned, are invariably brought about by prolifera- 
tion or other changes in living cells. Furthermore, just as the cells of 
the adult organism are the offspring of one original cell, the ovum, so 
are all the new cells which appear in the body under abnormal condi- 
tions derived from pre-existing cells by division. 
We shall now briefly summarize the morphological changes which 
cells undergo in division and shall then indicate the degree of regenera- 
tive capacity which various forms of tissues possess.1 
STRUCTURE OF CELL AND MODES OF DIVISION. 
The careful and minute study of cells during the act of division, 
which has been recently made, has revealed many most curious phe- 
nomena and has opened a new world of observation nearer to the elemen- 
tary expression of life than had seemed possible in earlier times. It will 
1 For a summary of much of our knowledge of regeneration, see Marchand, F., Process der Wundheil- 
ung, Stuttgart, 1901. PROGRESSIVE TISSUE CHANGES 
77 
suffice for our purpose briefly to indicate some of the more striking fea- 
tures of the new cell lore. 
It is well to recall at the outset that recent studies of cells have 
shown that even in their simplest forms they are highly organized, and 
that their different parts have special functions to perform. Thus the 
nucleus presides over the constructive metabolism or assimilative proc- 
ess of the cell and furnishes the physical basis upon which ihe trans- 
mission of hereditary characters depends. The cytoplasm of the body, 
on the other hand, is concerned in those phases of metabolism which 
result in the liberation of energy in movements of various kinds and in 
the formation of new chemical substances. The centrosome also in 
certain cells, though not apparently in all, appears to play an important 
part in the changes incident to division. 
In addition to the nucleus and its chromatin network, which with the 
central bodies and the attraction spheres play so important a part in the 
mechanism of cell fertilization and division, there are other constituents 
of the cell-the mitochondria1 and the plasmosomes-of which less is 
known. Besides these, many of the highly specialized celis carry specific 
granules, probably in many instances connected with the limited func- 
tional activity to which the cell is dedicated, for example, the Nissl 
granules of the nerve cell, the secretory granules of the salivary and pan- 
creatic organs, and the neutrophile and eosinophile granules of the 
leucocytes. These characteristic aggregates of cytoplasmic protoplasm 
are present chiefly at the full functional maturity of the cell, while the 
mitochondria and plasmosomes are abundant in practically all embry- 
onic tissue elements, including the sex cells, the blood, and the ganglion 
cells. They can be seen in unstained preparations and take up certain of 
the so-called vital stains, as, for example, Janus green.2 
In the process of fertilization, the mitochondria mingle and, it is 
thought by some, fuse as do the chromosomes. Apparently they arise 
in the cytoplasm and are connected with its metabolic processes, as they 
may disappear during great functional activity; but their relationship 
to the various morphological products of such activity is not yet clear. 
In tumor cells they may be absent or very scanty, an evidence that such 
cells are not truly "embryonic," as is so often stated.3 
The plasmosomes are structures which give rise to the granules 
characterizing many of the cells. They are genetically related probably 
to the secretion granules, the fat and glycogen deposits, and the various 
pigments which occur in cells.4 The Golgi apparatus is another peculiar 
structure present in the cytoplasm.5 
1 Synonyms: Chondriosomes, chondrioconts, chondriomes, cytomicrosomes, chondriomites, electo- 
somes, plastosomes, Altmann's granules, etc. 
2 Lewis and Lewis, Am. Jour. Anat., 1914-15, xvii, 340 (bibl.); Cowdry, E. V., Am. Jour. Anat., 1916, 
xix, 423 (bibl.) and The mitochondrial constituents of photoplasm, Contrib. EmbryoL, Carnegie Inst., 
Washington, 19IS, viii, 39 (bibl.). 
3 Altmann, Die Elementarorganismen, 2d edition, Leipzig, 1894; Barratt, Quart. Jour. Med. Sc., 
1913, Iviii, 553; Beckton, Arch, Middlesex Hosp., 1910, xix, 103, 111, 115; Benda, Verhandl. d. deutsch. 
path. Gesellsch., 1914, xvii, 5 (bibl.); Porcelli-Titone, Zieglers Beitr., 1914, Iviii, 237; Meres, Arch. f. 
mikros. Anat., 1908, Ixxii, 816. 
4 Benda, Verhandl. d. deutsch. path. Gesellsch., 1914, xvii, 5 (bibl.); Arnold, Anat. Anz., 1913, 
xliii, 433; Duesberg, Ergebn. d. Anat. u. Entwick., 1911-12, xx, ii, 567. 
6 Da Fano, C., Seventh Sci. Report, Imperial Cancer Research Fund, London, 1921, p. 67. 78 
PROGRESSIVE TISSUE CHANGES 
Besides the granules which occur in the cells, there are in many types 
fine anastomosing canaliculi demonstrable by special means. They have 
been described in the nerve cells, in glandular and columnar epithelium, 
and as especially well marked in the liver cells, and have been thought 
to afford means for the interchanges of fluids between the cell and the 
circulation.1 
In addition to these morphological elements, cells contain ferments 
which enable them to alter absorbed food materials, and either use them 
directly, as is the case with sugar, or store them in altered form, as with 
the proteins or their elements, the amino-acids. The number and 
capacity of these ferments vary greatly according to the cell. At least 
twelve have been identified in the liver cell. With the exception of the 
oxidase ferment found principally in the granular leucocytes, none can 
be easily demonstrated morphologically. 
Two modes of cell division are commonly recognized. First, indirect 
division (mitosis, or karyokinesis); second, direct division (amitosis).2 
Indirect (Mitotic) Cell Division. 
This is the most common mode of cell division and is especially char- 
acteristic of embryonic cells and those which are undergoing active de- 
velopment. While it presents great variations, its general features may 
be thus briefly summarized: 
Among the earlier changes which are to be seen in a cell about to 
divide by mitosis are a condensation and an increase in the staining capac- 
ity of the chromatin of the intranuclear network. This chromatin sub- 
stance gathers into a contorted thread or threads, called the spiremes 
(Fig. 45, 2), within the nucleus, whose membrane with the nucleolus 
gradually disappears so that the spireme lies free in the cytoplasm; and 
at the same time with, or preceding, these changes in the nucleus, there 
may be a division of the centrosome when this is present, the segments 
resulting from this division passing to opposite parts of the cell, usually 
outside the limits of the nucleus. Around each of the new centrosomes, 
which stain deeply with hematoxylin or other nuclear dyes, may be a 
clear zone of unstained material, or a series of fine radiating fibrils, or 
both; the whole forming a structure called a polar body (Fig. 45, 2 and 3). 
Now the threads of the spireme break across transversely, forming a 
series of more or less rod-like bodies called chromosomes, which form a 
somewhat flattened cluster or wreath between the polar bodies, lying in a 
plane at a right angle to a line passing between the latter. While this 
mass of chromosomes-sometimes called the monaster-has a stellar or 
wreath-like appearance when seen from the side, it is more band-like 
when viewed in profile (Fig. 45, 3 and 4). 
Between the polar bodies and across the monaster there may now be 
1 See, for bibl., Schafer, Quain's Anatomy, London, 1912, vol. ii, part 1, 25. 
2 For a general review of the theories of the mechanism of mitosis, see Meek, Quart. Jour. Med. Sc., 
1913, Iviii, 567; Schafer, Quain's Anatomy, London, 1912, vol. ii, part 1, p. 25; and Heidenhain, Plasma 
u. Zelle, Jena, 1907. For interesting results of the imitation of mitosis by diffusion of chemicals, see 
Leduc, La biologie svnthetique, Paris, 1912, PROGRESSIVE TISSUE CHANGES 
79 
stretched a bridge or spindle of delicate fibrils resembling those about the 
centrosome in the polar bodies. 
This fibril-spindle, together with the polar bodies, is called the achro- 
matic figure in distinction to the structure formed from the chromatin, 
which stains with nuclear dyes, and is called the chromatic figure. 
The whole complicated structure composed of both the chromatic 
and achromatic substance constitutes the mitotic figure. 
Now each chromosome splits lengthwise into exactly equal parts. 
These parts separate into groups which pass to the polar bodies at op- 
posite ends of the spindle. This is sometimes called the diaster phase of 
mitosis (Fig. 45, 5 and 6). 
Corresponding to the division of the chromosomes into equal parts, 
the cell body divides, each part containing one of the groups of daugh- 
ter chromosomes or diasters, together with one polar body and a part 
of the achromatic spindle (Fig. 45, 6). Now a new nucleus is formed 
Fig. 45.-Phases of Mitosis 
1. Resting cell. 2. Spireme phase: the centrosome has divided, the polar body is seen above, 
the nuclear membrane has not yet disappeared. 3. Monaster phase: the polar bodies have arranged 
themselves on either side of the monaster, here seen from the edge. 4. The monaster seen from the 
side. 5 and 6. Diaster phase: the chromosome clusters have separated and the achromatic figure is 
seen. In 6 the segmentation of the cell body has begun. 7. The completion of the nuclear division 
and segmentation of the cell body. 
about the daughter chromosomes which gradually assume the characters 
of the resting intranuclear network (Fig. 45, 7). The achromatic fibrils 
disappear from the new cell, while the centrosome may also disappear or 
may take its place in the cytoplasm beside the new nucleus. The 
number of chromosomes in different species is extremely variable. In 
the worm Ascaris megalocephala, there are four; in the fruit-fly Drosophila, 
which has been the subject of a remarkable series of studies in heredity, 
there are four pairs of chromosomes, three large and one small; in many 
plants there is a slightly larger number; while in man there are probably 
forty-eight in the somatic cells of the female and forty-seven in those of 
the male.1 In the spermatogonia of man there are forty-seven chromo- 
1 Winiwarter, HEtudes sur les spermatogen^se humain, Arch, de biol., 1912, xxvii, 91. 80 
PROGRESSIVE TISSUE CHANGES 
somes which reduce to twenty-three pairs, leaving the x or sex chromo- 
some unpaired. When the reduction division is completed, the x chromo- 
some remains in one cell, consequently spermatozoa are of two kinds, 
one containing twenty-four, the other twenty-three chromosomes. These 
numbers, however, are not finally accepted,1 for the technical difficulties 
in the study of the minute and interwoven structures are very great. 
There are countless other variations and details in the minute proc- 
esses of mitotic cell division and much interesting conjecture as to the 
meaning of the various changes in mitosis, which the scope of this work 
does not permit us to consider. But the facts already at hand are of 
extreme significance to the biologist and point toward large fields of 
research in pathology when the normal processes shall have been more 
clearly and exhaustively determined. What may be called a biological 
analysis of the results of mitotic division has yielded facts of great interest. 
As a result of Mendel's discovery of the unit or factorial type of heredity, 
the attention of biologists has been more and more focussed on the corre- 
lation between the appearance in the offspring of these segregated factors 
and certain structural details of the chromosomes. It is apparent that 
each chromosome of the egg and sperm has a constant regional distribu- 
tion in its structure of the elements which carry these factors into the 
next generation. It has been possible to predict, from a knowledge of 
the position of these factors, a new combination of qualities in certain 
artificially bred strains which have not been hitherto observed in nature.2 
Abnormal phases of mitosis are not infrequent. Thus, the mitotic fig- 
ures may be asymmetrical, so that the distribution of chromatin sub- 
stance to the daughter cells may be unequal (Fig. 46). There may be 
multipolar mitosis, so that, instead of two, several nuclei may form. Or, 
the new-formed chromosome masses may fail to share in the formation of 
the new nuclei. 
Such abnormal mitoses are 
frequent in certain tumors, and 
they may be experimentally in- 
duced by the application of 
various chemical substances to 
living cells.3 Too little is known 
about the conditions under which 
abnormal mitoses occur, and too 
little about the nature of the 
impulse to cell division in gen- 
eral, to justify to-day far-reaching conclusions as to the significance of 
these interesting abnormalities in the life of the cell. 
The Significance of Mitosis.-The term mitosis or karyomitosis is 
applied to this indirect mode of cell division, on account of the involve- 
ment of the nuclear threads. It is also sometimes designated as karyo- 
Fig. 46.-Abnormal Phases of Mitosis. 
In both cells the mitosis is asymmetrical, and in 
the cell to the left tripolar. 
1 Guyer, Accessory Chromosomes in Man, Biol. Bull., 1910, xix, 219; Montgomery, Jour. Acad 
Nat. Sc., Philadelphia, 1912, xv, 1. 
2 For an interesting r6sum6 of one phase of this work, see Morgan, T. H., The Mechanism of Mende- 
lian Heredity, New York, 1915. 
3 See Klemensiewicz, Zieglers Beitr., 1903, xxxiii, 51. PROGRESSIVE TISSUE CHANGES 
81 
kinesis, from the form changes which these threads undergo. Aside 
from its intrinsic biological interest, a knowledge of mitosis in proliferat- 
ing cells is of importance in pathology, because the recognition of mitotic 
figures often enables us to decide with certainty what particular cells or 
cell groups are involved in the formation of new tissue. The most sig- 
nificant feature, however, of the whole process of mitosis, with all its in- 
tricate variations, appears to be that the chromosomes, during their 
separation into two or more clusters to form the basis of new cells, undergo 
an exact longitudinal division. So that, under normal conditions, no mat- 
ter how unequal the division of the cytoplasm may be, all of the new nuclei 
share alike in the chromatin substance of the parent nucleus. This fact 
appears to be of extreme importance in the recognition of a physical basis 
of inheritance.1 
Direct (Amitotic) Cell Division. 
In this, which although relatively rare, appears to be the most simple 
mode of cell division, without those preliminary changes in the nucleus 
which are seen in the mitotic cell division, the nucleus with its membrane 
becomes constricted and finally divides into two or more parts which be- 
come new nuclei. At the same time or following this simple nuclear 
division the cell body divides, and thus two or more cells may form in 
the place of one. If the nuclear division is not followed by that of the 
cell body, multinuclear cells, or " giant cells," may be formed. 
The significance of the difference between the amitotic and the mitotic 
cell division is that, while in the former there is an exactly even division 
of chromatin to the daughter nuclei, the division in the latter is of the 
nuclear mass as a whole.2 
It has been claimed that amitotic division occurs in leucocytes, in 
some forms of epithelium, and in the cells of neoplasms; and its occur- 
rence has been described also in the cells of many vertebrates and of some 
of the lower aquatic forms. But there has recently been a change of 
opinion as to the nature of the process. While it is not denied that 
amitotic division of the nucleus may occur, recent opinion considers that 
there is no subsequent division of the cell body and that, therefore, the 
amitotic division of the nucleus is an entirely different process from the 
mitotic form.3 After amitotic division of the chromatin material in the 
cell, mitotic division may occur in the separated basochromatic masses 
or karyomeres. It has been thought, also, that these karyomeres may, 
when the cell actually divides, combine and furnish the usual number 
of chromosomes, which then unite in a single spindle and divide in 
a typical manner.4 Amitosis, therefore, according to these views, 
1 See summary by Wilson, E. B., Science, 1913, N. S. xxxvii, 814; see also Conklin, E. G., Heredity 
and Environment, Princeton, 1915. For a r6sum6 of physiology and pathology of the nucleus see 
Adami, Brit. Med. Jour., 1906, ii, 1760; Principles of Pathology, Philadelphia, 1908, i. See also in 
this connection Boveri, Entstehung maligner Tumoren, Jena, 1914. 
2 For a comprehensive summary of facts and theories concerning the cell, both in higher and lower 
forms of life, consult E. B. Wilson's masterly work, The Cell in Development and Inheritance, 2d 
edition, New York, 1911. 
3 Macklin, C. C., Biological Bull., 1916, xxx, 445. 
4 For an excellent r6sum6 of current views on amitosis, see Conklin, E. G., Biological Bull., 1917, 
xxxiii, 396. 82 
PROGRESSIVE TISSUE CHANGES 
is not to be considered a genuine divisional phenomenon, but merely a 
means of increasing the nuclear surface and of distributing nuclear 
material throughout the cell. Thus, it is comparable to the phenomenon 
of lobulation, fragmentation, or distribution of the nucleus, so familiar 
to students of hematopoietic cytology. 
GENERAL CHARACTERS AND LIMITATIONS OF CELL REGENERATION. 
It should be borne in mind, in studying the regeneration of various 
kinds of cells and tissues, that the acquirement by certain cells of special 
functional powers as the result of the physiological division of labor has 
involved the impairment of some of their more primitive general capaci- 
ties, among these that of reproduction. Thus it is that we find in the 
ganglion cells an almost total lack of reproductive capacity; while in 
many of the gland cells this is slight, in others considerable. In some of 
the less highly differentiated cells of the body, on the other hand, as in 
certain forms of epithelium, in blood-cells, and in the cells of the con- 
nective tissues, this primitive capacity of protoplasm to form new simi- 
lar cells by division is maintained, and may be evoked by the changed 
conditions which injury or loss involves. 
Although the occurrence of mitosis is the mark by which we espe- 
cially recognize the regenerative process in cells, it should be remembered 
that mitosis or some of its phases may occur in cells, without being fol- 
lowed by those further changes which lead to new cells or new tissues.1 
We may also often recognize new-formed cells and tissues by differ- 
ences in the shape and character of the cells and the arrangement of the 
tissue elements, these often approaching the embryonic type in form as 
well as in character of development. Furthermore, the atypical arrange- 
ment often seen in new-formed cells, both in regard to each other and in 
their association with older tissues, may aid in the identification of the 
formative process. 
Individual cells, even after having undergone marked structural 
changes-as, for example, in albuminous degeneration-or after a cer- 
tain degree of physical injury, may be restored to a normal condition. 
After destructive injury or loss, a full and complete replacement of 
cells and tissues can occur only as the result of a proliferation of cells of 
the same type as those to be restored. Thus a regeneration of epithe- 
lium occurs by proliferation and growth of epithelial cells alone; regen- 
eration of muscle by muscle cells, etc. In fact, however, in the higher 
types of tissue, after considerable injuries with loss of substance or after 
destructive pathological processes, complete regeneration is not common. 
This, as we have seen, is because the highly specialized cells of the body 
are limited in their capacity for reproduction closely to the domain of 
physiological regeneration. What we ordinarily call healing in exten- 
1 One is often disappointed in seeking for mitotic figures to find so few of them even in rapidly 
growing tissues. This is due to the fact that cell division even when active is not continuous, and 
periods of rest may follow the act of division. See Thoma, Text-book of General Pathology, English 
trans., vol. i, p. 481. For a summary of experimental work on this point see Woglom, Study of Experi- 
mental Cancer, New York, 1913 (bibl.). 83 
PROGRESSIVE TISSUE CHANGES 
sive wounds of the more highly specialized tissues is usually a provi- 
sional makeshift repair by means of new-formed connective tissue. 
We have seen that the regenerative capacity in the cells of the human 
body is most marked in the less highly differentiated types of cells, and 
that it is above all connective tissues, blood-vessels, and epithelium 
which most freely and most completely undergo regeneration. These 
are relatively lowly organized tissues and serve for the maintenance or 
protection of more highly specialized tissues, and with them regenera- 
tion may be complete with full restoration of function.1 But although 
the more highly organized tissues in man do not undergo after injury any 
considerable regeneration, they are, when uninjured, capable, under the 
stimulus of increased functional exercise, of compensatory hypertrophy, 
so that the loss to the organism of similar tissue is made good, an ex- 
ample of which is the structural hypertrophy and increased performance 
of one kidney after the removal of the other.2 
The capacity to regenerate lost or injured parts exists to a certain ex- 
tent in all animals but is most marked among the lower forms. Thus if 
an ameba be cut in two so as to leave one part with the intact nucleus, 
this part lives and the one-cell organism is completely restored. The 
fresh-water hydra, composed of many cells, may reproduce a large por- 
tion of the organism from a small severed fragment. The common earth 
worm can reproduce a severed head or tail. Crabs reproduce a whole leg 
if the severance takes place at a particular joint. Salamanders, snails, 
etc., can reproduce a leg or foot. It is further noteworthy in this connec- 
tion that the larvae of many lower forms, such as reptiles and insects, 
have a much greater capacity for the reproduction of lost parts than the 
same species have when in the adult condition.3 
REGENERATION OF SPECIAL TISSUES. 
Regeneration of the Nerve Tissue.-In the nervous system we find no 
evidence that the ganglion cells are capable of reproduction. Some phases 
of mitosis are occasionally found in them, although they do not appear 
to lead to proliferation. But if the essential parts of the ganglion cells, 
including the nuclei, be intact, a restoration may occur of their central 
as well as their peripheral branches. The fibrous and the neuroglia tis- 
sue of the central nervous system, on the other hand, may increase, and 
in this way, even with considerable loss of substance, injuries to the 
brain and cord may undergo a sort of patchwork repair. 
In the peripheral nerves extensive regeneration of fibers may take 
place after injury, when the corresponding ganglion cells are intact. 
This restoration may be effected in part by fibrous tissue which bridges 
1 Consult Morgan, T. H., Regeneration, New York, 1901; Barfurth, Regeneration u. Transplantation 
in der Med., Jena, 1910; Korschelt, Regeneration u. Transplantation, Jena, 1907. 
2 For an illuminating discourse on the surplus of functional provision in the body see Meltzer, 
The Factors of Safety in Animal Structure and Animal Economy, Harvey Lecture, Jour. Am. Med. 
Assn., 1907, xlviii, 655. 
3 For a suggestive study of the laws of growth and changes in cells and tissues during development 
and their relationship to the nature and cause of old age, see Minot, Harvey Lectures, 1905-1906, 
p. 230; also Pop. Sci. Monthly, 1907, Ixxi, 97. 84 
PROGRESSIVE TISSUE CHANGES 
the damaged region and affords guides or channels along which the axis- 
cylinders may grow out from the uninjured central segments, finding 
their way to their endings, as in embryonic development they stretch 
into the tissues far from the ganglion cells in which they originate. The 
restitution is possible here because the center of nutrition and at least a 
limited reparative control in the ganglion cell are intact. 
Further details as to degenerations and regenerations of nerves and 
nerve tracts may be found in the chapter devoted to The Nervous 
System. 
Regeneration of Muscle Tissue.-Regeneration of smooth-muscle tissue 
after injury is slight. Mitosis may occur in the cells, and preliminary 
phases of division of the body have been described, but it is doubtful 
whether, except possibly to a very slight extent, new cells are formed. 
Such healing as occurs after wounds and other injuries is largely effected 
by new-formed fibrous tissue. 
A partial regeneration of striated muscle occurs after various forms of 
damage and losses of substance. There may be division by mitosis in 
the sarcolemma nuclei (Fig. 47) associated with the accumulation near 
The nuclei of the sarcolemma have proliferated and are surrounded by a small amount of non-striated 
protoplasm. 
Fig. 47.-Regeneration of Striated Muscle after Injury. 
them of granular protoplasm, which becomes striated, either in situ or 
as independent cells. At the injured end of the muscle fiber a similar 
process may occur, so that these damaged fibers may be in part restored. 
If as the result of the injury some of the nucleated protoplasm escapes 
from the sarcolemma, a similar development of striated cells and cell 
masses may occur. 
It is especially in certain forms of degeneration of the contractile 
substance, after typhoid fever for example, in which the nuclei, the sar- 
colemma, and the general framework of the tissue are uninjured, that 
regeneration of striated muscle fibers is most complete. After injuries 
with considerable destruction of the muscle tissue, regeneration is apt to 
be irregular and incomplete. While there is often much nuclear divi- 
sion and often the formation of large numbers of more or less striated 
and variously shaped cells, these are apt not to develop into useful 
muscle fibers and may disappear by degeneration and absorption or by 
pressure atrophy. Here, as elsewhere in highly organized tissues, such 
restitution as is possible after considerable injury is achieved by fibrous 
tissue. 
It is interesting to note that such regeneration as does occur in 
striated muscle is initiated not by the highly differentiated contractile PROGRESSIVE TISSUE CHANGES 
85 
substance, but by the nuclei and small residual amounts of undifferen- 
tiated protoplasm, and that such more or less definitely striated cells as 
are formed are in many respects similar to certain forms of developing 
muscle cells in the embryo.1 
Although mitosis and nuclear division have been seen in the muscle 
fibers nf the heart after injury, there is no evidence that new muscle can 
be formed. Repair, which is not infrequent, is secured by fibrous tissue. 
Regeneration of Epithelium.-Owing to continuous shedding or to 
functional destruction of epithelium of the skin and mucous membranes 
and certain of their adnexa, physiological regeneration by mitosis is 
common. 
After injuries, also, regeneration of epithelium in these situations oc- 
curs by mitosis and may be extensive and complete. The new7 epithelium 
always forms from the old, and, when surface losses are to be made good, 
extends inward from the edges across the injured area after a suitable 
substratum has been formed by fibrous tissue and blood-vessels (Fig. 48). 
From a wound oi the tongue. At the left is normal epithelium; at the right the thin pellicle of new- 
formed cells is extending over the surface of the wound. 
Fig. 48.-Regeneration of Epithelium. 
The new epithelium is at first atypical in form and arrangement owing 
to the necessity for a gradual adaptation to the sustaining and associated 
tissues. Thus the epithelium which at first presses forward over a heal- 
ing wound of the skin, may be in the form of an irregular layer of cells 
(see Fig. 49) or of a thin smooth pellicle without the usual variations in 
size and shape by which it is later characterized when the papillae of 
the new cutis are formed and the new cells have adjusted themselves 
to these and to each other.2 In stratified epithelium it is the deeper 
layers from which the new cells chiefly arise. While amitotic division 
has been observed in the restitution of surface epithelium, this occurs 
in the more superficial cells and is believed not to be concerned in the 
regenerative process. 
Regeneration of gland epithelium after injury is of frequent occur- 
rence, though this capacity varies considerably in different glands. In 
many cases it appears to be by a proliferation of the epithelium lining 
the smaller excretory ducts that the restitution is accomplished, rather 
1 Pielsticker, Virchows Arch., 1909, cxcviii, 374 (bibl.); and Schmincke, Zieglers Beitr., 1908, xliii, 
519; 1909, xlv, 424. 
2 For a study of the regeneration of mucous membranes see Cornil and Carnot, Arch, de m6d. exp6r., 
1899, xi, 413; Amenomiya, R., Virchows Arch., 1910, cci, 231; and Ascoli, Arch. p. Ie sc. m6d., 1901, 
xxv, 257. For repair of bladder mucosa, see Lasio, Virchows Arch., 1904, clxxviii, 65. 86 
PROGRESSIVE TISSUE CHANGES 
than by the more highly differentiated secreting cells. This is of espe- 
cial interest because it affords an excellent example of the rehearsing 
under abnormal conditions and for reparative ends of a developmental 
phase of cell life. 
In the liver very extensive new formation of liver cells may occur 
after experimental removal of a portion of the organ.1 These new cells, 
arising largely from the epithelium of the small gall-ducts, do not form 
real liver tissue, however, since in this a definite relationship must exist 
between the liver cells and the gall-ducts, the blood-vessels and the 
interstitial tissue. Such a relationship can be secured only under the 
conditions of embryonic development when all the various tissues in- 
Fig. 49.-Regeneration of Epithelium. 
The epithelial cells advancing into and over the superficial portion of the granulation tissue at the 
right are fusiform and irregular in shape. They do not until later assume their usual forms and their 
relationships to one another and to the underlying tissue. 
volved are being formed together. After large destruction of liver cells 
in certain forms of toxemia-such as acute yellow atrophy of the liver- 
there may be an extensive and successful regeneration because the 
associated tissues are not at the same time destroyed. 
In the thyroid gland new gland tissue may be formed after injury.2 
In the kidney the regenerative capacity of the epithelium appears to 
be less marked, though proliferation of the epithelium of the collecting 
tubes may take place and epithelium to a considerable extent may be 
renewed if the blood-vessels and interstitial tissue remain intact.3 After 
poisoning with corrosive sublimate very complete regeneration of epi- 
thelium may take place. 
Regeneration of epithelium to a considerable extent may take place 
in the mammary4 and salivary glands. But here it is the less highly dif- 
1 Hess, 0., Zieglers Beitr., 1913, Ivi, 22. 
2 Halsted, W. S., Am. Jour. Med. Sc., 1914, cxlvii, 56; and Hunnicutt, J. A., ibid., 1914, cxlviii, 207. 
3 Consult Pearce, Jour. Med. Research,1909, N. S. xv, 53. 
4 Ribbert, Arch. f. mikros. Anat., 1891, xxxvii, 139. PROGRESSIVE TISSUE CHANGES 
87 
ferentiated cells of the excretory ducts rather than the secreting epi- 
thelium through which regeneration is secured. In the ovary1 and 
testicle a slight amount of regenerative capacity may be manifested 
through mitosis and division of epithelium, but its results are insig- 
nificant. The pancreas and spleen show little or no capacity for 
regeneration.2 
In all these cases of partial regeneration it is often difficult to deter- 
mine how much of the increase in parenchyma, which undoubtedly does 
occur, is due to a formation of new gland tissue and how much to a com- 
pensatory hypertrophy of the old. While, therefore, it is true that after 
injuries to the glands a considerable regeneration of epithelium may 
occur, when the loss of substance is extensive it is usually rather by a 
fibrous-tissue repair or by a compensatory hypertrophy or hyperplasia in 
the uninjured portions of the organ than by the new formation of true 
gland tissue that restitution takes place. 
Regeneration of Connective Tissue.-We have seen again and again 
in reviewing pathological regeneration that, in local restoration after 
injury, fibrous tissue plays an important part, either by itself or in asso- 
ciation w'ith various forms of parenchyma. New fibrous tissue readily 
forms in the adult to replace tissue which has been destroyed. It re- 
sults from many kinds of prolonged chemical and mechanical irritants. 
Atrophy of the parenchyma may be followed by interstitial fibrous- 
tissue growth, or new fibrous tissue 
may develop under the influence 
of bacterial and other toxic sub- 
stances, and it frequently forms 
dense capsules about the seat of 
old lesions or around foreign bodies. 
Many forms of compensatory 
fibrous-tissue development will be 
described in the second section of 
this book, such as thickening of 
the walls of blood-vessels, inflam- 
matory adhesions, replacement 
hyperplasia, etc. 
We have now to consider briefly 
the changes involved in the new 
formation of this fibrous tissue. 
Here, as in all other tissues of the 
body, it is the cells alone which take the initiative, the formation of 
intercellular substance being always secondary to the formation of the 
cells and always occurring under their influence. 
New connective-tissue cells may be formed by mitosis (Fig. 50), 
either from older connective-tissue cells, or, as now seems certain, from 
the endothelium of the blood-vessels3 and possibly from the cells of 
Fig. 50.-Mitosis in Granulation Tissue. 
Two of the new-formed connective-tissue cells 
show mitotic figures. Three leucocytes have 
wandered into the new tissue. 
1 Maximow, A., Virchows Arch., 1900, clx, 95. 
2 For a study of compensatory hypertrophy of hemolymph-nodes after removal of spleen, see 
Weidenreich, Arch. f. mikros. Anat., 1905, Ixvi, 270 (bibl.). 
3 See Baumgarten, Arbeiten Path. Inst. Tubingen, 1904, iv, 310. 88 
PROGRESSIVE TISSUE CHANGES 
the adventitia.1 In either case the cell about to divide shows an increase 
in the size of the body, which becomes more granular; the nucleus divides 
by mitosis, segmentation of the cytoplasm following. This process may 
be repeated so that many cells are derived from one, separated at first by 
a small amount of homogeneous intercellular substance. These cells, 
Fig. 51.-Plasma Cells, Highly Magnified. 
at first more or less spheroidal in form, may become larger, and polyhedral 
or elongated. Little by little, fine fibrils appear between the cells, some- 
times apparently as extensions of their cytoplasm, sometimes along their 
sides in the homogeneous material in which they lie. Such new con- 
nective-tissue cells concerned in the formation of fibrillar stroma are 
called fibroblasts (Fig. 52). As the fibrous stroma increases in amount 
Showing fibroblasts with a few new-formed intercellular fibrils between them. The walls of the blood- 
vessels are very thin. 
Fig. 52.-Regeneration of Connective Tissue. 
the cells, at first relatively abundant, become elongated and flattened, 
until as the new tissue approaches maturity the more or less dense 
1 Plasma Cells.-It has been held that plasma cells are concerned in the formation of new fibrous 
tissue, but this view has recently been abandoned, and they are now generally believed to be either an 
independent form of free connective-tissue cell or a modified lymphocyte, this modification appearing 
only under certain conditions and stimuli. Plasma cells are round or oval cells (Fig 51), usually larger 
than the blood or tissue lymphocyte, with an excentric oval nucleus or sometimes two nuclei. The pro- 
toplasm contains a fine basophile granulation, and adjacent to the nucleus there is a clear area which con- 
tains a central corpuscle. Such cells occur normally in the bone marrow, spleen, lymph-nodes, and gastro- 
intestinal mucosa, and are found under various pathological conditions, especially in chronic inflamma- 
tion about the cells of neoplasms and in granulation tissue. Their origin and significance are, however, 
as yet under discussion, and the reader is referred to larger monographs for details; for example, Wil- 
liams, Amer. Jour. Med. Sc., 1900, cxix, 702; Schaffer, Die Plasmazellen; Sammlung anatom, u. 
physiol. Vortr. u. Aufsatze, Heft 8, 1910; Weidenreich, Blutkorperchen u. Wanderzellen- ibid., Heft 
15, 1911; Die Leucozyten u. verwandte Zellformen, Wiesbaden, 1911. 89 
PROGRESSIVE TISSUE CHANGES 
fibrillar stroma preponderates, pressing the cells between its bundles or 
layers into variously shaped plaques, often fusiform or linear in profile. 
In the formation of fibrillar connective tissue from endothelium the 
endothelial cells of thin-walled blood-vessels increase in size, and stretch 
slender bud-like extensions into the adjacent tissue, where, after mitotic 
division, they assume a role altogether identical with that of the ordinary 
connective-tissue cell. Such cells form a portion of those included under 
the generic name of polyblast.1 The theory, recently advanced, that 
connective tissue is formed from fibrin, has not withstood criticism.2 
The formation of new connective-tissue cells may be large or it may 
be limited to the production of a single pair of cells; the stroma may be 
scanty or abundant, loose or dense; the process is essentially the same, 
namely, the division of cells by mitosis, and the formation by them, or 
under their influence, of more or less fibrillar stroma. This process, it 
will be seen, is practically identical with the formation of fibrous tissue 
in the embryo. 
But here, as elsewhere, the character and extent of new tissue pro- 
duction are largely influenced by the environment, and particularly by 
the nutritive supply, so that the formation of new connective tissue in 
any considerable amount is closely linked to the development of blood- 
vessels. 
Regeneration of Endothelium.-The regeneration of endothelium,3 
which seems to be closely related to that of connective tissue, takes place 
readily. The new cells advance over denuded surfaces in a manner 
similar to that in epithelial repair. Whether the new cells always origi- 
nate in the old neighboring endothelium or are more directly derived 
from fibroblasts is not yet fully determined. 
The Formation of Blood-Vessels.-The formation of blood-vessels in 
post-embryonic life is believed always to start in a budding or sprouting 
of the endothelial cells of pre-existing capillaries. The sprouts, directed 
outward from the endothelia of the capillaries, consist at first of buds, 
then of slender, conical, or filiform projections of cytoplasmic substance 
(Fig. 53). Now the cytoplasm of the cell from which the sprout springs 
may increase in amount and its nuclei divide by mitosis, so that the base 
of the sprout may consist of a multinuclear mass of cytoplasm or of a 
cluster of new-formed cells. The sprouts may extend for a long distance 
into the surrounding region, whether this be already organized tissue 
in which the vessels are increasing in number or unorganized lifeless 
material like blood-clot, which is to be replaced by new living structures. 
If a similar process be in progress in neighboring vessels, the sprouts may 
unite at their extremities, forming a slender solid protoplasmic bridge 
1 The word polyblast is a term introduced by Maximow (Zieglers Beitr., 1902, Suppl.-Heft 5; 1904, 
xxxv, 93; and Arch. f. mikros. Anat., 1906, Ixvii, 680) to designate the cells found in the connective tis- 
sues in inflammatory processes. Originally, the term included the small lymphocytes, the plasma cells, 
the adventitia cells, the clasmatocytes, and the free endothelial cells (the endothelial leucocytes of 
Mallory) which exist in the tissues in inflammatory processes. Later, Maximow excluded the plasma 
cells from this group, and other observers have preferred to exclude the lymphocytes also. Marchand's 
leucocytoid cell is synonymous with polyblast (Process der Wundheilung, Stuttgart, 1901). 
2 Baitsell, G. A., Jour. Exper. Med., 1916, xxiii, 739; Lambert, R. A., Proc. Soc. Exper. Biol, and Med., 
1916, xiv, 5. 
2 Oppel, Virchows Arch., 1901, clxv, 1. 90 
PROGRESSIVE TISSUE CHANGES 
from vessel to vessel. The sprouts now become thickened and gradually 
channelled out at the base by pressure of the blood in the vessel from 
which they spring. The blood enters these lengthening channels, 
forcing its way along them, forming a lumen as it goes. Simultaneously 
with this advance of the lumen, new nuclei are formed by division of the 
old along the sides of the vessel, and the new structure gradually assumes 
a distinctly cellular and vascular character. At length the channel is 
complete; the new vessels have well-defined endothelial walls and 
connective-tissue cells from without, or new connective-tissue cells 
which have been formed about the nuclei of the protoplasmic sprout, 
range themselves outside along the walls. So the new vessel takes its 
Fig. 53.-Developing Blood-vessels in New-formed Tissue. 
place in the vascular system of the part. Thus, in a short time, many 
new blood-vessels may form, furnishing nutritive centers about which 
the organization of tissue proceeds.1 
In the new formation of arteries it is believed that the smooth-muscle 
tissue is formed by a growth along the developing vessel from a pre- 
existing artery. 
The Formation of Lymph-Vessels.-The formation of lymph-channels 
in granulation tissue takes place in the same way as that of blood- 
vessels, the process being initiated by the formation of buds from the 
endothelium of existing vessels which push their way out into the new 
tissue, gradually acquiring lumina and forming anastomoses with other 
trunks.2 
Regeneration of Cartilage and Bone.-New cartilage may form by 
the proliferation either of connective-tissue cells or, to a slight extent, 
of cartilage cells, and the formation about the new cells of the character- 
istic basement substance. It is the connective-tissue cells of the peri- 
chondrium especially from which new cartilage is formed. 
The new formation of hone under pathological conditions is not 
brought about by the bone cells, but by the development, first, from the 
cells of the periosteum or of the marrow, of a cellular connective tissue, 
1 Faykiss, Beitr. klin. Chir. (Bruns), 1908, Iviii, 606. 
2 Talks, L., Zieglers Beitr., 1902, xxxii, 106. 91 
PROGRESSIVE TISSUE CHANGES 
or from the perichondrium of a form of hyaline cartilage.1 From these 
tissues, by processes essentially similar to those in the embryonic de- 
velopment, the new bone is formed under the influence of osteoblasts 
(page 1042). 
The regeneration of bone-marrow takes place through the activities 
of the characteristic marrow cells together with those of the blood- 
vessels and cells of the connective tissue and osteoblastic type.2 
Regeneration of Lymph-Nodes.-Regeneration of lymph-nodes may 
take place after partial removal. This appears to be more complete 
in the earlier years of life. After extirpation of lymph-nodes it has been 
shown experimentally that new nodes may form. These Bayer3 believed 
develop from fat tissue. Further studies are needed in the regeneration 
of lymph-nodes and the relationship of these and lymphatic tissue to 
fat and other forms of connective tissue.4 
Regeneration of Fat Tissue.-Fat tissue is formed by the accumula- 
tion of fat droplets in the cells of various types of connective tissue, 
particularly in the young or embryonic forms; but adult connective tissue 
Fig. 54.-Regeneration of Fat Tissue. 
The new-formed fat cells show a rim of cytoplasm containing the nucleus, which has been crowded 
to the sides of the cells by the accumulating fat. 
may change into fat tissue by a similar process. The repair of fat tissue 
takes place by the formation of young fibrous tissue, whose cells and 
stroma gradually assume the type of fat tissue. The cells of regenera- 
ting fat tissue are at first more or less spheroidal, and remnants of the 
cytoplasm may be seen as more or less crescentic masses pressed to one 
side by the accumulating fat (Fig. 54). New fat tissue which replaces 
atrophied organs or parts of organs, such as kidney, heart, lymph-nodes, 
etc., is formed in the same way.5 
Regeneration of Blood.-The formation of leucocytes appears to 
occur chiefly in the masses of lymphoid and myeloid tissue which are so 
widely scattered throughout the body in the lymph-nodes, the spleen, and 
the bone-marrow. In adult life the lymphocytes are probably formed 
1 Wolff, J., Virchows Arch., 1885, ci, 572; Fujinami, A., Zieglers Beitr., 1901, xxix, 432. 
2 For studies on the regeneration of bone-marrow, see Haasler, Arch. f. klin. Chir. (Langenbeck), 
1895, 1, 75; and Enderlen, Deutsch. Ztschr. f. Chir., 1899, lii, 293. 
3 Bayer, Arch. f. klin. Chir. (Langenbeck), 1895, xlix, 637. 
4 Consult for bibl. of regeneration of lymph-nodes and lymph-vessels, Meyer, Bull. Johns Hopkins 
Hosp., 1906, xvii, 185; also, Hammerschlag, Virchows Arch., 1908, cxciv, 320. 
6 For a study of regeneration, inflammation, etc., in fat tissue see Kraus, Ztschr. f. Heilk., 1906, 
xxvii, 243. 92 
PROGRESSIVE TISSUE CHANGES 
wholly in the lymph-nodes, and the granular leucocytes in the bone- 
marrow; in anemia and leukemia, however, new areas of myeloid and 
lymphoid tissue rapidly appear, and these assist the hyperplastic nodes 
and marrow in the production of large numbers of red and white cells. 
Under these conditions, a considerable proportion of the cells produced 
are distinctly abnormal in type and imperfect in structure. These lym- 
phoid and myeloid areas are most frequent in the nodes, spleen, liver, 
and kidney.1 Regeneration of red blood-cells seems to occur in the bone- 
marrow and possibly in the spleen and hemolymph-nodes through mitotic 
division of nucleated forms. The latter may, under pathological condi- 
tions, appear in the vessels in varying numbers (see Part II, Chapter I).2 
TRANSPLANTATION OF TISSUE. 
Transplantation of various types of tissue has been frequently at- 
tempted, and is, on both theoretical and practical grounds, of con- 
siderable interest. Transplantations have been successfully made from 
one part of the individual to another-autoplastic-or from another 
individual of the same species-homoplastic; but not from one species to 
another. 
A variety of general conditions favor successful transfer. The 
tissue to be transplanted must be alive and in good condition; young 
tissues are more readily transferred than old; the site to which the 
transfer is made must be adapted to the growth of the graft. A great 
difference is observed in the success of transplantation of various types 
of tissue. Thus, the epithelium of the skin and various forms of con- 
nective tissue may be, under favorable conditions, readily transplanted, 
and produce new tissue of similar type. Thus, deeply implanted 
epidermal tissue may grow and produce considerable new tissue, especially 
in the form of cysts resembling either simple or complex dermoid cysts. 
Experimental transplantation to another individual of the same species, 
of various gland and other special forms of tissue, such as portions of the 
kidney, liver, sebaceous, salivary and mammary glands, testicles, ovary, 
periosteum, bone, and cartilage, shows that there may be at first, if the 
conditions be favorable, a slight proliferation of the transplanted tissue 
cells. Together with this growth in the better-nourished parts of the 
tissue grafts there is apt to be a more or less extensive necrosis of other 
portions. But the proliferative activities of transplanted gland tissue 
are, as a rule, not permanent; they presently cease and sooner or later 
these tissues, with necrotic portions of the grafts, are absorbed. 
The body seems to react sooner or later to a transplanted organ as to a 
foreign body, and to accomplish its destruction in much the same fashion 
as in the case of invasion by infective agents. 
The many reported instances of successful homoplastic organ trans- 
* Sternberg, Zieglers Beitr., 1909, xlvi, 586; Werzberg, Virchows Arch., 1911, cciv, 272; Askanazy, 
Virchows Arch., 1911, ccv, 346; v. Domarus, Arch. f. exper. Path. u. Pharmakoi., 1908, Iviii, 319. 
2 For a general and extended study upon tissue regeneration see Marchand, Process der Wundheilung, 
Stuttgart, 1901. PROGRESSIVE TISSUE CHANGES 
93 
plantation lack a sufficiently careful anatomical control of the organs so 
transplanted. It is undoubtedly possible to make homoplastic trans- 
plantations of the thyroid,1 the parathyroid, the thymus,2 the spleen,3 
and the ovary; but after a shorter or longer period such transplanted 
tissue usually undergoes atrophy. If very large series of animals are 
used, a few successes will usually be obtained, often not more than one 
or two per hundred. Such homoplastic grafts succeed, therefore, in 
about the same proportion as transplant^ from primary tumors. Marine 
has found that thyroid grafts may remain alive for a long period. 
Transplantation of epidermis for practical purposes has become a 
part of surgery, aiding in the repair of surface losses of skin. The graft 
properly implanted upon the granulating surface becomes closely 
attached by the growth into it of new connective-tissue cells and blood- 
vessels. The old connective tissue of the graft, as well as most of the 
epithelium, especially the superficial layers, usually dies and is cast off 
or absorbed, while new epithelium formed from the remaining cells 
makes its way over the granulating surfaces. 
In transplantations of bone the grafts seem to furnish a nidus into 
which, hand-in-hand with its absorption, new bone grows under the 
influence of osteoblasts of the old periosteum, but does not itself appar- 
ently share in the new production of bone tissue. The transplantation 
of periosteum is possible, and new bone will form from it.4 
The possibility of successful autoplastic transplantation of organs has 
been shown by Carrel and others.5 In individual cases the results have 
been excellent, but the total number of successes is small and the surgical 
difficulties are enormous; and as the procedure has but little practical 
value it may be regarded simply as a demonstration of the possibilities of 
laboratory surgery. 
The only important practical form of transplantation is the homo- 
plastic or heteroplastic, and certain recent investigations point toward 
the possibility of its ultimate accomplishment. Bashford6 and Da Fano7 
some years ago showed that the resistance to tumor transplantation was 
not humoral, but was a factor of tissue activity and apparently corre- 
lated with the lymphocytic and plasma cell reaction in the neighborhood 
of the cells of the neoplasm. Working along this line, Murphy8 has found 
that the growth of tissues in vitro is inhibited by the presence of growing 
bone-marrow or spleen. After interference with the activity of these 
organs by treatment of the animals with Roentgen rays, which are known 
1 For study of transplantation of thyroid see Payr, Arch. f. klin. Chir. (Langenbeck), 1906, Ixxv, 
730; Manley, O. T., and Marine, D., Jour. Am. Med. Assn., 1916, Ixvii, 260. 
2 Marine, D., and Manley, 0. T., Jour. Lab. and Clin. Med., 1917, iii, 48. 
3 Manley, 0. T., and Marine, D., Jour. Exper. Med., 1917, xxv, 619; 1920, xxxii, 91. 
^Bancroft, F. W., Am. Jour. Med. Sc., 1914, cxlvii, 809 (bibl.). 
5 Carrel, Trans. Internal. Cong, of Surg., 1914. Payr, Arch. f. klin. Chir. (Langenbeck), 1900, 
Ixii, 47; Verhandl. d. deutsch. Gesellsch. f. Chir., 1908, xxxvii, 105; Dederer, Jour. Am. Med. Assn., 
1918, Ixx, 6. For an extremely thorough and conservative study of transplantation, with bibliography, 
see Schone, Die heteroplastische u. homooplastische Transplantation, Berlin, 1912. 
6 Bashford, E. F., Murray, J. A., and Haaland, M., Ztschr. f. Immunitatsforsch., Orig., 1909, i, 449. 
7 Da Fano, C., Ztschr. f. Immunitatsforsch., Orig., 1910, v, 1. 
8 Murphy, J. B., Jour. Exper. Med., 1913, xvii, 482; 1914, xix, 513; Jour. Am. Med. Assn., 1914 
Ixii, 1459; Murphy, J. B., and Morton, J. J., Proc. Nat. Acad. Sc., 1915, i, 435; Jour. Exper. Med. 
1915, xxii, 204. 94 
PROGRESSIVE TISSUE CHANGES 
to be especially destructive to lymphoid and marrow tissue, it was found 
that grafts of a mouse sarcoma would grow in irradiated rats for a longer 
time than in controls. Should the results of this experiment be shown to 
be more generally true, they may point the way to the possibility of 
successful heteroplastic surgery; but as yet confirmation is lacking, and 
those who have recently investigated the subject are unable to confirm 
Murphy's findings.1 
While we can thus summarize the differing capacities of the body- 
cells for regeneration; while we know many of the general conditions under 
which the impulse to cell proliferation and growth is manifested; while, 
further, we have learned something of the delicate mechanism through 
which division is controlled and effected, at the end we must acknowledge 
that we do not know why cells divide. We may say that it is due to a 
chemical or a mechanical stimulus, and it certainly may be associated with 
both; or that increased nutrition favors, while innutrition retards cell 
multiplication; we may cite direct or remote injury, or talk of the in- 
hibition of organic control, disturbed tissue equilibrium, diminished 
pressure, reversion, etc., but when all is said we are forced to recur to 
some unknown factor in the inherited constitution of the cell which 
determines the measure and character of its response to the most varied 
influences. 
The hypothesis of Ribbert, in accordance with which the capacities 
of cells to proliferate and grow, so manifest in embryonic life, are held in 
restraint in the normal adult body by a subtle correlation of cells and 
tissue, is most suggestive in this connection. When this mutual rela- 
tionship is disturbed, as is the case under many of the conditions in 
which regeneration takes place, the cells, in the conception of Ribbert, 
are freed from certain, at least, of their organic restraints. These re- 
straining conditions he calls "tissue tension," meaning thereby, however, 
something more complex and subtle than simple physical tension. Thus, 
free to exert their primitive capacities, formerly held in restraint by the 
environment, we can conceive how cells proliferate and new tissues are 
formed in the regenerative processes without assuming the acquirement 
of any new capacities and without the assumption of vague and special 
stimuli.2 
According to this conception, then, the regenerative processes lead- 
ing to the formation of new cells and tissues are not brought into play by 
stimuli furnished by injuries-the so-called "formative stimuli" of an 
The Impulse to Cell Regeneration. 
1 SittenfieM, M. J., Jour. Cancer Research, 1917, ii, 151; Stevenson, H. N., ibid., 1918, iii, 63. 
2 For a r6sum6 of Ribbert's hypothesis and its applications to regeneration, hypertrophy, etc., 
see Ribbert, H„ Allgemeine Pathologic, 5th edition, Leipzig, 1915. For a criticism of these views, 
see Adami, J. G., Principles of Pathology, Philadelphia, 1908, vol. i, p. 537 et seq. 
See also, for summary of a new phase of research and interpretation in the nature of the "formative 
stimulus" involved in artificially induced cell division and artificial parthogenesis, Loeb, J., Studies in 
General Physiology, Chicago, 1905, p. 253; Artificial Parthenogenesis and Fertilization, Chicago, 1913; 
and also, Science, 1915, xli, 704. For general bibliography of regeneration, compensatory hypertrophy, 
etc., see Aschoff, L., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1898, v, 22. For a full consideration 
of the subjects dealt with in this chapter, consult Chantemesse and Podwyssotsky, Les Processus gfndraux. 
I, Paris, 1901. 95 
PROGRESSIVE TISSUE CHANGES 
earlier time. But new cells and tissues form as the result of the release 
of inherent capacities of cells normally held in restraint after the develop- 
mental period, by their associations as parts of an organism. Thus, 
when conditions of nutrition, pressure, organic association, possibly of 
protoplasmic continuity or of nerve correlation, are disturbed, for ex- 
ample, through trauma, poisons, degenerations, prolonged hyperemia and 
various other vascular and nutritive cellular disturbances, the leash of 
organic control is loosened, and the primitive capacities of the cells are 
temporarily free to act. As we have seen, however, this resumption 
of an abeyant potency in the ordinary processes of repair is not limitless 
and, sooner or later, the old controlling relationships of organic asso- 
ciations are re-established and the reparative activities cease.1 
It is important, however, to dissociate the capacity to stimulate the 
growth of organs or even of whole organisms from the power to incite 
similar increased growth rates in cells. The addition of thyroid, pineal, 
or thymus gland tissue2 to the water in which tadpoles are living seems 
to increase the growth rate, but neither of these substances stimulates 
growth in tissue cultures when the cells are separated from the influences 
of the nerves and the supply of foodstuffs through the blood or lymph. 
It is now well established that the pineal and pituitary glands control 
sexual development and growth of the body as a whole;3 but the glan- 
dular substances or their extracts fail to influence either tissue cultures or 
tumor implants. 
The example most often cited as an evidence of direct growth stimulus 
is the extensive epithelial proliferation induced by the injection of dyes, 
such as Sudan III or Scharlach R, oils, tars, and many similar materials, 
into the corium. But it has been shown by very extensive experiments4 
that all these substances act in the familiar way by causing necrosis with 
consequent regeneration of the injured tissue and an excessive production, 
if the irritation is long continued. If such irritation is kept up for a 
sufficient length of time in animals of cancer age, epitheliomata may 
develop.5 
Again, it has been shown that there can be extracted from the corpus 
luteum and the placenta, substances of uncertain chemical nature which 
have an extraordinary power of inciting growth of the uterus and mam- 
mary gland. These hormone-like substances are capable also of stimu- 
lating subcutaneous grafts of uterine musculature and apparently of 
prolonging the life of such grafts.6 A similar stimulating effect has 
been observed when thyroid grafts are treated with iodine;7 but such 
stimulation is not noted in tissue cultures. Nevertheless, it is possible 
by suitable threshold exposures of such tissue cultures to x-ray or radium,8 
1 For a consideration of the bearing of this hypothesis on compensatory hypertrophy, see Ribbert, 
H., Lehrbuch d. allg. Path.,. 5th edition, Leipzig, 1915. 
2 McCord, C. P., Surg., Gynec., and Obst., 1917, xxv, 250 (bibl.). 
3 Cushing, H., The Pituitary Body and Its Disorders, Philadelphia, 1912. 
i Bullock and Rohdenburg, Jour. Med. Research, 1915-16, N. S. xxviii, 53. 
3 Yamagiwa, K., and Ichikawa, K., Jour. Cancer Research, 1918, iii»M. For the experimental 
production of sarcoma of the liver of rats, see Bullock, F. D., and Curtis, M. R., Proc. N. Y. Path. Soc., 
1920, xx, 149. 
6Frank, R. T., Surg., Gynec., and Obst., 1917, xxv, 329. 
7 Manley, O. T., and Marine, D., Jour. Am. Med. Assn., 1916, Ixvii, 260. 
3 Prime, F., Proc. New York Path. Soc., 1916, xvi, 90. 96 
PROGRESSIVE TISSUE CHANGES 
or by similarly exposing eggs of the lower animals, to obtain distinct 
increase in growth rapidity, so that it is not possible to deny that a direct 
growth stimulus may exist. It is, however, evident that the question 
has not yet approached solution. 
With protozoa, such as paramecium, which can be isolated and con- 
trolled in pure culture for long periods, many interesting phenomena 
have been observed. Rhythmic alterations of rapid and slow division 
have been traced, a phenomenon seen also in transplanted tumors. 
Regeneration of the strain after conjugation had been thought necessary 
for the continuance of the race,1 but Woodruff2 has demonstrated that if 
sufficient nutriment is supplied, the strain may be carried for at least 
five thousand generations without conjugation. 
After the development of the technique of tissue culture as initiated 
by Loeb and furthered by Harrison, Carrel, Lambert, and others,3 and 
the discovery by Murphy that tissues, and especially tumors, will grow 
in the membranes of the chick embryo, it was hoped that this addition 
to our experimental machinery would solve many questions concerning 
the biology of the cell. But, unfortunately, many limitations have been 
found which render the method less useful than it was thought. For 
while the simpler embryonic tissues may be cultivated for many genera- 
tions, adult tissues, complex organs, and especially tumors, grow with 
difficulty or not at all. The limit of time is measured in days, rather 
than, as was originally thought, in months, and the positive chemotaxis 
of the fibrin of the clot in which the tissue particles are placed, seems 
necessary for the induction of any considerable outgrowth. Little or no 
growth is obtainable in serum, even if support is given the cells by arti- 
ficial networks of bolting-cloth or perforated collodion membranes. 
Even in the embryo chick membranes, the growth of tissues, while at 
first vigorous, rapidly diminishes, and after a few weeks a tumor has to 
be "refreshed" by several passages through a suitable animal.4 
The conditions which underlie the extraordinary emancipation from 
tissue restraints exhibited by the growth of the cells of malignant tumors 
are still entirely unknown. 
The study of the vital activities of cells has been facilitated by the 
ingenious apparatus devised by Tashiro, which permits the measurement 
of the extremely minute quantities of carbon dioxide given off from even 
a single protozoon.5 
1 Calkins, G. N., Arch. f. Entwickelungsmechanik d. Organismen, 1903, xv, 139. 
2 Woodiuff, Arch. f. Protistenkunde, 1911, xxi, 263; Jour. Exper. Zool., 1911, x, 557; ibid., 1913, 
xiv, 575. 
3 For a r6sum6 of technique and results of cultures of adult and embryonic tissues see Harrison, 
Lambert, and Burrows, Jour. Am. Med. Assn., 1913, lx, 1660; Carrel, Jour. Exper. Med., 1912, xv, 516; 
ibid., 1913, xviii, 287; and Oppel, Gewebkulturen, Braunschweig, 1914. 
* Stevenson, H. N., Proc. New York Path. Soc., 1916, xvi, 60. 
6 Tashiro, S , A Chemical Sign of Life, Chicago, 1917. CHAPTER V. 
INFLAMMATION. 
General Considerations. 
The conception of inflammation was originally a clinical one in which 
the process was marked by special symptoms-redness, heat, swelling, 
pain, and impaired function. This conception was gradually enlarged 
to embrace the new formation of tissue which might be associated with 
or follow these symptoms, or which might be independent of them. 
After the knowledge of the importance of the cell became general it 
was upon the formation and accumulation of cells and other substances 
that attention was especially fixed. Finally, the processes and structural 
alterations embraced in the conception of inflammation became so 
varied and complex that a definition or even a characterization seemed 
not only difficult, but wellnigh impossible. 
It is only within the past decade or two that the processes and lesions 
involved in inflammation have been seriously considered in the light of 
comparative pathology and as biological problems divorced for purposes 
of research from the dominance of traditional clinical conceptions. In 
view of our increased knowledge of the structure of cells and of the im- 
pulses immediate and hereditary which determine their performances, it 
seems possible now to resolve the complex processes and lesions embraced 
in the general notion of inflammation into more simple factors, and to 
arrive, if not at an exact definition, at least at a reasonable conception 
of the relationship of its phenomena to each other, to those of normal 
physiology, and to other phases of disease. 
With this end in view it seems wise at first to rehearse as simply and 
briefly as is practicable some of the more typical of the phenomena and 
lesions which are commonly grouped under the term inflammation. 
While the death of tissue from trauma, and degenerative alterations 
in the tissues in the presence of various forms of poisons are often impor- 
tant factors in the inflammatory processes, we shall not consider them 
separately here, because they are incidental rather than inherent and 
have already been treated in the section on Degenerations and Necrosis. 
But it should be noted that various phases of albuminous degeneration, 
local or general, which are induced by the poisons of the pathogenic 
bacteria, are very often associated with inflammation, and not infre- 
quently modify, or may even determine, its occurrence. 
A comprehensive survey of the conditions under which inflammation 
most frequently takes place shows at once that it is almost always asso- 
ciated with some form of injury. This may be direct trauma, or exces- 
sive heat or cold. It may be poisons of various kinds-from the cruder 
97 98 
INFLAMMATION 
inorganic poisons inducing immediate and gross tissue destruction to the 
subtle toxic substances which result from the metabolism of micro- 
organisms or from the aberrant metabolism or degeneration of the body- 
cells themselves. Dead cells or tissues or foreign substances of many 
kinds within the body are common incitants of the inflammatory processes. 
Let us now look at some of the ways in which the living body re- 
sponds to injury, considering first an injury which is very slight and simple. 
Types of the Inflammatory Reaction of the Body to Injury. 
Injury to Non-vascular Tissue.-If a small clean cut be made in 
living fibrillar connective tissue, not involving blood-vessels, and affecting 
only the cells and fibers in the vicinity of the incision, and if the sides 
of the wound be immediately placed and held together, the resulting 
changes which lead to the complete restitution of the part are compara- 
tively simple. A small quan- 
tity of fluid which oozes from 
the tissue spaces sticks the sides 
of the cut together. Such con- 
nective-tissue cells as have been 
seriously injured, especially if 
the nuclei have suffered, die and 
disintegrate; and these, together 
with such tissue fragments as 
may be present, are removed by 
phagoyctes or through autolysis 
and absorption. But cells whose 
nuclei have remained intact, 
whether directly upon the inci- 
sion oi' in its immediate vicinity, 
become larger and more granu- 
lar, may divide by mitosis, ex- 
tend their bodies or processes 
across the plane of incision, bridging this at intervals with living pro- 
toplasm. Under the influence of these cells, new intercellular fibers 
are formed,, which in a short time bind the sides of the wound firmly 
together (Fig. 55). Thus, with but the slightest amount of tissue 
destruction, and with no involvement of the blood-vessels, a simple 
mechanical injury may be made good. This form of reaction to injury 
of living tissue is known to the surgeons as healing by "first intention." 
The mode of healing does not essentially differ if there be a slight injury 
to the blood-vessels. 
In injury to a non-vascular part, like the cornea, for example, the 
primary reaction to the damage manifested by the fixed connective-tissue 
cells is often complicated by the wandering in of leucocytes from the 
conjunctival blood-vessels in the manner indicated in the next section. 
This participation of distant blood-vessels and leucocytes is, no doubt, 
incited by a reflex stimulation of the nerves of the blood-vessels and may 
Fig. 55.-Healing of a Wound of the Cornea. 
Without involvement of blood-vessels a few new 
connective-tissue cells have formed along the line of 
slight injury (incision), and the sides of the wound 
are joined by the new cells and fibrils formed by 
them. The epithelium has regenerated over the 
surface. INFLAMMATION 
99 
be fostered under certain conditions by the absorption of injurious sub- 
stances which are carried to the nearest blood-vessels by the lymphatics. 
Thus it is that in injuries to the cornea, a non-vascular part, the lesion 
is often complicated by the secondary participation of the adjacent 
blood-vessels. 
Injury to Vascular Tissue.-Let us now look at the effect on a vascular 
tissue of an injury not immediately destructive. For this purpose the 
mesentery of the bladder of a curarized frog, drawn out upon a suitable 
plate1 upon the stage of the microscope and kept moist by irrigation with 
0.75 per cent, salt solution, affords a succession of most instructive pic- 
tures. The mechanical disturbance of the organs exposed, desiccation, 
and a variety of other physical and chemical vicissitudes to which they 
are subjected, are sufficiently damaging to incite a complex train of 
responses on the part of the living tissues. 
In studying the circulation of the blood in small vessels under the 
microscope it should be remembered that, while the walls of these vessels 
are made up of living tissue and are capable of responses by movement 
or by structural change to external agencies, whether applied directly or 
through the nerves, they are also elastic pipes through which fluid flows, 
and that both pipes and fluid are subject to the laws of mechanics. 
These mechanical laws are often modified in expression, it is true, by 
the subtle energies which living tissues wield, but, as Thoma more than 
any other has shown, they are not to be ignored by the serious student 
of the living body, either in health or disease. 
In the bladder or mesentery of the frog the arteries and veins with 
their connecting system of capillaries are clearly seen. When the cur- 
rent is rapid the cells of the blood in the arteries and veins are gathered 
into a red axial mass in which the separate cells may not be distinguish- 
able, owing to their crowding and the rapid flow. Outside of this, against 
the walls, is a clear marginal zone in which a leucocyte is occasionally 
visible. If for any reason the rate of flow be considerably diminished, 
the leucocytes, which are specifically lighter than the red cells, gather in 
the marginal zone. If the current become very slow or be arrested, the 
marginal zone disappears and the red and white cells intermingle.2 
Soon after the exposure of the bladder or mesentery the tissues be- 
come hyperemic.3 The arteries, veins, and capillaries dilate, and the 
blood, encountering less resistance from the walls, flows more rapidly 
through them. This increased rapidity of the blood current does not, 
however, last long, although the vessel still remains dilated. After a 
variable period, owing, it is believed, to changes in the endothelia of 
the vessels, the blood meets with so much resistance that it flows more 
slowly than under normal conditions. Temporary or even permanent 
stasis may occur in some of the vessels, but this is not a constant nor a 
1 See description of Thoma's frog-plate, p. 127. 
2 This distribution of the blood is almost, if not wholly, mechanical, and may be simulated in glass 
tubes with a fluid in which lifeless particles of different specific gravities are suspended. The particles 
of the lesser specific gravity assume, when the flow is established, the peripheral portion of the stream. 
3 For a review of some of the factors governing vascular dilatation and slowing of the blood stream, 
see Woolley, Jour. Am. Med. Assn., 1914, Ixiii, 2279. 100 
INFLAMMATION 
characteristic occurrence. White blood-cells-leucocytes-now begin 
to accumulate along the inner walls of the veins and to become fixed 
there, so that after a time the whole inner surface of the veins may be 
more or less thickly sprinkled, and even closely crowded, with adherent 
leucocytes. These may either lie firmly against the endothelium or be 
dragged slowly along by the current of blood sweeping past them. 
Some are dragged by the blood current into pyriform shapes, showing 
that they are adherent at a small point only, and thus they may be 
detached from the wall and rejoin the circulating blood. They may by 
ameboid movement crawl slowly along the interior of the wall, even 
against the current. In the capillaries, also, a similar comportment 
of the leucocytes may be seen. 
After a time, which varies considerably-in the bladder sometimes 
within an hour after its exposure; in the mesentery usually later-some 
of the leucocytes commence to make their way slowly through the walls 
of the veins and capillaries. At first a little shining knob appears on 
Fig. 56--Emigration of Leucocytes from the Blood-vessels of the Mesentery of the Frog. 
Some of the leucocytes are clinging to the interior of the vessels; some are passing through the 
walls; some are wandering away through the tissue spaces. There has been diapedesis of a few red 
blood-cells. 
the outside of the wall opposite to the cell which is sticking within, and 
this outer portion grows larger as the part still within grows smaller, 
until at length the entire cell is outside of the vessel. The cell now may 
immediately detach itself and wander off in the tissue spaces, or it may 
remain for some time attached to the outside of the wall (Fig. 56). This 
passage of the leucocytes through the walls of the capillaries and veins- 
it does not occur in the arteries-is called emigration. The emigrating 
cells are largely the polynuclear leucocytes, but mononuclear forms- 
lymphocytes-and eosinophiles may also pass out of the vessels. 
The cells pass between the endothelia through the cement substance, 
which apparently is in some way changed in the inflammatory process. 
They may pass through very rapidly, but usually their progress is slow 
and often interrupted, so that cells may be seen motionless for a long INFLAMMATION 
101 
time in various stages of progress through the walls. A half minute or 
even less, may suffice for their passage, or they may be hours about it. 
Thus, after a variable time, if the conditions have been favorable, the 
tissues immediately around the capillaries and veins, and even those 
somewhat remote from them, may be more or less densely crowded with 
leucocytes, some motionless and in the spheroidal form, others moving 
about through the tissue spaces (Fig. 57). Leucocytes may pass out of 
the tissues on to free surfaces of the inflamed part, or they may wander 
into the lymph-vessels and so re-enter the circulation. 
It is probable that the emigration of the leucocytes is due in part to 
a sort of filtration process with which the pressure of the blood within 
the vessels is concerned, and also to capillary attraction at the point of 
emergence. But the inherent contractility of the cells themselves forms, 
Showing extravasated leucocytes in the vicinity of the blood-vessels, with edema of the surrounding 
connective tissue. 
Fig. 57.-Exudative Inflammation in the Wall of the Appendix Vermiformis. 
doubtless, a very important factor.1 That in most cases chemotaxis plays 
a significant part in directing the course of the leucocytes seems to be 
well established, and it is largely to this agency that the gathering of 
leucocytes in the vicinity of the deleterious substances which incite 
inflammation is due. 
In regard to chemotaxis it should be said in brief that the direction 
of locomotion in protoplasm may be determined by chemical substances 
in the vicinity. This is the case not only in the lower forms of life, as in 
certain bacteria and protozoa, but also in such cells of higher organisms 
as have retained a certain independence of locomotion, for example, in 
the leucocytes and certain cells of the connective tissue. To this form of 
response to external agencies the name chemotaxis has been applied. In 
1 For a discussion of the various factors, see Schridde, Studien u. Fragen z. Entziindungslehre, 
Jena, 1910; Lohlein, Gesetze d. Leukozytentatigkeit bei entziind. Prozesse, Jena, 1913; Marchand 
Verhandl. d. deutsch. path. Gesellsch., 1913, xvi, 5. 102 
INFLAMMATION 
some cases the effect of chemical agents in the environment is not to 
attract, but to repel, protoplasm. This has been called negative chemo- 
taxis. Chemotaxis and certain allied responses to outside influences 
have been found to play an important role in health as well as in some 
forms of disease, and have been the subject of much careful study.1 
If we return now to our observation of the living mesentery it will be 
found that while emigration of leucocytes is going on, the red blood-cells, 
although for the most part carried along as usual in the current of the 
veins and through the capillaries, still often find their way in small, and 
sometimes in very large, numbers into the surrounding tissues. They 
are, it is believed, carried passively through the cement substance 
between the endothelia by minute streams of fluid which under these 
conditions are flowing in abnormal quantities through the walls. This 
extravasation of the red blood-cells is called diapedesis. It appears to 
follow the emigration of the leucocytes, which seems in some fashion to 
prepare the way for the more mechanical exit of the red cells. 
By this time it will usually be found that the tissue around the vessels 
is somewhat swollen and more succulent than normal, and fluid may be 
poured out on the free surface. The fluid which thus gathers is called 
serum. It is similar to the simple non-inflammatory transudates, 
except that it is richer in proteins and is mixed with cells. This serum 
has passed out of the blood-vessels along with the blood-cells, and, as its 
composition differs somewhat from that of blood-plasma, it is evident 
that it has undergone a change as it passed. The way in which this 
alteration in the composition of the blood-plasma occurs as it passes 
through the walls of the vessels and becomes 
the serum of exudation, we do not under- 
stand. But it is probably due to metabolic 
processes in the endothelial cells by which 
what has been called a " selective filtration " 
is secured. 
The fluid exudate contains fibrinogenous 
substance, and from this, when the condi- 
tions are favorable, fibrin may be formed 
(Fig. 58) by a change similar to that which 
occurs in the coagulation of the blood. The 
leucocytes which wander into the tissue spaces outside the vessels may 
encounter conditions inimical to life, from innutrition or from the pres- 
ence of deleterious substances, and thus these and other cells furnish, 
as they die and disintegrate, the fibrin ferment essential to coagulation. 
Clusters of fibrin fibrils may thus often be seen surrounding dead and 
disintegrating cells (Fig. 59).2 
If at this time the exposed bladder or mesentery of the frog be 
Fig. 58.-Fibrin in Inflammatory 
Exudate. 
i For a fuller consideration of chemotaxis, with bibliography, consult Davenport, Experimental 
Morphology, Part I., p. 32 et seq.; Verworn, M., Allgemeine Physiologic, 5th edition, Jena, 1909; 
Bayliss, W. M., Principles of General Physiology, London, 1915. For the forms of leucocytes which 
emigrate under various conditions see Adler, A. Jacobi's Festschrift, 1900, p. 309. 
2 For a discussion of the relationship of fibrin formation to cells which may furnish a substance 
inducing coagulation see Hauser, Virchows Arch., 1898, cliv, 335; also Arnold, Centralbl. f. allg. Path., 
1899, x, 313. INFLAMMATION 
103 
restored to the abdominal cavity and the animal placed under favorable 
conditions, the reaction of the vessels and cells to the unusual environ- 
ment may, if the injury have not been too severe, gradually subside. 
The circulation is then re-established, the serum is absorbed, the leuco- 
cytes which have not come out upon the surface or died in the tissue 
spaces may re-enter the lymphatics. Fibrin, if this have been formed, 
and red blood-cells which have escaped from the circulation are dis- 
posed of under the influence of ferments which leucocytes furnish (page 
121), or may be carried off by the wandering leucocytes; or, as is not 
infrequently the case, blood pigment resulting from the reduction of 
the hemoglobin which leaves the red blood-cells by osmosis may remain 
for some time, in situ, as the only mark of an earlier active inflammatory 
process. 
Fig. 59.-Fibrin Forming Around Dead Cells in the Interstices of Tissue. 
Thus in the living animal1 we can learn by direct observation the 
way in which the serum, fibrin, and red and white blood-cells get into 
tissues and upon free surfaces in certain forms of injury involving the 
blood-vessels. 
We can see also by this experimental observation just what the 
factors are which induce the so-called "cardinal symptoms" of inflam- 
mation-the redness and heat due to hyperemia; the swelling to accu- 
mulation of exudate; the pain to pressure on the nerves; and the impaired 
function to the disturbances of nutrition to which all of these factors 
contribute. The materials gathering in or upon the tissues under these 
conditions are called exudates, and this phase of inflammation is com- 
monly called exudative inflammation. 
Hand-in-hand with these changes, which are directly associated with 
lesions of the blood-vessels, there occur alterations of the cells of the 
affected part, especially of the connective-tissue cells, which are not 
readily observed in the experimental animal. These may suffer regres- 
sive changes-albuminous or fatty degeneration or necrosis; or, on the 
1 Thoma has shown by similar studies on warm-blooded animals that the reaction to injury is in 
them essentially similar to that in the frog. 104 
INFLAMMATION 
other hand, they may undergo progressive changes. The bodies may 
swell; mitosis may occur; and they may divide. This may take place in 
the cells of the fibrillar connective tissue and in the endothelium of the 
blood- and lymph-vessels. The new-formed cells may detach themselves 
from their original site and join the leucocytes as wandering cells. If 
there are small islets of lymphoid tissue, such as are widely scattered 
through the body (page 546), these may show hyperplasia, and appear 
as clusters of small spheroidal cells with large deeply staining nuclei and 
a small amount of cytoplasm. These clusters of small cells resembling 
lymphocytes are especially noticeable in the vicinity of the lymph 
channels near small blood-vessels. 
Let us now look at the effect upon a living vascular tissue of injury 
inflicted in a different way. 
Injury from Microorganisms.-Suppose we inject into the ear vein 
of a rabbit a small amount of a pure culture of a well-known and very 
common microorganism, Streptococcus pyogenes. Little masses of the 
living germ will enter the heart and be driven out again through the 
arteries in whose smaller twiglets or in the capillaries some of them will 
lodge as emboli. Here in the living tissues the bacteria may find good 
nutrient conditions and begin to proliferate, increasing so rapidly in 
number that they may distend 
the vessels in which they lie. If 
after twenty-four hours the ani- 
mal be killed, and one examine 
the organs in which the bacterial 
emboli have caught and grown 
-in the liver, for example-one 
finds small blood-vessels here 
and there distended with bac- 
teria. But the parenchyma and 
interstitial tissue about them 
appear to be intact (Fig. 60). 
If, however, the animal be 
allowed to live longer-say tw'O 
or three days-before the ex- 
amination, the condition of the 
tissue about the growing bacte- 
rial mass in the typical course of 
events shows marked and signi- 
ficant alteration. Immediately 
around the bacteria the nuclei fail to take the nuclear stains (Fig. 61); 
the cytoplasm is unusually granular or fallen into fragments. These are 
the marks of cell death, and from the situation of this area of dead tissue 
about the colony of growing bacteria we may infer-and the inference 
is confirmed by a host of tests and observations-that, in growing, the 
bacteria have set free in the tissue about them some chemical substance 
whose presence is incompatible with the continuance of the life proc- 
esses in the liver cells, which, in fact, has killed them. 
The bacteria have grown in a mass within the 
small blood-vessel. The liver cells in the vicinity 
appear unchanged. 
Fig. 60.-Bacterial. Embolus in the Liver. INFLAMMATION 
105 
But very soon the tissues near by show a different sort of reaction to 
this active poison set free upon the spot. Leucocytes gather on the 
borders of the necrotic area and may form a dense ensheathing mass 
about it (Fig. 62). If we look for the origin of these, we find that close 
outside the area of dead tissue and among the gathered leucocytes the 
smaller blood-vessels are dilated, overfilled with blood, and such marks 
of the emigration of leucocytes as a tissue removed from the animal and 
prepared for examination may show are unmistakable. Not infre- 
quently extravasated red blood- 
cells and fibrin and a distention 
of the tissue spaces with fluid 
still further characterize the 
process as exudative inflamma- 
tion. 
It was observed in the ex- 
posed mesentery or bladder of 
the frog that the leucocytes, 
once outside the vessels, wan- 
dered off in various directions in 
the tissues, some to the surface, 
some to the lymph-vessels, and 
some far from the veins or 
capillaries from which they 
emerged. Not so here. The 
extravascular leucocytes gather 
close in the border zone of the 
necrotic area or enter it. And 
we may usually see in the outer 
parts of such an area of dead tissue scattered leucocytes which are 
themselves undergoing changes indicating the death of the cell. They 
too have encountered the poison set free by the growing bacteria. 
The changes which have just been described as the result of experi- 
ment in the animal are practically identical with those occurring in man 
as the result of accidental inoculation. 
If the process continue, one may find on later examination that the 
dead tissue mass has softened through the action of proteolytic enzymes 
developed on the spot (page 122), the bacteria are scattered, and the 
whole central portion may be occupied by a grayish or yellowish gru- 
mous or fluid mass of dead cells, cell detritus, albuminous and fatty 
granules, bacteria, and leucocytes in various stages of necrosis and 
disintegration. 
Such a localized result of exudative inflammation with death and 
disintegration of tissue is called an abscess; the material which it contains 
is called pus. (For a more detailed consideration of suppuration and the 
characters of pus see page 227.9 
The changes by which, if the animal survive the formation of abscess, 
the active processes are brought to a standstill and repair is effected, we 
Fig 61.-Bacterial Embolus in the Liver, with 
Necrosis. 
The bacteria are still largely confined to the vessel, 
but a few are outside. There is a zone of necrotic 
liver cells about the growing mass of cocci. 
1 For a resume of forms of exudate cells, with bibl., see Helly, Zieglers Beitr. 1905, xxxvii. 17i. 106 
INFLAMMATION 
need not now follow. But it concerns us here to appreciate that this is 
a type of one of the most important phases of the inflammatory process; 
a phase in which a poison produced in the body by the metabolism of 
microorganisms incites a complex train of active and passive tissue 
changes. 
Instead of forming abscesses with softening of the tissue, the pus 
cells and other exudates may be distributed diffusely through the inter- 
stices of the tissues, forming a so-called purulent infiltration. 
Fig. 62.-Necrosis and Suppuration in the Liver from Bacterial Infection-Exudative and 
Necrotic Inflammation. 
The bacteria are scattered in masses, the liver cells about them are necrotic, while leucocytes have 
gathered in large numbers within the necrotic area. With slight further disintegration this mass of 
dead liver tissue and pus cells would form an abscess. 
A narrow canal leading to a focus or area of inflammation is called a 
fistula. 
In our study of illustrative phases of inflammation we now turn to 
the processes by which repair of injured tissues, after more or less involve- 
ment in the inflammatory phenomena, is brought about. 
Resolution in Inflammation.-In many cases of exudative inflamma- 
tion, after the subsidence of the active changes in the blood-vessels, 
the exudates are entirely, though often very slowly, absorbed, and the 
tissue returns to its normal condition; this is called resolution. 
If many new connective-tissue cells have been formed, these may 
produce fibrils and thus a certain amount of new tissue may develop, INFLAMMATION 
107 
compromising the blood and lymph circulation, so that for a long time 
the site of the inflammation may be swollen and hard. 
Under certain conditions, on the other hand-for example, in the case 
of a wound with loss of substance, or in an acute exudative inflamma- 
tion of a serous membrane in which the surface is deprived of its normal 
mesothelial1 covering, or in the healing of an abscess-a considerable 
amount of new tissue may be produced through the agency of old cells 
or of new cells formed in the inflammatory process. 
We shall now consider the way in which repair of a wound or injury 
with loss of tissue is effected. 
The way in which new inflammatory tissues are formed may be best 
understood by following the process of healing in a wound with loss of 
substance-for example, in a wound through the. skin or a mucous mem- 
brane into the tissue beneath. At first there may be hemorrhage. 
The Healing of Wounds.2 
Fig. 63.-Granulation Tissue. 
From a healing abdominal wound. Early stage with very thin-walled blood-vessels, leucocytes, 
and young connective-tissue cells. There are few intercellular fibrils. 
After this has ceased, the injury to the tissue, the unusual exposure of 
deep-seated parts, the presence of foreign substances, etc., may induce 
the same series of events which we have seen occurring in exudative 
inflammation with production of serum, fibrin, and pus. The blood- 
vessels dilate, the circulation becomes slower, serum transudes, and 
emigration sets in. Certain of the cells and fragments of intercellular 
1 The term mesothelium, suggested by Minot, is often used as a synonym for endothelium; but this 
is not correct. It should be remembered that the epithelium of the generative glands and of the con- 
voluted tubules and looped tubules of the kidney is derived from the mesoderm, and that while these 
cells may be referred to as mesothelial in origin they certainly cannot be called endothelial. Minot 
himself used the term endothelium for the lining of blood-vessels, and applied the term mesothelium to 
the lining cells of the pericardial, pleural, and peritoneal cavities and the thick epithelium of the renal 
organs only. See Minot, Science, 1901, xiii, 481. 
2 For a general review of this subject, see Wood, F. C., Keen's Surgery, Philadelphia, 1906, i, 348. 108 
INFLAMMATION 
substance near the seat of injury may die, and in time be cast off or 
disintegrated, or dissolved and absorbed or otherwise disposed of by 
phagocytes (page 114). The tissue may become soaked and swollen 
by the transuded serum, and the connective-tissue cells in the vicinity 
may undergo proliferative or degenerative changes. 
Granulation Tissue.-After a variable time, usually on the second or 
third day if all goes well, the surfaces of the wound may be more or less 
covered with tiny red nodules called granulations. These granulations 
contain numerous th in-walled blood-vessels which have sprouted out 
from the old vessels near the seat of injury, and around these a new 
Fig. 64.-Granulation Tissue from Wound of Skin. 
loose, succulent tissue is formed, largely, it is believed, from proliferation 
of connective-tissue cells. This is called granulation tissue (Fig. 63). 
On the surface of the granulations are usually pus cells in varying 
quantity, or the granulations may be more or less covered with dried 
exudate. The way in which the new blood-vessels form by proto- 
plasmic sprouts from the old, and the manner in which connective 
tissue develops from older connective-tissue cells, have been already 
described in the section on Regeneration. Let it suffice here to say that 
the cells of the granulation tissue are at first mostly small and spheroidal 
or polyhedral, and are usually packed closely together with only a 
small amount of fluid intercellular substance. Presently some of the 
cells become larger and polyhedral, elongated, fusiform, or branched, 
and after a while a delicate, fibrillar intercellular substance makes its 
appearance about them and grows more and more abundant (Fig. 64). 
These larger, variously shaped cells, which appear to be formed out of 
the small spheroidal or indifferent cells of the granulation tissue, are 
usually granular, and the nucleus is generally large and distinct. Some 
of these larger cells which seem to be more or less directly concerned in 
the formation of intercellular fibers are called fibroblasts (Fig. 65). 
The walls of the blood-vessels are thicker, and intercellular fibrils are forming. INFLAMMATION 
109 
As the granulation tissue grows, new, small, spheroidal cells are 
gathered by proliferation or by continued emigration. Some of these 
participate in the formation of the granulation tissue, while others, not 
finding conditions suitable for their further development, or even for 
their continued existence, die and pass 
off on the surface, together with some 
transuded fluid, as pus. 
The polynuclear leucocytes do not 
apparently share in the formation of 
new tissue. To what extent this new 
tissue is derived from old connective- 
tissue cells and cells of the endothelial 
type-the macrophages of Metchnikoff, 
the polyblasts of Maximow, the clas- 
matocytes,1 or the connective tissue mast 
cells2-or how largely it may come 
from emigrated lymphocytes, assum- 
ing the characters of "plasma cells" (page 88), is not yet certain; but 
probably no one of these motile types of cells is actively concerned. 
Cicatricial Tissue.-The new tissue gradually becomes more and more 
dense, the intercellular substance more abundant, while the cells decrease 
in number and become flatter and less conspicuous. The epithelium may 
Fig. 65.-Fibroblasts of New Connective 
Tissue in a Healing Wound. 
There are numerous new-formed intercellular 
fibrils. 
Fig. 66.-Healing Wound in the Tongue of a Dog. 
There was loss of substance-muscle, fibrous tissue, and surface epithelium. The lost tissue has 
been replaced by the vascular granulation tissue, which is oldest and most dense in the deeper portion, 
while on the surface is a layer of tissue detritus, pus cells, etc., partly dried and forming a scab over the 
granulations. New epithelium is pressing forward from the old at the edges over the surface of the new- 
formed tissue. 
now grow over from the sides, forming by mitosis from the old epithe- 
lium at the edges of the wound (Fig. 66), and finally cover the new 
vascular tissue. The new tissue, having at last undergone more or less 
1 Clasmatocytes (Ranvier, Arch, d'anat. micros., 1899-00, iii, 22) are cells found in the connective 
tissues in connection with inflammation. Their outline is very irregular, often with numerous long 
projections; the nuclear network is dense; the cytoplasm is spongy, and has embedded in it coarse 
refractile granules. The clasmatocytes are probably closely related to the fibroblasts of growing con- 
nective tissue. For experimental production of macrophages, see Simpson, M. E., Jour. Med. Res., 
1922, xliii, 77 (bibl.). 
2 Connective-tissue mast cells are cells which are frequently found in the normal tissues of some ani- 
mals and in inflamed connective tissues of man. They have faintly staining, small nuclei with but little 
chromatin, and a cytoplasm which contains large numbers of granules staining deeply and metachro- 
matically with basic stains. Apparently they play no important part in the inflammatory process. 110 
INFLAMMATION 
shrinkage, with atrophy of the blood-vessels, consists of a dense, firm 
mass composed largely of fibrillar basement substance with a few flat- 
tened cells (Fig. 67); and with this, which is the cicatrix, the healing is 
complete. The cicatricial tissue in its shrinkage, as it becomes more 
fibrillar and denser, often brings about considerable distortion of adjacent 
parts. 
Variations in the Healing Process.-Although in the production of new 
tissue, in connection with or following exudative inflammation, essen- 
tially the same processes are involved in all cases, there are yet very 
marked differences in the degree in 
which the different factors share. 
Thus the vascular and exudative 
phenomena may predominate and 
very large quantities of serum, 
fibrin, or pus collect, while the 
amount of new-formed tissue may 
be insignificant. The production 
of a large amount of exudate, 
particularly of pus cells-suppuration-usually marks the presence of 
microorganisms whose locally elaborated poisons complicate or retard 
the healing process. 
In other cases the formation of new tissue is the dominant feature, 
and the production of exudates seems to be almost entirely subordinated 
to this end. 
Fig. 67.-Cicatricial Tissue from a Healed 
Wound. 
Fig. 68.-Exuberant Granulations. 
From the inner surface of a granulating ovarian cyst containing pus. The tissue between the 
new capillaries is ill-formed, edematous, and with few cells, most of which have undergone fatty 
degeneration. 
The process of repair which is complicated by exudative inflammation 
or effected only by the gradual formation of a considerable amount of 
new tissue, is called by surgeons healing by "second intention" 
The distinction between healing by first and second intention, which 
is of practical importance in surgery, is, from the pathological stand- 
point, only a quantitative one; for the restitution of the parts to the 
healthy condition is in both cases brought about by exudation and prolif- INFLAMMATION 
111 
eration of cells usually under the influence of vascular changes, but in one 
case the latter changes are very slight, in the other more or less extensive. 
There is much variation in the formation of granulation tissue. Thus, 
sometimes the body cells respond but feebly to the unusual conditions, 
and neither cell proliferation nor blood-vessel growth is active. On the 
other hand, the development of blood-vessels may be excessive, while 
other tissue formation lags. Under these conditions, loops and tangles 
of thin-walled, contorted. new vessels may project from the granulating 
surface, while useful tissue formation remains in abeyance, or the new 
cells undergo fatty or other forms of degeneration (Fig. 68). The result 
of this disproportionate growth of ill-formed blood-vessels is the exuber- 
ant granulations ("proud flesh") which the surgeon frequently removes 
from unhealthy healing surfaces.1 
Fig. 69.-Regeneration of Epithelium over Superficial Wound of Cornea-Rabbit. 
The new epithelium has been formed in excess. 
Cavities formed by abscesses or by necrosis in any part of the body 
may be filled up and their sides drawn together in a cicatrix, by the for- 
mation of a provisional mass of granulation tissue similar in character to 
that which grows in external wounds. So, similarly, cysts may be obliter- 
ated and ulcers partially filled and drawn into cicatricial healing. Large 
free surfaces, like the pleura and the peritoneum, may, through the 
intervention of granulation tissue, pass from the denuded condition 
of an active exudative inflammation, either with or without adhesions, 
into a condition which, though by no means a return to the normal, we 
yet designate as repair. 
The so-called organization of a thrombus in a blood-vessel is brought 
about by processes practically identical with those which have just been 
described in the formation of new tissue in reparative inflammation in 
an external wound. The endothelial cells of the vessels and the con- 
nective-tissue cells in their walls proliferate, new blood-vessels develop 
by sprouts from the already existing smaller vessels in their walls or 
close about them. The new cells and new blood-vessels thus derived 
1 For a special study of granulation tissue, see Reinbach, Zieglers Beitr., 1901, xxx, 102. 112 
INFLAMMATION 
gradually penetrate the clot, forming new connective tissue, which 
replaces step by step the fibrin and blood which are gradually softened 
by autolysis and absorbed or removed by phagocytes. 
The part which the thrombus plays in its so-called organization is 
thus a wholly passive one. It acts only as a temporary supporting 
texture for the development of the new tissue derived from other sources 
which step by step replaces it.1 
In the processes of repair by the formation of new tissues, the latter 
are often developed in excess, the overproduction after a time ceasing, 
when the normal condition is restored. Thus, if the epithelium be 
scraped from a small area on the front of the cornea the new epithelium 
which covers the injury is often heaped up in excess (Fig. 69). 
Hyperplasia and Interstitial Inflammation. 
Hyperplasia of the fibrous interstitial tissue of the internal organs 
and other parts of the body-as, for example, in the liver, kidney, heart, 
nervous system, etc.-is of frequent occurrence and is usually associated 
with changes in the parenchyma. In some cases the formation of fibrous 
tissue clearly follows evident and often acute inflammatory processes 
and bears the same relation to antecedent reaction to injury that the 
cicatrix in a healing wound does to the granulation tissue from which it is 
formed. In other cases it is associated with long-continued hyperemia- 
chronic congestion-of the organ involved. Again, gradual hyperplasia 
of the interstitial tissue takes place by the slow increase of cells and 
stroma, without evidence of an active cell proliferation or marked involve- 
ment of the blood-vessels. Finally, hyperplasia of the interstitial 
tissue may be, and probably usually is, secondary to damage to or atrophy 
of the parenchyma, as in the spinal cord after degeneration in nerve 
tracts or in the heart after damage to the muscle fibers; in the liver and 
kidney in connection with atrophy of the specific epithelial cells. In 
such cases it is often spoken of as replacement hyperplasia. These forms 
of fibrous-tissue hyperplasia will be considered with more detail in the 
sections dealing with the special lesions of the viscera. They have all 
been usually regarded as marks of inflammation. Some of them unques- 
tionably are so; concerning others, doubt will continue until our knowl- 
edge as to their excitants considerably increases. In the meantime 
the term fibrosis is sometimes applied to the results of fibrous-tissue 
hyperplasia, though this is still most commonly included among the 
inflammatory processes.2 
Those important phases of inflammation which are due to damage 
from special forms of microorganisms will be considered in detail in the 
chapter of this book devoted to the Infectious Diseases. 
1 While this view of the scaffold value of fibrin in repair of wounds and its chemotropic power on 
connective tissue and endothelial cells has long been regarded as settled, some recent observations of 
Baitsell suggested the direct transformation of fibrin into connective-tissue cells. Lambert has in- 
vestigated the matter, using Baitsell's methods, but has found no support for the former's opinion. 
See, Baitsell, G. A., Jour. Exper. Med., 1915, xxi, 455; 1916, xxiii, 739; Lambert, R. A., Proc. Soc. Exper. 
Biol, and Med., 1916, xiv, 5. 
2 For a suggestive and interesting consideration of the relationship between inflammation and 
various forms of "fibrosis" see Adami, J. G., Middleton Goldsmith Lectures, Med. Rec., 1896, xlix, 
361, et seq. INFLAMMATION 
113 
Special Phases of Inflammation. 
The several phases of the inflammatory process which we have now 
considered are fairly typical of the reaction of the living body to various 
forms and degrees of injury. If we look at them together and seek to 
gather their dominant features, we find that the changes, varied as they 
are in character as well as in degree, are mostly of three kinds: first, 
those involving a greater or less amount of degeneration or necrosis; sec- 
ond, those involving local disturbances of the circulation, as w'ell as 
alterations in the distribution and character of the fluid and cellular 
elements of the blood-exudative changes; and third, regenerative, produc- 
tive, or reparative changes. 
Of these three groups of alterations in inflammation those involving 
the blood-vessels and their contents are, in a clinical sense, most striking 
and characteristic, and to many seem to dominate the inflammatory 
processes. But in fact all are closely associated. The various phases of 
inflammation depend upon the nature and extent of the injury, the 
inherent reactive vigor of the cells, and the character and position of 
the tissue involved. 
Special names have been attached to various forms of the inflamma- 
tory process, descriptive of the feature which from the particular stand- 
point of the observer seems most striking or important. Some of the 
names are descriptive of clinical symptoms, some express the duration 
or character or situation of the lesion, some seek to imply more or less 
well-founded views of the nature of the process. Thus among the forms 
of exudative inflammation, that in which the extravasated serous fluid 
is the most marked feature is often named serous inflammation. If 
fibrin predominate, it is called fibrinous; if associated with much blood 
extravasation, it is termed hemorrhagic. When the agencies are present 
which induce the necessary vascular changes and promote the emigration 
and gathering, and often the destruction, of leucocytes in considerable 
or large numbers, we have a suppurative or purulent inflammation. If 
much tissue death be associated with the process, it is named necrotic 
inflammation. 
Again, if certain mucous membranes or mucous glands be subjected 
to the inciting agencies, they may respond by an overproduction of 
mucus as well as by an increase of death of cells; this is mucous or catar- 
rhal inflammation. In inflammation of the mucous membranes fibrin 
intermingled with other exudate sometimes forms more or less well- 
defined and often tough pellicles or membranes upon the surface. This 
is called pseudomembranous inflammation. Finally, these various 
forms of exudate may be produced simultaneously, whence arise such 
compound designations as seropurulent, mucopurulent, etc., inflamma- 
tion. Inflammation with the formation of new tissue is called pro- 
ductive or reparative. 
Local inflammation, especially when incited by microorganisms, is 
often associated with systemic infection due to a distribution of the 114 
INFLAMMATION 
inciting agents through the body. This condition will be considered in 
the chapter dealing with the Infectious Diseases (page 232). 
Inflammation, especially of infective origin, is so frequently asso- 
ciated with degenerative changes in the more highly organized cells- 
the parenchyma cells-of organs that when these are conspicuously 
involved the term parenchymatous inflammation has been used. It is 
better, however, to hold the degenerations apart and consider them as 
associated but not identical with the inflammatory processes. Similarly 
the term interstitial inflammation, though very commonly employed, 
indicates a comparatively rare occurrence. That which is embraced 
under the term is usually an interstitial hyperplasia secondary to damage 
to the parenchyma cells of organs (page 112). 
It has seemed wise to many to attempt to draw a sharp distinction 
between those phases of inflammation which involve only the degenera- 
tion of tissues or the redistribution of already formed tissue elements- 
serum, fibrin, and blood-and those phases which are productive or 
reparative. But while this attempt aims at the recognition of a biolog- 
ical distinction of fundamental importance, it encounters the great prac- 
tical difficulty that both phases of the reaction of tissues to injury, the 
exudative and the productive, occur together, so that none of the named 
classes of inflammation represents a simple and unmixed form of tissue 
reaction. The important thing is to conceive, as clearly as our knowl- 
edge permits, the nature of the processes which underlie these various 
manifestations of disturbed cell function and their associated tissue 
alterations. Then the names may serve useful temporary ends at least 
without implying too much or concealing too little knowledge. 
The Disposal of Foreign and Dead Substances in the Body- 
Phagocytosis-Autolysis. 
It was stated at the beginning of this chapter that the injuries which 
lead to inflammation are extremely varied. The degree and character 
of the resulting inflammation are closely related to the inciting agents. 
We have already taken as general examples of the inflammatory response 
to injury, one in which there was a simple mechanical damage, and the 
other in which a more extensive and prolonged injury was effected by 
the presence of living bacteria. 
While it is not practicable to classify the various phases of inflam- 
mation according to the character of their incitants it is convenient to 
consider by themselves the effects of animal and of vegetable parasites, 
among the latter especially the bacteria. In subsequent chapters, 
under the headings of Animal Parasites and of Infectious Diseases, we 
shall study the special phases of injury induced by these agents and 
the response which the living cells and tissues of the body make to their 
presence. 
But there are many forms of injury to cells and tissues which, though 
not so extensive and striking as those which we have thus far considered 
in our preliminary survey of inflammation, are yet of great frequency INFLAMMATION 
115 
and importance. One of these we must now consider, namely, the 
presence in the body of foreign substances and of dead portions of the 
body itself. Here again, as in so many instances, we shall come upon 
physiological processes spurred to unusual activity by emergency 
demands upon them. 
The Forms and Origin of Foreign and Dead Substances.-Under the 
conditions of normal life, as the tissues grow and perform their functions, 
worn-out cells die; as bone grow's it is absorbed little by little to make 
room for the remodeling and growth of the larger structure; more or 
less constantly, floating matter in the air we breathe gathers in the respi- 
ratory organs. Under all of these conditions the dead cells, the hard bone, 
the foreign particles, are disposed of by certain lowly organized cells, 
leucocytes, lymphocytes, connective-tissue cells, endothelium and 
mesothelium, which are called phagocytes. 
On the other hand, there are many conditions under which foreign 
material abnormal in quantity and character is formed in or enters the 
body and must be disposed of. Thus organic pigments in the form of 
irregular particles or crystals are formed in the body, such as blood and 
bile pigment. Many foreign substances in finely divided form in large 
quantities enter from without, especially in the respired air, such as coal, 
iron, stone, smoke, and various kinds of organic dust. In various ways 
larger bodies, slivers of wood, particles of metal, bullets, and, in injuries 
or during surgical operations, fragments of clothing, ligatures, sutures, 
fragments of sponge, cotton, gauze, jute, etc., may remain as foreign 
substances doing more or less harm and inciting in various degrees the 
phenomena of inflammation. 
Finally, as the result of the greatest variety of injuries which lead to 
the necrosis of cells and tissues, such as mechanical damage, the action 
of corrosive poisons, excessive heat or cold, disturbances of circulation, 
various toxins, etc., the dead structures themselves become harmful to 
the living tissues about them, which respond in various ways to their 
presence, among others by certain forms of inflammation. 
Let us see how the body cells and tissues comport themselves in the 
presence of alien substances and dead structures. 
Disposal of Foreign Substances.-One of the simplest and most com- 
mon of the phenomena of this class is seen in the disposal of pigment and 
other solid particles, whether introduced from without or formed within 
the body under various abnormal conditions.1 When dusty air is 
breathed, whether of badly cleaned dwellings, places of business or assem- 
blage, or in occupations involving the loading of the air with the dust of 
coal, smoke, iron, stone, tobacco, lint, hair, etc., in the aggregate large 
numbers of the dust particles enter the respiratory passages. Here sooner 
or later they are taken up by cells-phagocytes-and if the particles 
are colored they may be seen lying within the cytoplasm surrounding, 
but not within, the nucleus (Fig. 70). These cells may be the epithelium 
of the respiratory passages or of the air chambers of the lungs, or leuco- 
1 For a study of the removal of alien substances from the peritoneal cavity, see Buxton and Torrey, 
Jour. Med. Research, 1906, N. S. x, 5. 116 
INFLAMMATION 
cytes which have wandered out upon the surfaces. Then a large part 
of the foreign particles, if these be not too numerous, are carried either 
on the lymph-currents or more frequently within cells into the lymph- 
channels, along which they make their way to the nearest system of 
lymph-nodes or -nodules or to the smaller areas of lymphatic tissue 
which are widely distributed in the lungs as well as elsewhere in the 
body (page 546). In these islets of 
lymphatic tissue or in the lymph- 
nodes of the lung the foreign particles 
both within and without the cells are 
deposited and may remain for an in- 
definite period. 
But the tissues in which they are 
deposited are not indifferent to the 
presence of any considerable accumu- 
lation of these alien substances. 
The connective tissue and endothelial 
cells swell and proliferate and new 
fibrils are formed inclosing the foreign 
material which may lie within the 
cells which brought them or be taken 
up by the new-formed or old connec- 
tive-tissue cells or lie free in the 
interstices of the fibrils. Thus in the 
lymph-nodes and along the lymph- 
channels masses of dense fibrous tissue may be formed, shutting in the 
foreign material and compromising in varying degrees, sometimes com- 
pletely destroying, the involved structures (page 550). 
Similarly bacteria, which are also foreign bodies, may be taken up by 
phagocytes (Fig. 70) and destroyed within them by agencies presently 
to be considered, though the possibility that organisms may also be pro- 
tected by such ingestion must not be lost sight of.1 
If a mass of foreign particles is placed beneath the skin, or if at the 
seat of a hemorrhage insoluble blood pigment is formed in considerable 
amount, a similar process may be observed. The pigment is more or 
less taken up by leucocytes or other phagocytic cells which have wan- 
dered in. A certain amount of fluid exudate may collect. New cells are 
formed from the old connective-tissue cells and from endothelium, and 
new fibrillar stroma is formed which becomes dense and assumes the 
character of cicatricial tissue. In these changes the new-formed cells, 
as well as the leucocytes, are capable of moving from place to place, 
that is, may become wandering cells. We have then, in this relatively 
simple response to a small local injury, the presence of fine foreign 
particles, a definite form of inflammation. This is marked, not by the 
phagocytosis, but by the presence of leucocytes and a certain amount of 
fluid exudate, by the formation of new cells, and by the production of new 
tissue. 
Fig. 70.-Phagocytes. 
The upper cell is epithelial from the lining 
of the air vesicles of the lungs. The pigment 
which it has ingested is coal dust from the 
air. The lower cells are leucocytes. One has 
taken in cocci, the other bacilli. 
1 Rous and Jones, Jour. Exper. Med., 1916, xxiii, 601. 117 
INFLAMMATION 
When the alien material out of place in the living tissue is in the 
form of a loose-textured mass, such as sponge, fabrics, jute, catgut, etc., 
or is a blood-clot, its interstices become filled with fluid exuded from 
adjacent blood-vessels, with leucocytes which wander in, and with new 
Fig. 71.-Giant Cells. 
The giant cells are at the border of a layer of granulation tissue formed about a mass of dead 
fibrous tissue which is being absorbed. 
connective-tissue cells derived from the surrounding parts and from 
the endothelium of neighboring lymph-vessels. Slender blood-vessels 
form from the old ones near by and penetrate the mass, and new con- 
nective tissue is developed, having the type of granulation tissue at 
Fig. 72.-Fragment of Sponge in a Healing Wound-Three Weeks. 
The sponge trabeculae are not dissolved in the new-formed fibrous tissue, which has completely 
inclosed them. 
first, then becoming denser. If the foreign substances are capable of 
solution, as is the case in the fibrin and cells of a blood-clot or of catgut, 
proteolytic enzymes1 furnished by the leucocytes or other cells may 
dissolve them; or they become fragmented and the fragments are taken 
1 See Wells, Jour. Med. Research, 1906, N. S. x, 149 (bibl.). 118 
INFLAMMATION 
up by phagocytic cells. These may be dissolved within these cells or 
may be transported to other parts of the body. Thus in the case of 
soluble material this may at length be entirely removed and its place 
taken by the new tissue which gradually assumes the character of 
cicatricial tissue. 
If the foreign substance be insoluble or largely so, as in the case of 
bullets, needles, hair, cotton, sponge, etc., the new cells gather about 
the objects; there are often giant cells among them (Fig. 71), and new 
blood-vessels develop among these, leading to the formation of new 
connective tissue which may completely invest them (Fig. 72), forming 
at last a dense connective-tissue capsule. In this condition such foreign 
Fig. 73.-Stellate Bodies in Giant Cells. X 750. 
objects may remain for long periods embedded in the body. If the 
masses of foreign bodies are small, so that the local reaction is limited 
and circumscribed, the new tissue often in a general way resembles a 
tubercle. Thus these new foreign-body tissue masses are sometimes 
called "foreign-body tubercles." 
Giant Cells.-When foreign objects of considerable size-such as 
fat crystals, wax, cholesterin,1 hair, cotton fibers, sponges, and various 
solid things-get into the living body, particularly if these be insoluble, 
in addition to the leucocytes and the new connective-tissue cells, there 
often form close about them large multinuclear cells called giant cells 
(Fig. 74). These are sometimes of extraordinary size and may have 
several score, even hundreds, of nuclei. They are apparently formed 
1 Stewart, Jour. Path, and Bacteriol., 1914-15, xix, 305 (bibl.). INFLAMMATION 
119 
either by the coalescence of new-formed cells derived from the connective- 
tissue cells or from old endothelium, or by the continuous division of the 
nuclei of a cell whose body continues to enlarge without dividing into 
separate cells.1 These giant cells seem to be concerned in the attempt 
to dissolve the foreign substance and appear to have their prototypes in 
the multinuclear cells called osteoclasts (Fig. 75) which are concerned 
in the physiological absorption of bone during its development. 
The Disposal of Dead Tissues.-The changes which we have now 
studied, through which alien substances are either removed from the 
body or rendered relatively harmless by processes which we must re- 
gard as belonging to inflammation, are similar to those by which the 
body responds to the injury of dead portions of its own tissue. 
Fig. 74.-Giant Cells Formed around Foreign Bodies-Cotton Fibers. 
From a wound delayed in healing on account of the cotton fibers left in the dressing. 
Thus, infarcts resulting from emboli, areas of tissue which have 
become necrotic from poisons or toxins, thrombi or masses of fibrinous 
exudate in the solid tissues or in the great serous cavities, are all virtu- 
ally alien substances, and are harmful in various ways as foreign bodies 
are, and incite similar inflammatory phenomena. They may be in part 
removed by solution through the proteolytic enzymes,2 or by phago- 
cytosis; they may attract leucocytes (Fig. 76); they may lead to the 
proliferation of connective tissue and endothelial cells and of blood- 
vessels which penetrate them and form new tissue which finally replaces 
or encapsulates them. The so-called organization of a thrombus or of a 
pleural or pericardial or peritoneal exudate is not, as we have already seen, 
brought about directly by the aid of the structural or other elements in 
either the thrombus or the exudate. These are passive, except as they 
may aid in their own solution by autolytic substances which they furnish, 
while the new tissue is formed from neighboring cells and vessels. 
Forms of Phagocytes.-There appear to be two most common forms 
of phagocytes in foci of acute exudative inflammations. First, and 
usually the most abundant, are the neutrophile polymorphonuclear 
1 Giant cells may be formed from epithelium under certain conditions. For a study of giant cells, 
with bibl., consult Hektoen, L., Jour. Exper. Med., 1898, iii, 21; Fuerst, Zieglers Beitr., 1898, xxiv, 415; 
and Buxton, Studies from Department of Pathology, Cornell University, New York, vol. i. 
For a study of peculiar stellate bodies in giant cells (Fig. 73), see Wood, F. C., Proc. New York Path. 
Soc., 1915, xv, 63. 
2 See Wells, Jour. Med. Research, 1906, N. S. x, 149 (bibl.). 120 
INFLAMMATION 
leucocytes-which so readily escape from injured vessels. The other type 
of the two more common phagocytic cells is usually larger than the poly- 
morphonuclears and has a single, relatively large, rounded or irregular 
shaped nucleus. These mononuclear phagocytes of the second type are 
Fig. 75.-Osteoclasts Dissolving Bone Lamella. 
probably derived from connective tissue or endothelial and mesothelial 
cells or from lymphocytes, and have been called by Metchnikoff macro- 
phages, while the smaller polymorphonuclear phagocytes are called 
microphages. 
From a case of rarefying osteitis. 
Fig. 76.-Fragments of Necrotic Muscle in Process of Absorption under the Action of 
Phagocytes. 
While the performances of these two types of cells are not fully under- 
stood, it appears that the macrophages are especially concerned in the 
disposal of various protein and other formed elements which they ingest, 
such as fragments of fibrin and tissue detritus, dead parenchyma cells 
of organs, red and white blood-cells, etc. That the lymphocytic 
macrophages have any power to act upon living cells, as has been sug- 
gested by Da Fano,1 Loeb,2 and Murphy,3 is doubtful. 
1 Da Fano, C., Ztschr. f. Immunitatsforsch., Orig., 1910, v, 1. 
2 Loeb, L., Jour. Am. Med. Assn., 1915, Ixiv, 726. 
8 Murphy, J. B., Proc. Nat. Acad. Sc., 1915, i, 435. INFLAMMATION 
121 
On the other hand, the polymorphonuclear leucocytes-microphages 
-are drawn to and ingest and destroy various kinds of microorganisms, 
especially the bacteria.1 
While we have thus far considered certain special cells, leucocytes, 
lymphocytes, and derivations of connective-tissue and endothei al cells, 
as the most common phagocytic cells in inflammation and repair of 
tissues, we should not lose sight of the fact that other types of cells also 
are capable of assuming this role.2 Thus the epithelium of the mucous 
membranes of the air vesicles of the lungs, of the liver, kidney, and other 
organs, frequently and under the most varied conditions ingest particles 
of foreign material. 
The Mode of Action of Phagocytes.-As to the processes by which the 
phagocytic cells convert into soluble and other forms the substances 
which they ingest there is still some difference of opinion, though the 
so-called intracellular digestion and the autodigestion of tissues have 
been the subject of much painstaking research. 
Recent studies3 indicate that each of the two types of phagocytes 
above designated is characterized by a distinct proteolytic enzyme 
through which its destruction of organic substances is effected. The 
enzyme of the polymorphonuclear leucocytes is capable of proteolytic 
digestion in the presence of a neutral or alkaline reaction, but not in an 
acid medium. This enzyme is called leucoprotease. The larger mono- 
nuclear cells, on the other hand, the "macrophages" or "macrocytes," 
which appear to be especially concerned with the ingestion and destruc- 
tion of cellular and other formed elements, contain an enzyme active 
in the presence of a weak acid, but inactive in an alkaline, medium. 
This enzyme is called lymphoprotease. Neither of these ferments is 
bactericidal. 
Blood-serum inhibits the action of leucoprotease, and lymphoprotease 
is not active in an alkaline medium. Hence, the living tissues of the 
body are not digested by the leucoprotease, which is active only within 
the bodies of the microphages, where it is free from the inhibiting action 
of the serum, while the alkalinity of the blood plasma protects the tissues 
from the action of the lymphoprotease. It is apparently the action of 
these proteolytic ferments, present in considerable quantities either 
within or without the cells or both, in foci of exudative inflammation, 
which leads to the softening of tissue which characterizes abscesses and 
which, in part at least, brings about the more gradual solution of necrotic 
tissues, fibrin, pneumonic exudate, etc.4 
The action of microorganisms, especially the bacteria, as incitants 
of inflammation through the injury which they cause, and the ways in 
which the body reacts to and disposes of them, through the action of 
1 For a consideration of the ways in which bacteria are destroyed by leucocytes, see pp. 187 and 
204. See also Buxton and Torrey, Jour. Med. Research, 1906, N. S. x, 5. 
2 See, for a study of this question, Bartlett and Ozaki, Jour. Med. Research, 1917, N. S. xxxii, 139. 
3 Miiller, Fr., Verhandl. d. Kong. f. inn. Med., 1902; Opie, E. L., Jour. Exper. Med., 1906, viii, 
10, 536; Jochmann, G., Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1913, 
i, 1301. 
1 Wells, Jour. Med. Research, 1906, N. S. x, 149; and Levene, Jour. Am. Med. Assn., 1906, xlv 
774, 866. 122 
INFLAMMATION 
phagocytes or otherwise, will be considered later under the heading of 
Infectious Diseases.1 
It should be borne in mind, in considering the varied and complex 
performances of phagocytic cells under abnormal conditions, that these 
are only the manifestation in exaggerated form in the presence of emer- 
gencies of physiological capacities of many kinds of cells. To Metchnikoff 
especially we owe our knowledge of the phagocytic powers of cells in 
general. In such lowly organisms as ameba and in many other cells 
throughout the animal kingdom, he has shown that through ingestion and 
intracellular digestion cells not only are nourished but protect them- 
selves against harmful agents and influences.2 
Autolysis.-All the manifestations of cell life are brought about by 
the breaking down or disintegration of chemical substances in the cyto- 
plasm by processes akin to those of combustion. It has long been 
believed that this was exclusively a property of living matter. But it 
has recently become known that dead cells also under certain conditions 
have the power of self-disintegration. This is called autolysis. It 
takes place in the absence of microorganisms through the action of 
which organic material is decomposed in the commoner processes of 
putrefaction. Thus portions of fresh organs removed from the body 
with the avoidance of bacterial contamination, that is, in a sterile con- 
dition, if immersed in chloroform water, or toluol, or other substances 
which do not cause alterations of the tissue but do prevent the growth 
of microorganisms, and kept at about body temperature, undergo 
gradual softening. This softening is accompanied by definite struc- 
tural changes in the cells. The nuclear chromatin disintegrates or goes 
into solution; the cytoplasm degenerates, chemical analysis showing 
products of the disintegration of protein substances. The changes are 
analogous with those taking place in organic material, cells, etc., under 
the influence of the digestive enzymes, pepsin and trypsin, but are due 
not to these but to other enzymes belonging to the cells themselves 
(page 117). 
It appears, for reasons into which we cannot enter here, that the 
proteolytic enzymes active in the autolysis of dead tissues are present in 
the living body and are probably concerned among other things in the 
gradual removal of dead and enfeebled structures as these become 
defective, useless, or harmful. It has been shown that the vigorous, 
living cells, in spite of their autolytic powers, probably maintain their 
integrity through the presence in the body-fluids of substances antago- 
nistic to the autolytic enzymes. Thus it appears that under normal 
conditions a very nice balance exists between the autolytic enzymes 
and antagonistic substances within the body. Under a variety of 
abnormal conditions, such as diseases of the respiratory and circulatory 
systems, phosphorus poisoning, and infectious diseases,3 autolysis may 
be in a marked degree exalted. 
1 For a consideration of Ehrlich's hypothesis as to the way in which bacteria are destroyed in the 
body, see page 202. 
2 See Metchnikoff, Comparative Pathology of Inflammation, English trans., 1893; and Immunity 
in Infective Diseases, 1905. Consult also page 224. 
* Flexne., Tr. Assn. Amer. Phys., 1903, xviii, 359; and Dernby, K. G , Jour. Biol. Chern., 1918, xxxv, 
179. INFLAMMATION 
123 
It is probable that the autolytic substances in the living body are 
important not only in disposing of damaged or dead or harmful tissues, 
but also in the protection of the body against invading microorganisms 
through their destruction (see Immunity and Bacteriolysis, p 'ges 185 
and 200), or by their share in the elaboration of substances which an- 
tagonize the action of their toxins (see Antitoxins, page 189).1 
Survey of the Inflammatory Process and its Significance. 
Inflammation a Modification of Physiological Processes. - If now, 
from the vantage-ground which we have won by our study of various 
typical phases of inflammation, we seek to gain an insight into the 
forces which dominate the varied processes, we note at once that from 
first to last the cell and tissue performances in inflammation, however 
exaggerated or perverted, are only the expression of physiological 
capacities which belong to the structures involved. Thus the contrac- 
tions and dilatations of the vessels are paralleled in health. The exuding 
of fluids through their walls occurs by processes akin to those by which 
blood pressure, osmosis, and selective filtration in endothelial cells main- 
tain the initial circulation into and through the tissue spaces. Emigra- 
tion is a physiological process which we find excessive here, because there 
are structural alterations in the walls of the vessels which permit a freer 
exit of the cells, and because there are also present new and active 
chemical agents which, just as in normal conditions though in exagger- 
ated fashion, excite and control the movement and direction of the leuco- 
cytes. The healing processes, complex as they seem to be, are actually 
but a rehearsal under the unusual and often difficult conditions of cell and 
tissue formation, which is characteristic of the normal period of develop- 
ment. Phagocytosis is a factor of the greatest importance in the normal 
as well as in these abnormal performances of the body cells. 
The degenerative phenomena, among which must be reckoned the 
formation of fibrin, are, as we have seen, incidental rather than primary 
factors in inflammation. 
Thus in all the manifold manifestations of abnormal cell performance 
in inflammation we find no new functions, no new cell capacities. 
The Significance of Inflammation.-We are now brought face to face 
with the final question: What does inflammation mean? 
In those phases which involve the repair of wounds and the regener- 
ation of lost tissues it is not difficult to recognize conservative and bene- 
ficial processes. But how is it with those phases of inflammation in 
which the blood-vessels are largely involved and exudates formed- 
serum, fibrin, and pus? Are we to be contented here with a simple 
summary of the phenomena and with the recognition that these are the 
results of exaggerated or physiological cell and tissue performances in 
the face of injury? Or, on the other hand, is there reason for the belief 
1 For an interesting r6sum6 of autolysis with bibl. see Levene, Jour. Amer. Med. Assn., 1906, xlvi, 
774, 866. For a fuller consideration of the subjects dealt with in this chapter consult the general 
pathology, Les processus generaux, of Chantemesse and Podwyssotsky, Paris, 1901, or Wells, Chem- 
ical Pathology, 4th ed., Philadelphia, 1920. 124 
INFLAMMATION 
that these abnormal manifestations of cell life in the presence of an 
unusual and deleterious environment may, after all, be in the main con- 
servative in their nature, and, even as normal cell functions do, tend- 
within the limitations of an emergency-to the welfare of the individual? 
The Role of the Exudates.-In the hope of gaining some light upon this 
question let us look a little more closely at the part which the exudates 
play in exudative inflammation; and first at the leucocytes. 
The Leucocytes.-It was through the painstaking and brilliant studies 
of Metchnikoff 1 that attention was directed to the importance in this 
connection of comparative studies upon the comportment of lower forms 
of life in response to injury. 
It was found that ameba, one of the simplest of organisms, when cut 
in two may undergo complete restitution of the part containing the 
nucleus, provided the latter be uninjured. The remaining portion may 
live for a time, but ultimately dies. Furthermore, it was found that 
ameba and other lowly forms of living beings are capable, by the use of 
their simple digestive processes, of destroying microorganisms which are 
taken into their interior and which might otherwise damage or kill them. 
Thus it was established that the digestive mechanism may become pro- 
tective in lowly organized cells. 
Rising in the scale of living beings, it is found that in forms in which 
considerable differentiation of some of the cells has taken place, whether 
there be a distinct circulatory apparatus or not, certain other cells are 
left in a more primitive state; these are phagocytic and can ingest or 
otherwise destroy deleterious material. 
When we come to man and other warm-blooded animals, it is upon 
the leucocytes which have retained so many of the capacities of undiffer- 
entiated protoplasm that attention is especially concentrated. It has 
been found, as we have already seen, that the movement of leucocytes 
may be directed toward (sometimes from) chemical substances set free 
in their vicinity. This chemotaxis is frequently manifested in the 
vicinity of dead cells or tissues which are the seat of destructive metab- 
olism. But it is especially in relation to microorganisms of various 
forms that chemotaxis in the leucocytes is of the highest significance to 
us here. 
Highly virulent microorganisms may for a time repel the leucocytes, 
probably through negative chemotaxis, but these may later approach. 
On the other hand, leucocytes most often migrate toward bacteria 
which have gained entrance to the body. It has been proved that 
leucocytes, especially the polynuclear neutrophiles, and frequently large 
mononuclear forms, may take into their interior and destroy living 
bacteria. Dead bacteria also, as well as other inert material, they can 
engulf and destroy. 
The Body Fluids.-This capacity of leucocytes and other mesodermal 
cells-endothelia, etc.-to take up living bacteria and kill and digest 
them was persistently and ably urged by Metchnikoff and his pupils as 
the chief protective agency in the body against bacterial incursions, and 
1 Metchnikoff, Comparative Pathology of Inflammation, Eng. trans., 1893. INFLAMMATION 
125 
to these observers all the other phenomena of inflammation formerly- 
seemed of secondary importance. But it was soon shown that this ex- 
treme view is not correct. For it was demonstrated by many observers 
that the body fluids, especially blood-serum, are capable of killing 
bacteria with which they come in contact. When, however, this i?mark- 
able quality of the body fluids was investigated, it was found that it is 
most pronounced under conditions which involve the breaking-down of 
leucocytes or the liberation of the destructive substances into the fluids. 
It was possible now to demonstrate that the leucocytes do, in fact, contain 
a germicidal protein substance or substances. These substances, which 
appear to be closely associated with or related to nucleinic acid, have 
been called "alexines" or "protective proteins."1 It has been further 
demonstrated that while the eosinophile cells may move toward bacteria, 
they are not phagocytic, but may set free granules which appear to favor 
the destruction of the germs. 
It thus appears that the earlier view of the almost exclusive impor- 
tance of phagocytosis is not sustained, but that even more than in the 
action of living phagocytes the protective agencies are to be sought in 
the body fluids. But it is also clear that the protective capacities of the 
body fluids are the result of cell activities, as indeed might have been 
inferred in advance of the long line of careful experiments which finally 
led to the demonstration. 
The importance of this protective power of the body-cells and body 
fluids is not exhausted with their germicidal action. For not less sig- 
nificant is the role which these may assume in the establishment of other 
phases of immunity to the incursion of microorganisms. This will be con- 
sidered later in the general survey of the infectious maladies (page 185). 
If now one seek for ways in which the other exudates, serum, and 
fibrin may be useful to the individual, it is obvious that in the dilution 
of locally engendered poisons and in their removal from a vulnerable 
region the fluid may at times be beneficial. Fibrin, too, by closing 
inflammatory foci, through temporary adhesions, or by the sealing of 
absorbent surfaces, may limit the extension of injurious agents, as is so 
frequently the case in local infectious injuries in the peritoneal and 
pleural cavities. That the regeneration and repair of tissue which may 
be associated with or follow the more active phases of inflammation are, 
as a rule, beneficent, is not doubtful. 
There is, of course, another side to the matter. For new cicatricial 
tissues which have formed in the process of repair may be so situated as 
to cause serious impairment of functional performance or even fatal 
strictures. The gathering of leucocytes, too, may be so excessive and 
their proliferation so extreme as to lead to delayed healing or to serious 
exhaustion from suppuration. But notwithstanding these irregularities 
and failures there seems to be good reason for the belief that, on the whole, 
the processes involved in inflammation are conservative, and, within the 
limitations which may be set by the varied and changing conditions of 
injury, tend to maintain the welfare and sustain the life of the individual. 
1 For further consideration of this subject see page 185. 126 
INFLAMMATION 
CHARACTERIZATION OF THE INFLAMMATORY PROCESS. 
The general conception of inflammation which we have just set forth 
looks beyond the gross manifestations of disordered function and altered 
structure, by which it was originally marked, and beyond the complex 
and varied expressions of aberrant cell activities, with which our later 
science has mostly dealt, to the fundamental qualities of living substance. 
And thus at last, with the heart of the subject in view, a characterization 
of inflammation becomes possible which is suggestive and useful, though 
it may not indeed be final. Perhaps among many such characterizations, 
that of Adami1 is on the whole the most clear and precise, and with him 
we may at present wisely consider inflammation as "the local attempt at 
the repair of injury." The fundamental conception upon which this 
characterization is based is that inflammation is an emergency measure 
incited by injury, in which the body adapts to unusual ends as best it can 
mechanisms and powers normally maintained for other purposes. 
This view of inflammation, however much it may be modified as our 
knowledge grows, recognizes a far-reaching significance in the complex 
processes involved. And while throwing light upon the practical prob- 
lems of the physician, it points the way to a broader conception of other 
abnormal conditions in which also the adaptation of physiological cell 
capacities to new conditions seems to furnish a clew to many manifesta- 
tions of disease as yet but little understood.2 
Now that we have gained a.conception of the inflammatory processes 
in general and some suggestions as to their significance, it does not seem 
necessary to enter here upon a detailed description of the variations 
which they present, since these are largely influenced by the character 
of the inciting agents and by the situation in which they act. Such 
details as may fall within the scope of this work are given in the section 
dealing with microorganisms as inciting factors in disease, and in the 
part dealing with the lesions of special organs.3 
The Experimental Study of Resorption of Foreign Material, Phagocytes, etc., in 
Inflammation. 
Aside from clinical material illustrating the healing of wounds and various phases 
of repair from the lower animals, one may obtain by very simple operations, to be 
done with local or general anesthesia, many valuable series of demonstrative lesions. 
1 For a fuller consideration of inflammation from the point of view which in general is here adopted, 
one may consult the excellent article on "Inflammation" by Adami in Allbutt's System of Medicine, 
1905, i, 702. 
In Thoma's work on General Pathology, vol. 1, is a clear exposition of the various processes con- 
cerned in inflammation, with a fuller recognition than is commonly accorded to them of the mechanical 
factors involved. In both of these works the more important bibliography may be found. 
For bibliography and critical r6sum6 of studies on pathological organization, inflammation, etc., 
see Borst, Lubarsch and Ostertag, Ergebn. d. allg. Path., 1897, iv, 461. See also under Regeneration, 
page 82. 
8 Consult, for a clear and comprehensive view of adaptation in pathological processes, Welch, 
Tr. Cong, of Am. Phys., 1897, iv, 284. 
3 For a systematic and extensive r6sum6 of inflammatory phenomena, phagocytosis, chemotaxis, 
emigration, diapedesis, protoplasmic poisons and irritants, the nature of exudates, and the general 
physical chemistry of the cell, with extensive bibl., see Heinz, Handbuch d. exper. Path. u. Pharmakoi., 
Jena, 1904, i. INFLAMMATION 
127 
Phagocytes.-The injection ot 1 per cent, agar-such as is used for bacterial 
cultures, which fluidifies at about 40° C. and becomes semisolid on cooling-into the 
anterior chamber of the eye or into the subcutaneous tissue of the rabbit gives most 
instructive pictures of absorption and phagocytosis. Phagocytes of connective-tissue 
origin bring about the solution of the mass and permeate it. If the agar be colorea vith 
Berlin blue in the form used for blood-vessel-injection masses, the phagocytes may 
become more or less filled with the blue granules as absorption proceeds. In the 
absorption from the anterior chamber in dark-colored rabbits the origin of the 
phagocytes in the iris is revealed by their pigmented character. Giant cells are often 
formed in this process, aiding in the resorption. 
The action of phagocytes in disposing of foreign material in the lungs may be 
seen by making intratracheal injections of a watery emulsion of lampblack or finely 
powdered charcoal in rabbits. The pigment particles will be found both free and 
within epithelial phagocytes in the air vesicles within a few days. The animal should 
be sacrificed and the lungs filled with formalin solution or alcohol through the 
trachea (page 1210), after which the tissue is embedded and sectioned. 
Very instructive studies may be made of the disposal of insoluble foreign bodies 
by the implanting of small fragments of cotton, jute, elder pith, etc., beneath the skin, 
and their removal after varying intervals.1 
Practical Study of Exudative Inflammation on the Living Frog. 
In the study of exudative inflammation it is of the highest value to see the phe- 
nomena of emigration, diapedesis, etc., in the living animal. The curarized frog is 
best adapted for this purpose,2 and either the mesentery or the bladder affords much 
clearer pictures than the tongue or the web, which are sometimes recommended. 
The Mesentery.-In a fully curarized frog an incision is made through the skin 
along the abdomen in the axillary line, care being taken to avoid or ligate a large vein 
which usually crosses the line of incision. The abdominal wall is then cut through in 
the same line, and a loop of small intestine drawn out, care being taken to bring out 
only as much as may be necessary to expose over the glass window of Thoma's frog 
plate3 (see Fig. 77) a small area of mesentery. The loop may be fixed by short pins 
passed through the superficial layers of the intestine into strips of cork which are 
crowded in beside the raised glass window. The exposed loop should be irrigated with 
0.75 per cent, saline solution which may be made to trickle over the part from a 
reservoir through a glass cannula held by the cannula-holder (see Fig. 77). Peristal- 
tic movements of the intestine sometimes cause the field of observation to shift and 
stasis may occur if the loop be drawn too tightly. But through a little attention to 
adjustment from time to time difficulties may be reduced to a minimum. For long 
observations a cover-glass may be laid upon the loop under which the irrigation 
proceeds. 
In this way observations may be made on arteries, capillaries, and veins, extending 
over several hours. Long focal distance, high-power lenses may be used. 
The Bladder.-The bladder of the frog is a bilobed organ opening into a cloaca 
just within the anus and common to it and the intestine. To expose the bladder an 
incision is made in the axillary line along the lower half of the abdomen, including the 
skin and the abdominal wall. The bladder frequently prolapses at once to a moderate 
extent through this opening. Now a glass cannula is made with a tapering tip with the 
1 For a full exposition of methods of experimental pathology relating to inflammation, see Heinz, 
Handbuch d. exper. Path. u. Pharmakoi., Jena, 1904, i, 255. 
For many suggestive studies in phagocytosis, see Metchnikoff's Immunity in Infectious Diseases. 
Consult, for the technique of studies on absorption from the peritoneum, Buxton and Torrey, Jour. 
Med. Research, 1906, N. S. x, 5. 
2 For the use of curare see page 42. 
3 Thoma's frog plates are of three forms, adapted for the study of the tongue, the mesentery, and 
the bladder or lung. They are plates of brass covered with hard rubber in which glass windows are 
set so that when put on the stage of the microscope the light passes up through the exposed organ to 
the eye. They are provided with cannula-holders for irrigation with physiological salt solution and 
with pipes for carrying away the waste irrigation fluid. The three forms of plate are shown in Fig. 77. 128 
INFLAMMATION 
The upper plate is adapted to the study of the circulation in the mesentery. The middle plate is for 
the bladder and lung. The lower plate is for the tongue. 
Fig. 77.-Thoma's Frog Plates. INFLAMMATION 
129 
tip for about half an inch bent to an angle of about 45° to the axis of the tube. The 
tube should be large enough to pass the anal orifice with difficulty except at the tip 
and along the bent portion. 
A thread is now passed through the skin just behind the anus, the ends being 
left free. The cannula and a short length of flexible rubber tubing slipped over the 
larger end are filled with 0.75 per cent, saline solution, this being retained by a clip 
on the tube. The bent point of the cannula is now inserted into the cloaca and its 
tip carried forward into the base of the bladder and fastened in place by the thread. 
The frog is laid on its back on the Thoma plate adapted to the bladder and lung (Fig. 
77). The rubber tube is attached to a slightly raised flask so that the salt will siphon 
into the bladder under a very low pressure. Now if the clip be released the bladder 
will appear in the opening of the abdomen and will be pressed out as a transparent bag 
by the salt solution over the glass window in the plate. Great care should be taken 
to avoid more distention of the bladder than is necessary to keep it spread over the 
glass, since the circulation is very easily disturbed or interrupted. A cover-glass may 
be laid upon the bladder or held in place over and touching it by an upright attached 
to the plate for this purpose, and irrigation with salt solution started and maintained. 
If the circulation is compromised one should see that the base of the extruded 
portion of bladder is not pressed upon by the abdominal walls; that it is not overfilled 
and is not pressed too much by the cover. By attending to those points in a frog not 
over-curarized one may maintain the circulation for hours. Since the wall of the blad- 
der is very thin, consisting of little else than the almost invisible epithelial lining, a 
membranous connective-tissue wall reinforced here and there by slender bundles of 
smooth muscle cells, and the blood-vessels, one secures in this organ pictures of the 
blood-vessels of incomparable clearness and may study the minutest phases of the 
circulation and its disturbances, emigration, etc. The contraction of the muscle 
bundles brings about occasional shifting of the field, but this is not usually a serious 
drawback to continuous observation even with high-power lenses. 
On the whole, though slightly more difficult to prepare, the bladder is to be pre- 
ferred to the mesentery for studies on the minute phenomena of emigration, diapede- 
sis, hemorrhage, etc., and it is admirably suited to the study of the local effect of drugs, 
such as adrenalin, on the circulation. 
In neither the mesentery nor the bladder is it necessary to injure the organ further 
than is inevitable in the preliminary operation and exposure, in order to incite the 
inflammatory phenomena in the vessels. In both organs the course of the emigrated 
leucocytes may be followed through the interstices of the tissues after they have left 
the vessels. It is most instructive after the observations on the living animal are 
completed to pith or decapitate the frog, fill the bladder with a fixative such as Orth's 
fluid, in which the organ after ligating is placed, and finally to scrape off the epithe- 
lium, stain with hematoxylin and eosin, and mount pieces of the wall in balsam for 
study. 
The Lung.-The circulation in the lung and various phases of its disturbance may 
be studied in the living frog by the use of the Thoma plate especially adapted for the 
bladder. The preliminary operation is made in the axillary line, the long incision 
reaching forward to the axilla. A cannula tapering to one end so as to pass between 
the folds of the glottis for five or six mm., but not to slip further in, is tied in place by 
a thread through the snout of the curarized animal. A flexible rubber tube over the 
free end of the cannula, which extends a couple of centimeters beyond the snout and is 
controlled by a clip, enables one to blow into the lung and force it out through the 
incision. The inflation should not be excessive and the base of the lung should not be 
constricted. The animal is placed on its back upon the plate with the distended lung 
over the glass window and irrigated in the manner above indicated for the bladder. 
The picture of the circulatory districts of the single-sac lung with the blood shooting 
through the rich capillary network and entering the veins is most interesting and 
important for one who would appreciate the significance of lung lesions involving, as 
most of them do, disturbances of the circulatory mechanism. CHAPTER VI 
ANIMAL PARASITES. 
INTRODUCTION. 
The relations between man and a host of parasitic plants and 
animals have an important bearing upon many of his activities. The 
opinion has been held, for example, that the Greeks were conquered 
much less by Roman military power than by the ravages of malaria; 
and it is unquestioned that the useful occupation of tropical regions by 
the Caucasian race has been possible only through the hygienic control 
of parasitic invasion, and the consequent decrease of malaria, yellow fever, 
dysentery, and other diseases. The improved conditions in Porto Rico, 
as an instance, have been due more to the hygienic campaign against the 
hookworm than to any other factor. Of late, many of the advances 
gained in hygiene have been obtained by experimental investigation; 
for example, the fixation of the transmission of malaria and yellow fever 
on the mosquito, of typhus on the louse, of plague on the flea. There 
has thus been a renewed interest in parasitism, increased recently by the 
varied and novel epidemics of the present time. 
Parasitic plants and animals may be classified as ectoparasites and 
endoparasites. The first live on the surface of the body, the latter in 
its interior. Of the plants, the moulds which induce skin lesions are the 
best examples of the ectoparasitic, the bacteria and yeasts of the endo- 
parasitic type. Both of these are considered in detail in subsequent 
chapters. In the animal kingdom, the ectoparasites, such as the fleas, 
and mosquitoes, are also classed as temporary for, after obtaining such 
food as they desire from the human host, they may abandon their prey 
for other purposes. The endoparasites as a group are much more likely 
to be permanent; such are the various intestinal worms, which may pass 
their entire existence in the alimentary tract of an individual unless 
changing conditions drive them out. A good example of this is the cos- 
mopolitan worm, Trichuris trichiuria, which undoubtedly remains in the 
intestines of its human host during its entire life, chiefly because it is not 
inimical to health. Other types, such as amebas or the malarial parasite, 
while causing serious or even fatal lesions in some instances, in others may 
be gradually eliminated either by healing of the parasitic lesions, or by 
destructive action of the natural defences of the blood and cellular organs. 
The action of the parasite on the host may be of the most varied 
nature. Some are harmless; others, such as the worms, vary greatly, 
passing from the harmless Trichuris just mentioned to the Anchylos- 
toma or Bothriocephalus which may incite fatal anemia by their poisons. 
Some act by invasion of the body, as the Trichinella; others act destruc- 
tively on specific cells, as the malaria plasmodium on the red corpuscles; 
130 ANIMAL PARASITES 
131 
others, by their general invasion of the organism and the toxic products 
which they give off, set up processes often leading to a series of apparent.t 
independent diseases, the best example being the Treponema, whose 
relationship to paresis and tabes has but recently been established. 
Still others, while relatively harmless may, as Ascaris, cause death by 
mechanical means, the invasion of the trachea inducing suffocation, or 
that of the bile-ducts setting up a serious and sometimes a fatal train of 
lesions. 
The action of the host on the parasite is of great biological interest. 
Unquestionably many human parasites originally infested animals and 
have only comparatively recently invaded man. Thus, there are many 
instances of incidental or facultative parasites, frequent in animals and 
occasional in man. The Balantidium coli is frequent in swine and rare 
in man; the same is true of the Dipylidium caninum, a dog tapeworm. 
Many of the worms have closely related forms found in fresh water which 
are not at present parasitic, though the possibility of their becoming so 
awaits only a suitable host. 
The influence of the host is also shown in the fact that many of the 
most highly adapted forms show evidence of devolutionary processes. 
The Tcenia saginata of the human intestine is unsuited for any situation 
except that in which it is now found. The suckers of the scolex which 
retains the worm in the intestine, and the highly developed hermaphro- 
ditic sexual apparatus admirably adapted to prolong the existence of the 
race by the production of enormous numbers of ova, are practically all 
that is left of what were at one time the complex organs of a highly de- 
veloped worm. Similar adaptation by atrophy is seen in Linguatula, 
related to the spiders, but because of its simple tape-like structure long 
considered to be a worm, as shown by its now abandoned name, Tcenia 
rhinaria. Even the ectoparasites show similar degenerations. The rudi- 
mentary wings of the bedbug are succeeded in the next downward phase 
by the wingless lice, all need for such organs having ceased long since. 
Finally, the ingenious mechanisms for propagation of the species by alter- 
nations of generations, passing from man through the lower animals, or 
in case of the Tcenia echinococcus, from the dog through man, show the 
most remarkable adaptations, doubtless requiring long periods of time. 
Some of these have lost their original significance as in Trichinella, for 
in this instance, where the active parasite is the embryo and not the 
parent worm, the encystment in human muscle serves no useful purpose 
in propagating the race, the normal host of which is the sewer rat. 
The effects of parasitism depend, therefore, to a certain extent upon 
the mutual relationship between the parasite and the host. The least 
perfectly adapted parasites are the ones which are apt to cause destruc- 
tion of the host and thereby, so to speak, defeat their own ends. Good 
examples of this are some of the fatal bacterial diseases, which by destroy- 
ing the life of the person in whom they develop check their own distribu- 
tion to other individuals. Virulence, therefore, may be synonymous 
with lack of adaptation. At the other end of the scale, are found examples 
of what is called symbiosis, in which the parasite and the host live ami- 132 
ANIMAL PARASITES 
cably together, neither causing damage to the other. An example of 
this is the occurrence of the colon bacillus in the human intestine, or, in 
the case of ectoparasites, of some of the lice which commonly infest 
birds; these do not suck the blood but eat only the dried epidermal 
scales shed by the skin and rarely affect the health of the carrier. A 
similar symbiosis may occur even in exceptional individuals who are not 
susceptible to a highly virulent parasite; for example, the frequently 
noted "typhoid carriers." In such cases the typhoid bacillus does not 
damage the host, in whose intestinal tract it may flourish for years. 
The limitations in space prevent the consideration of more than a 
small fraction of the animal parasites. For example, there are at least 
sixty nematode worms which occur in man, but only eight of these can 
be even mentioned. The student, therefore, is referred for details con- 
cerning the rarer parasites and technical methods to the larger works on 
the subject1 which also contain much interesting biological lore. 
Protozoa. 
General Characters of the Protozoa.-The protozoa are, with few 
exceptions, unicellular animal organisms of a primitive type, reproducing 
by division, by budding, and by spore formation. Some are very minute, 
others many millimeters in diameter. Some of them seem to lie between 
and to link the two great divisions of living beings somewhat arbitrarily 
established-the animals and the plants. 
While some of the protozoa are relatively simple in structure, others 
are extremely complex. The life cycle of some forms, also, is simple, 
while others, passing through sexual and asexual phases, present at 
different periods the greatest diversity in form and function. 
Some protozoa maintain an independent existence, others are para- 
sitic for men and animals. Among the parasitic forms are important 
groups which require residence in the body of more than one animal 
species for the completion of their life cycle. Many of the protozoa 
possess organs of locomotion, pseudopodia, flagella, or cilia. 
Our knowledge of the protozoa parasitic in man is of recent date, 
but is accumulating with great rapidity especially as regards tropical 
forms. Many forms are so difficult to study and to classify that for 
the moment, in numerous instances, conjecture and a balancing of 
probabilities and analogies are made to do duty in lieu of facts. 
Although not yet proved, it is widely believed that some, if not all, of 
the exanthemata, yellow fever, trachoma, molluscum contagiosum, and 
it may be hydrophobia, are incited by some form of parasitic protozoa 
belonging to the subgroup, Chlamydozoa. 
Modes of Transmission of Protozoan Parasites.-Some forms of pro- 
tozoa are transmitted by contact, as certain trypanosomes and the 
syphilis organism; others are ingested with food and drink. 
1 Mense, C., Handbuch d. Tropenkrankheiten, 2d ed., Leipzig, 1913; Stiles, C. W., New York Med- 
Jour., 1903, Ixxviii, 877; Brumpt, Precis de parasitologic, 2d ed., Paris, 1913; Neumann and Mayer 
Wichtige tierische Parasiten und ihrer Ubertrager, Munich, 1914; F antham, Stephens, and Theobald, 
Animal Parasites of Man, London, 1916. 133 
ANIMAL PARASITES 
Congenital transmission of the syphilis organism is of frequent 
occurrence. 
So confident are many observers that smallpox and scarlatina are 
incited by protozoan parasites, presumably by such as in the develop- 
ment of their life cycle form minute spores, that they venture to assume 
that in these diseases, at least, the infective agent may be air-borne in 
floating dust. 
Finally, in many instances, infection takes place through trans- 
mission by intermediate hosts. This occurs in malaria and yellow fever, 
and with certain trypanosomes and sporozoa. In the transmission of 
the malarial organism by the mosquito and in the case of some trypano- 
somes, important phases in the life cycle of the parasite take place in the 
body of the intermediate host. Other insects-lice, ticks, bedbugs, 
and leeches-act as intermediaries. 
The Effects of Protozoan Parasites upon their host are in many cases 
obvious, in many quite obscure. We shall consider some of these in the 
brief review of species which follows. 
Cultivation of Protozoa.-It has been found practicable to cultivate 
on artificial media, through a few generations at least, some forms of 
protozoa-amebas, trypanosomes, and the malarial parasite; but the 
knowledge thus far derived from such artificial cultivation is scanty. 
The scope of this book permits only a very limited consideration of the 
most significant forms of protozoa which are related to human pathology.1 
I. Rhizopoda. 
The protozoa of this division are usually of simple structure, char- 
acterized by motile organs in the form of pseudopodia. Reproduction is 
by division and by spores. 
Entamoeba histolytica (Amoeba dysenterise) is of considerable path- 
ologic importance. Councilman and Lafleur2 in 1891 first definitely 
established the significance of this protozoan parasite which they called 
Amoeba dysenterice, a name now superseded by Entamoeba histolytica of 
Schaudinn. 
It has been repeatedly found, most frequently in the tropics, in acute 
and chronic dysentery, in the intestinal contents, at the bottom of the 
intestinal ulcers, and in the secondary abscesses, especially of the liver, 
which may accompany ulcerative colitis, and is believed to be the in- 
citing factor, in some cases, in both the primary ulcerative colitis and 
its complicating abscesses (see page 768). 
This ameba (Fig. 78) is a spheroidal cell, from five to ten times 
the diameter of a red blood-cell, with granular protoplasm and a vesicular 
1 The best presentation of our present knowledge of protozoa is contained in Doflein, Lehrbuch d. 
Protozoenkunde, 3d ed., Jena, 1911, which includes an extensive and well-classified bibliography. 
Calkins, Protozoology, New York, 1910, is a readable epitome of the subject; and Park and Williams, 
Pathogenic Microorganisms, 7th ed., New York, 1917, contains a great deal of fundamental informa- 
tion on pathogenic forms. See also Prowazek, S., Handbuch d. path. Protozoen, Leipzig, 1912. 
2 Councilman and Lafleur, Johns Hopkins Hosp. Rep., 1891, ii, 395. 134 
ANIMAL PARASITES 
nucleus. It often contains larger and smaller vacuoles, bacteria, and 
phagocyted red corpuscles. Frequently, especially when the ameba is 
active, a portion of the protoplasm appears almost homogeneous-ecto- 
sarc-while the rest-endosarc-is granular. When moving it assumes 
various forms, thrusting out and withdrawing nearly homogeneous 
pseudopodia. It may also change its shape without progressive move- 
ment. In chronic or convalescent cases of amebic dysentery, when the 
feces have become formed, there may be found, in addition to the vege- 
tative forms, the encysted or generative stage. These are globular, 
yellow masses with a thick wall and from two to sixteen nuclear masses. 
Chromidial masses are often present, distinct from the nuclei. 
The parasite occurs in acute and chronic dysentery, frequently in 
the United States and Egypt, and occasionally in Russia, India, Panama, 
and the Philippines.1 It is capable of making its way between the 
epithelial cells of the gut, usually 
of the large intestine, and pene- 
trating to the submucosa. 
There it causes necrosis of the 
tissues with the formation of an 
abscess which breaks through 
the mucosa and discharges into 
the gut lumen, thus forming the 
characteristic amebic ulcer with 
overhanging walls. Abscess of 
the liver is often secondary to 
the intestinal lesion; abscesses in 
the lung are not infrequent; 
those in the brain and spleen 
are very rare. 
The organism has been arti- 
ficially cultivated,2 but only in symbiosis with bacteria. Animal inocu- 
lations are easily made, especially in young cats, with the production of 
an acute colitis. 
It is now generally acknowledged that the Entamoeba tetragena, 
described by Viereck, is identical with the Entamoeba histolytica, though 
the matter is still under discussion.3 
Other species of ameba have been found in the human mouth, intes- 
tines, and bladder, but are apparently not pathogenic. The Entamoeba 
coli is very frequently present in health and in intestinal disorders other 
than dysenteric.4 The coli type is differentiated from the histolytica by 
the lack of distinction between ectosarc and endosarc, by the more highly 
refractile and central nucleus, by absence of phagocyted red cells, and 
by the greater frequence of large encysted forms without chromidial 
Fig. 78.-Entamceba Histolytica. 
From the intestinal wall near an ulcer in amebic colitis. 
1 For full description, see Dobell, C., Amcbse Living in Man, London, 1919; Dobell, C., and O'Connor, 
F. W., The Intestinal Protozoa of Man, New York, 1921. 
2 Musgrave and Clegg, Bureau of Govt. Labt., Dept, of the Interior, Biol. Lab., No. 18, 1904. 
5 Craig, C. F., Arch. Int. Med., 1914, xiii, 917. 
* Craig, C. F., Jour. Infect. Dis., 1908, v, 324. ANIMAL PARASITES 
135 
masses. The type found in the mouth is supposed to be connected with 
peridental inflammation in the form of Riggs' disease.1 
There is reason to believe that amebas are acquired through drinking- 
water and uncooked foods. 
II. Mastigophora. 
These organisms are of definite or changeable shape, with or without 
a membrane. They are characterized by the possession of one or moz^ 
Fig. 79.-Trypanosoma Brucei. 
The protozoan parasite of the tsetse-fly disease of Africa. The two upper parasites show the dot-like 
blepharoplasts at their blunt posterior extremities. 
undulating or vibratile processes or flagella. Some forms seem to be 
closely related to the bacteria. 
Trypanosomes.-Among the flagellated protozoa the trypanosomes 
are of much significance, occurring as free-swimming parasites in the 
blood of both cold- and warm-blooded animals-mammals, birds, rep- 
tiles-and in the intestines of certain blood-sucking insects-flies, 
mosquitoes. 
1 Bass, C. C., and Johns, F. M., Alveodental Pyorrhea, Philadelphia, 1915; also Jour. Am. Meet 
Assn., 1915, Ixiv, 553. 136 
ANIMAL PARASITES 
Trypanosomes are elongated, and usually pointed, and may have one 
or two flagellae and an undulating membrane at the side attached to the 
flagella (Fig. 79). The membrane is often attached in folds or undula- 
tions so that the movement of the parasite in swimming is somewhat 
augur-like. There are two nuclei: one, large and near the center of the 
organism, is the trophic nucleus; the other, small and often rod-like, is 
situated in the posterior portion of the organism at the termination of the 
flagellum; this is the blepharoplast or kinetic nucleus. The flagellum 
forms an edge to the undulating membrane. Sometimes a small granule 
is situated at the origin of the flagellum; this is called the basal granule 
and is considered by some observers to act as the centrosome of the kinetic 
nucleus. The organisms divide by fission, which process is preceded by 
division of both nuclei. Small oval bodies without flagella may be found 
in the internal organs. 
In many instances the trypanosomes seem to be of no special sig- 
nificance to the host, but in several of the lower animals and in man 
some species are markedly pathogenic. 
Trypanosomes are common in wild rats in all countries. The species 
infesting these animals, Trypanosoma lewisi, can be readily transmitted 
with the blood to a fresh animal by injection and does not appear to inter- 
fere with the well-being of the rats. A certain immunity to subsequent 
injections seems to be conferred by the presence of these parasites in the 
blood of the rat, from which they usually disappear in two or three 
months. 
Novy and McNeal first successfully cultivated the Tr. lewisi and 
other forms on nutrient agar containing varying amounts of defibrinated 
or laked rabbit blood. 
Pathogenic Trypanosomes. 
Tsetse-fly Disease.-Among the more important of the trypanosome 
infections we may note Nagana or the tsetse-fly disease (Fig. 79). This 
infectious disease of cattle, horses, and mules occurring in Africa, espe- 
cially in Zululand, has long been known and was at one time of great 
economic importance. It is characterized by fever, emaciation, edema, 
etc. 
In 1894 Bruce discovered a trypanosome-Trypanosoma brucei-in 
the blood of the affected animals. He also found that the parasite was 
conveyed to healthy animals through the bite of a tsetse-fly of that 
country-Glossina morsitans-which had shortly before bitten an in- 
fected animal. The original source of the parasite was found to be the 
wild animals of the region, which did not appear to be affected by it. 
There is still some doubt as to the differentiation of this form from 
Trypanosoma gambiense and Trypanosoma rhodisiense.1 
Surra.-This disease of horses and cattle, occurring in India, and 
possibly in other tropical countries, has been shown to be due to a 
1 Bruce, Proc. Roy. Soc., Ser B., 1914, Ixxxvii, 526. ANIMAL PARASITES 
137 
trypanosome, Trypanosoma evansi, which is conveyed from infected to 
healthy animals by a fly. 
Several other diseases of wild and domestic animals are known to be 
incited by trypanosomes. 
Sleeping Sickness.-The "sleeping sickness" is very common and 
fatal among the negroes of equatorial Africa, assuming in the Congo 
region the character of a veritable pestilence whose victims number 
hundreds of thousands. White men are not exempt. The disease, 
still rapidly extending, is characterized by lethargy, debility, emaciation, 
drowsiness, coma, and death. The cerebral lesions resemble those of 
syphilis.1 The disease is incited by a trypanosome, Trypanosoma gam- 
biense, which also is conveyed by a tsetse-fly, Glossina palpalis. The 
Demonstrated by the India ink-method (see p. 311). 
Fig. 80.-Treponema Pallidum. 
lesions noted are congestion of the meninges with fluid exudate and en- 
largement of the lymph-nodes, spleen, and liver.2 
A second form, Trypanosoma rhodesiense,2 transmitted by Glossina 
morsitans, has been described as also causing an acute form of sleeping 
sickness, but its distinction from Trypanosoma gambiense is not yet 
certain.4 
Chagas has also described Trypanosoma cruzi as occurring in Brazil 
and transmitted by the bite of an insect, Conorhinus megistus. This 
parasite causes an acute meningoencephalitis, often fatal, and also an 
1 Spielmeyer, Lewandowsky, Handb. d. Neurologie, Berlin, 1912, iii, 538. 
2 For a summary of trypanosomes and diseases incited by them, see Novy, F. G., Jour. Am. Med. 
Assn., 1917, xlviii, 1; Laveran and Mesnil, Trypanosomes and Trypanosomiases, Trans, by Nabarro, 
Chicago, 1907, or 2d French ed., 1912. Also Mayer, M., Kolle and Wassermann, Handbuch d. path. 
Mikroorganismen, 2d ed., 1913, vii, 32P. For a study of trypanosomiasis with special reference 
to service in the Philippine Islands, see Musgrave and Clegg, Bureau of Govt. Labt., Dept, of the In- 
terior, Biol. Lab., No. 5, 1903. For a study of chemical therapy, see Terry, B. T„ Arch. Int. Med., 
1909, iii. 98. 
3 Stephens and Fant ham, Ann. Trop. Med. and Parasit., 1910, iv, 343. 
4 See, for some rather destructive criticism for using relative measurements as a basis for separating 
this parasite from Trypanosoma gambiense, Pearson, K., Biometrika, 1914, x, part I, 85. 138 
ANIMAL PARASITES 
acute thyroiditis with swelling of the superficial nodes. If the disease 
passes into a chronic type it resembles cretinism, often accompanied by 
paralysis and cerebral defects. 
Spirochaeta. 
Among the spirally curved bacteria it has been customary to recog- 
nize a genus called Spirillum, the members of which have a rigid spirally 
curved body, and a genus called Spirochaeta, in which the organisms 
are also spirally curved but are described as flexible. These genera have 
been considered to embrace closely related bacterial forms. 
The discovery by Schaudinn of Spirochaeta, now called Treponema, 
pallidum (Fig. 80), in the lesions of syphilis has given rise to many 
critical studies of spirochetes, and while we cannot enter here into the 
details of the matter, it has finally become probable, if not entirely 
proved, that the spirochetes are protozoa and not bacteria or at least 
that the protozoan characters are predominant in them.1 
The fact that the synthetical chemical compound of arsenic, dioxy- 
diamido-arsenobenzol, popularly known as salvarsan, has a specific de- 
structive action on the life, not only of the spirochetes of syphilis and 
of relapsing fever, but of trypanosomes as well, would indicate a rela- 
tionship between the spirochetes and the protozoa which tends to con- 
firm the evidence from morphology. 
The occurrence of spirochetes in tumors is of no pathological 
significance. 
Treponema pallidum (Spirochaeta pallida').-This organism, now be- 
lieved to be a protozoon and the inciting agent in syphilis, is described 
in connection with the lesions of that disease (page 308). 
A similar organism, Treponema pertenue (Spirochaeta pertenuis), has 
been found in yaws (page 326). 
Spirochaeta obermeieri (Spirochaeta recurrentis) and Spirochaeta duttoni, 
the protozoan organisms which are the cause of relapsing fever, are 
described in connection with that disease (page 324). 
In a disease known as rat-bite fever,2 there has been found a spiro- 
chete, called by the discoverers Spirochaeta morsus muris. The organ- 
ism is thicker than the Treponema pallidum, and usually has from 1.5 
to 6 bends at intervals of about 1 micron, with flagella at both ends. 
It is gram-negative, but stains easily with aniline dyes and silver, and can 
be demonstrated in the blood, skin, and lymph-nodes of persons suffering 
from the disease. It is present in about 3 per cent, of house rats and in- 
fects also white rats, mice, and monkeys. 
In a case of a similar disease following a rat bite, the Streptothrix 
muris ratti of Schottmiiller has been isolated;3 so that it appears probable 
that more than one organism can induce the uncharacteristic group of 
symptoms observed after rat bites. 
1 For a discussion of this subject, see Calkins, Protozoology, New York, 1910, p. 231; also Arnheim, 
Ztschr. f. Hyg., 1914, Ixxvi, 407. 
2 Futaki, Takaki, Taniguchi, and Osumi, Jour. Exper. Med., 1916, xxiii, 249; 1917, xxv, 33 (bibl.). 
* SchottmiUler, H., Dermat. Wchnschr., 1914, Iviii, Suppl. 77; Blake, F. G., Jour. Exper. Med., 
1916, xxiii, 39 (bibl.). 139 
ANIMAL PARASITES 
Another spirochete, Spirochaeta icterohcemorrhagice, is considered as 
causing the type of acute infectious jaundice known as Weil's disease.1 
This organism is found in wild rats, and measures from 3 to 4 or even 
40 micra, with about two coils to the micron. It is a facultative anaerobe, 
growing fairly well on ascitic fluid to which has been added a piece of 
sterile kidney,2 a method generally useful for the spirochete.3 Similar 
organisms have been found in persons suffering from acute jaundice in 
Japan, France, Belgium, and America. There are no characteristic 
lesions, though the liver may be the site of a catarrhal cholangitis or 
even of an extreme alteration resembling yellow atrophy. The kidney 
shows parenchymatous changes or a considerable tubular nephritis and 
contains large numbers of spirochetes which are, in consequence, abun- 
dant in the urine. They are not abundant in the spleen or lymph-nodes, 
though both are enlarged. The disease is not often fatal. 
A large number of cases of obscure infections, some with and others 
without jaundice, have been seen among the soldiers in the trenches 
during the present war. Spirochetes are usually abundant in the urine in 
these cases, and in many instances have been identified as Spirochaeta 
icterohcemorrhagice.^ Whether spirochetes of other species act as in- 
fectious agents in some of the fevers without jaundice has not yet been 
determined. 
Leishmania.-There are three diseases due to parasites of this genus, 
which is more closely allied to the genus Herpetomonas than to 
Trypanosoma. 
Leishmania donovani5 is the inciting agent of Indian kala-azar or 
dum-dum fever, a disease characterized by fever, emaciation, splenic 
tumor, anemia, and leucopenia. It occurs at all ages and is usually fatal. 
Cases have been observed in India, China, Syria, and the Soudan. The 
organism is rarely found in the blood, but is very abundant in the splenic 
pulp and in the endothelial cells of the capillaries of other organs. It does 
not invade the red cells, but is frequently phagocyted by the leucocytes. 
It is a small oval organism, measuring 2 by 3 microns, and having the 
nucleus and blepharoplast of the flagellates. It can be cultivated in 
artificial media. The extra-human host and transmitter of the disease 
is probably the bedbug. 
Leishmania tropica6 produces a disease known as Delhi boil, an indo- 
lent ulcerative lesion often confined to the exposed portions of the body. 
The disease is self-limited and immunity follows. The parasite is abun- 
dant in the tissues about the ulcerated area and in morphology resembles 
Leishmania donovani. It is infrequent in the blood. The disease occurs 
in India, Arabia, and the Mediterranean littoral. A very similar type, 
called uta, is found in South America.7 
Leishmania infantum8 causes a disease in children and dogs resembling 
1 Inada, Ido, Hoki, Kaneko, and Ito, Jour. Exper. Med., 1916, xxiii, 377; Noguchi, H., Jour. Exper. 
Med., 1917, xxv, 755 (bibl.). 
2 Ito and Matsuzaki, Jour. Exper. Med., 1916, xxiii, 557. 
3 Noguchi, H., Jour. Exper. Med., 1912, xvi, 199; Knoepfelmacher, Ergebn. d. inn. Med., 1910, v, 205. 
4 Dawson, Hume, and Bedson, Brit. Med. Jour., 1917, ii, 345 (bibl.). 
6 Leishman, Brit. Med. Jour., 1903, i, 1252; and Donovan, C., ibid., 1903, ii, 79; Lancet, 1904, ii, 744. 
3 Wright, J. H., Jour. Med. Research, 1903-04, N. S. v, 472. 
7 Strong, R. P., and others, Jour. Am. Med. Assn., 1913, lxi, 1713. 
8 Nicolle, Arch. Inst. Pasteur de Tunis, 1908, i, 26. 140 
ANIMAL PARASITES 
kala-azar and characterized by fever, anemia, leucopenia, enlargement 
of the spleen and liver, edema, and subcutaneous and submucous hemor- 
rhages. It is generally fatal. The parasites are rare in the blood, but 
can be easily demonstrated in fluid from splenic puncture. The disease 
is most frequent along the Mediterranean littoral. 
The parasite resembles Leishmania donovani in 
morphology, and differs from it but little in its 
biological characters. The dog flea is supposed to 
transmit it. 
All these species can be cultivated on artificial 
media.1 
Trichomonas vaginalis has an oval or pear-shaped body 
from 0.015 to 0.025 mm. long, with a cluster of flagella at 
one end and an undulating membrane, frequently mistaken 
for cilia, upon the side (Fig. 81). It is of occasional occur- 
rence in vaginal exudates. The possibility of mistaking the organism for human 
spermatozoa should be borne in mind in medicolegal examinations, although to an 
observer familiar with either structure such a mistake could hardly occur. 
Some forms of Trichomonas have been found in the urine of man, in the intestines, 
and in the sputum.2 
Lamblia intestinalis is a pear-shaped flagellate with eight flagella, which is found 
in its vegetative form in the small intestine, but more usually encysted in formed feces. 
It is thought to be responsible for certain tropical diarrheas, in which condition the 
flagellate forms are found in the fluid stools. 
Cercomonas hominis, an oval parasite, 10 to 12 micra long, with a single flagellum, 
has been found in diarrheic stools. It is related to trypanosoma. In all probability 
no one of these flagellates is very pathogenic for man. 
Fig. 81.-Trichomonas 
Vaginalis. 
After Dock. 
III. Ciliata (Infusoria). 
The infusoria are the most highly differentiated of the protozoa. 
They have numerous motor appendages or cilia, which may persist 
through life or in some forms be replaced in 
the adult stage by suctoria. They reproduce 
chiefly by fission or budding. Among the 
ciliated infusoria, few if any are pathogenic 
in man. The Balantidium coli (Fig. 82) is 
an ovoidal organism from 0.06 to 0.1 mm. long; 
it is a common parasite of swine in some re- 
gions, and has been found in the intestinal 
tract of man under conditions which indicated 
its pathogenic significance as the inciting agent 
in the causation of acute and chronic dysen- 
tery, often with ulceration of the bowel. 
The parasite is not infrequently present in the stools of inhabitants of 
Northern Europe, China, the Philippines, and North and South America.3 
Fig. 82.-Balantidium Coli. 
After Braun. 
1 For full details concerning leishmaniases, see Laveran, I.es leishmanioses, Paris, 1917. For details 
of anemia caused by these parasites, see page 545. 
2 For original studies of Trichomonas with historical summary and bibliography, see Dock, G., Am. 
Jour. Med. Sc., 1896, cxi, 1. See also Lynch, K. M., Jour. Parasitol., 1916, iii, 28. 
* Walker, Philippine Jour. Sc., 1913, Sec. B, viii, 333; Behrenroth, Ztschr. f. klin. Med., 1903, xix, 
321; Strong and Musgrave, Bull. Johns Hopkins Hosp., 1901, xii, 31; Askanazy, Verhandl. d. deutsch' 
path. Gesellsch., 1903, v, 224; and De Buyc, L. R., Am. Jour. Dis. Child., 1918, xvi, 123. ANIMAL PARASITES 
141 
Chlamydozoa.-This name was proposed in 1907 by Prowazek for a 
group of hypothetical parasites supposed to be the inciting agents of 
hydrophobia (page 327), vaccinia and variola (page 337), trachoma 
(page 340), and measles (page 342), all of which belong to the class of 
diseases thought to be due to filterable viruses. The organisms are para- 
sites of epiblastic tissues; that is, they are found only in cells of epidermal, 
conjunctival, and nerve tissue. While at one time thought to be merely 
cell-inclusions or degeneration products, these bodies are now believed 
to be true parasitic organisms. Some of them have, in fact, been 
cultivated.1 
The parasites will be discussed in connection with the specific lesions 
of the diseases enumerated above. 
Molluscum Contagiosum.-This is an epithelial hyperplasia with 
characteristic morphology, which is due, according to some authors2 to 
an organism belonging in the group of Chlamydozoa. The virus is 
probably a filterable one, as the organism described is very minute. 
The disease is unquestionably infectious, and occurs in epidemics; the 
period of incubation varies from fourteen days to four months. The 
lesions consist of small elevated nodules of thickened epithelium contain- 
ing the characteristic molluscum bodies,3 which are, in all probability, 
altered and degenerated epithelial cells. There is usually a small opening 
on the surface of the skin through which a cheesy material containing a 
large number of these cells can be squeezed. 
IV. Sporozoa. 
The sporozoa are all parasitic, living at some period of their life 
cycle in the cells of their host, and are especially characterized by their 
reproduction through encystment and spore formation and absence of 
definite motile organs. Many forms of the organisms, especially the 
spores, are very minute and difficult of identification. 
The sporozoa are widely distributed, being found as parasites in 
nearly all classes of animals. They may invade the gastrointestinal 
canal and the kidney and their adnexa, the blood, muscle, connective 
tissue, and skin. While many of them appear to be harmless to their 
host, others may do serious damage by blocking the tissue spaces and 
thus, or in other ways, inducing necrosis, atrophy, or cell death. Some 
forms are wholly intracellular, others remain for only a part of their life 
cycle within single forms of cells, passing then to other cells or to the 
body cavities or to hosts of a different species. The life cycle of many 
forms is extremely complex. On account of their strict parasitism and 
the requirements in some instances of an interchange of hosts, precluding 
the methods of culture applicable to many of the lower organisms, the 
life history of many forms is still unknown or obscure. 
The classification of the Sporozoa is still tentative, but one may con- 
veniently recognize the following orders: 
1 Noguchi and Cohen, Jour. Exper. Med., 1913, xviii, 314. 
2 Lipschutz, Prowazek, Handbuch d. path. Protozoen, 1912, i, 219; Wile, U. J., and Kingery, L. B., 
Jour. Cutan. Dis., 1919, xxxvii, 431. 
3 Kromayer, E., Virchows Arch., 1893, cxxxii, 62. 142 
ANIMAL PARASITES 
1. Gregarinida.-These are round or elongated parasites, some of the 
higher forms presenting partitions in the cell with special development 
of one end for attachment. They are parasitic in certain cold-blooded 
animals, especially the invertebrates. The young stages only are in- 
tracellular, mature forms occurring in the body spaces. 
2. The Myxosporidia are parasitic in certain of the invertebrates, 
in fishes and batrachians. Epidemics among silk worms incited by a 
parasite of this class have occasioned serious 
losses. Many species are concerned in diseases 
of fish, in which they may cause extensive deep 
foci of necrosis and ulceration. 
3. Coccidiidea.-Organisms of this order are 
parasitic in certain of the invertebrates, in 
birds, reptiles, and mammals. They are round 
or oval, usually intracellular parasites having 
no free motile adult stage. They are most 
frequently found in the epithelium of the in- 
testine and liver. One of the most common forms in the mammalia is 
Coccidium oviforme (Elmer ia stiedoe) (Fig. 83) which is of frequent oc- 
currence in the intestine and liver of the rabbit, forming a part of the con- 
tents of yellowish, irregular shaped masses, resembling tumors, or in the 
form of cysts.1 
The parasites surround themselves with a capsule within which elon- 
gated sporozoites develop. This encapsulated form may be taken up 
by a new host in which the 
sporozoites are set free and 
enter the epithelial cells in 
which they again become en- 
capsulated. The occurrence 
of Coccidium oviforme has 
been recorded in the liver, 
kidney, intestine, and heart- 
muscle of man. 
Another smaller form, 
occurring in the intestinal 
epithelium of dogs, cats, and 
rabbits, has been found in 
two cases in a similar situa- 
tion in man. 
4. Sarcosporidia.-In this 
order of the Sporozoa the usually elongated slender early stage is found 
in between the muscle fibers and bundles of vertebrates-mouse, hog, and, 
in a few instances, in man. These are commonly known as the " tubes of 
Miescher" or "of Rainey" (Fig. 84). Reniform or falciform spores are 
developed. The adult forms are spheroidal or elongated. The life cycle 
is not well known.2 
Fig. 83.-Coccidium Oviforme. 
This shows the encapsulated 
form of the parasite, with the 
formation of spores. 
Fig. 84.-Sarcocystis Muris. 
'See Tyzzer, E. E., Jour. Med. Research, 1902, N. S. ii, 235. 
2 For a study of the production of sarcosporidia in the mouse, see Smith, Th., Tr. Assn. Am. Phys., 
1901, xvi, 576. ANIMAL PARASITES 
143 
5. H(Emosporidia.-1These parasites of the blood form a large group 
occurring in the corpuscles or plasma of vertebrates-amphibia, reptiles,1 
birds, and mammals. Some forms are among the most important of the 
protozoan parasites of man. They are of small size; the adult form is 
motile. One stage in the life cycle is passed in the blood of the verte- 
brate host; another in the body of some insect, as an intermediate host. 
Among the mammalian hemosporidia we may mention the hemato- 
zoon of malaria and the hematozoon of Texas fever. 
Malaria.-The characters of the malarial hematozoon, for which the 
mosquito acts as intermediate host, are described in detail on page 344. 
Texas Fever.-Texas fever (tick fever), a disease of cattle marked by 
fever, debility, and hemoglobinuria, occurs in many parts of the world- 
North and South America, Europe, and Africa. The hematozoon in- 
ducing Texas fever was discovered by Theobald Smith and Kilbourne2 
and is now called Babesia bigemina. In one stage it is a minute pyri- 
form organism occurring often in pairs in the red blood-cells of its host. 
Free forms have been found in the blood. While its life cycle has not 
been completely worked out, Smith and Kilbourne showed that a cattle 
tick acting as an intermediate host transmits the parasite through her 
eggs and larvae. It is through these young ticks that fresh cattle be- 
come infected.3 Other species of Babesia have been found in the dog 
in various countries; still others in horses and sheep. 
Methods of Study of the Protozoa. 
The protozoa may be studied in the living condition in the fluids in which they are 
found or they may be killed by a saturated sublimate solution and stained with iron 
hematoxylin. 
The movements of the Entamoeba histolytica in the feces or in the contents of 
abscesses, may be studied on the warm stage. Its morphology may be studied in 
tissue containing it, such as intestinal ulcers, abscesses, etc., which have been hardened 
and stained with either methylene blue or iron hematoxylin. 
The attempts to obtain pure cultures of certain forms of ameba and similar or 
allied forms of protozoa have been partially successful. The method by which Mc- 
Neal and Novy obtained pure culture of trypanosomes, namely, by the use of ordinary 
nutrient agar containing rabbit's blood, is of high promise in related forms of protozoa.4 
Metazoa. 
Among the multicellular parasites, the worms-the flat flukes and 
tapeworms as well as the round worms and a few insects-form the most 
important classes for our consideration. But for the details concerning 
these as well as the other larger parasites we must refer to special 
works on parasitology. 
It may be said in general that the metazoan parasites may be harm- 
ful to the structure or the function of the host, though the damage is 
1 For discussion of hemosporidia in American reptiles and batrachians, see Langmann, New York 
Med. .Tour., 1899, Ixix, 1. 
2 Smith, Bureau of Animal Industry, Bull. No. 1, 1893. 
3 For a summary of observations on Texas fever (hemoglobinuria of cattle) see Schilling, C., and 
Meyer, K. F., Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1913, vi, 481. 
4 For details of this method as well as a resume of the cultivation of protozoa, consult McNeal 
and Nmy, Contributions to Medical Research, Vaughan Anniversary Volume, 1903, p. 549. 144 
ANIMAL PARASITES 
often very slight,either by their local presence, occluding canals, obstruct- 
ing vessels, inducing local irritation, or structural damage; or by 'their 
movements about the body; or by the appropriation of food belonging to 
the host; or finally, by the setting free of deleterious metabolic products 
of their own manufacture. 
This toxic action of certain parasites is especially marked by the 
more or less pronounced eosinophilia present in a large proportion of 
patients who are the victims of invasion by parasitic worms.1 
The frequent anemia associated with the presence of metazoan 
parasites and the local injuries inflicted by them, especially on the mucous 
membranes, through which the body is made more vulnerable to second- 
ary bacterial invasion, are all of considerable importance. Some of 
these effects will be referred to in the following brief series of individual 
forms of metazoan parasites. 
Worms. 
TREMATODA (Flukes). 
These worms are small, flat, tongue-shaped, or leaf-like creatures, 
with an intestine and a discoidal structure on the under surface, by 
means of which they attach themselves. There are several genera 
and species found in man. Of these, Fasciola hepatica {Distomum 
hepaticum, liver fluke) is a frequent and usually fatal parasite of sheep 
(Fig. 85); about 28 cases of infection in man have been observed, usually 
without symptoms, though in severe cases enlargement of the liver and 
Fig. 85.-Fasciola Hepatica. 
About natural size. 
jaundice have been noted. Fasciolopsis buski (Distomum buski) is a 
larger parasite, measuring 70 mm. as a maximum. Its normal site is 
the intestine of the pig; but it occurs frequently in the intestine of man 
in India, Siam, and China. Paragonimus ringeri (Distoma pulmonale) 
and its related form Paragonimus westermanni are frequently found in the 
lungs, pleurae, and bronchi of the Chinese and Japanese, inciting serious 
acute and chronic inflammatory lesions. The eggs are found in the 
sputum. 
Opisthorchis felineus (Distoma lanceolatum) is a small parasite, 8 to 11 
mm. in length, and 1.5 to 2 mm. in diameter, which normally inhabits 
the gall-bladder and bile-ducts of the domestic cat. In some places in 
Siberia it is the most frequent parasite of man, occurring in some 6 per 
cent, of autopsies. Elsewhere the parasite is extremely rare. 
Clonorchis sinensis (Distoma siense) is a parasite of local distribution 
in certain parts of China. In man the parasite is found in the bile-ducts. 
'See, for a study of the influence of parasites on the host, Ward, Science, 1907, xxv, 201; consult 
also Shipley and Fearnsides, Economic Biol. Jour., 1906, i, 41. ANIMAL PARASITES 
145 
Schistosoma haematobium {Distoma haematobium, Bilharzia hoematobia) 
is a Cylindrical worm with distinct sexes. The female, which measures 
about 20 mm. in length and 0.25 mm. in diameter, is clasped in a long 
groove on the ventral surface of the male, which measures 12 to 14 mm. 
long and about 0.5 mm. in diameter. The parasites occur in the veins 
of the portal system. The eggs, which are responsible for many of the 
pathological conditions induced by the parasites, are ovoid, chiefly with 
terminal spines, and are found abundantly in the liver and in the stools 
and urine. Serious inflammatory lesions of the bladder and rectum 
Fig. 86.-Schistosoma Japonicum in the Liveb, 
are frequently caused by the irritation of the eggs, and may result in 
the production of carcinoma in these regions. The parasites are widely 
distributed in Africa and are especially frequent in Egypt.1 Another 
species, Schistosoma mansoni, occurring in the Congo, the West Indies, 
and Brazil, differs slightly from the previous parasite, and is thought to 
form eggs with lateral spines only. Schistosoma japonicum is a parasite 
differing but slightly from those just described and occurring in Japan, 
China, and the Philippines. It is found in domestic animals and in man. 
The lesions are chiefly of the intestine and liver, the bladder remaining 
free. The presence of the parasite in the liver may incite extensive 
cirrhosis due to the irritation (Fig. 86). 
1 For description of parasite and report of case seen in New York, see Short, J. JJour. Amer. Med. 
Assn., 1919, Ixxii, 630. 146 
ANIMAL PARASITES 
CESTODA (Tapeworms). 
These important worms consist, in the mature state, of more or less 
rectangular or elongated flat segments, each 
one representing a single individual, arranged 
in a linear series to form a colony. At one end 
of this, called the head, is a variously formed 
structure for the attachment of the colony to 
its host. The neck and head are called the 
scolex, while the segments are called proglot- 
tides. These worms have neither mouth nor 
alimentary canal. They are hermaphrodites, 
the sexes being united in the proglottides. 
The head and neck (scolex) may exist as an 
immature form in various tissues and organs 
where they are encysted, and are often called 
cysticercus. 
Taenia solium is of infrequent occurrence 
in man. It may be several meters in length, 
and may be coiled up or stretched out in the 
small intestines. Several worms may be in 
the gut at one time. The head, about the 
size of a pin's head (Fig. 87), has a projecting 
proboscis or rostellum, around which is ar- 
ranged a double row of horny booklets. 
Below these are four sucking discs at the 
sides of the head. The booklets of the anterior row are larger than 
those in the posterior row, and 
are from 0.16 to 0.18 mm. long. 
The proglottides, when fully de- 
veloped, are from 10 to 12 mm. 
long and from 5 to 6 mm. wide, 
but those nearest the head are 
much shorter and immature. 
The eggs of Taenia solium are 
ovoidal structures, about 0.03 
mm. in diameter. The embryo 
of this worm is most commonly 
seen in the muscles of the pig as 
an encysted scolex, commonly 
called a "measle." It occasion- 
ally occurs in man in the muscles, 
brain, eye, etc., and is called 
Cysticercus celluloses. It is usu- 
ally about the size of a pea, but 
may be as large as a pigeon's 
egg, and is surrounded by a 
connective-tissue capsule. 
Infection with the worm occurs in the human subject from the inges- 
Fig. 87.-Head of T.®nia 
Solium. 
X about 40. 
Fig. 88.-T/enia Saginata. Head and 
Proglottides. 
A, head X about 15. B, mature proglottid, 
showing generative apparatus. C, head and frag- 
ments of immature proglottides, showing gradual 
tapering of the neck. Natural size, 147 
ANIMAL PARASITES 
tion of insufficiently cooked "measly" pork, or, in the case of Cysti- 
cercus cellulosae, from the ingestion of the eggs, which may, in a variety 
of ways in uncleanly persons, get into the food. 
Tcenia saginata {Tcenia mediocanellata Leuckart).-The head of 
this species is somewhat cuboidal, with neither rostellum nor booklets, 
but with four sucking discs (Fig. 88). The segments are generally 
broader and shorter than in Taenia solium, and the worm is usually larger. 
In the embryonal form the scolex occurs as the Cysticercus tcenice medio- 
canellatce in the form of small cysts in the muscles of cattle, from the 
eating of which in the uncooked condition the infection occurs. This is 
the most common tapeworm in the United States. 
Tcenia echinococcus.-This worm in the mature condition forms a 
short, small colony inhabiting the intestine of the dog. The head is about 
0.3 mm. in diameter and has a double row of booklets around the rostel- 
lum. The proglottides are three or four in number, the last being the 
larger. The entire colony is not more than 4 to 5 mm. in length. The 
significance of this parasite in human pathology depends upon the cysts, 
called hydatids, which it forms, in the immature or cysticercus stage, in 
various parts of the body. Intimate association with dogs favors the 
acquirement of this parasite. When the eggs of the mature worm get 
into the intestinal canal of man they undergo partial development and 
find their way into the tissues and organs, most frequently into the liver. 
Here cysts are formed which become encapsulated by a connective- 
tissue membrane produced by the inflammatory reaction of the organ. 
The cyst wall of the parasite is formed of two layers-an outer, finely 
lamellated layer called the cuticula (Fig. 89), and an inner, granular 
layer containing muscle fibers and blood-vessels, called the parenchyma- 
tous layer. Inside of the primary cyst, secondary cysts sometimes form, 
called daughter cysts; and within the latter, tertiary cysts, called grand- 
daughter cysts, may develop. On the inner surface of the cysts, either 
primary, secondary, or tertiary, the scolices or heads of the immature 
worm are formed. These de- 
velop in the walls of the pedicu- 
lated vesicles called brood cap- 
sules. The walls of these vesicles 
have a lamellated cuticula and 
a parenchymatous layer similar 
to those of the primary cysts. 
The scolices, of which there may 
be several in each brood cap- 
sule, are similar to the heads of 
the mature tapeworm. They 
are about 0.3 mm. in diameter, 
having a rostellum surrounded by a double row of booklets and four 
sucking discs (Fig. 90). At the posterior end of the scolex is a 
pedicle by which it is originally attached to the wall of the brood 
capsule. Little, lamellated concretions of lime salts are often present 
in the scolex. The anterior portion of the scolex, the rostellum, 
Fig. 89.-Cuticula of Echinococcus Cyst. 
Showing lamellated structure. 148 
booklets, and suckers, are often invaginated in the posterior portion. 
The scolices may be free inside of the brood capsules, or, owing to the 
rupture of the latter, they may be free in the cavity of the primary 
cysts. They may die and degenerate, forming a granular mass in which 
the booklets may be embedded, 
or the booklets may be free in 
the brood capsules or in the 
primary cysts. Sterile cysts are 
often found, that is, those in 
which neither brood capsules 
nor scolices are developed. 
The cysts contain, in addi- 
tion to the scolices, a clear, 
gelatinous fluid. This fluid may 
become turbid by admixture 
with disintegrated scolices or 
fragments of the parenchyma- 
tous layer, or it may contain 
fatty detritus, cholesterin crys- 
tals, and particles of lime salts. 
The fluid may be partially absorbed, leaving a thick, grumous material 
within the cysts, which may become calcified or converted into a stony 
mass. When the scolices are not found entire the diagnosis may be 
made by the discovery of the separate booklets (Fig. 91) or fragments of 
the characteristically lamellated cyst walls. The connective-tissue walls 
of the primary cysts may become fatty, or caseous, or calcified. 
Sometimes the secondary vesicles project outward instead of inward, 
forming a series of cysts outside of the primary one. This variety of 
development is sometimes seen in man, but is more common in the 
domestic animals. It is called A chinococcus scolecipariens or exogena. 
Another variety of echinococcus, 
called Echinococcus multilocularis, is 
almost always found in the liver, and 
appears to be the result of incomplete 
and disturbed development of the em- 
bryos or cysts. It consists of a congeries 
of irregular, usually small cysts (Fig. 
536, p. 841), surrounded by broad and 
narrow bands of connective tissue, and 
sometimes containing gelatinous fluid 
and scolices or booklets; but the latter 
structures are commonly absent or difficult of detection. The whole is 
often surrounded by a dense connective-tissue capsule which may be 
calcified. The entire mass often presents an alveolar structure and was 
formerly regarded as a tumor-alveolar cancer. The diagnosis may be 
established by the discovery of the booklets or scolices, or fragments of 
the lamellated cuticula. It is possible also to obtain complement fixa- 
ANIMAL PARASITES 
Fig. 90.-Scolices of Tenia Echinococcus. 
In one the rostellum is projected; in the others it 
is withdrawn. 
Fig. 91.-Hooki.ets from Scolex of 
T^nia Echinococcus. ANIMAL PARASITES 
149 
tion in the blood in echinococcus disease, using the wall of the cyst as 
antigen. This form of the parasite is rare in America. 
There are several other species of tapeworm occurring in man. 
Hymenolepis nana (Tcenia nano).-This species occurs in the form 
of small colonies, about 10 to 45 mm. in length. The rostellum is sur- 
rounded by a single row of booklets. It is frequently found in the in- 
testinal contents of Italian children, of the inmates of asylums for the 
insane, and of a considerable portion of the population of some of the 
Southern States.1 Hymenolepis diminuta (Tania flavopunctata), a 
species about which little is known, has been reported five times in 
America as occurring in the intestine of young children. 
Dipylidium caninum (Tania cucumerina).-This species occurs in 
colonies about 20 cm. long. The head is very small and spheroidal and 
has four rows of booklets. It is frequent in the small intestine in dogs 
and cats, and occurs occasionally in man. Its scolex inhabits the dog 
louse or flea, and infection may occur by the transference of the lice or 
the embryos of the parasite to the mouth, as the result of the filthy 
habit of kissing dogs and cats or permitting the face to be licked by them.2 
Bothriocephalus latus.-This, the largest of the human tapeworms, 
has very broad, quadrangular proglottides. The head is ovoidal and 
about 2 mm. long and 1 mm. broad. It has no proper sucking discs and 
no booklets, but by long grooves on either side of the head the animal 
attaches itself to its host. The neck is long and filiform. It occurs most 
frequently in Europe, particularly in the northern provinces, though a 
few cases have been reported from Norwegian settlers in Minnesota. 
The eggs undergo partial development in water, and the larvae are eaten 
by the Cyclops strenuus and Diaptomus gracilis;3 these are then taken up 
by the pike and eel-pout, and perhaps by other fresh-water fish, from the 
ingestion of whose flesh in an imperfectly cooked condition human in- 
fection occurs. The especial importance of this parasite lies in the severe, 
often fatal, anemia which occasionally accompanies its presence in the 
intestine. Two other species of Bothriocephalus have been described as 
of rare occurrence in man: Bothriocephalus cordatus in Greenland and 
Iceland and Bothriocephalus cristatus. 
NEMATODA (Round Worms). 
These worms are in general cylindrical, elongated, usually pointed 
at the ends, and sometimes filiform. The surface is sometimes smooth, 
sometimes irregularly beset with hairs and papillae, or possesses longi- 
tudinal elevated striae or transverse rings; but the body is not segmented. 
There is a mouth at the anterior portion, and a ventral anus near the 
posterior end. The intestine is straight. The sexes are in most forms 
distinct, the male being in general smaller than the female. 
1 Ransom, B. H., Tapeworms of the Genus Hymenolepis parasitic in man, Bull. 18, Hyg. Lab., 
U. S. P. H. S., 1904; Stiles and Garrison, Prevalence of intestinal worms in man, Bull. 28, U. S. P. H. S., 
1906. For a study of the occurrence of the worm in children, see Schloss, O. M., Arch. Pediat., 1910, 
xxvii, 100. 
2Blanchard, Arch. d. Parasitologic, 1907, xi, 439. 
8 Janicki and Rosen. Cor.-Bl. f. schweiz. Aerzte, 1917, Ixvii, 1505. 150 
ANIMAL PARASITES 
Ascaris lumbricoides.-This is one of the most common of the human 
intestinal parasites, and is of particularly frequent occurrence in chil- 
dren.1 It is of a light-brownish or reddish color. The female is from 30 
to 40 cm. long and from 5 to 6 mm. thick. The male is somewhat more 
than half as large (Fig. 92). Both sexes are pointed at the ends, the 
posterior end of the male being curved into a spined hook. The eggs, 
from 0.05 to 0.06 mm. in diameter, are surrounded by an albuminous 
Fig. 92.-Ascaris Lumbricoides. About half natural size. 
A, Male. B, Female. After Peris. 
envelope (Fig. 93, A; and are quite resistant to destructive agencies. 
The ova when laid are not developed, so that autoinfection, common with 
oxyuris, is not possible. After thirty to forty days in water or moist 
soil, the ova reach full development, and are then transported to the 
human host by the ingestion of contaminated vegetables. Their usual 
seat in man is the small intestine, but they may wander into the stomach, 
and exceptionally get into the mouth, nose, bronchi, lungs,2 gall-passages, 
peritoneal cavity, etc. They may be single in the gut or present in great 
numbers, as many as 1000 worms 
having been found in one individ- 
ual. Such masses of worms may 
cause intestinal obstruction; and in 
addition a very irritating substance 
is given off by the worm, which 
causes intestinal disturbances. 
Eosinophilia is frequent.3 
Oxyuris vermicularis (Thread- 
worm or Pinworm).-This species 
is very small; the female has a 
pointed tail and is about 1 cm. 
long. The posterior end of the 
male, which is about 4 mm. long, is blunt, and after death somewhat 
curled (Fig. 94). The eggs (Fig. 93, B) are produced in great numbers, 
are ellipsoidal, and about 0.052 mm. long. This parasite is very common 
in children, and may be present in large numbers in the small intestine 
and cecum, and less frequently in the colon. The worm is known to in- 
fest only the human subject, and infection and also autoinfection doubtless 
occur by the ingestion of the eggs, which are widely distributed in a variety 
of ways on many objects, fruits, etc. The worm may also migrate to the 
A, Eggs of Ascaris lumbricoides, X about 300. 
B, eggs of Oxyuris vermicularis, X about 250. 
Fig. 93.-Eggs of Nematode Worms. 
1 For a study of the frequency of occurrence of intestinal parasites in children and the clinical symp- 
toms, see Schloss, O. M„ Am. Jour. Med. Sc., 1910, cxxxix, 675, and McLean, S., Jour. Amer. Med. Assn. 
1920, Ixxiv, 1774. 
2 Ransom, B. H., Jour. Amer. Med. Assn., 1919, Ixxiii, 1210. 
8 Herrick, Arch. Int. Med., 1913, xi, 165. 151 
ANIMAL PARASITES 
nasal passages or through the vagina to the uterus and tubes, where the 
eggs may be deposited. If they escape from the tube, they may become 
encysted in hard masses of inflammatory exudate in Douglas's pouch. 
Local irritation about the anus is caused by the parasites which crawl 
out of the gut to deposit their ova. The worm is frequently found in the 
appendix and may cause lesions of the mucous membrane, but that it 
is an important agent in the incitement of acute lesions is doubtful. 
It does, however, frequently give rise to appendical 
colic by its penetration of the mucosa.1 
Eustrongylus visceralis (Strongylus gigas).-This is 
a slender red worm, the female being sometimes 1 
meter long and over 1 cm. in diameter. There are 
nine authentic records of its occurrence in the pelvis 
of the kidney in man. It is more common in the 
wolf, fox, horse, seal, and some other animals. 
Uncinaria {Hookworm).-There are two forms of 
hookworm widely distributed throughout the world: 
one, the type originally described from Europe, the 
Uncinaria duodenalis (Anchylostoma duodenale); the 
other, the variety first described by Stiles2 from the 
United States, Uncinaria americana (Necator americanus). 
In the Anchylostoma duodenale, the male, which can be recognized 
by a large caudal bursa, is 8 to 11 mm. long, and 0.45 mm. thick, while the 
female, which terminates in a fine spine, is 10 to 18 mm. long, and 0.6 
mm. thick. The worms are pale pink in color, often with an intense 
reddish tone in the posterior third; if there is much blood pigment in the 
cells of the intestine, the parasites may be dark. The mouth is furnished 
on the dorsal wall with four teeth, the ventral wall having two teeth in 
addition. The adult worms live in the jejunum, less frequently in the 
duodenum. They feed on the mucous membrane of the gut, and, as a 
rule, contain no blood unless a small vessel of the submucosa has been 
injured, in which case the parasite may be found filled with blood. The 
eggs are ellipsoidal, with a clear shell, measuring 56 to 61 by 34 to 38 
micra. When found fresh in the feces they usually contain two to four 
blastomeres. The larval stage is found only after the feces have been 
kept for some time.3 
In the Necator americanus, the male is 8 mm. long, and the female 
9 to 11 mm. The head is sharply bent dorsally, which distinguishes the 
worm from the Anchylostoma duodenale. The buccal cavity is smaller 
than in the anchylostoma and there are no visible teeth. The spicules 
of the male are hooked at the extremity. The eggs are more pointed at 
the poles than those of the anchylostoma, measuring 64 to 72 by 36 micra. 
In fresh feces the segmentation is apt to be more complete, and not in- 
frequently the larval worm may be seen inside the shell, or even free in 
A. B. 
Fig. 94.-Oxyuris 
Vermicularis. 
A, Female. B, Male. 
1 Cecil and Bulkley, Jour. Exper. Med., 1912, xv, 225; Aschoff, Berl. klin. Wchnschr., 1914, li, 1504; 
Suzuki, K., Surg., Gynec., and Obst., 1915, xxi, 702. 
2 Stiles, C. W., Am. Med., 1902, iii, 777; Prevalence and Geographic Distribution of Hookworm 
Disease, Bull. 10, Hyg. Lab., U. S. P. H. S., 1903. 
3 For details of the development and morphology of the various stages, see Brumpt, Precis de para- 
sitologie, 2d ed , Paris, 1913. 152 
ANIMAL PARASITES 
the feces. It has a slow motility, which serves to differentiate it from the 
similar larval form of Strongyloides stercoralis. 
The anchylostoma is found in Africa, Egypt, Europe, Japan, and 
China, and in association with the necator is seen in India, in the southern 
part of the United States, and in South America. The Necator ameri- 
canus is widespread, involving the people of the southern part of the 
United States and the adjacent islands, where it is of great importance 
and is the cause of extreme anemia, hemorrhage, gastroenteritis, and 
general debility. It is estimated that in some districts 90 per cent, of 
the inhabitants are affected. As the worm was undoubtedly imported 
by the negro slaves brought from Africa, the recent demonstration of 
its presence there is not astonishing; in the same fashion it has been 
spread in South America. In the Philippines both types are found. 
The reverse migration is also taking place, for Southern Europe is be- 
coming infested with Necator americanus imported by emigrants return- 
ing from Brazil. 
After the feces have been passed, the eggs develop in moist soil, 
and infection takes place either through water or contaminated food, by 
dust, especially in coal mines, or, by far the most frequent method, by 
infection through the skin. The mature larvae when in contact with the 
skin cast their shells and rapidly bore their way through the superficial 
scales of the epidermis or enter the hair follicles; they then pass to the 
lymphatics or to the blood-vessels. By the first channel they reach the 
lymph-nodes, where many are retained and perish; afterwards they enter 
the blood-stream. If they enter a blood-vessel directly, they travel to 
the lungs, where leaving the stream, they enter the small bronchi, from 
which they travel into the trachea and larynx and thence to the esophagus 
and stomach. Ova can be found in the feces seven to ten weeks after 
the penetration of the skin. This skin transmission gives rise to what is 
known as ground itch, a reddening and swelling of the affected parts 
accompanied by most intense itching. 
That the skin is the most important portal of entry has been shown, 
for when the inhabitants of infected districts are compelled to wear shoes, 
the extent of the disease is greatly checked. The other phase of the 
hygienic control of the disease is the proper disposal of the excreta. 
The diagnosis is easily made. A marked anemia due to the toxins 
formed by the worm is usually present; eosinophilia is the rule, if the 
anemia is not extreme. Large numbers of eggs are usually present in the 
feces; if they are few in number, the fecal material should be shaken up 
with a saturated solution of sodium chloride. The eggs float and with a 
pipette can be removed to the slide for microscopic determination. 
Trichocephalus dispar (Trichuris trichiura).-The males and females 
are of nearly equal size, 4 to 5 cm. long. A little less than one-half of the 
body (the posterior portion) is about 1 mm. thick, and in the male is 
rolled into a flattened spiral, but in the female is but slightly bent. The 
anterior part of the body is very slender (Fig. 95) and is embedded 
in the mucous membrane of the host. The eggs are elongated, oval- 
shaped, about 0.05 mm. long and about one-half as wide, with a thick 153 
ANIMAL PARASITES 
brown capsule. The eggs of this parasite are frequently found; in France, 
in at least 70 per cent, of the stools examined; in London, in 7 per cent.; 
in parts of Germany, in 45 per cent.; in the United States, in 9 per cent.1 
The worm is commonly found in the cecum, usually in small, but some- 
times in very large, numbers. It is generally of little pathological sig- 
nificance, commonly producing no symptoms, not even eosinophilia. 
The eggs require some months for develop- 
ment in water or moist earth. They are 
then transferred by uncooked food or soiled 
hands (as of miners, farmers, brickmakers) 
to the mouth; mature worms develop in 
about a month. 
Trichinella spiralis (Trichina spiralis). 
-The female of this common2 parasite is, 
in the mature condition, about 3 mm. long, the male from 1 to 1.5 
mm. long; they are filiform in shape and white in color. The young 
are born in the form of tiny worms about 0.01 mm. in length and 
somewhat similar to the adult in shape. Infection occurs in man from 
the ingestion of insufficiently cooked pork. The muscle of the diseased 
pig contains the embryos of the parasite in an encysted condition. In 
the stomach the capsule of the worm is dissolved and the embryos are set 
free. They very rapidly mature, increasing in size, and the females give 
birth in the small intestine to very large numbers of young. It is esti- 
mated that a single female may give birth to from 1,300 to 1,500 young. 
Fig. 95.-Trichocephalus Dispar. 
From the skin of the mons veneris. 
Fig. 96.-Trichinella Spiralis. 
The parasites are encysted in muscle. In one capsule the parasite has died, and the granular 
material replacing it is calcified. 
These find their way through the mucous membrane and wall of the gut, 
by way of the lymph-channels, into various parts of the body. In heavy 
infections the parasites can be demonstrated in the blood,3 and occa- 
sionally in the spinal fluid,4 in the latter case sometimes giving rise to 
clinical symptoms of meningitis. 
1 French and Boycott, Jour. Hyg., London, 1905, v, 274. 
2 Williams, Jour. Med. Research, 1901, N. S. i, 64. 
3 Herrick, W. W., and Janeway, T. C., Arch. Int. Med., 1909, iii, 263; Staubli, Trichinosis, Wies- 
baden, 1909. 
4 Van Cott, J. M., and Lintz, W., Jour. Am. Med. Assn., 1914, Ixii, 680; Meyer, J., ibid., 1918, Ixx, 
588 (bibl.). 154 
ANIMAL PAHASITES 
After entering the circulation, they are carried to the voluntary 
striated muscle tissue, which they penetrate, and enter the muscle fibers. 
Here they cause a disintegration of the contractile substance, and coil 
themselves inside of the sarcolemma. In this situation they become 
encapsulated by material in part furnished by themselves, in part by 
means of the inflammatory reaction which their presence induces in the 
connective tissue of the muscle. The worms are surrounded inside the 
capsule by granular material (Fig. 96). The capsule after a time be- 
comes partially calcified, and in this condition may be readily seen by the 
naked eye as a tiny white speck. In this encysted state they may remain 
inactive but living for an indefinite, often for a very long time. Most 
frequently the cysts contain but one embryo, but they may contain from 
two to four. The embryo may die and its remains become calcified. 
The same course of events follows when the muscle trichinae are eaten 
by the pig or a variety of other animals. 
The embryos in the muscle are killed by a temperature of 55° C. and 
by some of the methods of curing pork. 
The embryos may mature and a new generation be born within from 
five to eight days after the ingestion of the diseased meat. 
As the result of the presence of these parasites in the body, if the 
invasion be severe, nutrition may be impaired and catarrhal enteritis, 
high fever, great pain in the muscles, bronchopneumonia, hyperplasia 
of the mesenteric lymph-nodes, and fatty degeneration of the liver may 
occur. Leucocytosis with a great increase in the number of eosinophile 
cells is common.1 The bone-marrow is often hyperplastic and contains 
large numbers of cells with eosinophile granules. The encapsulated em- 
bryos may be found in enormous numbers almost exclusively in various 
voluntary muscles of the body, but they are most apt to be found, when 
not very abundant, in the muscles of the neck and larynx, in the inter- 
costals and the diaphragm. They tend to collect toward the tendinous 
extremities of the muscles. Trichinae also occur in the rat, cat, mouse, 
and other animals. 
Dracunculus medinensis (Filaria medinensis, Guinea worm).-This is 
a thread-like worm, the female being sometimes as much as 80 cm. long 
and from 0.5 to 1.7 mm. thick. The male, which is rarely found, is much 
smaller, measuring only about 4 cm. in length. It is common in the East, 
and inhabits the subcutaneous connective tissue, in which it often gives 
rise to abscesses and ulcers. Eosinophilia is commonly present. The 
embryos live for a time free in fresh water, and are taken up by a species 
of fresh-water crustacean, in whose body they undergo further develop- 
ment, and by the ingestion of which the infection of the human subject 
occurs. 
Filaria sanguinis hominis (Filaria bancrofti).-The larva of this 
parasite, which inhabits the blood and lymph of man, especially in Brazil, 
Egypt, and some parts of the Orient, and occasionally occurs in this 
country, is about 0.35 mm. long, rounded anteriorly, and pointed at the 
1 See Brown, T. R., Jour. Exper. Med., 1898, iii, 315; and Albert, H., Am. Jour. Med. Sc., 1910, 
cxl, 167. ANIMAL PARASITES 
155 
tail (Fig. 97). It has about the diameter of a red blood-cell. It occurs, 
sometimes in great numbers, in the blood during the night time, being as 
a rule absent during the day. It may occur in the urine in connection 
with chyluria and hematuria. The mature female is from 8 to 10 cm. 
long, and has been found inhabiting the lymph-vessels of man, particu- 
larly in the scrotum and lower extremities. Owing to the obstructions 
which it causes in the lymph circulation, and to the local irritation 
which its presence induces, it some- 
times gives rise to lymphangiectasis,1 
edema, abscesses, and perhaps elephan- 
tiasis. Eosinophilia is common. One 
of the embryonic stages of develop- 
ment is believed to take place in 
the body of a species of nocturnal 
mosquito. Through the bodies of 
the dead mosquitoes, which are liable to fall into the drinking-water, 
it is believed the spread of the parasite may occur. 
There are several other species of filaria occasionally found in man 
which it is not necessary to enumerate here.2 
Strongyloides stercoralis.-A small filiform worm, from 1 to 2 mm. in 
length, is found, often in enormous numbers, in the intestine and biliary 
and pancreatic ducts of man in Cochin China, Italy, and South and 
Central America, giving rise to endemic diarrhea. The adult worm lives 
in the mucous membrane of the small intestine; and the eggs hatch in the 
feces, so that only the rhabditiform larvae are found. These pass out 
with the feces, penetrate the skin, like the uncinaria, and enter the 
intestinal wall, thus completing the cycle.3 
Fig. 97.-Filiaria sanguinis hominis 
-Larval Form from the Blood. 
Methods of Study of Worms. 
Filaria sanguinis may be demonstrated in fresh blood, and its detailed morphology 
studied by preparing a smear of the blood containing it on a slide in the usual way 
(page 349), and staining with methylene blue. 
The larger parasites may be hardened in formaldehyde and studied whole after 
dehydration in alcohol and clearing in oil of cedar or origanum. Or sections may be 
made after embedding, and stained and mounted in the usual way. 
The examination of muscle for trichina is often of great practical importance. For 
this purpose small pieces of fresh muscle are squeezed into a thin sheet between two 
slides, and examined with a low power. A considerable number of bits of muscle 
should be examined, particularly from the above-mentioned favorite situations, be- 
fore excluding trichina in a suspected case, because they are sometimes present in small 
numbers. A thorough search is of special importance in the examination of pork, 
since, owing to the enormous fertility of the parasites, even a moderate number may 
give rise to a severe infection. 
For the minute examination of the parasite, bits of muscle are hardened in Orth's 
fluid and alcohol, decalcified if necessary, and, after embedding, thin sections are cut 
and stained with hematoxylin and eosin, and mounted in balsam. Bits of muscle may 
be also teased, the embryos picked out with a needle, and the cysts either broken 
1 For a study of filarial lymphatic varix, see Opie, Tr. Assn. Am. Phys., 1901, xvi, 314. 
2 See Fillleborn, Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1913, viii, 
185. 
3 Askanazy, Centralbl. f. Bakteriol., Orig. I, 1900, xxvii, 569; Price, Jour. Am. Med. Assn., 1903, 
xli, 713. 156 
ANIMAL PARASITES 
open under a lens with the needle, or squeezed under the cover-glass. The embryo 
worm thus set free may be mounted in a mixture of equal parts of glycerin and satu- 
rated aqueous picric acid. The adult forms, which may be obtained by feeding 
rabbits with uncooked trichinous muscle, and examining after the proper interval, 
may be hardened in Orth's fluid, and mounted in a mixture of equal parts of picric 
acid and glycerin, or in the same mixture which has been lightly tinged with eosin. 
Arthropoda. 
The scope of this work does not permit us to enter in detail into the 
subject of external parasites, which will be found described in treatises 
on diseases of the skin or in the general works on parasites referred to 
below.1 But, owing to their frequent occurrence and practical impor- 
tance, we may briefly describe a few of the more common forms of ar- 
thropods. 
The common "itch insect"-Sarcoptes scabiei (A car us scabieP)-is 
shaped somewhat like a turtle, with a chitinous covering, and presents 
the general appearance seen in Fig. 98. The female is about 0.45 mm. 
long, the male a little smaller. 
The parasite bores little tunnels in the skin, in which the eggs are 
laid and the young hatched. After a few days these bore fresh channels 
in the skin. For their detection a bit of the superficial layer of the skin 
is snipped out with curved scissors, dehydrated and cleared up with oil 
of cloves, and examined under a low power, when the tunnels and the 
parasites, if present, will be readily visible. 
Fig. 98. - Sarcoptes Sca- 
biei - the "Itch Insect." 
Fig. 99.-Pediculus 
Capitis-the "Head 
Louse." 
Female; back view. After 
Furstenberg. 
Male. After Braun. 
The head louse, Pediculus capitis, is from 1 to 2 mm. long, the female 
being slightly the larger. The general appearance of the insect is seen 
in Fig. 99. 
Pediculus pubis (Phthirius inguinalis) has recently become of hygienic 
interest as the possible carrier of the inciting agent of typhus fever. 
1 Bibliography.-Especially to be recommended for detailed description of human and animal 
parasites is the small work of Brumpt, Precis de Parasitologic, Paris, 2d ed., 1913. 
Consult also, especially for the forms of eggs and other parts of animal parasites which may be 
found in the excreta, vonJaksch, Wood, or Simon, or other works on clinical microscopy. 
The Reports of the Bureau of Animal Industry of the U. S. Department of Agriculture contain 
many valuable data relating to animal parasites and the diseases of animals in the United States. 
See for a general study of the effects of parasites on their host, Ward, Science, 1907, xxv, 201. 157 
ANIMAL PARASITES 
Pediculus corporis or vestimenti has been considered as the carrier of 
relapsing and trench1 fevers (pages 324 and 351). 
The rat flea, Xenopsylla cheopis, a cosmopolitan parasite, is apparently 
the most important carrier of the plague. 
Demodex folliculorum is an arachnoid parasite, frequently found living 
in the Meibomian and sebaceous glands, particularly of the face and of 
portions of the eyelids. It has been stated that in the latter situation 
they incite an acute inflammatory lesion, but there seems to be no founda- 
tion for this assumption, and in all probability they are practically harm- 
less. It has been suggested, however, on somewhat doubtful grounds, 
that there may be a connection between cancer and the occurrence of 
demodex in the skin.2 The male parasite measures about 0.3 mm., the 
female about 0.4 mm. (Fig. 100). 
Fig. 100.-Demodex Folliculorum. 
Methods of Study of Insects. 
These, if small, may be cleared in turpentine and mounted in balsam, or sections 
may be cut after fixation in alcohol or formaldehyde and embedding in paraffin. 
1 For experimental proof of the transmission by lice of the virus of trench fever, see Trench Fever, 
Report of Commission, Medical Research Committee, American Red Cross, Oxford, 1918. 
' Barrel, A., Ann. de 1'Inst. Pasteur, 1909, xxiii, 97. CHAPTER VII 
PLANT PARASITES. 
The plant parasites of man belong among the simplest o-f living 
organisms. Three distinct groups are of frequent occurrence in or upon 
the body. These are: 
1. Bacteria, or fission fungi (Schizomycetes). 
2. Yeasts, or yeast fungi, or sprouting fungi (Blastomycetes). 
3. Moulds, or mould fungi (Hyphomycetes). 
The first group, the bacteria, is of the greatest significance, because 
it contains organisms which are very frequently the excitants of serious 
disease. 
The scope of this work does not permit more than a brief outline of 
the rapidly increasing knowledge of the forms, nature, and performances 
of the bacteria. For details we refer to special treatises on bacteriology.1 
I. Bacteria. 
Bacteria are minute unicellular plants devoid of chlorophyll, multi- 
plying by transverse division and in some cases preserving the species 
by the formation of spores. 
The colorless, sometimes granular protoplasm is inclosed by a mem- 
brane, and some forms are surrounded by a transparent capsule. Not 
MORPHOLOGY, PHYSIOLOGY, AND DISTRIBUTION. 
Fig. 101.-Bacteria with Flagella. 
Fig. 102.-Typical Forms of Bacteria. 
Cocci, Bacilli, and Spirilla. 
infrequently parts of the protoplasm appear less dense than the rest, 
as if from vacuolation, and a few observers have claimed to demonstrate 
in certain forms a nuclear substance. 
Many of the bacteria, especially bacilli and spirilla, less frequently 
the cocci, have hair-like processes called flagella which are apparently 
organs of locomotion (Fig. 101). These maybe single or in tufts; may be 
1 Hiss and Zinsser, Text-book of Bacteriology, 4th ed., New York, 1918; Park and Williams, 
Pathogenic Microorganisms, 6th ed., New York, 1917; Kolle and Wassermann, Handbuch d. path. 
Mikroorganismen, 2d ed., Jena, 1912-13; Muir and Ritchie, Manual of Bacteriology, 6th ed., London, 
1913. 
158 PLANT PARASITES 
159 
at one or both ends or over the general surface. Their number and 
distribution seem sometimes to be characteristic of special forms. (See 
Motility below.) 
Forms of Bacteria.-Bacteria may be grouped in three classes (Fig. 
102). 
1. Spheroidal bacteria.-Cocci or micrococci (singular, coccus,1 micro- 
coccus). 
2. Rod-like bacteria.-Bacilli (singular, bacillus). 
3. Spiral bacteria.-Spirilla (singular, spirillum). 
All straight bacteria which have one axis longer than the other are 
called bacilli, even though the form is oval rather than rod-like. The 
ends of bacilli may be square or rounded, and in stained preparations, in 
some cases, concave. 
While the cocci elongate a little in preparation for fission and in this 
condition present a slight irregularity in the length of their axes, and thus 
resemble bacilli, the complete observation of their life cycle rarely permits 
error in the determination of the primary group to which a given micro- 
organism belongs. 
Variations in Form and Size.-Some bacteria present slight modifica- 
tions of the fundamental form in certain phases of their growth and under 
various chemical and physical conditions. Thus some of the cocci after 
division are slightly flattened on their contiguous sides-biscuit-shaped; 
certain bacilli may bulge slightly in the middle-clostridium forms; others 
may be larger at one end than at the other-racket-shaped; bacilli from 
the same culture may present considerable irregularities in breadth and 
especially in length. The morphology may 
differ somewhat under different growth con- 
ditions. But these slight variations in form 
rarely give rise to serious difficulty in classifi- 
cation. 
Finally, when bacteria are placed under 
conditions unfavorable for the maintenance 
of their life processes, and when they are 
dead, they are often irregularly swollen and 
contorted or may undergo partial disintegra- 
tion, giving rise to what are known as " involution forms." 
While all bacteria are minute2 there is among them considerable 
diversity in size, some being many times larger than others.3 
Certain bacteria, those of the diphtheria group for example, contain 
deeply staining bodies called metachromatic granules the nature of which 
is as yet undetermined. 
Reproduction of Bacteria.-When the bacteria are about to multiply 
by fission they elongate, a dividing septum forms, they become con- 
Fig. 103.-Bacteria with Cap- 
sules. (Pneumococcus.) 
1 Pronounced kok'-us, plural kok'-si. The term microorganism includes all of these forms of minute 
and lowly plants. They are sometimes spoken of collectively as germs or microbes. 
2 Some forms, those for example inducing the pleuropneumonia of cattle, are beyond the present 
resolving power of the microscope-ultramicroscopic. For a review of ultramicroscopic bacteria or 
filterable viruses see Wolbach, Jour. Med. Research, 1912, N. S. xxii, 1. 
3 For convenience of expression microscopists have agreed to let the letter n stand for the word 
micromillimeter, which is one-thousandth part of a millimeter. This unit of measure, equal to about 
one-twenty-five thousandth of an inch, is often called a micron- 160 
PLANT PARASITES 
stricted at a right angle to the axial elongation, and finally two inde- 
pendent organisms are produced. The multiplication of bacteria by 
fission may, when the conditions are favorable, occur so rapidly1 as to 
give rise within a few hours to an enormous number of new individuals. 
Aggregations of Bacteiia.- 
In many cases, the new individuals 
thus developed fall apart in a form 
identical with that of the parent 
cell. In some species, on the other 
hand, the new-formed individuals 
are prone to cling together with 
greater or less tenacity, thus giving 
rise to growth aggregates which are 
more or less characteristic (Fig. 104). 
Thus among the cocci there are 
those in which a large part of the 
new individuals cling together in 
pairs. These forms are called diplo- 
cocci. In others the pairs cling 
together in longer aggregates or 
chains. Such are called streptococci. 
A similar occurrence in the 
bacilli gives rise to diplobacilli and streptobacilli. Some of the spiral forms 
are due to the close junction end to end of oppositely curved segments. 
Certain cocci divide in two directions at right angles to each other, 
giving rise to four cocci clinging together and lying in the same plane. 
These are called tetrads or merismopedia. 
Finally cocci may divide along three planes at right angles to each 
other, giving rise to cuboidal packets of eight germs or some multiple of this 
-such growth groups are called sarcina2 (Fig. 105). 
Higher Bacteria.-There is a family of fila- 
mentous or branching organisms which are often 
spoken of as polymorphous or higher bacteria, some 
of which may indeed be links between the bacteria 
and higher plant forms. Filamentous bacteria are 
more or less distinctly segmented, and the segments 
may be inclosed in a common sheath. The modes 
of reproduction and a certain specialization of func- 
tion of different parts of the filaments which is 
frequently present indicate affiliations with higher 
forms. By this specialization of function is meant the attachment of the 
threads at one end to the substance on which they grow, and the forma- 
tion at the free ends of structures which appear to be concerned in the 
reproduction. Several groups of these organisms have been named, but 
Fig. 104.-Growth Aggregates of Bacteria. 
1, Diplococci; 2, streptococci; 3, meris- 
mopedia; 4, diplobacilli; 5, streptobacilli; 6, 
curved bacteria forming chains. 
in cuboidai masses. 
Fig. 105.-Sarcina. 
1 A. Fischer has estimated that the cholera spirillum may undergo complete fission at intervals of 
about twenty minutes so that a single organism might give rise under favorable conditions, could these 
be secured, to 1600 trillions in twenty-four hours. 
2 Bacteria in masses embedded in and held together by a more or less abundant homogeneous 
material which they elaborate are called zodglea. PLANT PARASITES 
161 
few of them have as yet been adequately studied. The groups strepto- 
thrix, cladothrix, crenothrix, leptothrix may be cited. Among these the 
streptothrix (Nocardia) is of the most significance here, since pathogenic 
forms are known.1 The Streptothrix actinomyces, and closely related 
species, and the lesions which they induce, will be described later. 
There are many reasons for the belief that the forms called streptothrix 
and actinomyces are more closely related to the moulds than to the 
bacteria, but the scope of this work does not permit the discussion of the 
subject, particularly difficult as it is on account of the confusion of terms 
and the lack of sufficient knowledge of the life history of the organisms 
involved (see Actinomyces, page 262). 
Variations in Forms.-Their apparently simple structure and the 
lowly position which bacteria occupy in the scale of living things have 
given rise to the conjecture that marked changes in form within the 
limits of the primary groups, or even changes from one primary group 
to another, may be brought about by alterations in environment, food, 
etc. In the early days of the exact study of bacteria this belief in 
pleomorphism in bacteria found ready currency. But the more exact 
study of separate forms, which the new technique has made possible, 
has led to the general acceptance of the view that variations do not occur 
except within comparatively narrow limits, and that what we are 
accustomed to call species of bacteria maintain their morphological 
characteristics with tenacity under the most varied changes in environ- 
ment, even though these persist through the countless generations which 
may pass within the limits of a single experiment. The physiological 
characters of bacteria are, as we shall presently see, subject to wide and 
significant variation, but, so far as we can now see 
monomorphism widely, if not exclusively, prevails. 
Spores.-Under a variety of conditions, the limi- 
tations of which are not very well understood, the 
species is perpetuated, not by simple division, but 
by the development of spores. The most common 
mode of spore formation is called endogenous. A 
small, shining mass makes its appearance within 
the protoplasm from which it is formed, grows more 
and more distinct, and finally appears as a sharply 
defined spheroidal or oval, strongly refractile color- 
less body surrounded by a limiting membrane (Fig. 106), which can be 
separately stained and may remain within a cell membrane or may free 
itself by degeneration of the latter. Endogenous spore formation is com- 
mon in bacilli, rare in spirilla and in cocci. The spores appear to be sur- 
rounded by a dense envelope, and are, as a rule, much more resistant to 
deleterious agencies, such as heat, drying, chemicals, etc., than are the 
vegetative forms of the bacteria themselves. 
Spores, when placed under favorable conditions in the presence of 
moisture and nutriment, swell, become less refractile, and develop into 
Fig. 106.-Bacilli Show- 
ing Spores. 
The bodies of the bacilli 
are stained with methy- 
lene blue, the spores with 
fuchsin. 
1 Some organisms commonly called bacilli-tubercle bacillus for example-may belong in this 
group. 162 
PLANT PARASITES 
the usual vegetative form. The actual observation of this transformation 
is, in doubtful cases, the only absolute guarantee of the spore nature of 
these bodies, though staining methods are useful. Another method of 
sporulation-arthrogenous-has been described, but its nature is not well 
understood. 
Motility.-Some bacteria are capable of performing rapid movements, 
others are not; and the same form may be at one time motile and at 
another immotile, depending upon external conditions. Movement is 
largely confined to the rod-like and spiral forms, but has been observed 
in the spheroidal. 
It has been shown that certain of the motile bacteria, when sus- 
pended in fluids, are attracted toward, or repelled from, dissolved chem- 
ical substances. This is called chemotaxis (see page 101), and it is termed 
positive or negative according as the organisms are attracted or repelled. 
Conditions of Life, Growth, and Multiplication.-The bacteria require 
for their nutrition carbon, hydrogen, oxygen, and nitrogen, and certain 
mineral salts. These they can obtain from proteins and carbohydrates. 
Free oxygen is necessary for the growth and activities of some forms of 
bacteria and not for others. 
Nitrogen may be obtained by some bacteria from inorganic salts of 
ammonia, from nitrites and nitrates. Bacteria grow best as a rule in an 
organic food medium, especially soluble albuminous material which is 
neutral or slightly alkaline. Most of these materials are rendered avail- 
able as food by the action of enzymes-inverting, sugar-splitting, proteo- 
lytic, etc., often given off by the organisms and acting upon the albu- 
minous materials. 
Those bacteria which require free oxygen are called aerobic. Those 
which do not grow in its presence are called anaerobic. But between 
these extremes there are forms which make shift to grow without oxygen 
under favorable conditions, though they make use of it when present; 
others grow in its presence, though flourishing best in its absence: these 
are called facultative aerobes or facultative anaerobes, in distinction from 
those first mentioned, which we call obligate aerobes or anaerobes. 
Bacteria are active only in the presence of moisture. When this and 
other conditions favoring their activity fail they do not necessarily die; 
some forms may remain, either as spores or as fully developed organ- 
isms, for long periods dry and inert, but capable of resuming their ac- 
tivity whenever they are again restored to favorable conditions. 
Effects of Temperature, Light, etc.-Some bacteria are and some are 
not very sensitive to changes of temperature. At a temperature below 
+ 5° C. they are incapable of marked activity or proliferation. At + 7° C. 
a slow growth has been observed in various species. Many forms may 
remain alive for long periods frozen in ice, while some are not killed by a 
temperature of -250° C. As the temperature is raised their activities 
increase up to a certain point. It may be said in general that they are 
most active at about the temperature of the body, although species differ 
considerably in this respect. In fluids many bacteria are killed by a 
prolonged exposure to a temperature of from 50° to 70° C. or even less. PLANT PARASITES 
163 
On the other hand, certain species grow at a temperature of from 60° to 
75° C. Such are called thermophilic bacteria. When dry they resist 
much higher temperatures than when moist. All known bacteria, save 
a few very invulnerable spore-forming species, are killed by a short ex- 
posure in the presence of moisture to a temperature of 100° C. The 
spores are, as a rule, more resistant to high temperatures than the bacte- 
ria themselves, some having been exposed, dry, to a temperature of 140° C. 
without destruction of life. Fluids containing the spores of bacteria 
which resist very high temperatures may be sterilized by boiling for a 
short time, then being allowed to stand at ordinary temperatures for 
several hours, and then again boiling; this process being repeated several 
times. In this way, although the spores themselves are not killed by the 
heat, the bacteria into which, if the conditions be favorable, they develop 
during the intervals are killed, so that finally the medium is entirely freed 
from both living spores and adult bacteria. Strong light is in general 
inimical to the life and growth of bacteria, and by direct sunlight many 
forms are readily killed. Ultraviolet rays in sufficient intensity and of 
wave lengths such as are given off by a quartz mercury arc, kill bacteria 
almost instantly. Various physical agents, such as ionic discharges 
from high voltage terminals, radium, and Roentgen rays, have some 
destructive action. Rapid and continuous shaking of fluids containing 
bacteria may kill the organisms. 
Germicides.-Certain chemical agents, when brought into contact 
with bacteria, greatly reduce their activities or destroy their life alto- 
gether; but different species differ greatly in their capacity of resistance 
to these agents. The spores of certain bacteria are exceedingly re- 
sistant, much more so than the bacteria themselves, to the action of 
disinfecting agents. Among the chemical substances commonly used 
as disinfectants may be mentioned formaldehyde, carbolic acid, mercuric 
chloride and especially solutions of free chlorine, which are very inimical 
to the life of most bacteria and their spores, even in extremely dilute 
form. 
Metabolism of Bacteria.-The metabolism of bacteria may be destruc- 
tive or constructive. Their destructive or catabolic activities find expres- 
sion in the fermentation of carbohydrates and in the cleavage of pro- 
teins and fats. Their constructive or anabolic activities are exemplified 
by their building up of nitrogenous compounds in the soil. We cannot 
here enter into the details of these processes, which must be sought in 
special treatises. 
But it may be said in brief that a large number of complex chemical 
substances are elaborated during the growth of bacteria, their nature 
varying with the species of bacteria and the composition of their nutrient 
material. Some of the chemical compounds set free by the growing 
bacteria are bad-smelling or aromatic; some are inert and harmless sub- 
stances; some are powerful poisons, and may, when they have accumu- 
lated in the fluids where they grow, inhibit activity and growth or even 
destroy the bacteria which have produced them. 
Fermentations and putrefactions are due to the activities of micro- 164 
PLANT PARASITES 
organisms, some to bacteria, some to yeasts, some to moulds. Putrefac- 
tion is a form of fermentation in which nitrogenous compounds are de- 
composed by microorganisms setting free, especially in the absence of 
oxygen, bad-smelling substances. 
Bacteria which induce fermentation are called zymogenic-and each 
species induces fermentation of a particular character in the presence of 
a special substance, as glucose, or members of a certain class of substances 
such as carbohydrates. Some of these fermentations are important in 
the arts; some are concerned in the changes which food products undergo 
under natural or artificial conditions, such as the development of kou- 
myss from milk and the common butyric, lactic, alcoholic, and other 
fermentations. 
The chemical changes which are induced by microorganisms in the 
process of fermentation are extremely complex and little understood. 
Bacteria may develop, in their metabolic activities, soluble ferments1 
or enzymes of various kinds resembling diastase, pepsin, trypsin, rennet, 
etc. These may remain in the bacterial cell or may be diffused into the 
surrounding media. It is through these enzymes that the fermentations 
and protein, or rather amino-acid, cleavages so characteristic of many 
phases of bacterial metabolism are carried on. 
Many bacteria form pigments as they grow (chromogenic bacteria). 
This pigment may be developed in or upon the germs themselves or may 
be diffused through the surrounding media and may be developed only 
in the presence of light, oxygen, etc. Gas-producing bacteria are called 
aerogenic. Certain species when growing in masses emit a phosphor- 
escent light-photogenic bacteria. 
Bacterial Poisons. 
Ptomaines.-Certain basic chemical compounds which are formed by 
the action of bacteria upon various kinds of organic matter are called 
ptomaines.2 Some of the ptomaines resulting from the breaking up of the 
protein molecule by bacteria in decomposing meat, fish, etc., are poison- 
ous, though not apparently of as much importance as was once believed. 
But ptomaines should be distinguished from the true toxins now to be 
considered. 
Toxins.-True bacterial toxins are poisonous substances produced by 
bacteria. They are probably highly toxic proteins with some analogy 
to the enzymes, and, like the secretory and excretory products of the 
body-cells, may be given off during the metabolic activities of the bac- 
teria, in artificial cultures as well as in infective processes. The poison- 
ous substances elaborated in the growth of the diphtheria and the tetanus 
bacilli are typical toxins. These toxins are especially characterized by 
their capacity to stimulate the body-cells, when the latter are called upon 
1 See Bayliss, Nature of Enzyme Action, 3d ed., New York, 1914. Also, for technique, Wohlgemuth, 
Grundriss der Fermentmethoden, Berlin, 1913. See, for studies showing inability of many bacteria 
to cleave native proteins, Rettger, Berman, and Sturges, Jour. Bacteriol., 1916, i, 15. 
2 The terms ptomaine and leucomaine are falling into disuse as the chemical structure of many of the 
toxic bases is being elucidated. See Barger, The Simpler Natural Bases, New York, 1914. PLANT PARASITES 
165 
to adapt themselves to their presence, to the formation of antibodies 
(see page 201). 
Endotoxins.-On the other hand certain bacteria which develop toxic 
qualities do not set these free as they are formed but store them in or 
build them into the structure of their bodies whence they are freed 
only after the death or disintegration of the bacterial cell through autoly- 
sis or some external agency. Such toxic substances stored in the texture 
of the bacteria are called endotoxins and they do not appear directly to 
stimulate the organism to the formation of antibodies, although the 
bodies of the bacteria have specific antigenic powers due to their char- 
acteristic proteins. 
It is not certain, however, from present knowledge, whether these 
so-called endotoxins are strictly comparable with the toxins given off 
by bacteria of the type of the Bacillus diphtheria) or Bacillus tetani. 
They are, if of truly toxic nature, much more firmly bound to the protein 
molecule of the organism, and are not separable by mechanical or chemical 
means. The toxic action seems to be released only when the bodies of 
the bacteria of this group are dissolved by the ferments of the blood and 
tissues, and the proteins thus set free from combinations with the cells 
of the host. When this has been accomplished, they give rise to the usual 
types of antibodies, agglutinins and-bacteriolysins, and may also induce 
anaphylaxis. 
When the bacterial proteins are split, it is possible that, in addition, 
certain non-specific general protein derivatives are produced, wholly 
independent of the type of organism giving rise to the infection, and that 
general protective substances may be formed in response. This is 
illustrated, for example, by the beneficial therapeutic results often seen 
following injections of killed typhoid bacilli in chronic streptococcus in- 
fections in man. 
The important thing to remember in this connection is that it is 
through the action of these substances, whether soluble and eliminated 
during the life and functional activities of the bacteria or stored up in 
their bodies to be set free only upon their disruption, that the most strik- 
ing damage is wrought in the organisms when body-cell and bacterial cell 
strive to adapt themselves to one another in the processes of infection 
which we are presently to study. 
It is probable that there is still another group of non-specific toxic 
substances derived not directly from the bacteria but from the action 
of certain products of bacterial metabolism upon amino-acids of the blood 
and tissues, so that it may be through these secondary toxic products 
that some of the serious manifestations of infection and intoxication are 
induced. 
The Role of Bacteria in Nature.-The bacteria play a very important 
r61e in nature in virtue of their power of feeding upon and decomposing 
dead organic material. A part of the new chemical compounds which 
are thus formed may be used by the bacteria for the purposes of their own 
nutrition and growth, while the rest are set free to serve, sooner or later, 
as food for other forms of plants or animals. In the decompositions 166 
PLANT PARASITES 
which are brought about in nature by the bacteria those compounds of 
nitrogen and carbon dioxide are set free which are essential for the nutri- 
tion of the higher plants. 
Without the activities of bacteria, life could not be long maintained 
upon the earth, since the necessary carbon, hydrogen, oxygen, and nitro- 
gen would soon be permanently locked up in unavailable form in organ- 
ized material. Through the action of the various nitrifying bacteria in 
the soil, ammonia is decomposed with the formation of water and nitrous 
acid; nitrous is converted into nitric acid. The so-called denitrifying 
bacteria reduce nitrates to ammonia and to nitrites. In these ways, 
among others, water percolating through the soil may be freed from 
objectionable organic compounds. There are certain soil bacteria which 
aid special groups of plants to fix nitrogen from the surrounding media 
and make it available for the uses of the plant. 
Distribution of Bacteria.-Bacteria are widely distributed in the air, 
in water, and in the superficial layers of the soil, where they may be pres- 
ent in enormous numbers. They are especially abundant among the 
habitations of man, or wherever under favorable conditions of moisture 
and temperature animal or vegetable substances are undergoing decay. 
They cling tenaciously to moist surfaces, but when dried, and especially 
when dried upon comminuted material, they may float in the air as dust. 
In quiet air they gradually settle with other forms of dust on to horizon- 
tal surfaces, and thus in closed, still rooms the bacteria-laden air may in a 
few hours almost wholly free itself of its living contaminations by a proc- 
ess analogous to sedimentation in water. 
This wide-spread transportation of bacteria as dust by moving air, and 
the spontaneous cleansing of the latter by the settlement of the germs, 
are important factors in the sanitary problems which the complex con- 
ditions of modern life present. 
While bacteria may live for long periods in the dried state in dust 
they do not in this condition multiply. But the upper three or four feet 
of the soil forms the great abiding, and when moist, the breeding place 
of the myriads of germs which are concerned in the salutary work of 
food preparation for higher plants. Large numbers of mould spores are 
frequently mingled with the bacteria in dust and soil. 
Surface waters almost always contain bacteria, which may have en- 
tered by aerial dust or from the wash of adjacent soil or from direct 
human or animal contamination. Many bacteria find in water favorable 
conditions of life and flourish on what to other forms would be but scanty 
nutriment. Many pathogenic bacteria may remain alive for consider- 
able periods in water, but they do not usually thrive there. 
The water which in many places lies in hollows of the rocks, bathing 
the deeper layers of the soil or gathered in caverns and recesses beneath, 
is called ground water. This under favorable conditions is almost wholly 
free from microorganisms; these, through the complex processes of filtra- 
tion, germ metabolism, etc., which go on in the upper soil layers, having, 
together with inorganic contaminations, been largely retained or trans- 
formed as the surface water has slowly sought the lower levels. 167 
PLANT PARASITES 
The Relationship of Bacteria to Other Living Beings.-So far as we 
know, with few exceptions, the bacteria whose natural habitat is the soil 
or air or water are not, under usual conditions, harmful to man. On the 
other hand, it is germs from the bodies of men or animals who are the 
victims of infectious disease, gaining access in one way or another to 
these great reservoirs and sources of distribution, which occasionally 
render the bacterial flora of soil and air and water of direct personal 
significance. 
It will be seen from what has been said about bacteria and their 
various modes of life that some live in or upon and at the expense of 
other living beings-the hosts; these are parasites. Others which live 
and grow apart from a living host are called saprophytes. In either class 
there are forms which, through the capacity of adapting themselves to 
their environment, can maintain at one time a parasitic, at another a sap- 
rophytic life. Such germs are called, respectively, facultative parasites 
or facultative saprophytes. Those, on the other hand, whose life is strictly 
limited to the parasitic or saprophytic condition are called obligatory 
parasites or saprophytes. 
Not all the bacteria which live in or upon the bodies of men and 
animals are in the stricter sense parasites. The terms messmates and 
commensals have been applied to such organisms as simply live with, but 
do not necessarily derive nutriment from, the host. 
In some cases parasitic life on the part of the microorganism may 
contribute to the welfare of the host. This is the case in some bacteria 
which live upon the roots of certain leguminous plants, to whose 
nutrition they contribute by rendering atmospheric nitrogen directly 
available for the host. This condition of life is called symbiosis. 
Species and Varieties.-As has already been indicated, the morpho- 
logical characters of bacteria are so little subject to permanent variation 
under the widest diversity in the conditions to which they are subject 
that we are justified in the belief in fixed species. But so susceptible to 
external conditions are the functional activities of many species that not 
only is the occurrence of what may be called varieties within specific 
limits frequent under natural conditions, but more or less permanent 
variations may be experimentally produced. 
Modifications of Functional Characters.-Almost all of the functional 
activities of bacteria upon which we rely as descriptive characters may be 
experimentally altered; thus the color-producing capacity may be dimin- 
ished, the peptonizing and fermentative activities lowered, the patho- 
genic powers reduced or exalted, and even the capacity for spore forma- 
tion abolished. 
These more or less permanent modifications of function in bacteria 
may be induced by artificial cultivation under adverse conditions of tem- 
perature and nutrition, by the presence of deleterious chemical agents, 
antiseptics, etc., or by association with the body-cells and juices in sus- 
ceptible or insusceptible animals. 168 
PLANT PARASITES 
CLASSIFICATION OF BACTERIA. 
The beginning of the systematic study of bacteria by exact and re- 
liable methods is of such recent date, they are so minute, and our present 
optical apparatus reveals so few differential morphological characters, 
and so few, withal, of the many existing forms have as yet been studied, 
that a satisfactory classification or nomenclature of the bacteria is not yet 
possible. 
Outside of the limit of the primary classes above described and based 
upon the form, position of flagella, and motility, we are obliged to use for 
the purposes of identification and description the results of physiological 
activities which the special forms of bacteria display when placed under 
diverse and usually entirely artificial conditions of food, temperature, and 
general environment. It is evident from this condition of affairs that 
what in our attempts at classifications we are wont to call genera and 
species, are not such in the strict sense in which these terms are used in 
other domains of biology. That which corresponds to the generic name 
in the more exact vocabularies is in ours usually the growth form which 
indicates the primary class to which the germ belongs, as coccus, bacillus, 
or spirillum, or some growth modification of this, as diplococcus, strep- 
tococcus, streptobacillus, and the like. To this is usually appended a 
more or less distinctive specific name, which ordinarily indicates some 
noteworthy physiological capacity of the germ, such as its peptonizing 
power, the pigment which it elaborates, some prominent chemical reac- 
tion which it initiates, some marked effect upon an artificial culture 
medium, its disease-producing power in men or animals, or some fact 
about its habitat, or the situation in which it was found. All of these and 
other heterogeneous characteristics, largely functional, which may be 
developed under natural or artificial conditions, constitute data in the 
life history of germs upon which the classification and nomenclature of 
bacteria are at present based. 
Notwithstanding the value of this principle of grouping and nomen- 
clature, its inadequacy even for temporary use is becoming painfully 
evident as research proceeds, partly because of the large variations to 
which physiological activities are liable, and partly because we cannot 
always sharply distinguish between races, varieties, and species. 
Fig. 107.-Sterilized Cotton Swab in a Sterilized Tube, for Collecting Fluids Containing 
Bacteria. 
Material obtained from the human body which is to be subjected to bacterial ex- 
amination should be collected with every precaution against accidental contamination. 
A convenient mode of collection and transportation of small quantities of fluid or 
semi-fluid material, such as exudates, discharges, etc., for purposes of bacterial exami- 
nation is to twist a small wad of absorbent cotton on to the end of an iron or steel wire 
Collection of Material for Bacterial Cultures. 169 
about five inches long, put this, swab end foremost, into the tube (Fig. 107), plug the 
mouth with cotton, and sterilize the whole in a dry oven for an hour at 160° C. 
Several of these cotton swabs may be prepared at once and kept on hand. The 
swab, carefully removed and saturated with the material to be examined, is at once 
returned to the tube; this is plugged, and may be thus safely transported.1 
PLANT PARASITES 
II. Yeasts. 
These microorganisms-larger than bacteria and mostly saprophytes 
-consist of oval or spheroidal cells with granular protoplasm and a thin 
membrane. They multiply by sprouts or buds from the parent cell 
(Fig. 108). The new individuals may separate from the old, or may 
cling to them so that chain-like combinations may 
occur. They sometimes form endogenous spores, 
known as ascospores. Some species develop bright 
colors in their growth. 
There are many forms of yeasts which are con- 
cerned in various phases of fermentation. Some of 
these, alcoholic fermentation for example, are of great 
economic importance.2 Certain forms of yeasts flourish 
in the stomach during digestive disorders and in the bladder in diabetes 
without inciting lesions. Various yeasts have been proved to be patho- 
genic in lower animals and in man.3 
Coccidioidal Granuloma.4-Infection with the Coccidioides immitis is 
rare, only twenty-four cases having been published up to 1914. It occurs 
almost exclusively in adult males, most of the patients having been day- 
laborers, and the majority of cases have been reported in the San Joaquin 
Valley, California. It is probably not spread from person to person as in 
ordinary contagious disease, but rather seems to be acquired from some 
external source, possibly from domestic animals or through the bite of 
some insect. Judging from the clinical and pathological evidence the 
portal of entry of the parasite into the body is through the skin in many 
cases, by inhalation or by ingestion in others; but there is still much 
obscurity in regard to the definite mode of infection. The prognosis is 
very grave; in only two of the twenty-four cases recorded is recovery 
known to have occurred. The clinical course of the disease has shown 
little constancy; but there is usually a more or less irregular fever. Some 
of the skin lesions resemble mycosis fungoides. Slow, painless, sub- 
cutaneous abscesses have occurred in several cases; in others, glandular 
lesions imitating tuberculosis have been noticed. Invasion of the bone in 
various portions of the body, acute pulmonary symptoms, and meningitis 
v ,no v 
Saccharomyces. 
1 For further suggestions for the collection and examination of specimens for microorganisms, and 
for references to studies on the bacteria of the human body, see pp. 175 and 176. For methods of mor- 
phological study of bacteria, see Hiss and Zinsser, Text-Book of Bacteriology, 4th ed., New York, 
1918; Park and Williams, Pathogenic Microorganisms, 6th ed., New York, 1917; and Kolle and 
Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1912-13. 
2 For a consideration of the relationship of microorganisms to various forms of fermentation, with 
bibl., consult Jorgenson, Microorganisms and Fermentation, Eng. TransL, 1900. 
3 Stoddard, J. L., and Cutler, E. C., Torula infection in man, Monograph No. 6, Rockefeller Inst., 
New York, 1916; Pierson, P. H., Jour. Am. Med. Assn., 1917, Ixix, 2179. 
4 MacNeal, W. J. and Taylor, R. M., Jour. Med. Research, 1914, N. S. xxv, 261 (bibl.); also Brown, 
P. K., and Cummins, W. T., Arch. Int. Med., 1015, xv, 608; and Cummins, W. T., and Sanders, J., 
Jour. Med. Research, 1916, N. S. xxx, 243. 170 
PLANT PARASITES 
have been described. Several instances of acute generalized infection 
without localization and in a general way resembling typhoid fever have 
been seen. Microscopically the lesions resemble those of tuberculosis, 
and can be distinguished only by noting the presence of the spherical 
parasite with double contoured wall and filled with a granular proto- 
plasm, sometimes vacuolated, sometimes segmented. The segmentation 
or endogenous spore formation and absence of budding permits its dis- 
tinction from the Cryptococcus dermatidis described by Gilchrist1 and more 
usually known as Blastomycetes or Oidiomycetes. While the exact clas- 
sification of the parasite is still under discussion, it is unquestionably a 
fungus. The organism as it occurs in the body is a doubly contoured 
sphere varying from 5 to 50 micra or more in diameter. The capsule is 
hyaline, and varies from 1 to 5 micra in thickness. Within the cell is a 
From skin lesion, showing giant cells containing the oidium with mast cells and eosinophile cells 
in the adjacent tissue just beneath the epithelium. 
Fig. 109.-OimoMYcosis Cutis-Blastomycotic dermatitis. 
granular protoplasm, vacuolated, or segmented into numerous irregular 
daughter cells. In some cases a large sphere may be found, filled with 
numerous smaller spheres each surrounded by its individual capsule. 
Ruptured capsules are commonly found in the lesions; but the small 
parasites, either naked or encapsulated, which have escaped from these 
larger capsules, are not ordinarily recognizable until they have enlarged 
somewhat and the distinguishing capsule has developed. The parasite 
grows either aerobically or anaerobically. In the aerobic cultures made 
upon suitable media, mycelium develops. 
The extrahuman habitat of Coccidioides immitis is not known. 
Many animals are susceptible to inoculation, guinea-pigs, rabbits, and 
monkeys being most conveniently employed for experimental work. 
* Gilchrist and Stokes, Jour. Exper. Med., 1898, iii, 53. 171 
Blastomycotic dermatitis1 (Oidiomycosis) is a localized inflammation, 
papular and pustular in character, leading to warty outgrowths, to the 
formation of abscesses beneath the skin, and to ulcers. Deeper parts, 
such as bone, may be involved. Hyperplasia of epithelium and develop- 
ment of granulation tissue beneath with the formation of giant cells 
(Fig. 109), mast cells, and eosinophilic cells may be associated with the 
local growth of the blastomycetes and the formation of abscesses, the 
latter often intraepithelial. The local lesion may extend to the involve- 
ment of large areas of skin and subcutaneous tissue. 
The organism-Oidium-is present in the involved tissues as a rounded 
double contoured body (Fig. 110), varying in diameter from 10 to 20 
micra. It sometimes buds and contains 
various rounded refractile or granular 
structures. These organisms may be in- 
closed in a homogeneous jelly-like mass. 
They are readily cultivated in artificial 
media and can be successfully inoculated 
into animals, such as the guinea-pig. 
Generalization of the blastomycotic in- 
fection may take place and be fatal. In 
the systemic disease the lungs, spleen, and 
kidneys are especially involved in the 
formation of abscesses and local tissue 
hyperplasia containing the organism.2 
Thrush.-A microorganism, related to 
both the fungi and the yeasts, and fre- 
quently found in the mouth, fauces, and 
esophagus of children, in the form of a 
whitish pellicle, is the so-called Oidium albicans, which consists of 
branching, jointed threads and spores which penetrate between the epi- 
thelial cells. This fungus may assume considerable importance, when in 
very feeble children it blocks the esophagus, or when, as is rarely the 
case, from the surface of ulcers it penetrates the blood-vessels and gives 
rise to visceral metastasis. 
A tropical disease called sprue is thought to be due3 to a distinct 
species, Monilia albicans. 
PLANT PARASITES 
Fig. 110.-Oidium from a Case 
of Oidiomycosis Cutis (Blastomy- 
cotic dermatitis). 
III. Moulds. 
The moulds are considerably more complex in structure than either 
the bacteria or the yeasts. Some of the forms are very common and 
universally known. In general, it may be said that the moulds consist 
of a series of delicate, translucent, branching jointed threads-mycelium 
-usually giving rise to hyphce, from which, either directly or in more 
1 Gilchrist, Johns Hopkins Hosp. Rep., 1896, i, 269. For a r6sum6 of pathogenic blastomycetes 
with experiments and bibl., see Fullerton, Jour. Path, and Bacteriol., 1900, vi, 37; Sternberg, C., Zieglers 
Beitr., 1902, xxxii, 1; Ricketts, H. T., Jour. Med. Research, 1901, N. S. i, 377; Otis and Evans, Jour. 
Am. Med. Assn., 1903, xli, 1075; Bassoe, Jour. Infect. Dis., 1906, iii, 91; Irons and Graham, ibid., p. 
666; and Stober, A. M., Arch. Int. Med., 1914, xiii, 509. 
2 Fontaine, Hasse, and Mitchell, Arch. Int. Med., 1909, iv, 101. 
3 Ashford, B. K., Am. Jour. Med. Sc., 1915, cl, 680; Wood, E. J., ibid., p. 692; and Nicholls, L., Jour. 
Trop. Med , 1919, xxii, 21. 172 
PLANT PARASITES 
complex forms through the intervention of a special structure, the sporan- 
gium, the spores are developed (Fig. 111). The moulds which are apt to 
occur in the human body may be of the former, more simple, or of the 
latter, more complex, type.1 Among the simpler forms of moulds which 
occur in the body may be mentioned 
the Achorion Schonleinii, Micro- 
sporon furfur, Trichophyton ton- 
surans. There is a close morpho- 
logical resemblance between these 
forms. 
The Favus Fungus (Achorion 
Schonleinii), is formed of a much- 
branching mycelium from which 
the spores are directly developed 
(Fig. 112). It grows readily on 
artificial culture media, such as 
nutrient agar and gelatin, at the 
temperature of the body. This 
fungus is most apt to grow upon 
the hairy part of the head, where 
it forms small surface crusts and 
grows into the shafts and root 
sheaths of the hair, exciting inflam- 
mation in the adjacent tissue. 
Ringworm (Tinea circinata; Herpes tonsurans).-The inciting agents 
of this readily communicable disease are several species of Trichophyton 
tonsurans, which develops in the form of a moderately branching 
mycelium, forming comparatively few 
spores. It grow's in the skin, either about 
or apart from the hairs, or in the nails, 
inducing the lesions of various phases of 
ringworm which differ considerably, de- 
pending upon the particular structures in- 
volved. At body temperature it grows 
readily on artificial culture media, differing 
markedly in appearance from Achorion. 
Pityriasis versicolor.-Microsporon fur- 
fur, the mould fungus causing pityriasis 
versicolor, is more prone than the Achorion 
to the development of many spores, but 
otherwise considerably resembles it mor- 
phologically. It grows with some difficulty 
on artificial media. By its infiltration of 
the epidermis, especially of the body and upper extremities, it causes 
larger and smaller yellowish or brownish patches. 
The Higher Moulds.-The more complex types of moulds are only 
Showing mycelium, from which arise the spore- 
bearing structures, the sporangia, borne upon the 
hyphse. 
Fig. 111.-Aspergillus Glaucus. 
Fig. 112.-Achorion Schonleinii- 
Favus. 
From a culture. 
1 See Renon, Etude sui I'aspergillose chcz les animaux et chez 1'homme, Paris, 1897; Leopold and 
Levi, Gaz. des hopitaux, 1897, Ixx, 1141 (bibl.); Pearson and Ravenel, University Med. Mag., 1900, 
xiii, 391; and Sayer, Pneumonomykosis aspergillina, Jena, 1900. PLANT PARASITES 
173 
occasionally dwellers in the human body and appear to be but rarely 
the cause of disease, passing, rather, a saprophytic existence on dead 
material in parts of the body which are in communication with the air. 
Thus they may be found growing on accumulations in the external audi- 
tory canal, in dead tissue in the lungs, on walls of cavities, dilated 
bronchi, etc. Many cases have been reported, however, in which the 
moulds, especially aspergillus, have been the apparent excitants of 
serious lesions in men and animals.1 
Sporotrichosis:-An interesting group of fungi inciting lesions in man 
was discovered by Schenck2 in 1898, was later studied by Hektoen and 
Perkins,3 and has recently been more fully described by de Beurmann and 
Gougerot.4 The disease induced by these parasites had usually been con- 
fused with syphilis or tuberculosis until examination of sections and isola- 
tion of moulds from the lesions showed that they were due to a group of 
organisms differing slightly from each other in their cultural and mor- 
phological peculiarities. These organisms have been named for their 
discoverers, Sporotrichum Schencki, Sporotrichum Beurmanni, Sporo- 
trichum Jeanselmei, and Sporotrichum Gougeroti. Whether all these 
represent distinct organisms is still a matter of discussion.5 The lesions 
which they induce are chronic, often ulcerating granulomata. Large 
abscesses with secondary lymphangitis may occur, and the bones and 
synovia are occasionally involved. Cases of pyelonephritis, of general- 
ized infection, and of bronchopneumonia due to the fungus have been 
described. Three deaths are on record. The clinical diagnosis is not 
difficult to one who is familiar with the disease, but it is usually necessary 
to make sections or cultures from the lesions. In sections the character- 
istic oval spores may be found, either free or in connection with the myce- 
lium or in phagocytic tissue cells. The fungus grows abundantly at room 
temperatures on Sabouraud's medium, which is composed of water, 
1,000 g.; peptone, 10 g.; glucose, 40 g.; agar, 18 g. When the mould is 
removed from the medium and examined it is found to be composed of a 
branching mycelium with oval or pear-shaped spores attached in contin- 
uity or forming lobulated masses at the ends of the mycelial threads. 
Methods of Studying Yeasts and Moulds. 
The yeast organisms are in general stained and cultivated by the same methods as 
those used in studying the bacteria. By treating unstained sections of tissue contain- 
ing them with a solution of caustic potash the organisms may often be readily 
demonstrated. 
The higher moulds may be simply teased and studied in glycerin or in glycerin and 
water. They may be stained with alkaline-methylene-blue solution Loeffler's solu- 
1 For r6sum6 and bibl. of relationship of yeasts and moulds to human diseases consult Ricker, G., 
Lubarsch-Ostertag, Ergebn. d. allg. Path., 1896, i, 892. See also Hektoen, L., and Perkins, C. F., Jour. 
Exper. Med., 1900, v, 77; Plaut, H. C., Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 
2d ed., 1913, v, 1; Buschke, A., ibid., p. 155; Gougerot, H., ibid., p. 211. 
2Schenck, Bull. Johns Hopkins Hosp., 1898, ix, 286. 
3 Hektoen and Perkins, Jour. Exper. Med., 1900, v, 77. 
4 de Beurmann and Gougerot, Trait6 des sporotrichoses, Paris, 1912. See also Hamburger, W. W., 
Jour. Am. Med. Assn., 1912, lix, 1590; Taylor, K., ibid., 1913, lx, 1142; Meyer, ibid., 1915, Ixv, 579 
(bibl.); and McLean, ibid., 1917, lxix, 1774. 
5 Meyer and Aird, Jour. Infect. Dis., 1915, xvi, 399. 174 
PLANT PARASITES 
tion). When spores have formed in considerable numbers on the more complex forms 
of moulds, these are not easily wetted by the usual staining fluids, because the air 
clings so closely among the spore masses. In a mixture of four parts of alcohol and 
one of aqueous solution of ammonia they are instantly wetted, and may then, with or 
without staining, be teased and mounted in glycerin. In studying the moulds in the 
above-described skin diseases it is well, when crust-like masses are to be teased apart, 
to allow them first to soak for a few minutes in a 5 per cent, solution of caustic potash. 
In this solution they may be studied, or they may be teased and mounted in glycerin 
for preservation. Most of the more common moulds are readily grown on the ordinary 
culture media. CHAPTER VIII. 
THE RELATIONS OF MICROORGANISMS TO DISEASE-INFECTION 
AND IMMUNITY. 
THE PRESENCE OF BACTERIA AND OTHER MICROORGANISMS IN THE 
BODY: ITS PROTECTIVE MECHANISM. 
The Presence of Bacteria.-Bacteria are invariably present in greater 
or less numbers in the mouth, nose, upper air passages, gastrointestinal 
and genitourinary tracts of men and animals.1 Into these places they 
are more or less constantly brought by the respired air,2 by food and 
drink, and in other ways. They are always abundant upon the skin and 
about the hairs, and the sweat and sebaceous glands. But common and 
often abundant as are these germs upon the external and internal surfaces 
of the body, they do not often pass through the healthy mucous or cuta- 
neous surfaces,3 so that under normal conditions the tissues, the viscera, 
and the circulating fluids are practically sterile. 
Except for certain pathogenic forms which may, under unsanitary 
conditions, have been set free and transported from men or animals 
suffering from infectious disease, the bacteria upon the cutaneous or 
mucous surfaces of the body are for the most part harmless; while cer- 
tain intestinal forms may even be useful, though not necessary, in pro- 
moting digestion. Such symbiotic relationship may continue uninter- 
rupted throughout life unless some injury offers a portal of entry or the 
reduction of the natural resistance permits stray organisms, which have 
penetrated the natural boundaries, to obtain a foothold. 
The Safeguards of the Body.-The body is guarded in various 
ways from the incursions of pathogenic and other bacteria, which may be 
commonly present or only occasionally lodged upon its surfaces. Among 
the protective agencies of the body may be mentioned the firm, dense 
skin which while intact protects the interior from the entrance of almost 
all known microorganisms; the epithelial investment of the mucous mem- 
branes, in several places swept by cilia; the protected situation of most of 
the mucous surfaces, the germicidal qualities of some of the secretions, 
.such as the saliva, gastric juice, mucus, etc.4 
1 For a summary of facts concerning the bacterial flora of the body surfaces consult Welch, Surgical 
Bacteriology, System of Surgery; see also Ford, Trans. Assoc. Amer. Phys., 1900, xv, 389 (bibl.); and 
Setter, Ztschr. f. Hyg., 1906, liv, 363. 
2 For a r6sum6 of microorganisms in the air see Gottstein, A., Lubarsch-Ostertag, Ergebn. d. allg. 
Path., 1897, iv, 87; also Firth, Studies from the Department of Pathology, Col. Phys, and Surg., 
Columbia University, 1899-1900, vii; and Chapin, C. V., Jour. Am. Med. Assn., 1914, Ixii, 423 
3 It should be remembered that the gastrointestinal canal, the lungs, and other viscera which are 
in communication with the exterior, although within the limits of the body, still form, strictly speaking, 
its outside, in distinction from the intimate recesses of the tissues in which the life processes go on. 
4 For a r6sum6 of the protective action of the skin, mucous membranes, etc., see Metchnikoff, Im- 
munity in Infective Diseases, 1905. 
See for summary of protective agencies of the lungs, p. 684. For a study of the action of saliva on 
bacteria see Clairmont, P., Wien. klin. Wchnschr., 1906, xix, 1397 (bibl.). For bactericidal action of 
mucus see Arloing, Jour, de phys. et de path. g6n., 1902, iv, 291 (bibl.). 
175 176 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
The Portals of Entry.-But notwithstanding the safeguards of 
the body against the access of microorganisms, these do frequently enter; 
this may occur in severe injuries to the skin or mucous membranes or 
through very slight and unnoticed abrasions or other solutions of con- 
tinuity. Entrance may be gained to the tissues through the minute ducts 
of the sebaceous or sweat glands; from the mouth, tonsils, gastrointes- 
tinal canal,1 and the respiratory passages and surfaces, either with or 
without obvious injuries to the investing epithelia. The role of insects 
in the conveyance of infectious agents is of great importance.2 Micro- 
organisms may enter the body during intrauterine life.3 
There is abundant evidence that even in health, through the pharynx, 
tonsils, and intestines, a small number of bacteria frequently enter 
the recesses of the body, but are safely disposed of through the 
protective mechanism presently to be considered. So that while we 
may, as above stated, consider the interior of the healthy body as 
practically sterile, it is still possible by careful and discreet searching 
to discover here and there bacterial detritus and bacteria on their way 
to destruction.4 
The Protective Mechanism.-When in one way or another bacteria 
or other germs have entered the tissues, they may encounter a series of 
obstacles to their spread or continuance as well as to their proliferation 
there, even should the general nutritive conditions be favorable. In the 
first place the lymph-nodes filter out of the tissue fluids microorganisms 
which have entered them, holding them back from the general circula- 
tion or destroying them.5 The power of certain of the body fluids and of 
living cells-phagocytes-under favorable conditions to kill and dispose 
of germs, is of great importance and will be referred to again.6 The elimi- 
nation of microorganisms from the body through its secretions,7 such as 
urine, bile, milk, sweat, saliva, etc., is a matter of great significance, but 
one upon which the scope of this book does not permit us to enter.8 
1 For bibliography concerning the permeability of the gastrointestinal canal for bacteria refer to 
p. 774. 
* Nuttall, Johns Hopkins Hosp. Rep., 1900, viii, 1. For a r6sum6 with bibl. of the transmission of 
infective material by flies and other insects see Chapin, Sources and Modes of Infection, 2d ed.. 
New York, 1912; also Graham-Smith, Flies in Relation to Disease, Cambridge, 1913; for study of 
economic loss by insects see Howard, U. S. Dept. Agricult., Bureau of Entomology, Bull. 78, 1909. 
' For a r6sum6 of studies on the congenital transmission of infectious agents see Wassermann and 
Keysser, Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1912, i, 659 
(bibl.); also, Balantyne, Antenatal Pathology, 1902; and Lynch, Bull. Johns Hopkins Hosp., 1902, 
x, 283. 
4 Adami, J. G., Jour. Am. Med. Assn., 1899, xxxiii, 1509, 1572; and Brit. Med. Jour., 1914, i, 177; 
and Wrzosek, A., Virchows Arch., 1904, clxxviii, 82; see also for an experimental study of the disappear- 
ance of bacteria from the blood, Schwarz, Ztschr. f. Heilk., Abth. f. Path. Anat., 1905, xxvi, 295. 
6 Manfredi, L, Virchows Arch., 1899, civ, 335, for a study of the germicidal and other action of 
lymph-nodes; also Bezancon and Labbe, Arch, de m6d. exp6r., 1898, x, 389. 
6 For studies of the capacity of the living body to dispose of bacteria when these are injected into the 
blood, see Werigo, Ann. Inst. Pasteur, 1894, viii, 1; also Bail, Arch. f. Hyg., 1905, lii, 272; and Buxton 
and Torrey, Jour. Med. Research, 1906, N. S. x, 5. 
7 Consult Sherrington, C. S., Jour. Path, and Bacteriol., 1893, i, 258; Biedl and Kraus, Arch. f. 
exper. Path., 1895, xxxvii, 1 (bibl.); Hintze and Lubarsch, Lubarsch-Ostertag, Ergebn. d. allg. Path., 
1896, i1, 287. For study of disappearance of bacteria from the body, see Pawlowsky, Ztschr. f. Hyg. 
u. Infectionskrankh., 1900, xxxiii, 261; also Asch, Centralbl. f. d. Krankh. d. Harn- u. Sex.-Org., 1902, 
xiii, 249, 324. 
8 For a suggestive summary of the various factors which are or may be concerned in the protection 
of the body against the invasion and action of microorganisms, see Meltzer, Trans. Cong. Am. Phys, 
and Surg., 1900, v, 12; see also ref. to Wassermann above. 
See also for the importance of a lesion in animal tissues for the lodgment and multiplication of 
bacteria within it, Cheesman and Meltzer, Jour. Exper. Med., 1898, iii, 533; and Brewer, G. E., on THE RELATIONS OF MICROORGANISMS TO DISEASE 
177 
ACTION OF BACTERIA AND THEIR PRODUCTS IN THE BODY. 
The Bacteria.-When bacteria do enter and grow in the body, the cells 
and tissues near them may show very marked alterations, due to their in- 
fluence. The cells may be swollen, or their nuclei may disappear, and the 
protoplasm may be converted into hyaline material or into a mass of 
transparent or coarsely granular particles, or may completely disintegrate. 
The intercellular substance near the bacteria may also soften and disin- 
tegrate. In a word, the tissue in their immediate vicinity is often 
found in a condition of necrosis of one kind or another. The walls of 
blood-vessels near which they lie may be damaged and the blood which 
these carry may form thrombi. The bacteria may themselves enter the 
vessels and proliferate in the blood; they may be swept away as emboli 
to remote parts of the body (Fig. 61, page 105), and establish new foci 
of bacterial proliferation and tissue necrosis-septicemia. 
Some bacteria, instead of inducing a simple necrosis, incite at the 
same time, as we have already seen, a more or less intense inflammation 
(Fig 62, page 106). This inflammation may be of a simple productive 
form, similar in its effects to that incited by the presence of any irri- 
tating foreign body; or it may be active, progressive, and exudative in 
character; or the bacteria may determine, in some way as yet unknown 
to us, very peculiar and characteristic inflammatory changes, which result 
in the formation of new tissues of various kinds (see Tuberculosis). 
Some forms of bacteria find in the blood, others in the tissue spaces and 
lymph-vessels, the conditions most favorable for their proliferation. 
Others seem to select certain sites for their activities; for example, the 
Streptococcus viridans usually attacks the heart valves; the pneumo- 
coccus, the cornea and the lungs. 
Bacterial Poisons.-But the presence of microorganisms themselves 
is not indispensable for the incitement of either local or general pathologi- 
cal processes. These may be induced by various chemical products 
eliminated or stored up in their protoplasm by the metabolism of the 
germs. These deleterious bacterial products may, as we have already 
seen, be those substances called toxins, or they may be albuminoid sub- 
stances-toxalbumins or toxalbumoses. Stored up in the protoplasm of 
the germs themselves, this poisonous material has been called bacterio- 
protein and endotoxin. 
It seems probable that the toxic effects of some bacteria may be due 
not to their immediate product but to the action of bacterial enzymes, 
whose effects upon certain body proteins result in the development of 
the toxic albumoses which are the active damaging factors.1 
unilateral infection of the kidney following injury, Surg., Gynec., and Obst., 1906, ii, 485; also on the 
significance of granulation tissue in wound infection, Afanassieff, Zieglers Beitr., 1897, xxii, 11; Cobbctt 
and Melsome, Centralbl. f. allg. Path. u. oath. Anat., 1898, ix, 827 (bibl.); and Jiirgeliinas, A., Zieglers 
Beitr., 1901, xxix, 92 (bibl.). For the role of the spleen in infection and intoxication see Courmont and 
Duffau, Arch, de med. exp6r., 1898, x, 431, Nicolas and Beau, Jour, de physiol, et path., 1909, iii, 68; 
Morris, D. H., and Bullock, F. D., Ann. Surg., 1919, Ixx, 513. 
1 Much of the literature on this subject has been brought together by Vaughan and Novy, Cellular 
Toxins, 4th ed., Philadelphia, 1902. See also Vaughan, Protein Split Products in Relation to Immunity 
and Disease, New York, 1913. The general chemical relationship of bacterial products to other organic 
compounds is set forth in Wells, Chemical Pathology 4th ed., Philadelphia, 1920, p. 101; see also Pick. 
E. P., Kolle and Wassermann, Hanbunch d. path. Mikroorganismen, 2d ed.,1912, i, 685. 178 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
Thus, it has been found that the maceration of blood serum for a few 
hours with dead bacteria or trypanosomes, with minute quantities of 
agar or peptones, or even with insoluble materials such as kaolin or 
barium sulphate, produces in the serum a toxic body capable of causing 
anaphylactic shock.1 Such a body must exist in the blood in a highly 
labile condition, since it is influenced by substances whose functions must 
be exhibited solely in their colloidal condition. That such colloidal 
states may be of importance is shown by the fact that an intravenous in- 
jection of a freshly prepared aqueous solution of a dye, Bordeaux red, is 
harmless, but that if the colloidal state of the solution is altered by 
boiling for a short time or by standing for a few hours, almost instan- 
taneous death of the animal results from the injection. This effect seems 
due to intravascular clotting. The toxic powers of bacteria may be due, 
therefore, in some instances, not to specific toxins produced from their 
bodies, but merely to alteration in the condition of an otherwise harmless 
protein of the normal blood serum. 
A similar change may lie at the root of a phenomenon discovered by 
Bail, who found that when one injects into animals sterilized exudates 
induced by the action of various pathogenic microorganisms-tubercle, 
typhoid, and dysentery bacilli, pneumococcus, staphylococcus, etc.- 
together with sublethal doses of cultures of the organisms themselves, 
the death of the animal is brought about much sooner than when the 
bacteria alone are introduced. Bail, as the result of many experiments, 
assumes that under these conditions the exudate contains substances 
which foster the deleterious effects of the living organisms by inter- 
fering in some way with the protective agencies of the body. These 
hypothetical substances he has called aggressins, and he believes them to 
be formed by the bacteria as they grow in the body.2 This aggressin 
theory has not found general acceptance and much experimental evi- 
dence has been brought forward to controvert it.3 
Intoxication-Toxemia.-Some of the poisons act locally at or near 
the seat of their manufacture by the growing germs. Others gain access 
to the body at large and are widely distributed, inducing what may be 
called the phenomena of septic intoxication-toxemia. 
The phenomena of septic intoxication may be induced by the prod- 
ucts of bacterial growth outside of the body when these in considerable 
quantity are in any way taken into it. This is true not only of poisons 
elaborated outside the body by pathogenic bacteria, but also of many 
forms of bacteria usually harmless. Thus are caused many kinds of 
food poisoning which simulate but are not actually infectious diseases, 
because there is no development within the body of the disease-inciting 
germs. 
Similar local and general effects may be induced in the body by other 
poisons than those of bacterial origin. Ricin and abrin, for example, 
well-known vegetable poisons, and the venom of scorpions and of certain 
1 Novy, F. G., and DeKruif, P. HJour. Am. Med. Assn., 1917, Ixviii, 1524. 
2 For a discussion of the so-called aggressins see Bail and IFeiZ, Centralbl. f. Bakteriol., Orig. I, 
1906, xlii, 51, 139, 241, 335, 437, and 433. 
3 See Sauerbeck, Ztschr. f. Hyg. u. Infectionskrankh., 1907, Ivi, 81. THE RELATIONS OF MICROORGANISMS TO DISEASE 
179 
snakes are closely similar in their action to the toxins which the bacteria 
form either within or without the body. 
It should be remembered in this connection that effects closely resem- 
bling those due to bacterial or allied poison may be induced by toxic 
agents developed within the body as a result of defective elimination or 
faulty cell metabolism-autointoxication (page 482). 
Thus the deleterious effects of pathogenic bacteria upon the body are 
but in small measure simply mechanical. Local necrosis and inflam- 
mation, albuminous degeneration of cells, leucocytosis and1 other altera- 
tions of the blood, fever, structural lesions and functional disturbances 
in the nervous system, irregularities in the circulatory and respiratory 
mechanisms, hemolysis and agglutination of the red blood-cells, and 
thrombosis,2 etc., may follow the distribution in the body of bacterial 
toxins,3 a good example of which is the extract of tubercle bacilli known 
as tuberculin. 
PROOFS OF THE INFECTIVE NATURE OF BACTERIA FOUND IN THE BODY 
It will be seen, from what has now been said of the bacteria, that in 
different parts of the system in health, and in a large number of abnor- 
mal conditions, various forms of bacteria occur; but it is quite evident 
that the significance which we must attach to their mere presence varies 
greatly. In a large number of cases, especially when on parts exposed 
to the air or in the gastrointestinal canal, they are evidently of no more 
importance than so much inorganic dust. When, however, special 
forms of bacteria are uniformly present in connection with well-defined 
diseases, or in their lesions, and especially if these largely preponderate, 
the conjecture is certainly justified that the microorganisms may have 
something to do with their incitement. Yet in all such cases we have to 
consider the possibility that it is the abnormal state of the body or the 
character of a lesion, brought about perhaps in other ways, which 
affords conditions suitable for the growth of this form of bacteria, and 
that these may consequently be present in considerable numbers, while 
in the absence of such conditions they would be unable to develop. 
Even the constant presence in the body, in certain diseases, of bacteria 
which evidently produce well-marked local effects, either inflammatory 
or degenerative, does not absolutely prove their etiological relationship 
to the disease, although it renders it in a high degree probable. 
It is desirable in every case in which the evidence of the etiological 
relationship of a specific microorganism to a disease is to be set forth, 
that we should be able to demonstrate the constant presence in the body 
of the special form of microorganism during some period of the disease, 
obtain this by culture in a pure condition unmixed with any other living 
thing or with any chemical substance not belonging to it, and finally, by 
the introduction of the purified organisms into a healthy animal, be able 
1 See Flexner, Johns Hopkins Hosp. Rep., 1897, vi, 259. 
2 For bacterial hemolysins see Pribram, Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 
2d ed., 1913, ii, 1328. 
3 On the theory of bacterial infection, see Radziewsky, Ztschr. f. Hyg. u. Infectionskrankh., 1901, 
xxxvii, 1. 180 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
to induce the disease in some definite form. When all this is done, and 
not before, can we assert that the evidence establishing the causative 
relationship between a given form of bacteria and any special infectious 
disease, is entirely at our command. 
But the fulfilment of these strict logical requirements is very difficult 
in many cases, and in some, apparently, almost if not quite impossible; 
for we must remember, in the first place, that the lower animals, upon 
which alone, for the most part, inoculation experiments are practicable, 
are apparently not subject to certain important diseases of man; and, 
second, that they present among themselves the most marked differ- 
ences in the degree and manner in which they are affected by inocula- 
tion with pathogenic bacteria. Desirable as is the complete fulfilment 
of the above requirements in every case, it must be admitted that a rea- 
sonable certainty regarding the bacterial origin of a given disease may 
sometimes be arrived at without positive results from the inoculation 
of the bacteria associated with its lesions. The agglutination test and 
the tests for specific lytic substances or opsonins applied under proper 
conditions may afford valuable evidence of the nature of an infection 
(see pages 213 and 222). 
The complete demonstration which is desirable has as yet been fur- 
nished in but a moderate number of diseases. In many others, however, 
enough has been done in the way of study and experimentation to render 
it altogether certain that they are infectious and to establish beyond 
reasonable doubt the identity of the microorganism or microorganisms 
involved. 
CONDITIONS INFLUENCING THE OCCURRENCE OF INFECTIOUS DISEASES. 
Conditions of the Body.-It has been learned as a result of a great 
deal of observation and experiment, that although certain diseases are 
always associated with the presence and growth in the body of particular 
species of microorganisms, there are still various other accessory factors 
which have an important bearing upon the inception and course of the 
diseases. Thus, while the presence in the body of a particular species of 
microorganism is the most significant and fundamental of the determin- 
ing agencies in the infectious diseases, the numbers in which they are 
present-i.e., the size of the dose-and the varying virulence which the 
same species under different conditions possesses, as well as the varying 
capacity of resistance to the incursions of the germs which the body-cells 
at different times and under differing conditions exhibit, are all factors 
of the greatest moment. 
Malnutrition, mental or physical overwork, injuries, bad hygienic 
surroundings, the abuse of alcohol and other forms of intemperance, as 
well as many other conditions which lead to deterioration in the general 
health, are often decisive factors in determining the intensity or even 
the occurrence of the diseases due to bacterial incitement. It is thus 
clear that the action of a given germ in the living body depends only in 
part upon its intrinsic capacities-which in themselves are very variable 
-but also and in marked degree upon the capacities, also variable. THE RELATIONS OF MICROORGANISMS TO DISEASE 
181 
which exist at the moment in the body-cells among which the lot of the 
germs is cast. 
It should be always borne in mind that the human body is a great 
aggregate of groups of coordinated cells which, under normal conditions, 
all act in harmony for the maintenance of the life and functions of the 
individual. The cells and cell communities in health not only do this, 
but they have the power of resisting and to a certain extent overcoming 
various deleterious agencies to which the body is more or less constantly 
liable. 
What we call hereditary or acquired predisposition to an infectious 
disease, such as tuberculosis, for example, is simply a lack of the usual 
capacity of the cells of the body-whether through a structural or physi- 
ological fault we do not yet know-to cope with-that is successfully to 
adapt themselves to-the destructive tendencies of the living micro- 
organisms w'hen once these gain a foothold in the body. 
Conditions of the Microorganisms.-On the other hand, the varying 
potencies of the bacterial species concerned in a given infection, which 
are linked especially to their toxins, and the influence of environment 
upon these, exalting or reducing them, as the germs adapt themselves to 
antagonistic or to congenial hosts; the origin of the strains and the 
numbers involved-these are all factors in virulence of supreme impor- 
tance; but our space does not permit us to consider them further here. 
We thus see that, in studying the conditions under which infectious 
diseases occur, the work is by no means complete when the bacterial 
species which incites the disease has been discovered, but that then the 
more obscure determining and influencing agencies must be worked out 
in each case.1 
Infection and Immunity. 
INFECTIOUS DISEASE AND THE NATURE OF INFECTION. 
Infectious diseases are those which are incited by the entrance into the 
body and proliferation there of pathogenic microorganisms. Infection 
is the act or process by which such diseases are incited. The process of 
infection is "the interaction between the organism and the micro- 
organism." 
In the more exact usage of the words "infectious" and "infection" 
which our new knowledge demands, it is customary and convenient to 
limit the term "microorganism" to the fungi-bacteria, yeasts, and 
moulds-and to the protozoa representing the animal kingdom, exclud- 
ing altogether the entozoa and other animal parasites.2 
The modern conception of infection implies the presence in the body 
of the living microorganisms themselves; that is, of something capable 
of multiplication, or at least of reproduction and development, and not 
1 For a resum6 of the nature and conditions of infection, see Wassermann and Keysser, Kolle and 
Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1912, i, 555 (bibl.); for a study of the 
general reaction of the body in infection, see Blumenthal, ibid., 1st ed., i, 326. 
2 With this somewhat arbitrary limitation, neither trichinosis nor scabies, for example, would be 
considered an infectious disease, although they are often, for the lack of a distinctive word, thus desig- 
nated. Infestious and injestion are not infrequently employed for animal parasites. 182 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
alone of the poisons which they may and usually do produce. It is 
customary to look upon the effects of the absorbed poison which micro- 
organisms furnish as intoxications, whether these poisons be formed 
inside the body in infectious diseases and in other conditions, or outside 
of it and subsequently introduced. That condition in which there is 
evidence of wide distribution of pathogenic microorganisms and their 
products in the blood is called septicemia (page 232). 
It is evident from what has been said that infectious disease cannot 
exist without the presence in the body of microorganisms. But, on the 
other hand, microorganisms can and do frequently exist in the body 
without the incitement of infectious disease. Whether a microorgan- 
ism be pathogenic or not depends upon the variable susceptibilities of 
the host as well as upon its own-also variable-nature and qualities. 
No microorganism is intrinsically pathogenic; the very conception 
implies a relationship. This obvious fact is overlooked by those who see 
in the microorganisms alone the essential specific features of infectious 
diseases; who would classify these diseases exclusively by the nature of 
their excitants, and who look upon the latter as the true "causes" of 
the phenomena through which disease is manifested (page 6). 
INCUBATION PERIOD. 
It is characteristic of infection that a certain time elapses between 
the entrance of the infective agent and the manifestation of symptoms 
or the development of lesions. This interval is called the " incubation 
period" of the infection and varies with different infective organisms. 
This incubation period is that time during which the microorganisms 
are increasing sufficiently in number or virulence in the body to induce 
symptoms and lesions or are passing through developmental cycles 
marking their adaptation to the environment furnished by the host. 
During this incubation period the body may become very sensitive to a 
renewed infection with the same organism, and may show such sensitiza- 
tion in various ways. Thus, a quiescent tuberculosis renders the whole 
organism reactive to an injection of tubercle-bacillus toxin, while the 
sensitization of the skin affords a convenient diagnostic reaction, which 
bears the name of v. Pirquet.1 
FORMS OF INFECTION. 
Mixed or Concurrent Infection.-It should be borne in mind that the 
body which is already the seat of an infectious disease is usually espe- 
cially susceptible to the action of other pathogenic germs, should these 
once gain entrance; and also that the lesions which are associated with 
many of the infectious maladies afford portals of entry through the skin 
or mucous membranes to other microorganisms, against the entrance of 
which the healthy body opposes most efficient barriers. In fact, we now 
know that the action of two or more pathogenic microorganisms in the 
body at the same time is of very frequent occurrence, many of the 
1 ®. Pirquet, Die Serumkrankheit, Vienna, 1905. THE RELATIONS OF MICROORGANISMS TO DISEASE 
183 
so-called complications of the infectious diseases being due to secondary 
infection with a new germ species. Numerous examples of this " mixed " 
or, better, " concurrent," infection are noticed in other parts of this 
book.1 
Many important facts have been revealed by the study of bacterial 
association in cultures as well as in infectious diseases of men and ani- 
mals which cannot here be considered.2 It may be said in general that 
in animals as in man concurrent infection with a second microorganism 
increases the gravity of the original situation. On the other hand, cer- 
tain experiments seem to indicate that sometimes the concurrent action 
of a second germ-streptococcus, for example, with the anthrax bacillus 
-may render a virulent organism comparatively innocuous. But the 
conditions of the experiments are in either case so complex that the full 
significance of many curious phenomena is not yet apparent. 
Congenital Infection.-Infection of the fetus through such lesions of 
the placenta as permit of the passage of pathogenic microorganisms from 
the blood of the mother to that of the child is of occasional, but not 
frequent, occurrence. While the barriers against such transmissions are, 
under normal conditions, effective, disturbance in the placental circula- 
tion, lesions of the vessel walls or of the tissues and covering of the 
chorionic villi favor it. But infection may occur without demonstrable 
evidence of such lesions. Thus fetal infection is known to have occurred 
in various phases of suppurative inflammation, in tuberculosis, typhoid 
fever, anthrax, syphilis, the exanthematous fevers, etc. There is con- 
siderable evidence that rarely the tubercle bacillus may be transmitted 
from mother to offspring, and remaining for a time inactive may later 
induce the characteristic lesions.3 
Terminal Infection.-The victims of chronic disease of the heart, 
blood-vessels, kidneys, liver, etc., are particularly susceptible to the 
incursions of pathogenic microorganisms and to infectious diseases of 
one kind or another. Such persons, with or without definite lesions, 
are in fact liable finally to succumb to the complicating disease. The 
phrase "terminal infection" has been applied by Osler and others to 
this concurrence of diseases of such different nature, in which the chance 
infection of a vulnerable organism is so apt to prove fatal.4 
Great care is, however, necessary in determining the significance of 
the various forms of bacteria which may be present in the body after 
death. Not only may bacteria develop to a considerable extent in the 
body during the hours which precede death when the natural protective 
agencies are halting or abeyant, but this may occur without such a 
reaction on the part of the body-cells as is necessary to constitute an 
actual infection. Furthermore, multiplication and distribution of bac- 
1 For bibliography of mixed infection see Bernheim and Gruber, Lubarsch-Ostertag, Ergebn. d. allg. 
Path., 1895, ii, 1; also Wassermann and Keysser, Kolle and Wassermann, Handbuch d. path. Mikro- 
organismen, 2d ed., 1912, i, 632. 
2 Consult Th. Smith, Trans. Assn. Am. Phys., 1894, ix, 85: also Moore, Pathology and Differentia 
Diagnosis of Infectious Diseases of Animals, 1906. 
3 For bibliography and summary of fetal infection, see Lubarsch, Lubarsch-Ostertag, Ergebn. d. 
allg. Path., 1896, il, 427; also Fischl, in Grancher, Comby, and Marfan, Trait6 des Maladies de 
1'Enfance, Paris, 1904, i, 454 (bibl.). 
4 For a study of this class of cases, see Flexner, Trans. Assn. Am. Phys., 1896, xi, 229. 184 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
teria in the body after death is of frequent occurrence and must in every 
case be taken account of in weighing the evidence for terminal infection. 
It is important in practical dealings with the infectious diseases to 
consider them in the light of the relative liability of transmission of the 
actually known or assumed microorganisms from diseased to healthy 
individuals.1 
In the first place, it should be borne in mind that the lower animals 
are insusceptible to the ravages of some of the microorganisms which 
readily incite infectious disease in man. Thus the lower animals with 
the exception of the primates and the rabbit are, so far as we know, 
naturally immune to syphilis. To certain diseases of the lower animals, 
on the other hand, man is not subject. But to certain other infectious 
diseases, tuberculosis for example, both men and lower animals are sus- 
ceptible, and both are, in fact, under the prevailing conditions of modern 
life, frequent victims. 
So far as the liability to the transmission of the infectious agents from 
man to man is concerned, there is a very marked and significant differ- 
ence between the infectious diseases. It is common usage to speak of the 
transmission or communication of disease, as if disease were a self-exist- 
ent thing. This usage fosters much loose thinking. What we call dis- 
ease is a process involving a departure from, failure in, or perversion 
of normal physiological action, either in the material constitution or in 
the functional integrity of the living organism. When, therefore, we 
speak of the transmission or communication of disease, w'hat we really 
mean is not that the disease, but the agent capable under suitable con- 
ditions of inciting the disease, is transmitted or communicated. If we 
hold this obvious implication in mind, it is useful to group the infectious 
diseases of man into two great primary classes: 1st, Those which under 
the usual conditions of life are not readily communicable. 2d, Those 
which under the usual conditions of life are readily communicable. 
But while, for convenience, we may speak of non-communicable and 
communicable infectious diseases, we should remember that these two 
classes merge into each other, and that in fact the agents of infection 
may at least artificially in all cases be conveyed from one individual to 
another. It is only when the conveyance under natural conditions occurs 
in a round-about way, or through intermediary agencies, such as the 
mosquito for example, in malaria or yellow fever, that one may advis- 
edly speak of non-communicable infectious diseases. 
Among the communicable infectious diseases there exists the widest 
difference in the liability to transmission under ordinary circumstances. 
Thus the infectious agents in measles are given off from the body under 
such conditions as render possible and frequent their direct transmission 
to another individual without the obvious contacts of person or discharges 
with which the conveyance of infective agents is associated in most of the 
COMMUNICABILITY OF INFECTIOUS DISEASES. 
1 See Chapin, Sources and Modes of Infection, 2d ed., New York, 1912. the relations of microorganisms to disease 
185 
communicable diseases. In syphilis, tetanus, and rabies, on the other 
hand, transmission of the infectious material is rare or impossible without 
a direct inoculation. 
Between these extremes the widest diversity exists in the liability to 
transmission of the infectious agents of the diseases of this class. In 
fact the liability to infection on the part of a healthy individual in the 
presence of a victim of infectious disease is largely dependent upon the 
intelligent care which is exercised in the disposition of the material con- 
taining the pathogenic microorganism, usually secretions or excretions, 
which in one way or another the infected body sets free. 
So that while it may be useful to arrange the communicable infectious 
diseases in groups, or in such serial order as may indicate the degree of 
communicability of each under the ordinary conditions of life, it should 
always be borne in mind that this classification is not fundamental, as is 
that by which the infectious diseases as a whole are set apart from other 
diseases, but is closely dependent upon the sanitary conditions under 
which each case may be placed. Thus tuberculosis, or diphtheria, or 
pneumonia may be high on the list as readily communicable if the 
patient be housed in a crowded tenement with ignorant or careless attend- 
ants, while if subjected to the intelligent ministry of sanitary science 
these diseases may be accounted as relatively slightly communicable.1 
Communicable infectious diseases sometimes affect a considerable 
number of persons in a community. This constitutes an epidemic, and 
the term epidemic disease is used. So also if an infection is constantly 
present in a certain locality it is said to be endemic. The term pandemic 
is used to indicate the involvement in a particular infectious disease of 
persons scattered over a large territory. 
IMMUNITY. 
Nature and Forms of Immunity. 
We have seen that an infectious disease is one incited by the entrance 
into the body and proliferation there of pathogenic microorganisms, and 
that infection is the act or process by which such a disease is incited. 
The fact that all animals are not equally susceptible to the ravages of 
pathogenic microorganisms, and that in man an individual and often a 
changing predisposition or invulnerability to the incursions of these 
organisms exists; the further observation that one attack of an infectious 
disease often protects the victim for a longer or shorter time against a 
recurrence; finally, the fact that recovery is ever possible when once 
self-multiplying disease-producing germs have obtained a foothold in the 
body-all these facts and observations are of such singular import and 
interest that, especially of late years, there has been much study on 
the nature of the agencies which the body brings into play in establish- 
1 Before the knowledge of pathogenic microorganisms had become precise, readily communicable 
diseases were called contagious in a rather loose and ill-defined way, and the unknown excitant was 
called the contagtum. The word "contagious" is still used, in various senses, to the detriment of 
science and should be replaced by the word "communicable" as above indicated. 186 
ing immunity in the face of microbic invasion, and in coping with the 
various deleterious factors at work when once a foothold is obtained. 
The scope of this book does not permit us to enter in detail into this most 
fascinating and important field. We can give only a brief summary of 
some of the more important features. 
Immunity is insusceptibility, or capacity for resistance on the part of 
the body to disease or, in the more limited sense, to infection or intoxication 
or their effects. 
If we recall the ways in which bacteria damage the organism, it will 
be evident that immunity may be due to the fact that the microorgan- 
isms in question simply do not proliferate in the body, failing, even 
should they gain entrance, to find the necessary conditions.1 On the 
other hand, though the conditions be in general favorable, substances 
may exist or be formed in the body which destroy the invading germs. 
In other words these may at once or soon be disposed of by germicidal 
substances, either in cells or in solution in the body fluids. 
Or, the toxic substances which microorganisms set free, as in the 
process of their nutrition they decompose organic ingredients of the tis- 
sues or body fluids, may be rendered inert by further decomposition or 
combination with substances present or formed in the tissue fluids. Or, 
furthermore, the cells which are susceptible to the presence of the toxins 
may become less vulnerable by adaptation to the deleterious effects of 
the latter. 
Immunity from an infectious disease may be natural or hereditary.2 
The absolute or relative insusceptibility of turtles and fishes for 
tetanus, of rats for anthrax, and of many of the lower animals for syphilis 
and for scarlatina, are examples of hereditary or natural immunity which 
we need not further consider here. Immunity is variable and rarely abso- 
lute, and is subject to individual, as well as racial, variation. 
On the other hand, immunity may be acquired. Acquired immunity 
may be secured by an attack of the disease from which the individual 
has recovered-natural immunization. Or, immunity may be acquired 
by the introduction into the body of some material which gradually 
diminishes susceptibility without inducing distinct disease-artificial 
immunization. Acquired immunity may be transmitted from parent to 
offspring. 
Most of the infectious diseases appear to confer a certain degree of 
insusceptibility to subsequent attacks of the same disease, though this 
may be partial and temporary. The exanthemata afford the most 
striking examples of acquired immunity after an attack of infectious 
disease. 
Let us now look more closely at some of the ways in which the body 
may thus protect itself from the consequences of infection. 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
1 For a most suggestive and valuable paper on the adaptation of pathogenic bacteria to different 
species of animals, see Theobald Smith, Philadelphia Med. Jour., 1900, v, 1018. 
2 For a study of the theories of natural immunity, see Mailer, Infection u. Immunitat, 1912. For a 
study, with bibl., of the protective processes in natural immunity, see Kisskalt, Ztschr. f. Hyg. u. Infec- 
tionskrankh, 1904, xlv, 1, and ibid., 1904, xlvii, 243. For a study of inherited immunity, see Kleine and 
Mbllers, ibid., 1906, Iv, 179. THE RELATIONS OF MICROORGANISMS TO DISEASE 
187 
It is well known that bacteria artificially introduced into the blood 
of animals may, after a short time, wholly disappear from the circulating 
fluid, and be found in large numbers in leucocytes and other cells. We 
have already seen in the study of inflammation (page 114) that cer- 
tain cells of the body are capable of taking up not only various kinds of 
alien substances, but also microorganisms which enter the tissues, into 
their cytoplasm (Fig. 70, page 116) and may there kill and destroy them 
(Fig. 113). This mode of destruction of microorganisms, largely by 
leucocytes, but also by other mesodermal cells, which when thus engaged 
are called phagocytes (page 115), plays a most important part in the 
establishment of immunity. On the other hand, certain ingredients 
of the body fluids, formerly called alexins or "defensive proteins," 
acting outside of cells, have been shown to possess marked germicidal 
In fluid from the peritoneal cavity of an immunized guinea-pig a few hours after the introduction 
of the bacilli of typhoid fever. Degenerative changes are seen in many of the bacteria within the cells. 
powers. While thus it might appear that two fairly distinct agencies 
are of importance in enabling the body to resist the incursions of patho- 
genic germs-cellular or "phagocytic," and what may be called "hu- 
moral" or chemical-it is obvious that whatever destructive power the 
body possesses toward microorganisms must ultimately be due, directly 
or indirectly, to cell activities. This phase of immunity has been char- 
acterized as antimicrobic, antibacterial, or bacteriolytic immunity, because 
it is a mode of protection in which bacteria themselves are destroyed or 
their growth in the body is limited or prevented. 
Not less important is another phase of immunity-antitoxic immunity 
-by which the body protects itself against the toxic substances through 
which, in many instances, the most serious manifestations of infection 
occur. 
These two forms of immunity-antitoxic and antibacterial or bac- 
teriolytic-will be considered in detail in a following section. 
Furthermore, the microbic toxins which are set free by the micro- 
organisms, like other poisons, may be eliminated together with the waste 
products of body metabolism through the kidneys, skin, etc. 
Artificial Immunization. 
General Methods and Principles of Artificial Immunization.-It was 
not possible to gain a clear conception of the factors entering into the 
complex problems of immunity until animal experimentation had 188 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
revealed a host of significant facts bearing directly upon questions which 
for a long time had seemed insoluble. It has been found as the result 
of experimental researches that artificial immunity can be secured by 
gradually rendering the body tolerant to the presence of the infective 
or toxic agencies without actually inciting the characteristic specific 
disease. 
I. In one class of procedures artificial immunity is secured directly or 
indirectly through, the action in the body of bacteria or other microbes or 
microbic poisons whose virulence has been in one way or another reduced 
but not rendered altogether inert; or by the action on relatively insusceptible 
animals of microbes or microbic poisons of unimpaired virulence. Im- 
munity induced in this way as the result of direct adaptation of the body 
cells to the new conditions is called active immunity. 
1. Active immunity to particular forms of infectious disease may be conferred by 
inoculation with cultures of the germ inciting the infection whose virulence has been artifi- 
cially reduced-attenuated cultures. This reduction of virulence may be accomplished 
in various ways: by cultivation at temperatures above their optimum; by successive 
inoculations into insusceptible animals; by prolonged artificial cultivation in the pres- 
ence of oxygen; by exposure to certain inorganic chemical substances, as the diphtheria 
bacillus to trichloride of iodine, anthrax to bichromate of potash, etc.; by exposure of 
cultures to organic extracts or products of animal or vegetable cell metabolism; by 
drying (hydrophobia), or by exposure to sunlight; by killing the germs by heat or 
by ether, using for injection emulsions of their dead bodies containing the so-called 
endotoxin; and in other ways. 
With the virulence of the microorganisms reduced in varying degrees in one or 
other of the ways just mentioned, the gradual habituation of the bodies of animals to 
the presence of pathogenic germs may be pursued until cultures of full virulence are 
tolerated.1 
2. Active immunity may be conferred by the injection, in gradually increasing 
doses, of the metabolic products of bacterial growth, either with or without the dead 
bodies of the germs themselves-the bacilli of typhoid fever, for example. The pri- 
mary virulence of these usually toxic products of microbic growth may be in various 
ways diminished, by heating, by mixing with organic extracts such as that of the thy- 
mus gland, or with an inorganic chemical substance such as trichloride of iodine, or by 
small doses of the already prepared antitoxin-see below. 
3. Active immunity may be secured in some cases by the inoculation of animals, 
which are but moderately susceptible to the species employed, with small but increas- 
ing quantities of germs having unimpaired virulence. Under these conditions the 
animal becomes less and less responsive to the germ, until finally it may display no 
reaction after a quantity of the virulent culture which at first would have been in- 
evitably fatal. In man the use of the so-called sensitized vaccines has produced 
valuable results. Live bacteria are macerated with an excess of antiserum, and the 
combination is injected. 
4. Immunization in man by the direct use of dead bacteria or bacterial poisons or of 
virus of diminished virulence lias been largely practised in typhoid fever, cholera, and 
hydrophobia. 
In active immunity the protective material is elaborated by the 
immunized individual, the process requires considerable time, and the 
1 On the contrary the virulence of a particular strain of pathogenic bacteria may be exalted by a 
series of "passages" through a susceptible animal. When the infection from inoculation has developed 
in the first animal, cultures derived from it are used to infect a second, and so on through a series of 
"passages." 
In this way, it is assumed, the self-protective adaptations of the bacteria are made evident in the 
increasing potency of the toxins which they produce, the toxins being one of the important factors in 
injuring the protective mechanism of the host. THE RELATIONS OF MICROORGANISMS TO DISEASE 
189 
effect lasts for a considerable period. The recent developments in scien- 
tific practice seem to point to the fact that in many instances an attack 
on the toxins of the bacteria is not the way of ultimate success. The 
real object is to destroy the invader and the only advantage in neutralizing 
the toxin is the protection of the cells of the organism from serious injury 
while they are preparing to carry out this destruction. 
The beneficial effects ascribed to the injection of bacterial cultures 
killed by heat have been recently shown to be due in many instances to 
mere non-specific stimulation of the hematopoietic system, in which 
antibodies are produced, together with a mobilization of the serum 
ferments,1 and not to any specific bacterial protein. Thus, the bene- 
ficial results noted clinically in typhoid fever after injections of large 
numbers of killed typhoid bacilli could be duplicated by injections of a 
proteose. 
II. In a second class of procedures artificial immunity is secured by the 
direct mingling of the body fluids from an individual already immunized in 
some of the above ways, with those of the individual to be protected. Im- 
munity secured in this way, in which the immunizing substance used has 
been elaborated by another individual, is called passive immunity. 
1. Extracts of various organs and tissues of animals suffering from infectious dis- 
ease rendered germ-free and injected into healthy animals, have been found in some 
cases to confer a certain degree of immunity. 
2. The blood serum of animals naturally immune to a particular infectious disease 
has been found, on injection into those which are susceptible to the same disease, to 
impart in some cases a certain degree of insusceptibility. 
3. The blood serum, finally, of animals which have been rendered in one way or 
another artificially immune to certain diseases, if introduced under proper conditions 
into another susceptible animal, has been found not only to confer a temporary immu- 
nity, but, if administered to an already stricken individual, to aid him in the most 
marked and efficient way to overcome the deleterious agencies at work. 
The use of blood serum of artificially immunized animals for this purpose is of far 
greater practical importance than either of the methods 1 or 2. 
In passive immunity the protective material is furnished ready made, 
the effect is secured at once and is temporary. 
Antitoxic Immunity. 
It appears from a study of the results of artificial immunization, as 
well as of the immunity which is involved in the natural recovery from 
infectious disease, that one of the ways in which immunity is secured is 
by the formation of substances in the body fluids which in some way 
neutralize or suspend the action of toxins-antitoxic immunity. 
Thus in diphtheria and tetanus the antitoxic substances are largely 
developed, while in many other infectious diseases, such as cholera and 
typhoid fever, it appears to be, in part at least, through the bacterio- 
lytic substances that protection is secured. While in many instances 
i Jobling and Petersen, Jour. Am. Med. Assn., 1916, Ixvi, 1753; Miller', and Lusk, ibid., p. 1756; 
Miller, ibid., 1917, Ixix, 765; and Hektoen, Jour. Infect. Dis., 1918, xxii, 28. 190 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
both of these types of protective substances may be formed during im 
munization, one or the other is usually preponderant.1 
The antitoxic substances are most closely related to the globulins, 
but beyond this their chemical nature has not been definitely ascertained.2 
The effect of antitoxin in the blood in rendering harmless the toxic 
substances which they form apparently is accomplished, not by the 
destruction of the toxins, but by a chemical union of toxin with anti- 
toxin, whereby the former is deprived of its capacity to injure cells. 
The knowledge of this antitoxic immunizing action of specially 
endowed blood-serum has been most fully developed in diphtheria and 
tetanus. 
During the growth of the diphtheria bacillus in nutrient broth a 
toxic substance is developed which mingles with the broth. This is 
called diphtheria toxin, and subcutaneous injections of this toxin in 
animals-guinea-pigs, for example-prove fatal, in appropriate dosage, 
with symptoms and lesions similar to those caused by inoculation with 
the living germ. It has been found that by repeated injections of the 
diphtheria toxin in susceptible animals, at first with small, then with 
gradually increasing, doses, the animal may at length become so insus- 
ceptible to the action of the poison that many times the usually fatal 
dose is borne without sensible reaction. Similar immunity can be con- 
ferred in certain animals by the use of the living cultures of the diphtheria 
bacillus either fully virulent or with reduced virulence (page 188), 
administered at first in small doses which are gradually increased. 
In whichever way immunity be conferred, it has been found that the 
blood of the artificially immunized animal contains a substance, or sub- 
stances, called diphtheria antitoxin, which, on being introduced with the 
blood serum into other susceptible animals, may not only confer a 
quickly established immunity-passive immunity-but, without destroy- 
ing the diphtheria germ, may protect against its toxic effects when 
the disease is already under way. Thus, through the artificial immuniza- 
tion of horses and the hypodermatic use of the serum of their blood in 
man, the so-called "serum therapy" has assumed a very important and 
beneficent r61e in the prevention and treatment of diphtheria.3 
Results similar to those obtained in the study of diphtheria antitoxin 
have been realized in the investigations of tetanus. But the practical 
value of the tetanus antitoxin as a therapeutic agent is less obvious, as 
the toxin is rapidly fixed by the cells of the central nervous system and so 
1 The damage or destruction of bacteria by antibacterial, bactericidal, or bacteriolytic substances 
naturally limits or prevents the formation of toxic materials by the microorganisms, although the 
cells of the body may be very susceptible to the action of these. So that the absence of evidence of the 
establishment of antitoxic immunity in an infectious disease may mean, not that the body is incapable 
of this, but only that no opportunity is offered for its development. 
2 Hiss, F. H., and Atkinson, J. P., Jour. Exper. Med., 1900, V, 47. 
5 The antitoxic value or power of each specimen of antitoxic serum is experimentally determined 
by finding the amount of the serum required to protect the test animal against the action of a definite 
amount of toxin of known strength. Various standards have been adopted, the value of the serum being 
expressed in terms of the "antitoxin unit." For example, in the determination of antitoxin value made 
use of by the Department of Health of the City of New York, an antitoxin unit is the amount of anti- 
toxic serum required to protect a guinea-pig weighing 250 grammes from death, when one hundred times 
the fatal dose of diphtheria toxin is mixed with the serum and the mixture injected subcutaneously into 
the animal. The usual dose for human administration may contain from three hundred to six thou- 
sand units. THE RELATIONS OF MICROORGANISMS TO DISEASE 
191 
becomes relatively inaccessible to the antitoxin. This does not detract 
from the value of the serum when exhibited early and in large amounts. 
Experience in the use of prophylactic injections of antitetanic serum in 
the past four years has shown its extraordinary value. 
A serum against the toxins of the B. aerogenes capsulatus has recently 
been developed and seems to promise well. It has been shown, further, 
that antitoxic sera may be developed in the body during immunization 
to snake venom, the poison of the spider and scorpion, vegetable poisons, 
such as ricin and abrin, and to other albuminous animal and vegetable 
materials. Thus, also, through experimental adaptation, the living 
body-cells may elaborate and set free into the serum substances which 
suspend the action of ferments, like rennet, pancreatin, fibrin ferment, 
etc. 
Not all toxic substances, however, are capable of inciting the living 
body to the formation of antitoxic substances; nor are these apparently 
formed in such considerable amount in most of the infectious diseases, 
as is the case in diphtheria and tetanus. 
The action of these antitoxic substances is, within certain limits, 
specific; that is, the antitoxin of diphtheria protects against diphtheria, 
that of tetanus against tetanus, etc.1 
EHRLICH'S "SIDE-CHAIN" HYPOTHESIS. 
We have seen that a most remarkable series of facts is developed by our studies of 
infectious diseases illuminated by the results of animal experimentation. When the 
living body is invaded by a certain toxic complex organic material, not always of mi- 
crobic origin, the body adapts itself to the new conditions by the elaboration of sub- 
stances which protect it from the action of that poison. Each new protective sub- 
stance is effective against the particular poison which induced its formation. Not 
only this, but if the blood serum containing these new protective substances be trans- 
ferred to another individual they protect him also-passive immunity-against the 
special poison which called them forth in the body of the first. 
How are we to conceive of this wonderful adaptive power of the living body under 
conditions which seem to be wholly new in the life of the individual; a power which 
at first appears to transcend the known capacities of the body-cells? 
This singular capacity of the body-cells to develop in emergencies apparently new 
substances has naturally given rise to much study and to many speculations and hy- 
potheses. The scope of this book does not permit even of enumeration of these. But 
it is necessary to bring forward at least in outline the so-called " side-chain " hypothesis 
of Ehrlich by which he strove to account for the phenomena of antitoxic immunity as 
exemplified with especial clearness in diphtheria and tetanus. Without his hypothesis 
we are to-day still practically at sea in our views of the nature of antitoxic immunity, 
while this remarkable capacity of the body to manufacture the greatest variety of 
potent specific antidotes to the most subtle and virulent poisons becomes, for the first 
time, comprehensible in the light of this ingenious conception. It is now several years 
since Ehrlich's hypothesis was enunciated, and, whatever may be its merit as a direct 
1 For a detailed consideration of the specificity of infectious agents, see Kolle, W., Kolle and Wasser- 
mann, Handbuch. d. path. Mikroorganismen, 2d ed., 1912, i, 869. 
The monograph by Citron, Die Methoden der Immunodiagnostik und Immunotherapie (Eng. 
trans., 2d ed., Philadelphia, 1914) contains many facts of practical importance in the application of 
theories of immunity; while Kraus and Levaditi's Handbuch der Technik und Methodik der Immunitats- 
forschung (Jena, 1914) furnishes a most valuable survey of the entire subject from the point of view of 
method. 
For a summary of the results of serum therapy, see Kolmer, Infection, Immunity, and Specific. 
Therapy, 2d ed., Philadelphia, 1917. 192 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
contribution to science, there can be no doubt that it has been, in a remarkable degree, 
an inspiration to the most fruitful research. It is practically impossible to follow the 
recent work on immunity without a knowledge of this hypothesis and familiarity with 
the nomenclature to which it has given rise. 
In order to comprehend the hypothesis of Ehrlich regarding the origin and nature 
of antitoxin, it is necessary for us to form with him a clear conception of cell 
assimilation. 
We conceive of the cell as a mechanism for the storage of energy derived from 
without and for its release under definite conditions. This storage of energy is possible 
through the assimilation and building up by the cell of complex molecular combina- 
tions. These, owing to their instability, are readily changed into less complex and 
more stable combinations with the release of the stored-up energy. Thus is the life of 
the cell manifested. 
This broad conception of the cell is a purely intellectual one, however, for the de- 
tails of cell metabolism still elude the keenest scrutiny of the chemist. He cannot 
formulate protoplasm nor express its chemical changes by proportionate symbols. 
Now, accepting this condition of affairs as for the moment inevitable, Ehrlich 
seeks to express his view of the character of the cell's performances in general terms, 
disregarding its morphological peculiarities, somewhat as follows: We may conceive of 
the cell as consisting of a central group of very complex molecular combinations which 
maintains the characteristics and special capacities of the cell as an organism under all 
Fig. 114.-Diagram Illustrating the Action of Receptors in the Nutrition of the Cell. 
.4, Portion of cell body; a, food molecule; b, c, d, receptors. 
the vicissitudes of its existence. Associated with this central organic group are many 
and various subsidiary atom-complexes which by means of their unsatisfied affinities 
bring the central group into relationship with food material through those chemical 
combinations which in living protoplasm characterize assimilation. 
These unsatisfied affinities by which assimilable material is fixed or united to the 
cell have been called "side chains," a term adopted from the chemist. Not to press 
too closely, however, the analogy between the chemical processes in lifeless substances 
and assimilation in living matter, these affinities or "side-chains" of protoplasm are 
now commonly called receptors. 
If we seek to illustrate Ehrlich's conception we shall be obliged to use graphic 
figures of extreme crudity. If the arc of a circle in Figure 114 represents a portion of THE RELATIONS OF MICROORGANISMS TO DISEASE 
193 
the periphery of a cell, we may indicate the side-chains or affinities or receptors by 
projections whose special shape shall indicate their special capacity to combine with 
any substance coming in contact with them under favorable conditions. Suppose in 
this figure we let a represent a nutrient molecule which is capable of combining with 
the receptor b, belonging to the cell A. Through its union with b, and only through 
this, is it capable of entering into the metabolism of the cell. This molecule a cannot 
unite with the receptor c or d, but only with such receptors-to use the crude expression 
which our illustration requires-as it fits. Through the receptors c and d other 
forms of food molecules may enter into the metabolism of the cell. 
Thus it is in Ehrlich's conception, which after all is only a graphic way of illustrat- 
ing the preliminary phases of assimilation by living protoplasm, that the cell is capable 
of selecting, or "fixing," out of the host of various substances with which it comes in 
contact, just those and only those to which its receptors bear a definite chemical 
relationship. 
The same thing is true of toxic as of nutrient substances. In order to be toxic to 
the cell they must enter into chemical combination with a suitable receptor of the 
cell. Then only can they lead to the forms of damage which we 
are here considering.1 
As the result of many studies on the nature and effects of 
toxins, Ehrlich was led to believe that the toxin molecule con- 
sists of two forms of affinities: one through which the chemical 
union with the cell is effected-called the haptophorous group; 
and the other-called the toxophorous group-by which the 
damage to the cell is brought about when once the toxin mole- 
cule is anchored to it.2 
This conception may be illustrated as in Figure 115, in which 
the toxophorous group a of the toxin molecule can be effective 
in damaging the cell only when united to the latter by the 
haptophorous group b. 
Having now conceived of the living cell as consisting of a 
central essential complex molecular group, brought into rela- 
tionship with its food materials by means of a great number of 
the most varied receptors, through which, under normal conditions, assimilation is 
secured, let us see what may happen if toxins come in contact with living cells which 
are furnished with receptors capable of uniting with them. 
The union of the toxin molecule with the living cell being effected, the cell is more 
or less damaged. If the damage be sufficient, the cell dies. But suppose the damage 
to be but slight, as may be the case in artificial immunization or in early stages of an 
infection. The cell is at least deprived of the useful offices of the receptor to which 
the toxin molecule is now united. This is in itself a loss to the cell, and through the 
regenerative impulses common to all living cells it proceeds to regenerate the lost parts, 
which in this case are the receptors. But as more receptors are thrown out of function 
by the continued action of the toxin, the necessity for compensation continues. 
Now it is a fact long known to pathologists, and especially emphasized by Weigert, 
that the regenerative impulse is apt to be in excess of the obvious requirements and 
leads to overproduction of new cells, tissues, chemical substances, etc. This is what 
now happens to the cells, some of whose receptors have been rendered useless by com- 
bination with the toxin. New receptors are formed, more than the cell requires; so 
-Ob 
-b 
Fig. 115.-Diagram 
Illustrating Sup- 
posed Character of 
the Toxin Molecule. 
a, Toxophorous group; 
b, Haptophorous 
group. 
1 It is evident, from what has been said about the conditions under which substances can be toxic, 
that the natural immunity of one animal to a given agent which is toxic in another may be simply due 
to the fact that the cells of the former have no receptors with which this agent can unite, or, if this 
union does take place, that the cell is not thereby damaged. This consideration has an important bear- 
ing upon our conception of natural immunity. 
This so-called " fixing " or "binding" of toxin to tissues may be demonstrated by mixing some of 
the potent tetanus toxin with fresh brain tissue of the horse or guinea-pig, whereupon the mixture, if 
made in suitable proportions, becomes innocuous. 
2 Ehrlich was led to this belief in the complex nature of the toxin molecule through the curious 
fact that diphtheria toxin may under a variety of conditions lose its toxicity, but still retain its capacity 
of neutralizing antitoxin and also of uniting with cells, and thus inducing the formation of antitoxin 
in the animal body. Such toxin molecules deprived of the toxophorous group are called toxoids. 194 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
numerous may these become that many are at last cast off into the blood. Here is the 
point at last. These receptors or substances, normal and useful to the body, but now 
formed in excess through over-compensation, and set free from the cells into the body fluids, 
are the antitoxin. 
For, set free in the body fluids, these superfluous receptors still retain their com- 
bining power for the free toxin molecules, which, also, are in solution in the body fluids, 
and unite with them. This union having been effected, the toxin molecules are no 
longer a menace to the cell, because the affinities are now satisfied through which they 
joined the receptors while these were still apart of the cell, and in this way could have 
become harmful. This now inert combination of toxin molecules and detached re- 
ceptors is physiologically indifferent stuff, and may be removed from the body by the 
usual processes of excretion. 
But the antitoxin which has not united with toxin in the body of the animal 
which produced it, is still available on the transference of the serum to another in- 
Fig. 116.-Diagram Illustrating the Formation and Action of Antitoxin in Accordance 
with Ehrlich's "Side-Chain" Hypothesis. 
A, Portion of cell-body; b, receptors combined with cell protoplasm; c, receptors separated from 
cell; a, toxin molecules; y, free receptors-antitoxin. 
dividual whose blood contains diphtheria toxin, and who may thus secure passive 
immunity. 
If we have recourse again to the graphic method, the hyperproduction of recep- 
tors by the damaged cell, their separation, and their action as antitoxin, may be indi- 
cated, as in Figure 116. Let A represent a portion of a cell-body. The toxic molecule 
a, uniting with the receptors b, leads through the injury to the cell, as well as by its 
deprivation of the normal use of b, to the production, and at length to the overproduc- 
tion, of new receptors of the same kind. These superfluous receptors c are now set free THE RELATIONS OF MICROORGANISMS TO DISEASE 
195 
into the body fluids,1 where, as at x, they may freely unite with the toxin molecules, 
forming harmless compounds and preventing further access of the toxin to the cell, 
where alone the damage can be done. Or, when free, as at y, the receptors may be 
transferred in the serum, becoming effective as antitoxin in another individual. 
It is well to note that so long as the receptor maintains its connection with the cell 
it is not antitoxin, but an element of vulnerability to the cell. It is only when the 
receptor has been set free from the cell that it is antitoxin. 
The antitoxin substance which neutralizes the action of the toxin molecule of diph- 
theria is not effective for the poison of tetanus, for example, simply because it does not 
combine with the molecule of tetanus toxin. It is specific for diphtheria, because it 
was the diphtheria toxin which excited its overproduction through a chemical union 
identical in character, whether this union takes place while the receptor is a part of the 
cell, in which case the toxin becomes harmful, or when the receptor is detached from 
the cell, in which case the combination is harmless. 
In the light of this hypothesis the specific character of the antitoxic substances 
appears to be but the result of adaptation to unusual conditions of cell capacities 
evolved and fostered for the every-day maintenance of life. The specific relationship 
between the toxin and the antitoxin is not developed during immunization, but 
existed beforehand as a necessary condition of toxic action. 
This hypothesis not only accounts for the formation, protective action, and speci- 
ficity of antitoxin, but reveals, also, a special significance in the incubation period, dur- 
ing which the conservative forces are mustering. We can realize, furthermore, in the 
light of this hypothesis, how it is that the protection secured in active immunization is 
less immediate and also why it is more prolonged than in the passive, since in the latter 
the available antitoxin is limited to the dosage and is not replenished as in active 
immunity by the continued cell activities of the affected individual himself. 
The conception of Ehrlich as to the nature of antitoxin is that of the chemist, and 
carries over to the performances of protoplasm the presumptions upon which chemical 
reactions in general are conceived and formulated. But this is not an easy matter, 
since our knowledge of the ultimate phases of protoplasmic metabolism is very incom- 
plete. The physiological chemist presents to us as his final achievement in analysis an 
extremely elaborate complex which he calls the protein molecule. This he does not 
yet venture to formulate. Thus it is that when we attempt to illustrate in graphic 
fashion our conception of the performances of protein molecules, either in normal me- 
tabolism or in poisoning, we are forced to use the crudest of symbols. The use of such 
symbols is not without hazard, for these toxins and these receptors are, in truth, not 
histological structures, but molecular groups; they are not alone upon the surfaces, but 
through all the mass, of the protoplasm. They do not "break" off from the cell, but 
are set free as are other chemical substances which result from molecular transfor- 
mations. Thus, if one cannot at last translate these uncouth symbols into the nice 
conceptions of the chemist, they will prove but stumbling-blocks. 
There has been much discussion of Ehrlich's hypothesis, and it has withstood many 
assaults, mostly inspired by misconceptions of the fundamental claims. The scope of 
this book does not permit us to consider the many and ingenious experiments by which 
this view of antitoxic immunity has been sustained, nor is it practicable now to call 
attention to many of the phenomena not yet accounted for or seemingly inconsistent 
with the interpretations here set forth. 
It is a working hypothesis which no doubt indicates but crudely the nature of the 
subtle processes concerned, as must indeed be the case while our knowledge of the 
phases of energy which sway and determine life is still very meager; but it has already 
inspired much fruitful research which is an important feature of working hypotheses 
in whatever field, and whatever their ultimate fate.2 
1 These receptors of various kinds, cast off into the body fluids under the most diverse conditions 
Ehrlich called " haptines." 
2 For a general criticism of Ehrlich's hypothesis from a physicochemical aspect, see Arrhenius, 
Immunochemistry, New York, 1907. 196 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
Bactericidal or Antibacterial Immunity (Bacteriolytic Immunity.) 
General Considerations.-An extended series of studies on artificial 
immunization has shown, as we have seen, that the protection is secured 
by the formation of antitoxic substances in relatively few instances, nota- 
bly in diphtheria and tetanus, whose inciting bacteria set free in 
cultures, as in the body, soluble toxins of great potency. Nevertheless, 
when in some of the ways detailed above (page 187) an animal has been 
gradually adapted to cultures of pathogenic bacteria either living or dead, 
or to their products, it has been found that the body fluids do contain pro- 
tective substances. The protective action in these instances has occa- 
sionally been shown to be associated with the induction of morpho- 
logical changes in bacteria which indicate their damage or destruction- 
bacteriolysis. Active immunization in man with the dead bodies of 
their respective bacteria has been widely practised in typhoid fever, 
Asiatic cholera, and plague, with apparently favorable results, while the 
use of the serum of immunized animals, in these and certain other dis- 
eases, has not been thus far very encouraging in conferring passive 
immunity. 
While, therefore, the data at hand in those artificial immunizations 
which are not antitoxic, point to the bactericidal and bacteriolytic action 
of substances developed in the body as the important, if not the domi- 
nant protective factors, there may be many other processes contributing 
to the same end, which are as yet not clearly defined. Thus, there may 
be increased phagocytosis; vulnerable body-cells may become less suscep- 
tible, the growth of bacteria may be inhibited though they be not 
destroyed, etc. But these possibilities cannot be discussfed here. 
Furthermore, it should not be forgotten that the antitoxic action of 
protective sera may often be associated with those agents which directly 
damage the infecting organism. 
As regards the destruction of bacteria in the body, we have seen that 
this may take place directly through the action of phagocytes or by the 
action of the body fluids. But the details and exact nature of this de- 
structive process have been extremely difficult of study, owing to their 
complexity and the minuteness of the microorganisms. Of late, however, 
a series of remarkable studies in a related field have led to a clearer con- 
ception of the ways in which bacteria and many other alien organic 
substances are destroyed in the body, under ordinary circumstances as 
well as under the special conditions which infection involves. 
"Pfeiffer Phenomenon."-Some time ago, Pfeiffer1 showed that 
the blood serum of a guinea-pig artificially immunized against the 
cholera vibrio, was capable, under certain conditions, not only of immobil- 
izing and killing cholera germs in a short time, but also of causing their 
disintegration and destruction. This significant capacity of immune 
serum was, after a long series of experiments, finally found to be due to 
two distinct substances. One of these appeared to be formed in the body, 
as the result of the gradual adaptation of the animal to the cholera 
1 Pfeiffer, Ztschr. f. Hyg., 1894, xvii, 355. 197 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
microbe, and was called the immune substance. The other seemed to 
be normally present in the serum of the warm-blooded animals, and to 
be identical with the substance which had long been regarded as in 
itself germicidal, and which had been called by Buchner alexin. It was 
presently found that lysis of the cholera microbe occurred only when 
these two substances act together, neither of them when separate having 
lytic power. If the two substances, the immune substance and the alexin, 
lytic when together, are heated to 56° C., the lytic capacity is lost. But 
if a small amount of fresh blood-serum containing alexin be now added, 
the lytic power is at once restored. These curious facts, set forth in 
part by Pfeiffer and further developed by Bordet and Metchnikoff, 
obviously have a significant bearing upon our conception of the proc- 
esses by which those phases of immunity are secured in which the 
destruction of microorganisms plays an important part. 
But the study of the effects of lytic sera upon bacteria is one of great 
technical difficulty, so that it is only since an important series of obser- 
vations were made upon the lytic action of the body fluids on other and 
more easily studied forms of cells that our conception of the nature of 
bacteriolysis has become at all clear. 
It is therefore necessary for us to look briefly at a new line of research 
bearing upon bacteriolytic immunity which has already led to most sig- 
nificant results and opened biological fields of great scope and complexity. 
CYTOLYTIC SUBSTANCES-CYTOLYSIS. 
Hemolysins-Hemotoxins.-It has been known for nearly fifty years 
that the blood serum of one animal species, when injected into the vessels 
of another, may do serious damage and even kill the latter through a rapid 
separation of the hemoglobin from the red blood-corpuscles. This 
dangerous effect brought to a speedy end attempts which were at one 
time made to sustain the ebbing forces of life by the transfusion of alien 
blood. But the significance of this so-called "laking" of the blood by 
mixture with alien sera was overlooked. 
Bordet, however, in 1898, inquired whether, if the animal body be 
capable of adapting itself to toxic substances and to bacteria in such a 
way as to neutralize the effects of toxins and to destroy bacteria as had 
been shown by earlier experiments, it may not respond similarly to the 
introduction of other foreign substances such as alien red blood-cells, 
for example. 
The blood serum of the guinea-pig is not normally lytic for the red 
blood-cells of the rabbit; that is, it does not cause the separation of the 
hemoglobin from the stromata, with a partial destruction of the latter.1 
Now, Bordet injected a few cubic centimeters of the defibrinated blood of 
the rabbit, containing the serum and red blood-cells, into the subcutane- 
ous tissue or peritoneal cavity of normal guinea-pigs. This operation, 
which does not markedly interfere with the well-being of guinea-pigs, 
1 While the serum of the guinea-pig is not normally lytic for the corpuscles of the rabbit, the serum 
of the rabbit is lytic for the corpuscles of the guinea-pig. Similarly, normal rabbit serum is not lytic 
for the beef corpuscles, but beef serum is lytic for the corpuscles of rabbits and guinea-pigs. 198 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
was repeated five or six times at intervals of a few days. When 
blood was drawn from the treated pig, allowed to clot, and the clear 
serum secured, it was found to have become markedly lytic for rabbit 
corpuscles. A very small proportion, mixed with rabbit's blood diluted 
with physiological salt solution, in a short time brought the hemoglobin 
into a clear ruby solution in which the stromata or "ghosts" of the 
corpuscles floated as a pale and scarcely visible cloud. This process is 
called hemolysis; serum possessing this capacity is called hemolytic or 
hemotoxic serum. 
This adaptation of one animal to the red blood-cells of another species 
may be accomplished without difficulty with a great variety of animals. 
But a most remarkable thing about this newly acquired lytic capacity 
of the serum is that it is limited to the red corpuscles of the species of 
animal whose blood was used for the injection-in Bordet's experiment 
to the corpuscles of the rabbit. Red blood-cells of the dog, cat, sheep, 
ox, fowl, etc., are no more affected by this serum of a guinea-pig which 
has been adapted to the blood of the rabbit than they were before. In 
other words, the adaptation to foreign corpuscles is specific. 
The statement that this adaptation to alien blood is specific-that is 
to say, that the serum becomes active only for the corpuscles of the 
species injected-should be so qualified as to recognize the curious fact 
that a slight degree of lysis may often be induced in corpuscles of species 
of animals very closely related to those from which the injected blood is 
derived. For example, if a rabbit be adapted to human blood by intra- 
peritoneal injections, the serum of this rabbit, now strongly lytic for the 
corpuscles of man, may be slightly lytic for the corpuscles of monkeys. 
Similarly, serum artificially lytic for the red cells of goats may be slightly 
lytic for those of sheep, but not for the corpuscles of cats, dogs, man, 
etc. (See, for technique of hemolysis tests, page 222.) 
This form of test, delicate beyond anything hitherto known in physi- 
ological chemistry, may thus prove of value in defining the relationships 
and limitations of animal species.1 
This preliminary observation of Bordet was followed by a series of 
studies upon artificial hemolysis, the results of which we can only briefly 
summarize. In the first place, to what is this remarkable acquired lytic 
capacity of the serum due? Bordet heated for half an hour at 56° C. 
some of the lytic serum secured by adapting the guinea-pig through 
subcutaneous injections to the red blood-cells of the rabbit. He found 
that it had completely lost its new lytic power. Such serum is said to be 
inactivated. But when he now added to this inert serum a little fresh 
blood-serum from a normal guinea-pig, which is not in itself lytic (page 
197), the original dissolving power of the heated serum for rabbit cor- 
puscles was at once restored-reactivated. The inference from this 
experiment is obvious. The dissolving capacity of this artificially lytic 
serum is due to two distinct substances. One of these, that one which 
results from the adaptation of the animal to the alien blood, is stable 
1 For further data on this subject, see Nuttall, Blood Immunity and Blood Relationship, Cambridge, 
1904. THE RELATIONS OF MICROORGANISMS TO DISEASE 
199 
at 56° C.; the other, which is present in normal serum, is rendered inert 
at 56° C.; that is, it is very labile. These two substances were named 
early and have been often renamed. For the present we may speak of 
the stable substance resulting from the adaptation to the alien blood 
as the immune substance or immune body, and of the other, more sensi- 
tive to heat, present in normal serum, and not increased in the processes 
of immunization, as alexin, a name which was long ago applied by 
Buchner to a substance or substances in normal serum, to which its 
germicidal capacity, first clearly demonstrated by Nuttall, was attributed. 
This alexin is now called complement for reasons given on page 204.1 
There now followed a series of important studies by Ehrlich and his 
associates which throw still further light upon these curious lytic agents. 
Separation of Alexin and Immune Substance.-We have seen that in 
order to secure the immune substance free from the alexin one has only 
to heat the lytic serum to 56° C. for half an hour, when the alexin is 
destroyed. If one wishes to secure the alexin apart from the immune 
substance he makes use of a very curious property of the latter; namely, 
its capacity of uniting with the cellular element under whose influence it 
was elaborated. For example, if one places a small portion of the serum 
of a rabbit which has been adapted to beef blood in contact with beef 
corpuscles at a low temperature2 for a few hours, he will find that the 
immune substance has formed so stable a combination with the cor- 
puscles that on their separation from the fluid by centrifugation in the 
cold, none of the immune substance, but all of the alexin, will be left in 
the fluid. 
That the corpuscles under these conditions actually contain the 
immune substance is readily shown by carefully washing them in salt 
solution and centrifuging them again in the cold and finally adding to them 
a little normal serum-containing alexin, but no immune substance- 
whereupon the lysis will at once take place, as shown by the red color of 
the fluid. This union of the immune substance with corpuscles, called 
''fixation" of the immune substance, is specific, occurring only with the 
corpuscles of the animal species used in the adaptation. The alexin may 
also be absorbed by a number of substances, including emulsified tissues, 
tissue extracts, yeast cells, bacteria, and even inert substances such as 
kaolin. Of its chemical nature nothing is known. It was at one time 
supposed to be of lipoid character, but this view has not been sustained. 
Many other points of extreme interest and significance have been 
revealed in these studies on artificial hemolysis which the scope of this 
book does not permit us to touch upon. 
Multiplicity of Immune Substances and Alexins.-The question of a 
multiplicity of immune substances and of alexins has been brought for- 
ward, and it seems probable, especially from the researches of Ehrlich, 
1 It has been found that the hemolytic capacity of the normal blood serum, which in many animals 
as we have seen, is very marked for the corpuscles of alien blood, is also due to two substances which 
in character and action are similar to those which have been so carefully studied in the lytic sera of 
artificially adapted animals. 
2 It is necessary to reduce the temperature in this experiment in order to inhibit the action of the 
lytic agencies. 200 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
that in adaptation of each animal species to a single form of cell several 
immune bodies may be developed. It is possible, though not yet proved, 
that more than one alexin may be normally present in the blood serum 
of each animal species, and that a single immune body may be capable 
of uniting with several forms of alexin.1 
Bacteriolysis.-It is evident that this artificial hemolysis, secured by 
the adaptation of one species of animal to the red blood-cells of another, is 
quite analogous to the process by which immunity is secured against 
pathogenic bacteria-those of cholera, for example, whose most obvious 
poisonous elements are endotoxins-and which is called bacteriolysis. 
Both are specific examples of the general process called cytolysis, meaning 
cell destruction. This reaction of hemolysis is one of extraordinary 
delicacy, and is easily observed under conditions quite within our con- 
trol; and it is useful as an aid to the understanding of such elaborations 
and variations as involve great technical difficulties when we are directly 
engaged with the phenomena of bacteriolysis. 
Thus these studies of hemolysis have a practical significance in their 
bearing upon our conceptions of bacteriolytic immunity quite apart from 
the interesting general biological field into which they have led the way.2 
Special Cytolysins-Cytotoxins.-The development of cytolytic capaci- 
ties in the blood-serum of the living animal as the result of adaptation 
to bacteria and to alien red blood-cells being known, it was natural to 
extend the method to other cells. Thus it has been asserted that in the 
adaptation of one animal to the spermatozoa of another species by 
intraperitoneal injections, a serum is obtained which quickly brings to 
an end the movements of fresh spermatozoa of the species used-spermo- 
lytic serum. 
There have been produced many other cytotoxic sera which were 
thought to have specific action on the cells of the organs used as antigens, 
and it was expected that much light might be thrown upon the nature of 
many of the degenerative lesions which occur in the organs, especially 
the liver and the kidney, and that an approach might be made toward 
a specific therapy of cancer; but such is not the case. While a nephro- 
lytic serum when injected may give rise to extensive lesions of the kidney, 
similar lesions aro produced in other organs, also; and the effects seem due 
mainly to the hemagglutinative power of such sera, causing capillary 
thrombosis.3 
It appears, therefore, that cytotoxic specificity is not so much a matter 
of cell morphology as of molecular structure, and that an organ-specific 
serum is not obtainable. In this connection it is of interest to recall 
that five separate antigens have been demonstrated in protein of the hen's 
egg.4 Autocytotoxins cannot in general be produced. 
1 See, for general review of the alexin question, Zinsser, Infection and Resistance, 2d ed., New York, 
1918. 
2 For technic of hemolysis experiments and the adaptation of animals to alien substances see pp. 
222 and 224. 
3 Pearce, R. M., Jour. Exper. Med., 1906, viii, 64. 
4 Wells, H. G., Jour. Infect. Dis., 1913, xii, 341. For an interesting study of the chemical indi- 
vidualities of tissue elements and their biological significance, see Levene, P. A., Jour. Am. Chern. Soc., 
1917, xxxix, 828. See, for in vitro tests showing non-specificity of cytotoxins, Lambert, R. A., Jour. 
Exper. Med., 1914, xix, 277, 201 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
So far as they have been studied, the nature of the active agents in 
these various cytolytic sera and their mode of action are analogous with 
those in hemolytic sera. Here, as there, the action is due to two groups 
of substances: one, the "immune body," stable and increased by the 
adaptive process; the other, the alexin, occurring normally in the body, 
not increased in adaptation, and readily destroyed or rendered inactive 
by heat. 
All of these last-mentioned forms of cytolytic sera require more 
extended study before far-reaching conclusions should be drawn from 
them. But it is now evident that the different functional types of cells 
in one animal are capable, in the adaptation to the economy of another, 
of inciting more or less definitely specific responses, as shown by the 
various types of cytolytic sera which are formed. 
When one musters all the possible combinations in this form of adap- 
tation and considers the probability that multiple immune bodies may 
develop in each instance, and that these, furthermore, may correspond to 
multiple alexins, the complexity of artificial cytolysis becomes evident. 
Antigens.-We have seen that the introduction into the living organ- 
ism of alien protein substances of many kinds, derived from animals or 
plants, some of them poisonous, many of them not, incites the formation 
of so-called antibodies of divers sorts. It has been found convenient to 
call these " antibody producers," or "antibody incitors," antigens.1 
They are probably all protein in nature. It has not been shown that fats, 
lipoids, or carbohydrates can act as antigen.2 
Anticytolysins.-But now still another phase of this subject demands 
a word These cytolytic or, as some prefer to call them, cytotoxic sera, 
when introduced into the living bodies of the species from which the cells 
inciting their formation are derived, act as toxins to which the organism 
responds, each after its kind, by the development of antitoxic substances. 
These are called anticytolysins or anticytotoxins. 
Let us look at an illustration of this interesting point. The blood 
serum of the normal guinea-pig has, as we have seen, no lytic action on 
the red blood-cells of the rabbit, but after the adaptation of the guinea- 
pig to the blood of the rabbit by repeated intraperitoneal injections, the 
guinea-pig serum is strongly lytic for the rabbit corpuscles in test-tubes 
outside the body. But this lytic serum is not less toxic wThen introduced 
into the body of the rabbit. Under these conditions the rabbit, if it sur- 
vives, produces an antitoxin, an antihemolytic substance, which is in 
solution in his serum. If a little of this antihemolytic serum be mixed 
with some of the lytic serum from the adapted guinea-pig, it will be found, 
on the addition of rabbit corpuscles, that the lytic serum has lost its 
power, just as diphtheria toxin loses its harmful properties on mixture 
with diphtheria antitoxin. Thus may be formed a great variety of spe- 
cific "antibodies"-anticytolysins-from sera which are normally lytic 
or have become so through experimental adaptations. 
1 For a study of the locus of antibody formation see, Hektoen and Curtis, Jour. Infect. Dis., 1915, 
xvii, 409; Hektoen, L., ibid., 1915, xvii, 415; 1918, xxii, 28; Simonds and Jones, Jour. Med. Research, 
1915, N. S. xxviii, 183; ibid., p. 197; Becht and Leuckhart, Am. Jour. Physiol., 1916, xl, 366. 
2 Kolmer, Infection, Immunity, and Specific Therapy, 2d ed., Philadelphia, 1917, p. 161. 202 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
Isolysins and Autolysins.-In view of the remarkable results of the 
adaptation of the body to alien cells from different animal species which 
we have reviewed, it was natural to ask how an animal would respond to 
the introduction into the recesses of his body of cells-red blood-corpus- 
cles, for example-from another individual of the same species. It was 
found, in fact, that under these circumstances lytic substances are 
sometimes, though not uniformly, developed. The possibility of the 
formation of isolytic substances was thus established. But if this be 
possible, why, it was asked, may not autolytic substances be formed by 
the adaptation of an animal to his own cells experimentally displaced? 
Such substances have, however, not been found under the experimental 
conditions thus far observed. The spontaneous occurrence of isolysins 
and isoagglutinins in human blood is, of course, well known (see chapter 
on Blood). 
It has been demonstrated (see page 114) that cells and tissues worn out 
from use, or dead as the result of injury, inflammatory exudates, etc., 
are constantly removed from the living body by processes apparently 
analogous to, if not identical with, those which can be experimentally 
evoked; so that autolysis in some form seems to be an important factor 
in the maintenance of the integrity of the body (see page 122). Just 
what the agencies are under which normal living tissue cells are pro- 
tected from the action of autocytolytic substances is not yet clear. 
But the multiplicity of known "antibodies" justifies the conjecture 
that such substances-anticytolytic-may be constantly formed and 
act as safeguards to living and useful cells (see page 193). Many of the 
phenomena of autolysis, however, are unquestionably due to the release, 
on the death of the cell, of ferment activities contained in its own cyto- 
plasm. These proteases seem to be present in all body-cells except per- 
haps the red corpuscles. 
The Application of Ehrlich's Hypothesis to Cytolysis.-If we now turn to the 
various hypotheses which have been advanced to account for the formation and 
action of these cytolytic substances, we find that an elaboration of Ehrlich's views as 
applied to antitoxin is here a source of great illumination. It is evident at once, how- 
ever, that the matter is not so simple as in the case of antitoxin, because we have here 
two substances at work, the immune body and the alexin. Neither the immune body 
nor the alexin alone induces cytolysis. They must act together. 
The phenomena are, in the main, accounted for if we assume that it is the alexin 
which, when the necessary conditions are fulfilled, exerts the destructive action upon 
the bacterial or animal cell. But the alexin cannot enter under ordinary conditions 
into direct chemical combination with the cell receptors. The union is effected only 
by the intervention of the substance which is increased in amount in the process 
of adaptation; namely, the immune body. 
A long series of experiments has led to the belief that the immune body has two 
free atom complexes which enable it to form chemical unions. Through one of these 
atom complexes it unites with the cell or bacterium to be destroyed; through the other 
it is joined to the alexin. Then, and not until then, is the alexin so linked to the cell 
that its toxic or destructive action upon the cell occurs. 
This conception may be illustrated, as in the case of antitoxin, by crude figures. 
Here it should be remembered we are illustrating, not the production of the cyto- 
lytic substances, which we shall speak of later, but the action of them upon the cells 
to be destroyed. THE RELATIONS OF MICROORGANISMS TO DISEASE 
203 
Let a-Fig. 117, A-be the cell which is to be destroyed, with one of its receptors 
indicated at d. Let b represent the immune body with one atom complex e capable of 
uniting with the cell receptor d, and with another f capable of uniting with the alexin 
c through g. Now the alexin which appears to be the effective agent in the destruction 
cannot unite directly with the cell receptor. When, however, it becomes linked to the 
cell by means of the immune body, b, its destructive capacity can come into play. 
In a similar way one may indicate the action of anticytolytic substances which may 
be effective through union either with the alexin or with the immune body, as shown 
in Figure 117, B and C. In B the " antibody " h prevents the linking of the alexin c to the 
immune body b by itself uniting with the former. It then acts as an antialexin. In 
C the antibody "i" prevents the linking of the immune body b to the cell receptor d, 
and hence acts as an antiimmune body. We shall see in a moment why at present the 
substance here spoken of as antialexin is usually called the anticomplement. 
The experimental evidence that the anticytolytic substances may be thus due to 
the formation of adaptive substances of two classes, antiimmune substances and anti- 
complements, cannot be entered upon here. 
ABC 
A-a, Cell; b, immune substance (amboceptor): c, alexin (complement); d, cell receptor; e, atom 
complex of the amboceptor capable of uniting with the receptor, d; f, atom complex of the amboceptor 
capable of uniting with the haptophorous group, g, of the complement, c. 
B-a, Cell; b, immune substance (amboceptor); c, alexin (complement); d, cell receptor; h, anti- 
alexin (anticomplement). 
C-a, Cell; b, immune substance (amboceptor); c, alexin (complement); d, cell receptor; i, anti- 
mmune substance (antiamboceptor). 
Fig. 117.-Diagram Illustrating Cytolysis in Accordance with Ehrlich's Hypothesis. 
In view of the rationale of cytolysis, as just set forth, we may consider the immune 
substance to be an intermediary between the alexin and the cell to be destroyed; or, on 
the other hand, we may consider the alexin as the complement to the immune sub- 
stance, since only through their union is the toxic action possible. 
In fact, following Ehrlich, one sometimes speaks of the immune body as the inter- 
mediary body, or intermediary substance; but since it is furnished with two combining 
affinities, it is now usually called the amboceptor. Furthermore, since the experimental 
analysis of the lytic process by the new technique has shown that the germicidal and 
destructive action of blood-serum, formerly supposed to be due to a single substance 204 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
called alexin, is really due to the combined action of two substances, the use of the 
word alexin for one of them is misleading and has now been largely given up. The 
substance present in the serum of both normal and adapted animals through which 
lysis is effected when it is linked to the cell by the amboceptor is called the complement. 
Other names have been applied to these hypothetical complexes or substances which 
we cannot consider here.1 
This, then, is the rationale in accordance with Ehrlich's hypothesis of the action of 
these cytolytic or cytotoxic substances, either existing naturally, as they do in some 
animals, or being called forth in larger quantities in the process of adaptation to the 
cells which they destroy. This view has been most fully tested upon hemolytic sera, 
since here the reaction is most easily studied. But so far as one can see, it applies as 
well to the phenomena of bacteriolysis, whose direct study is much more difficult. It 
should, however, be borne in mind that the erythrocytes are very delicate and very 
peculiarly constituted cells, and it is possible that inferences drawn from hemolysis 
are not applicable without qualification to other and less vulnerable cell types. 
The origin of the amboceptors of these cytotoxic substances is accounted for in the 
same way as in the case of antitoxin. The alien cells or substances which are intro- 
duced into the animal, and to which it proceeds to adapt itself, lead, through union 
with such body-cell receptors as may be fitted to them, to the overproduction of these 
special complex receptors. These are presently cast off as superfluous to the body-cell 
producing them, and are then free as amboceptors in the body fluids. 
As in the case of antitoxin formation, it is probable that the cell receptors which 
are thus increased are normally concerned in cell assimilation, and it is not unlikely 
that their complex character may have some relationship with the complexities of the 
"giant" protein molecules, which must suffer initial changes before becoming fit 
for assimilation. At any rate this hypothesis assumes that in the process of adapta- 
tion either to toxic substances or to foreign cells or other protein material, the body 
develops no new capacities, but only an exaggeration of those already existing. 
As to the exact source of the amboceptors in artificially immunized animals we 
cannot yet speak with certainty, but the experiments of Hektoen2 point strongly to 
the fact that they are produced in the lymphatic tissues, the spleen, and the bone- 
marrow; for if animals are exposed to large doses of x-rays, they do not develop 
antibodies. It is not possible, however, to exclude the occurrence of serious injury 
to other organs, though morphologically the chief damage seems to be to the hema- 
topoietic system. 
The Action of Phagocytes in Cytolysis.-It was inevitable that the 
remarkable studies on cytolytic sera just summarized should have led 
to a clearer conception of the manner in which phagocytes destroy bac- 
teria and other organic substances. It is no longer permissible to hold 
as distinct and unrelated processes the action of phagocytes and the 
action of the body fluids in the destruction of foreign substances in the 
body. 
Metchnikoff, the learned and able advocate of the importance of 
phagocytosis in the protection of the body against microorganisms, 
1 It was natural in the early studies on bacteriolysis, which were incidental to researches on im- 
munity, that the new substance which was found in the serum as the result of the immunizing process 
should be called the immune substance or immune body. It was natural also, although less appropriate, 
to apply the same term, "immune substances,'' to the analogous substances which appeared in the 
serum as the result of the injection in the same fashion of cells and other materials which were not infec- 
tious, not disease-producing, and against which, therefore, the body is not, in the old sense, immunized. 
But these new uses of the word are, I think, unfortunate because the word "immunity" has come 
to have a special and useful significance in relation to infection, intoxication, and other conditions of 
natural or acquired tolerance to obviously and seriously harmful agents. The process in both instances 
is, indeed, one of adaptation, and the newly acquired capacities of the serum are due to substances 
resulting from this adaptation. They arise from a functional modification of parts of the body, and 
hence maybe appropriately called adaptive substances. It seems to the writer that it would be better 
to consider immunization as a special phase of adaptation, and so limit the application of the word that 
it shall still connote infection and intoxication in the traditional sense. 
2 Hektoen, L., Jour. Infect. Dis., 1918, xxii, 28. THE RELATIONS OF MICROORGANISMS TO DISEASE 
205 
recognized the importance of the adaptive substances, some of which may 
be largely increased in amount in the processes of immunization. More 
strenuously than other observers, however, he insisted upon the phago- 
cytic cells, especially the leucocytes, as the originators of the substances 
concerned in cytolysis, and held that under ordinary conditions it is 
only within these cells that these substances are effective. In artificially 
immunized animals, however, the intermediary substances, it was con- 
ceded by Metchnikoff, may be set free from the cells which produce them 
and mingle with the body fluids. The complement, on the other hand, 
which he, in common with others of the French school, called cytase, in 
recognition of its ferment-like characters, Metchnikoff did not believe 
to be set free in the body fluids except through some damage to the 
leucocytes in which it is formed; such a damage, for example, as 
befalls the leucocytes in the clotting of the blood; for in this process it 
is assumed that the setting free of the fibrin ferment involves the destruc- 
tion-phagolysis-leucolysis-of the leucocytes. 
The views advanced by Bordet and others of the French school 
regarding the union of the amboceptors with the cells to be destroyed 
are less precise than those of Ehrlich. Both, however, recognize the 
importance of an association of the amboceptor as a condition for the 
effective action of the complement (cytase). It is for this reason that 
the amboceptor is called by Bordet, Metchnikoff, and others, the sensi- 
bilizing substance (substance sensibilisatrice) or the fixative (fixateur). 
Finally, a long and ingenious series of experiments has led Metchni- 
koff and his associates to believe that there are two forms of cytase, one 
called macrocytase, formed by the macrocytes (large lymphocytes 
derived from the spleen, lymph-nodes, and certain endothelial and 
connective-tissue cells) and concerned in the destruction of animal cells, 
such as red blood-cells, leucocytes, spermatozoa, various parenchyma 
cells, etc.; and microcytase, derived from the microcytes (polymorpho- 
nuclear leucocytes), which is active in the destruction of bacteria (see 
page 120). 
The greatest diversity of view concerning the cytolytic process 
between Metchnikoff and his followers and the observers of the Ehrlich 
school relates to the question whether the complement (cytase) does or 
does not exist free in the blood plasma, for upon the answer to this 
question depends largely our belief as to the relative significance of 
intra- and extracellular cytolysis. This is one of the points concerning 
which more data are urgently needed. But even now the views of 
Metchnikoff are not inconsistent with the hypothesis of Ehrlich, and the 
present tendency is to revert to the opinions of the French school as 
simpler and equally logical in the explanation of the phenomena. 
There is reason to believe that bacteria are destroyed within phago- 
cytes by the action of enzymes1 in a manner analogous, at least, w'ith 
that of their destruction in the bacteriolytic fluids which we have just 
considered. But just how these intracellular processes are fostered by 
protective sera is not clear. 
1 See Opie, E. L., Jour. Exper. Med., 19'6, viii, 410, 536. 206 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
Agglutinins.-There are important adaptive resources of the living 
body, when it is called upon to deal with foreign material of special char- 
acter introduced in unusual ways into its recesses, in addition to those 
just considered. 
The phenomenon of agglutination has been widely known for several 
years, especially on account of its practical application in diagnosis. 
The general fact is that as an individual adapts himself-that is, becomes 
immunized-to a special bacterium or its toxic products, either in the 
course of an infectious disease or as the result of artificial processes, 
his serum, if placed under suitable conditions in contact with cultures of 
this special microorganism, may speedily immobilize the organism if it 
be motile, and, whether motile or not, lead to its clumping into irregular 
masses. This reaction has been used, not only as a clinical test of 
special infections,1 but also as a means of differentiating species or 
varieties of bacteria. 
Group Agglutination.-But the serum of an animal adapted to a particular 
bacterial species sometimes has the power of agglutinating closely related organisms, 
such, for example, as the interagglutinations of the colon-typhoid group. 
However, the organism used for adaptation-the so-called "homologous" organ- 
ism-usually agglutinates in so much greater dilutions than do the other organisms of 
this group-the heterologous organisms-that with due care, in spite of the group 
agglutination, the test is useful. 
Recent studies have emphasized the fact that agglutination is a 
much more general phenomenon than has been commonly supposed, and 
is by no means limited to the sera of animals immunized against bacteria 
and bacterial products, for hemagglutinins for human corpuscles are 
present in the blood of certain normal persons; even autoagglutination 
has been found to occur.2 
The interesting problems involved in the application of our knowledge 
of isoagglutinins and isohemolysins to transfusion will be found dis- 
cussed in the chapter on the blood (page 531). 
For example, in the adaptation of one animal to the red blood-cells 
of another species, the serum of the adapted animal may become not only 
lytic but agglutinative also for the corpuscles used for the injections. 
This is true not only in adaptation to red blood-corpuscles but to other 
cells as well. We have, then, to add agglutinative substances or agglu- 
tinins to the list of those which are developed in the body in this form 
of adaptation. These also, within the limits already set forth, are 
specific. 
Just as the specific red blood-cells are capable of "fixing" the immune 
substance in lytic serum, so also the agglutinating substance may be 
"fixed" and removed from serum by placing in contact with the serum 
AGGLUTINATIVE SUBSTANCES. 
1 For the general demonstrative tests for agglutinin, see p. 222. For details of special applications of 
the agglutination test, see Wood, Chemical and Microscopical Diagnosis, 3d ed., New York, 1917, or 
other works on clinical pathology. 
2 For a study of a case of autoagglutination in man, see Clough and Richter, Bull. Johns Hopkins 
Hosp., 1918, xxix, 86. THE RELATIONS OF MICROORGANISMS TO DISEASE 
207 
some of the corpuscles of the particular animal species or some of the 
bacteria under whose influence the agglutinative substances were formed. 
While agglutinative substances are developed in the process of 
immunization, they are not, so far as we know, directly protective, though 
by the grouping of microorganisms the action of phagocytes may be 
favored. The virulence of pathogenic bacteria is not reduced by 
agglutination. 
The agglutinative seem to differ in many ways from the lytic sub- 
stances. Thus their activities are not suspended by a temperature of 
56° C. They become inert, however, at a higher temperature-70° to 
78° C.-and their agglutinating capacity is not restored by the addition 
of normal serum; in other words, their activities are independent of 
complement and, in all probability, are largely of a physicochemical 
nature. It is inferred from this fact that the receptors concerned in 
agglutination are of simpler character than those through which lysis 
is secured. 
The normal blood-serum of some animals contains substances which 
are agglutinative for the red cells of other species. Thus, normal beef 
serum is agglutinative for the corpuscles of the cat and rabbit. This 
capacity of the normal serum sometimes is, sometimes is not, associated 
with marked lytic capacity. Isoagglutinins, either with or without 
isohemolysins, are frequent in human blood. 
The mode of action of these various agglutinins is not yet very 
clearly understood. It has been shown by Bordet and others, however, 
that it is not the agglutinin that agglutinates, but that there is formed a 
complex of antigen and agglutinin which under proper physicochemical 
conditions of reaction and salt content permits the agglutinin to perform 
a purely secondary action of agglutination. 
The specific character of the agglutination reaction has led to its 
use in determining the nature of many infections, the serum of the 
infected individual being used with cultures of known microorganisms. 
On the other hand, the test is often useful in determining the specific 
character of closely related microorganisms and their variations.1 
PRECIPITATING SUBSTANCES. 
Precipitins.-There is still another way in which the body reveals 
adaptive alterations in the presence of foreign protein substances. If 
a few cubic centimeters of the blood-serum or exudate containing globulin 
from one animal be injected into the subcutaneous tissue or peritoneal 
cavity of another species in repeated doses, it is found that, on adding a 
little of the blood-serum of the adapted animal to a dilution of the fluid 
injected, a precipitate is formed. This reaction is also specific, save 
that in some instances body fluids from closely related species, such as 
man and monkey, fowl and pigeon, sheep and goat, horse and ass, dog 
and fox, may both afford a precipitate. But this precipitate is invari- 
ably much more marked in the fluid used for adaptation than in the 
similar fluid from the related species. 
1 See, for agglutination tests in classification. Park, Jour. Infect. Dis., Suppl. No. 2, Feb., 1906, p. 1. 208 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
This reaction is extremely delicate; and it has been possible to recog- 
nize human blood in a dilution of 1:50,000. 
By the use of this test Nuttall, who has made very extensive observa- 
tions, has been able to demonstrate in a most striking fashion phylo- 
genetic relationships between animal species and groups of species, both 
warm and cold-blooded, which have an important bearing upon classi- 
fication.1 
• 
The Precipitin Test in Forensic Medicine.-The use of this precipitation test 
has been urged in forensic medicine to reinforce the present unsatisfactory methods of 
distinguishing between human and other blood. For if one have a rabbit or other 
animal artificially adapted to human blood from which fresh serum can be secured 
(even the dissolved dried serum will answer), he has only to dissolve in a little salt solu- 
tion a suspected blood-clot, and, mixing the two, observe the result. If, under suitable 
conditions of dilution, cloudiness develops within a short time or if a precipitate be 
formed, it is claimed that the suspected material could have been derived from no 
other animal than man. Since, however, it has been found that the blood not only of 
monkeys but of some other of the lower animals may give slight precipitates under 
these conditions, and since other human fluids containing albuminous substances, such 
as saliva, pus, inflammatory exudates, etc., may also give precipitates, it is evident 
that the result of this test should be interpreted with great caution.2 (See technique 
of precipitin test, page 222.) 
The white of a hen's egg, injected into the peritoneum of a rabbit, after 
a time gives rise to substances in the rabbit's serum which induce a 
precipitate in fresh solution of hen's egg albumen. No precipitate is 
produced by this serum in albumin solutions from the blood of the 
mammalia, and only a slight precipitate is formed in the egg albumen of 
related fowls, such as the duck, for example. 
By the adaptation of the living animal to extracts of muscle tissue 
from another species, precipitating substances may be formed in the serum 
which are specific for the muscle used in the injection and may be em- 
ployed in the detection of food substitutions. 
Milk of one animal thus introduced into the body of another gives 
rise to a substance in the adapted animal which causes a precipitate in 
the diluted milk used for injection, but not in the milk of another species, 
save sometimes in slight degree in milk from closely allied animals. 
This reaction is also applicable to plant albumins. Thus, if an ani- 
mal be adapted to a given species of bacteria, its blood-serum, on being 
added to the clear filtrate of the pure culture, throws down a precipitate 
which is in some instances light, in others voluminous. This reaction is 
again specific, except within the group limits of related species. Thus, 
it has been shown3 that precipitating substances which are developed by 
the adaptation of the rabbit to the typhoid bacillus induce a slight pre- 
1 See Nuttall, Blood Immunity and Blood Relationship, Cambridge, 1904. 
2 For a study of the precipitation test for blood, see Graham-Smith, Jour. Hyg., London, 1903, iii, 
269 (bibl.); also Ewing and Strauss, New York Med. News, 1903, Ixxxiii, 871 (bibl.); also Nuttall, 
Blood Immunity and Blood Relationship, Cambridge, 1904. For the suggestion of a method of differ- 
entiating bloods by an hemolysis test, seeVeis ser and Sachs, Berl. klin. Wchnschr., 1905, xlii, 1388. 
For a discussion of the medicolegal value of the test, see Hunt, E. L., Boston Med. and Surg. Jour., 
1917, clxxvi, 48. For a general review, see Hektoen, L„ Jour. Am. Med. Assn., 1918, Ixx, 1273. 
3 Norris, Jour. Infect. Dis., 1904, i, 463. 209 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
cipitate in the culture filtrate of the colon bacillus, but not in the filtrate 
of B. prodigiosus, for example. 
Numerous experiments have shown that other vegetable albumins call 
forth specific adaptive precipitins. 
This precipitation test is so delicate that it appears possible not only 
to distinguish the albumins from different animal and vegetable species, 
but to differentiate also some at least of the various albuminous sub- 
stances in the individual. 
Antiprecipitin.-Finally, it is worthy of note that it has been possi- 
ble, by the adaptation of a fresh animal of the appropriate species to 
these precipitating sera, to obtain "antibodies;" in the case of milk 
adaptation, for example, by the use of the so-called lactoserum, to 
secure an antilactoserum capable, when added to the test fluids, of 
preventing the formation of the specific precipitate. 
Nature of Precipitin.-A great deal of most careful research has been 
devoted to the nature of the precipitating substances which the scope 
of this book does not permit us to touch upon. But it should be said 
that in their resistance to heat and in other ways the precipitating sub- 
stances appear to be more closely related to agglutinating than to lytic 
substances. It has been shown that the specific serum precipitates are 
capable of fixing complement and removing it from solutions as immune 
substances may be fixed and removed-red blood-cells for example- 
by the specific elements which incite their formation (see page 199).1 
The Adaptive Bodies not Permanent.-The effects of foreign cells and 
their derivatives upon whatever body-cells produce the lytic, agglutin- 
ating, and precipitating substances, are apparently not lasting, since if 
the injections be suspended they gradually disappear from the serum. 
The time of their disappearance, however, like that of appearance, is 
not regularly the same, even in the same animal. 
OPSONIC SUBSTANCES-OPSONINS. 
The importance of phagocytosis among the agencies protective 
against microorganisms has been for some time fully recognized and 
many facts are known about their ingestion and intracellular destruction. 
But the exact processes by which this is secured and the effects of natural 
and artificial immunization upon phagocytosis are still obscure. It 
has been assumed that the protective substances in the plasma of immu- 
nized individuals stimulate the phagocytes to the ingestion and destruction 
of microorganisms, and so-called stimulins have been the subject of 
much discourse. It has been claimed that through the germicidal 
power of the serum, bacteria are killed and are then, more readily than 
when living, engulfed by phagocytes. But the existence of stimulins 
has not been demonstrated, and it is now well known that living as well 
as dead germs are ingested and destroyed by phagocytes. It has been 
assumed by many that the promotion of phagocytosis by immune sera 
1 See Gay, Centralbl. f. Bakteriol., Orig. I., 190.5, xxxix, 603. This capacity of precipitates to fix 
complement has an important bearing on the accuracy of the Wassermann and Noguchi tests. 210 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
is due to a sensitizing substance (substance sensibilisatrice') which by 
action on either the leucocytes or the bacteria changes a negative 
chemotaxis into a positive. 
In 1904 Wright and Douglas,1 by the use of methods suggested by 
Leishman,2 discovered in normal human serum, and in larger amounts in 
the serum of persons who had been immunized to certain microorgan- 
isms, substances which when placed in contact with the specific bacteria 
are capable, without inducing appreciable morphological changes, of 
so modifying them that they are more readily taken up by polymor- 
phonuclear leucocytes than are the bacteria which have not been sub- 
ject to this preliminary treatment (see Fig. 118). These substances 
Wright and Douglas called opsonins.3 The opsonins tested by these 
Fig. 118.-Phagocytes, Showing the Effect of Opsonic Substances in Preparing Bacteria 
for Ingestion by Leucocytes. 
In the cell to the left the staphylococci were placed in contact with normal serum; in the cell to 
the right the coc<i had been in contact with the serum of an animal artificially immunized to the micro- 
organism. The cocci thus sensitized by the opsonic substances in the serum of the immunized animal 
have been taken up much more abundantly than those not thus prepared. 
observers were found to be rendered inert by heating for half an hour at 
60° C.; but later studies of others have shown that some opsonins- 
the opsonin of immune sera, for example-are more thermostable, 
resisting temperatures above 70° C. It was shown by suitable experi- 
ments that opsonins do not act upon the phagocytic cells, but only upon 
the bacteria. 
Many studies of the serum of normal and immunized men and animals 
have been made by others since the announcement of Wright and 
Douglas. They are in general confirmatory and many new and interest- 
ing facts have been discovered relating to these protective substances 
-opsonins-present in the serum of normal individuals and markedly 
increased in the serum of those who have undergone natural or artificial 
immunization to special forms of bacteria.4 
Neufeld and Rimpau5 found in the serum of artificially immunized 
1 Wright and Douglas, Proc. Royal Soc., 1903, Ixxii, 357; also ibid., 1904, Ixxiii, 128. 
2 Leishman, Brit. Med. Jour., 1902, i, 73. 
8 From the Latin opsono, I prepare food for. 
4 The substance or substances which Wright and Douglas called opsonins had apparently been 
previously described by Metchnikoff as fixateurs, of which there seem to be two forms, bacteriolytic 
and phagocytic; see LShlein, Ann. Inst. Pasteur, 1906, xx, 939. 
6 Neufeld and Rimpau, Deutsch, med. Wchnschr., 1904, xxx, 1458: also Ztschr. f. Hyg. u. Infectiona- 
krankh., 1905, li, 283. THE RELATIONS OF MICROORGANISMS TO DISEASE 
211 
animals, substances acting, not upon the phagocytic cells, but upon the 
bacteria in such ways as to promote their ingestion. These substances 
Neufeld and Rimpau called bacteriotropic in distinction to bacteriolytic 
substances sometimes formed in immunization, but they are apparently 
identical with opsonins. 
It has been shown by Hektoen and Ruediger1 that the opsonins in 
serum and plasma resemble toxins in that they apparently have toxoph- 
orous and haptophorous molecular groups (see page 193), by which, on 
the one hand, they secure union with the bacteria, and, on the other, 
effect changes in these organisms which render them susceptible to 
phagocytosis. 
The opsonic substances occurring normally or developing in immune 
serum are capable of preparing not only bacteria, but other formed ele- 
ments as well, red blood-cells, for example, for cell ingestion.2 Sub- 
stances opsonic for red blood-cells have been called hemopsonins or 
erythrocyto-opsonins, in distinction to the bacterio-opsonins. The relation- 
ship of opsonins to other immune substances-amboceptors and agglu- 
tinins-formed in similar adaptive processes is not yet clear, but they 
appear to be distinct. 
Phagocytosis of red blood-corpuscles by endothelial and other cells 
in the lymph-nodes, bone-marrow, spleen, etc., is common in various in- 
fections, notably in typhoid fever (see page 270), as well as in toxic and 
anemic conditions. 
Hektoen3 found that normal serum may contain opsonins for heterolo- 
gous as well as homologous erythrocytes, and that the adaptation 
of animals to alien blood commonly gives rise to the accumulation of 
hemopsonins in the blood. He showed, furthermore, that leucocytes 
in varying degrees may be phagocytic for opsonized red blood-cells. 
An interesting example of spontaneous phagocytosis by leucocytes has 
been noted occurring after direct transfusion in a case of pernicious 
anemia.4 
Opsonins of immune sera appear to be specific, each uniting only with 
the formed elements under whose influence the special adaptation is 
secured. In this union-called "fixation" of the opsonin-the formed 
elements-bacteria or red blood-cells-are said to be sensitized, and 
from a serum containing several specific opsonins each can in turn be 
removed by fixation to its special cells and the separation of these by 
centrifugalization, just as specific amboceptors may be separated from 
hemolytic or bacteriolytic sera. (See page 199.) 
The nature of the alterations which bacteria and other cells undergo 
by their union with opsonins is not understood. The bacteria are not 
killed or their capacity for growth diminished by it. The opsonins of 
immune sera of the lower animals sensitize bacteria and erythrocytes 
to human leucocytes, and vice versa. Thus the leucocytes of animals 
1 Hektoen, Jour. Infect. Dis., 1906, iii, 721. 
2 Neufeld and TOpfer, Centralbl. f. Bakteriol., Orig. I., 1905, xxxviii, 456. 
3 Hektoen, L., Jour. Infect. Dis., 1906, iii, 434. 
4 Hopkins, J. G., Arch. Int. Med., 1910, vi, 270. 212 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
as well as those of man may be used in the determination of the presence 
of opsonins in sera. 
It is clear that opsonic action is of the highest importance in promot- 
ing phagocytosis. It is also evident from the numerous studies which 
have been made on the subject that in many instances this mode of de- 
struction of bacteria by phagocytes is often effective under conditions 
in which extracellular bacteriolysis does not suffice for the protection of 
the infected individual. 
The mere fact of phagocytosis, however, is not evidence of success- 
ful protection, since the ingested bacteria may destroy the phagocyte at 
once, may possibly gain in its interior by adaptation an exalted viru- 
lence, or may be transported to various parts of the body. 
The virulence of bacteria has an important bearing upon the effect- 
iveness of phagocytosis. It has been found that bacteria of high viru- 
lence are much less susceptible to phagocytosis than are the less virulent 
strains of the same species, both in normal and in immune sera. It 
would appear that virulent bacteria may be protected from phagocytosis 
both by their insusceptibility to opsonification and their capacity to 
produce substances harmful to the phagocytes. 
In the light of our present knowledge of opsonins and their relations to 
phagocytosis, the occurrence of leucocytosis in various infections becomes 
of special significance. For if either a local or general leucocytosis be 
fostered hand in hand with the effective production of opsonins, the 
conditions would appear to be most favorable for the control of the 
infectious processes. 
Clinical Significance of Opsonins.-The determination of changes in 
the opsonic power of the blood serum was thought by Wright and his fol- 
lowers to be of great practical importance as a guide to the administration 
of immunizing substances in the treatment of certain forms of infection. 
For a rise in the opsonic content marks, in accordance with this view, the 
successful development of those protective substances in the body which, 
by uniting with the bacteria, favor phagocytosis. If, on the other hand, 
after the administration of immunizing substances, the opsonic power 
falls, as is sometimes the case, and continues low, the indication is for a 
reduction or suspension of the dosage. 
Remarkable curative results are recorded as the result of the admin- 
istration of sterilized and standardized suspensions of the dead bodies 
of Staphylococcus pyogenes aureus in chronic furunculosis, and of the 
tubercle bacillus in tuberculosis, especially in its local phases, as well as 
other infections. The greatest value seems to lie in the prophylactic 
inoculation against typhoid and paratyphoid fevers, and against dysen- 
tery and cholera. The dead bodies of bacteria used in this way are called 
by Wright and his followers "vaccines."1 
1 This use of the word vaccine is not altogether to be commended, since the analogy between these 
substances and those used in the traditional vaccination for smallpox is not close. For a summary 
of the methods of preparing vaccine, see Hiss and Zinsser, Text-book of Bacteriology, 4th ed., New 
York, 1918; and Kolmer, Infection, Immunity, and Specific Therapy, 2d ed., Philadelphia, 1917. For 
an interpretation of present-day uses of vaccines, see Theobald Smith, Jour. Am. Med. Assn., 1913, lx, 
1591. 213 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
Opsonic Power and its Determination.-Studies of the effects of opsonins upon 
bacteria as marked by phagocytosis are readily made outside the body. The 
simplest form of observation may be made by mixing equal parts of defibrinated blood 
and a suspension of a bacterial culture in 0.85 per cent, solution of sodium chloride, 
keeping this for fifteen to twenty minutes at 37° C., staining smears made upon a 
slide, and then determining the average number of bacteria found in the polymorpho- 
nuclear leucocytes. Since, however, under these conditions, the leucocytes are too 
few to obtain readily the averages of a large number, it has been found desirable for 
most purposes to concentrate the leucocytes by the centrifuge. The blood is diluted 
as it is drawn with a solution of sodium citrate 1.0 percent, in 0.85 per cent, solution 
of sodium chloride. This prevents coagulation, and the performances of living 
leucocytes are not interfered with. This dilution can be effected by drawing blood 
from the finger tip into small glass capsules (Fig. 119) containing the sodium-citrate 
solution. This blood dilution may now be centrifugalized, and the leucocytes, 
which take a place above the red cells, may be drawn off by a pipette, washed with 
salt solution, and centrifugalized twice to remove the citrate, and then mixed with 
the bacterial suspensions and with the serum to be tested. This mixture is incubated 
for fifteen to twenty minutes; the smears are stained by the Jenner method (see 
page 530). 
Fig. 119. -Glass Capsule fok Drawing a Small Amount of Blood from the Finger Tip. 
As suggested by Wright. 
In comparative studies it is necessary to free the leucocytes from their own serum 
by repeated washing in salt solution with centrifugalization, before testing their phago- 
cytic power with bacteria exposed to an heterologous serum. Such washed leucocytes 
are found to be incapable of ingesting many forms of bacteria.1 
Opsonic Index.-If the phagocytic count obtained with the use of the serum of 
normal man be considered as the unit, the proportion which the phagocytic count of 
the special serum bears to the unit is called the opsonic index.2 
The determination of the opsonic power of sera in routine practice has been almost 
entirely abandoned owing to the laboriousness of the technique and the possibility 
of error in making the counts. The use of "vaccines" of dead bacilli is now very ex- 
tensive, and the practice has to a large extent become standardized as to dosage and 
time intervals for injection. Part of the therapeutic effect in many chronic conditions 
is undoubtedly due to nonspecific protein reactions. 
Although we have considered separately the development in the body 
of cytolytic, agglutinating, precipitating, and opsonic substances, it 
should be remembered that these may be and often are formed together 
in the same animal. 
1 For an excellent summary of phagocytosis and opsonins, see Hektoen, Jour. Am. Med. Assn., 
1906, xlvi, 1407. For bibl. and summary of opsonins, seePotter, Ditman, and Bradley, Jour. Am. Med. 
Assn., 1906, xlvii, 1722, 1798. Also see Wright, Studies on Immunization, London, 1909. 
2 In his studies upon opsonins Wright has devised many delicate and clever technical procedures for 
collecting, measuring, standardizing, and mixing the various elements involved in the reactions, and with 
these the worker in the field should make himself familiar. See Wright, A. E., Technique of the Tea 
and Capillary Tube, London, 1912. 214 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
We have seen that the phagocytes, particularly the polymorpho- 
nuclears, are possessed of very subtle and, in the aggregate, very powerful 
capacities for bacterial cell destruction, both in their interior and through 
the substances which they may furnish to the body fluids. 
It is apparent that, in the complex series of adaptations to one 
another in infection of the body-cells on the one hand and the micro- 
organisms on the other, the balance must often be very nice in this 
muster of opposing forces. 
Hiss proposed,1 therefore, that the overtaxed or threatened phago- 
cytes might be aided in an emergency if an extract of cells of their own 
kind in diffusible form such as might be secured by a sterile emulsion 
of dead cells were introduced into the body. He prepared such extracts 
and they have been administered both to men and to animals in divers 
infections with benefit in some cases. Cases of cerebrospinal meningitis, 
lobar pneumonia, and staphylococcus and streptococcus infection have 
been thus treated; and in experimental animals the infective processes 
induced by the pyogenic bacteria, meningococcus, typhoid and dysentery 
bacilli, and others have been markedly modified. It is now regarded as 
probable that such effects are due not, as was originally thought, to the 
neutralization of the bacterial poisons, but to the leucocytosis induced by 
a non-specific chemotactic reaction, following the injection of foreign 
protein. 
Preparation of Leucocyte Extracts.-Exudates which contain a large proportion 
of leucocytes are secured from rabbits by intrapleural injection of sterilized aleuronat 
(page 223). After twenty-four hours the copious exudate is withdrawn, and the cells 
are separated by the centrifuge. These cells are extracted with sterile distilled water 
and after careful control as to the freedom from bacteria of the final emulsion, this 
is introduced beneath the skin.2 
LEUCOCYTE EXTRACT. 
FIXATION OF COMPLEMENT. 
We have seen when considering hemolysis (page 197), that when hemolytic serum 
which contains amboceptors is heated to destroy its complement, the amboceptor, if 
placed in contact with the species of red blood-cells to which it has been adapted, 
unites with them. Such blood cells are said to be "sensitized," because if now a 
small amount of complement in the form of fresh normal serum, "activating serum," 
be added, hemolysis takes place. 
Similarly when heated bacteriolytic amboceptor in the form of an immune serum 
is added to its homologous bacteria-antigens-the latter are sensitized and are thus 
capable of absorbing and using up complement if fresh normal serum be added. 
This delicate hemolytic reaction several years ago was made the basis of an 
ingenious method of testing for the presence of immune body by Bordet and Gengou.3 
The Bordet-Gengou test has been characterized as the method of fixation of comple- 
ment for reasons which will be made clear through an example, as follows: 
If one take bacteriolytic amboceptor in the form of, say, heated typhoid immune 
serum and add to this, first, an emulsion of typhoid bacilli and, second, complement in 
the form of fresh normal serum, and allow these to stand for five hours, it is evident 
from what we have seen above that the complement, if this has been added in proper 
1 Hiss and Zinsser, Jour. Med. Research, 1908, N. S. xiv, 321. 
2 For a study of bactericidal substances in leucocyte extracts, see Zinsser, H., Jour. Med. Research, 
1910, N S. xvii, 397. 
» Bordet and Gengou, Ann. de 1'Inst. Pasteur, 1901, xv, 129. 215 
proportion, will have been all absorbed in the bacteriolytic reaction between itself, 
the amboceptor, and the typhoid bacilli. So that if we now add sensitized red blood 
cells, i.e., heated hemolytic serum and red blood-cells, no hemolysis will take place 
because the complement necessary for this was previously absorbed, that is "fixed," 
in the bacteriolytic reaction. 
That this is actually the case may be shown by replacing in the above experiment 
the heated typhoid immune serum by heated normal serum. In this case on the 
addition of the sensitized red blood-cells hemolysis occurs. 
This method assumes that in the activating serum the hemolytic and bacteriolytic 
complement are identical at least in their combining capacities. 
This "fixation of complement" has been brought more recently into practical use 
in testing for immune bodies in diagnosis (the Wassermann reaction), as well as in the 
determination of bacterial species and in the differentiation of proteins. 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
ALLERGY AND ANAPHYLAXIS. 
Under the general term "allergy" are classed a number of complex 
phenomena of immunity, the name signifying an altered reactive quality 
of the body or the individual tissues. This changed reactivity may be 
due to previous disease or to the administration of foreign substances, 
as the injection of drugs or of horse serum, or to the occurrence of a dis- 
ease like tuberculosis, which renders the body unusually susceptible to 
products of the tubercle bacillus. The altered reactivity of the body 
may express itself in three forms: 1, as an alteration in the speed of the 
reaction; 2, as an alteration in the amount of the reaction; and, 3, as an 
alteration in the quality of the reaction. Those substances which are 
capable of altering the reactive power of the organism are called allergins, 
which is a broader term than the word antigen, the latter being employed 
to designate those highly specific generators of immunity present in the 
proteins giving rise to antibody formation when placed in contact with 
the body cells. The term anaphylaxis is now being limited to that form of 
allergy due to the sensitizing of the body cells with some form of protein. 
The other form of allergy is due to substances which do not act as anti- 
gens but are, as a rule, well characterized chemical substances, as, for 
example, salvarsan, which sensitizes the tissue so that frequent doses 
may cause very severe reactions, or morphine, which acts less powerfully 
with each dose owing to the fact that the body cells ultimately develop 
a capacity to oxidize this alkaloid with greater activity than when ad- 
ministration is first begun. 
The toxins of bacteria, such as the diphtheria and tubercle bacilli, 
may induce the production of antitoxins which neutralize the toxins or 
may sensitize the cells so that a second dose of the toxin may cause the 
death of the animal with symptoms of the disease which the particular 
toxin in question has the power to produce; for instance, a second dose 
of tetanus toxin may kill an animal with all the symptoms of tetanus. 
It is believed that the mechanism of death under these conditions is 
different from that which occurs in true anaphylaxis due to the intro- 
duction of a foreign protein into the circulation. If a dilute solution of 
tuberculin is dropped into the conjunctival sac of a person suffering from 
tuberculosis, there occurs a violent inflammatory reaction which is 
allergic in nature. The classic example of true anaphylaxis is that which 216 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
follows the spaced injection of foreign protein. If, for example, a guinea- 
pig is inoculated with a small quantity of horse serum and then seven to 
eleven days afterward a second injection is given, the animal often dies 
in a few minutes with symptoms of dyspnea, convulsions, involuntary 
defecation and urination, and fall of temperature. If the animal does 
not die it is immune and does not react to further injections of the same 
serum. If the second injection is made within a few days after the first 
no anaphylactic symptoms are produced nor can they ever afterward be 
produced by large or small doses. This anaphylactic condition can be 
transferred by injection into other animals of blood from an animal 
potentially anaphylactic. The condition may also be transmitted from 
mother to child, irrespective of whether the mother was rendered hyper- 
susceptible before or after the beginning of pregnancy; it is not, however, 
transmitted in the milk. 
Numerous theories have been proposed to explain this phenomenon, 
von Pirquet and Schick1 thought that the reaction was a simple one be- 
tween antigen and antibody, with the setting free of a product whose 
action on the remnants of the antigen still circulating in the blood caused 
the disturbance. Wolff-Eisner2 believed that the first injection produced 
a ferment from the cells, capable of splitting the foreign protein injected, 
and that when this protein was injected a second time it was split rapidly, 
one of the split products being toxic. This theory, according to which the 
reaction takes place in the blood, received a good deal of support from the 
work of Vaughan.3 Gay and Southard4 suggested that a portion of the 
protein introduced in the first injection is assimilated by the cells, but that 
a fraction which is not digestible remains in the circulation and renders 
the tissue cells abnormally sensitive to reinjections of the same form of 
protein. The toxic nonassimilable substance, they called anaphylactin. 
Besredka5 held that the antigen and the substance producing anaphy- 
laxis are different. His theory was that the sensitizing protein contained 
an active element which gave rise in the injected animal to a specific 
antibody, which was circulated in the blood and stored up in the cells of 
the central nervous system; and that on a second injection a reaction 
took place between the specific antibody and a third substance present 
in the protein, which acted upon the nerve cells and gave rise to the symp- 
toms. Doerr and Russ6 regarded anaphylactic shock as an intracellular 
precipitin reaction.7 Weil8 believed that anaphylaxis is due to a reaction 
i u. Pirquet and Schick, Die Serumkrankheit, Vienna, 1905; for a complete review with bibl. to 1910, 
see v. Pirquet, Arch. Int. Med., 1911, vii, 259, 383. 
2 Wolff-Eisner, Centralbl. f. Bakteriol., Orig., I., 1904, xxxvii, 350, 566, 684; and Berl. klin. Wchn- 
schr., 1904, xli, 1105, 1131, 1156. 
3 Vaughan, Protein Split Products in Relation to Immunity and Disease, Philadelphia, 1913. 
4 Gay and Southard, Jour. Med. Research, 1907, N. S. xi, 143. 
6 Besredka, Compt. rend. Soc. de. biol., 1907, Ixiii, 294; also Besredka and Steinhardt, Ann. de 1'Inst. 
Pasteur, 1907, xxi, 384; and Besredka, Anaphylaxie et antianaphylaxie, Paris, 1917. 
6 Doerr and Russ, Ztschr. f. Immunitatsforsch., 1911, Orig., 1909, iii, 181. 
7 For an extensive review of the facts leading to the humoral theory of anaphylaxis, see Friedemann, 
Jahresb. 6. d. Ergebn. d. Immunitatsforschung, 1901, vi, 31; and Ztschr. f. Immunitatsforschung, 
Orig., 1909, ii, 591; and Rosenau and Anderson, Arch. Int. Med., 1909, iii, 519 (bibl.). For the views of 
Richet, who did much of the pioneer work on this subject, see L'anaphylaxie, Paris, 1912. See also 
review by Doerr, Kolle and Wassermann, Handbuch. d. path. Mikroorganismen, 2d ed., 1913, ii, 947 
(bibl.). 
8 Weil, R., Jour. Med. Research, 1913, N. S., xxii, 497. THE RELATIONS OF MICROORGANISMS TO DISEASE 
217 
between specific antibodies present in the cells and the introduced 
antigen, and that when passive sensitization is produced by the intro- 
duction of the blood of an anaphylactic animal, the body cells of the 
recipient absorb the introduced antibodies from the blood, and the cells 
thus become anaphylactically sensitive. This takes a certain time, 
usually twenty-four hours, at the end of which the animal can be killed by 
a single dose of antigen, because it has in its circulation an insufficient 
amount of antibody to protect the cells from the toxic effects of the in- 
troduced antigen or its split products. Weil held that an immunized 
animal is potentially anaphylactic but is protected by the immune 
bodies in the circulation, and that the difference between immunity 
and anaphylaxis lies solely in the fact that in the former the antibodies 
predominate in the serum, while in the latter they predominate in the 
cells, the cells being thus left unprotected. 
This limited sketch of a few of the views on anaphylaxis is necessarily 
incomplete, since it is impossible in a work of this sort to do more than 
refer the student to larger treatises. Many of the observed phenomena 
do not fit any of the hypotheses. For instance, it is not clear why ana- 
phylaxis should be prevented by placing the animal under the influence 
of chloral hydrate,1 while morphine does not have this effect. Auer and 
Lewis,2 having shown that the rapid death is due to asphyxiation induced 
by tetanic contraction of the smooth muscles of the bronchioles, showed 
also that atropine will prevent anaphylactic death. It must be remem- 
bered, also, that typical anaphylaxis to sera is seen chiefly in the guinea- 
pig. Other animals react quite differently to horse serum and may not 
be sensitive, though highly sensitive to other proteins. It is evident 
that our knowledge of this subject is still imperfect in spite of the enor- 
mous amount of investigation which has been carried out in the last 
ten years. 
This much, however, is clear. The work of Longcope3 has shown that 
the anaphylatoxin, whatever its nature, is destructive in its action upon 
the liver, kidney, and myocardium; and the part played by the liver has 
been emphasized by more recent studies.4 It is now believed that some 
of the effects of the invasion of the system by bacteria, previously ascribed 
to endotoxins, may be rather a prolonged or chronic anaphylaxis produced 
by splitting of the bacterial proteins and setting free of a toxic moiety. 
It is probable, also, that the anaphylactic phenomena form the patho- 
logical basis of many hitherto but little understood and uncorrelated 
entities such as asthma, hay fever, eczema, and food intoxications. The 
frequence of a moderate eosinophilia in these conditions and also in 
experimental anaphylaxis is of interest. Food intoxications or sus- 
ceptibilities have been much studied of late5 and tests have been worked 
1 Banzhaf and Famulener, Jour Infect. Dis., 1910, vii, 577. 
2 Auer and Lewis, Jour. Exper. Med., 1910, xii, 151. 
3 Longcope, Jour. Exper. Med., 1913, xviii, 678; 1915, xxii, 793; Boughton, Jour. Immunol., 1916, 
i, 105. 
4 Weil, Jour. Immunol., 1917, ii, 525 and 571. 
5 For a review of the subject see Longcope, Am. Jour. Med. Sc., 1916, clii, 625; also Talbot, Boston 
Med. and Surg. Jour., 1914, clxxi, 708; and Blackfan, Am. Jour. Dis. Children, 1916, xi, 441. 218 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
out to demonstrate the type of protein causing the reaction. This is 
most often egg albumen, and the inoculation of a scratch in the epidermis 
with a dilute solution of egg albumen will give rise to a sharp inflamma- 
tory reaction in a sensitive person. The intracuticular injection of a 
minute quantity of the same protein will produce similar effects; but great 
care must be observed, as almost instantaneous death has occurred 
following the use of less than half a cubic centimeter of egg albumen by 
this method. By careful treatment many of these persons can be im- 
munized against the protein to which they are sensitive. 
Of the diagnostic reactions the tuberculin, luetin, and mallein tests 
are anaphylactic in nature; the Schick test is not. 
THE ABDERHALDEN REACTION. 
It was thought by Abderhalden1 that the introduction into the blood 
stream of a foreign protein of any type would incite the formation of a 
specific ferment which would act upon this protein primarily, and not 
be generally potent. On this assumption, he based a very delicate pro- 
cedure for determining the presence of the cleavage products of the 
protein. One method was the detection of the alpha-amino-acids pro- 
duced, by means of a substance known as ninhydrin. The blood-serum 
was allowed to act upon a carefully prepared substrate of the protein which 
the specific ferment was supposed to attack, as, for example, carcinoma 
tissue or placental tissue, and after digestion had gone on for a certain 
length of time, care having been taken to exclude bacterial action, the 
fluid was subjected to dialysis, and the dialysate tested. Another method 
was to determine the change in the optical rotation which occurred under 
the influence of the ferment. 
While it is perfectly true that the injection of a foreign protein into 
the blood does alter that fluid, so that when serum from the recipient acts 
upon the antigen minute quantities of the products of protein cleavage 
are formed, there is no question, also, but that such digestion may be 
produced, though usually not to the same extent, by the use of normal 
sera.2 For these reasons it has been believed that the digestion is accom- 
plished by the enzymes normally present in the serum, rather than by 
any new-formed ferment; and as the studies of the most careful workers 
have not confirmed the claims of Abderhalden and his school, the diag- 
nostic value of the procedure is extremely doubtful.3 
The Bearing of the New Studies on Serum Therapy.-We have seen 
in an earlier section that the use of the blood-serum of animals immunized 
against pathogenic microorganisms for protective purposes in man has 
1 Abderhalden, Abwehrfermente, 4th ed., Berlin, 1914; and for a later review, Cor.-Bl. f. schweiz 
Aerzte, 1917, xlvii, 1745. 
2 Bronfenbrenner, Jour. Lab. and Clin. Med., 1915, i, 79; Smith and Cook, Jour. Infect. Dis., 1916, 
xviii, 14. 
3 For further infor nation, see Wells, Chemical Pathology, 4th ed., Philadelphia, 1920; Elsesser, 
O. J., Jour. Infect. Dis., 1916, xix, 655; Van Slyke, Arch. Int. Med., 1917, xix, 56; and Jobling, J. TP., 
and Petersen, W. F., Bull. Johns Hopkins Hosp., 1915, xxvi, 356. 
For the view that Abderhalden's specific ferments are merely the ferments of the pancreas and the 
intestinal mucosa circulating in the blood, see Boldyreff, Quart. Jour. Exper. Physiol., 1916, x, 175. 219 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
been of practical value in but few instances, and these mainly in cases in 
which the protective action was antitoxic. Protective sera for pneu- 
monia and typhoid, streptococcus septicemia, plague, tuberculosis, 
cholera, and many other infectious diseases whose chief toxic incitors seem 
to be endotoxins have been persistently tested and found to be for the 
most part of doubtful value in man. A serum available for one type of 
pneumococcus has, however, recently been found, as well as one effective 
against the toxin of Bacillus aerogenes capsulatus. 
It is possible that the reason why the serum of an animal immunized 
against a given pathogenic microorganism is not protective is that neither 
this serum nor the body fluids of the individual into whom it is injected 
for protective ends contain sufficient or suitable complements. 
We have seen in our review of hemolysis that hemolytic serum 
heated to 56° C. loses its lytic power owing to the destruction of the very 
labile complements. We have seen, further, that this power is restored 
by the addition of a little fresh serum from a normal animal; that is, serum 
containing complement. Now it has been found that this "reactivation" 
of the serum, as it is called, can often be brought about by the sera of 
various animals. Thus, for example, the serum of the guinea-pig 
adapted to the erythrocytes of the rabbit is lytic for these cells of the 
rabbit. If such serum be heated to 56° C. it is no longer lytic, the activi- 
ties of the complement are destroyed; but the serum can be reactivated 
by a little fresh serum, not only from a normal rabbit, but from the goat 
and the rat. The serum of many other animals, however, is ineffective 
under these conditions. The reason for this, of course, in accordance 
with Ehrlich's hypothesis, is that the complements of the reactivating 
sera have combining capacity with the special amboceptors, and so can 
become effective, while in other sera, the linking of the complement to 
the red cells through the amboceptors being impossible, there can be 
no restoration of the lytic action. 
It is not difficult to secure immune substances (amboceptors) by the 
adaptation of animals to various kinds of pathogenic bacteria. These 
may be formed in such abundance as to be out of proportion to the 
complements. But unless these immune substances, when injected into 
the body for protective purposes, either carry with them or find in the 
new environment an abundance and appropriate forms of complements, 
they are not wholly available in destroying bacteria. One of the great 
problems of the immediate future, then, so far as serum therapy is con- 
cerned, seems to be to secure suitable complements to act with immune 
substances if the former do not exist in the human fluids, or to reinforce 
these substances from the sera of suitable animals if the human stock be 
scanty. There is, however, much ground for believing that in order to 
be most effective the complements with which we may seek to reinforce 
the potency of bacteriolytic sera in man should come from species 
closely allied to him. 
If the securing of an appropriate complement is thus of such impor- 
tance in the attempt to prepare bacteriolytic sera for therapeutic purposes, 
the maintenance of sufficient complements in the human body must be 220 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
of the utmost significance in its intrinsic protective mechanism against 
infection. That this consideration is not without support in fact is 
shown by the studies of Abbott, Longcope, and others,1 who have found 
that after the continuous administration of alcohol and in various chronic 
as well as acute diseases, the amount of complement in the blood may be 
notably reduced. We have thus a definite contribution to our knowledge 
of one of those factors in predisposition to infection which, in a general 
way, are so fully recognized, but which are, for the most part, but ill- 
defined and little understood. 
But the securing of effective bactericidal and bacteriolytic agents 
would not in itself be a satisfactory solution of this urgent problem in 
serum therapy. One can readily conceive that complete success in this 
respect might be an added source of danger to the victim of infection. 
For in the case of those bacteria whose harmful effects in the body seem to 
arise largely through the setting free of endotoxins, it is probable that 
if these were not at once and properly combined or otherwise cared for, 
the wholesale destruction of the bacteria might prove a curse and not a 
blessing. And this, in effect, is the trend of modern thought. The 
diminution of complement in the serum of animals suffering from ana- 
phylactic shock has been noted. In addition, the production of anaphyla- 
toxins by the exposure of proteins or bacteria to the action of fresh 
complement-containing serum suggests that the real defense of the or- 
ganism may not take place in the blood current so much as was originally 
thought by the Ehrlich school; and the tendency to-day is to look upon 
the leucocytes and fixed cells of the body rather than the antibodies of 
the plasma, as the ultimate resource against the invader. 
The Specific Character of Artificial Immunization.-It is not yet 
possible to say in many cases to what extent the immunization effected 
in any of the various ways indicated above is specific. In some cases 
it appears to be so. That is to say, the protection which is afforded, for 
example, by an attack of diphtheria or by the gradually increased ad- 
ministration of the diphtheria toxin, or by the use of the immunizing 
serum, is limited to this particular disease, and is not to be secured, at 
least in such marked degree, by the use of other bacteria or bacterial 
products. In some instances, on the other hand, immunization against 
one microorganism or its toxins, or against special toxic substances, 
affords protection against infection or intoxication by entirely different 
agents. Thus animals may be immunized against anthrax by inocula- 
tion with Bacillus pyocyaneus. Again, in an animal adapted to typhoid 
bacilli, the intravenous injection of a non-specific proteose will incite a 
great enrichment of the blood with typhoid antibodies, apparently by 
direct stimulation of the hematopoietic system.2 
It should be borne in mind, however much importance we may attach 
to the formation and action of the antitoxic substances, that these are not 
necessarily always present in either natural or acquired immunity to 
bacteria or their toxins. Tolerance to bacterial toxins may be established, 
1 For a study of this subject, see Lonycope, Jour. Hyg., 1903, iii, 28. 
2 See, for further examples, Gay, Jour. Lab. and Clin. Med., 1915, i, 13. 221 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
as may tolerance to other kinds of poisons, without the intervention of 
antitoxic or other chemical agents. 
The Complexity of the Processes Involved in Immunization.-It thus 
appears that while we know a great deal about the ability of the living 
body to protect itself against the incursions of microorganisms and the 
ravages of their poisons; while a field is opened for the study of artificial 
immunization which is of the highest promise, both for the advancement 
of science and for practical benefit to the victims of infectious disease; 
while illuminating and far-reaching hypotheses are current which account 
for many of the complex phenomena, we are yet very far from compre- 
hending many of the details of the processes by which immunization is 
secured. 
We do not know why the cells of certain animals or why different kinds 
of cells in the same animal are more susceptible than others to the presence 
of particular poisons; why, for example, the rabbit is less susceptible than 
man to morphine; why strychnine should affect the nerves while curare 
acts upon the muscles; why the common fowl should be extremely insus- 
ceptible to the tetanus toxin so powerful in many other animals. We are 
even ignorant as yet in most cases of either the chemical or structural 
changes in cells by which the deleterious action of poisons is effected. 
This is, indeed, not surprising when we reflect that the processes which 
are involved are of the most subtle and complex nature and that our 
knowledge of cell metabolism even under normal conditions is most 
crude and fragmentary, consisting largely in rather gross determinations 
of end-products and leaving out of the account the numberless molecular 
transformations and combinations through which the life processes of the 
cell are carried on. 
The living body-cell is very nicely adapted to its normal environment; 
the living bacterium is almost equally sensitive to the conditions under 
which its metabolism takes place. Thus it is that, when these subtle 
organisms react upon each other, we are wholly unable with our present 
knowledge to follow the steps by which the more gross manifestations of 
disturbance which we call disease are reached. 
But there seems to be abundant ground for the belief that the pro- 
tective agencies which are evoked in both natural and artificial immuni- 
zation are simply those which the body makes use of in its normal metab- 
olism, exaggerated and diverted to different ends, it is true, in the face 
of emergencies and the establishment of new cell environments, but giving 
evidence of the birth of no new physiological capacities.1 
1 The hypothesis of Ehrlich, which so closely correlates the action of toxins with the assimilation 
of nutrient stuff, has led to new conceptions of the details of the relationship of foods transformed by 
the preliminary digestive process to the material which is finally placed at the disposal of the cells. It 
seems not unlikely not only that through the action of the cell receptors the food material which arrives 
in the body fluids may be adapted to the specific uses of the cells, but that by the formation of count- 
less varieties of substances analogous to the so-called "antibodies" of immunization, the cells are pro- 
tected against equally various toxic substances. It this be true, the hope seems justified that, follow- 
ing the lines of research suggested by this new technique, we may be able ultimately to understand 
more clearly the details of the so-called internal secretion and those disturbances of chemical adjust- 
ment which give rise to many important phases of autointoxication. 222 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
Technique. 
For Microorganisms.-The serum to be tested is mixed in the proportion of 
1 c.c. to 9 c.c. with 0.85 per cent, sodium chloride solution, making a dilution of 1:10, 
and cleared from red corpuscles if necessary, by filtration. From this solution various 
dilutions are prepared in a diminishing series, 1:20, 1:50, 1:100, etc. These solutions 
may be put into slender test-tubes, and to each is added an equal quantity of a sus- 
pension in a 0.85 per cent. NaCl solution of a twenty-four-hour-old agar culture of 
the microorganism to be tested. 
To secure these suspensions add 5 to 10 c.c. of the salt solution to the culture, dis- 
tribute with a platinum needle, allow the larger lumps of culture to settle, and pipette 
off the turbid supernatant portion. This suspension of the culture in 0.85 per cent, 
salt solution is now mixed with the diluted serum to obtain the requisite proportions. 
Thus, 1 c.c. of the 1:10 serum mixed with 1 c.c. of the suspension gives a 1:20 dilu- 
tion; 1 c.c. of the 1:10 serum with 2 c.c. of the suspension, a 1:30 dilution. These 
suspensions of the culture in the series of tubes of diluted serum are now kept for from 
one to twenty-four hours at 37° C. The clumps of bacteria when agglutination has 
taken place may be seen by a hand glass. The clumps oftentimes sink in the tube and 
the fluid becomes clear. Microscopic study of agglutination is made by mixing the 
diluted serum and the bacterial emulsion on a cover-glass which is then inverted on a 
hollow glass slide and sealed with vaseline. For special and for diagnostic purposes 
more exact methods are required, for which see works on bacteriology or on clinical 
diagnosis.1 
For Blood-cells.-A demonstration of the agglutinability of red blood-cells 
may be made by adding to a 5 per cent, dilution of defibrinated blood in 0.85 per cent, 
salt solution, a small quantity of an aqueous emulsion of ricin. The blood-cells soon 
clump and settle, leaving the fluid clear and colorless. 
Agglutination Tests. 
Precipitin Test. 
While the precipitin or so-called biological test for human blood has been sug- 
gested and used in medicolegal cases of importance, its limitations are not yet fully 
determined and one should not enter upon its practical applications in cases of im- 
portance without large experience of the method and the possibilities of error.2 
For demonstrative purposes, however, the technique is simple. A fragment of 
blood-clot to be tested as to its human origin is dissolved in a small quantity of 0.85 
per cent, salt solution and passed through filter paper to secure a clear fluid. To this 
solution in a test-tube is added about twice the quantity of the serum of a rabbit or 
guinea-pig which has been injected with successive doses of human serum. This 
adaptive serum should have been tested with a known human serum to insure its 
reliability. Control tubes should be made containing mixtures of the several ingredi- 
ents used, without the clot solution to be tested. The tubes are now all kept for one 
hour at 37° C., when if the suspected clot is of human blood the tube which contains 
it will show a precipitate while the controls will remain clear. The characteristic 
precipitate should soon settle in the tubes, leaving the fluid clear. 
Hemolysis Tests. 
In comparative observations on hemolysis it is convenient to make a 5 per cent, 
dilution of defibrinated blood with 0.85 per cent, salt solution. One may use narrow 
test-tubes, 5 mm. in diameter, putting into a series of these 1 c.c. of the diluted blood, 
adding to each the serum or other hemolytic agent to be tested, and filling up with 
1 Hiss and Zinsser, Text-book of Bacteriology, 4th ed., New York, 1918, or Wood, Chemical and 
Microscopical Diagnosis, 3d ed., New York, 1917. 
2 For technical and other details of the precipitin test, see Uhlenhuth and Weidanz, Praktische 
Anleitung zur Ausfiihrung des biologischen Eiweissdifferenzierungsverfahrens, Jena, 1909; Leers, Die 
forensische Blutuntersuchung, Berlin, 1910. THE RELATIONS OF MICROORGANISMS TO DISEASE 
223 
salt solution to, say, 2 or 2.5 c.c. The tubes are shaken and placed for an hour at 37° 
C., then in an icebox. A control tube of the blood in simple isotonic salt solution 
0.85 per cent, should accompany each series. If the hemolytic serum is old comple- 
ment must be added. 
Following the suggestion of Wright, tests for hemolysis may be made in capillary 
tubes, each long tube containing several tests or dilutions by the intervention of a 
bubble of air between each segment of the mixed test fluid and diluted blood. 
To Secure Sterile Inflammatory Exudate Containing Leucocytes and other Living cells. 
It has been found that the injection of wheat gluten into the pleural cavity of 
rabbits or dogs induces an exudative inflammation, the exudate usually containing, at 
the end of twenty-four hours, many living leucocytes. Leucocytes secured in this way 
have been largely used in determining the chemical character of their cytoplasm, as 
well as for experiments on phagocytosis. The most convenient preparation is the 
so-called aleuronat, a mealy food preparation. A convenient method is to inject into 
the pleural cavity 10 c.c. of a suspension of aleuronat in starch water (aleuronat, 5 
grams; starch, 1.5 grams; water, 100 c.c.). The exudate may be removed with 
a capillary pipette if small quantities only are required, or the animal may be sacri- 
ficed if larger quantities of the exudate are necessary. 
Polymorphonuclear leucocytes may also be secured in considerable quantity by 
the injection of 10 grams of sterile bouillon into the peritoneum of the rabbit. The 
exudate is removed at the end of twenty-four hours. 
To secure an exudate containing a preponderance of mononuclear cells one may 
inject into the peritoneum of the rabbit a solution containing 1 mgm. of pilocarpin, the 
exudate to be removed at the end of twenty-four hours. 
The Study of Hemophagocytosis. 
If the serum of rabbits adapted by successive injections into the peritoneum to the 
blood of guinea-pigs be injected into the peritoneal cavity of guinea-pigs, after a time 
the peritoneal fluid as well as the spleen and other blood-forming organs are found to 
contain various cells which have ingested the erythrocytes. The peritoneal fluid may 
be secured for examination at various intervals by a capillary tube inserted into the 
peritoneal cavity. 
Hemophagocytosis in vitro may be studied by procedures similar to those em- 
ployed in the study of bacteriophagocytosis. (See opsonins, p. 213.) The serum of 
an animal adapted to alien blood, if lytic, is deprived of this power by destroying the 
hemolytic complement by heating for half an hour at 60° C. A small portion, say, 
0.1 c.c. of this serum, is now mixed with an equal quantity of a 5 per cent, suspension 
of washed red blood-cells in 0.85 per cent, salt solution. To this is added a small 
quantity of living leucocytes of man or of the guinea-pig or dog secured from citrated 
blood or, in animals, from fresh aleuronat exudates (see above), and the mixtures kept 
for an hour at 37° C. Smears are then made and stained with the Jenner or other 
double stain.1 
To Collect Small Samples of Serum for Agglutinative, Precipitin, or Hemolysis Tests. 
The suggestions of Wright are most helpful in the technique of serum collection 
in small quantities. The finger is constricted by the handkerchief or a bandage, not 
tightly enough to stop the blood flow, but enough to induce marked congestion; and 
the puncture is made by a needle or a fine-pointed glass. The drop of blood as it 
exudes is drawn into a small capsule of the form shown in Fig. 119, held so that it will 
act as a siphon. When partly filled, the ends are sealed, first the straight end; then as 
the air here cools, the blood will be drawn back from the capillary end, when this is 
closed. The tube is set slightly aslant for clotting, after which the serum may be 
secured in capillary pipettes by breaking off the straight end of the capsule after 
scratching it with a file. 
1 See Hektoen, Jour. Infect. Dis., 1906, iii, 434; also Jour. Am. Med. Assn., 1906, xlvi. 1407. 224 
THE RELATIONS OF MICROORGANISMS TO DISEASE 
The adaptation, or immunization, as it is called, of animals to various alien sub- 
stances, sera, red blood-cells, etc., in order to secure lytic agglutinating and precipitat- 
ing substances, is readily accomplished. For general demonstration purposes the 
rabbit is well suited. The simplest method is that of intravenous injection. The 
external lower surface of the ear is shaved or the hair is removed with depilatory paste, 
and the skin is then disinfected with dilute lysol. The ear is warmed or rubbed so as 
to dilate the vein, and about 0.5 c.c. of washed corpuscles are injected into the vein 
from a sterile syringe, a fine needle being used so as to avoid bleeding after withdrawal; 
if this occurs, the edge of the ear may be clamped with a small clip or touched with 
tincture of ferric chloride. The injection is repeated once or twice at intervals of 
two days. At the end of ten days the ear vein is incised, and a few drops of blood are 
drawn into a Wright capsule; the blood is allowed to clot in the capsule; and the 
serum is secured. If large quantities of serum are desired, the animal may be bled 
to death, the blood being drawn into sterile receptacles by means of a glass cannula 
tied into the carotid artery. Only a certain proportion of animals will give good 
hemolytic or other sera. If a satisfactory result is not obtained in any instance, the 
animal should be discarded, and other animals inoculated. It is quite unnecessary 
to use larger quantities of blood than 1 c.c. 
For agglutinative or bactericidal sera, a suspension of the bacillus against which the 
serum is desired should be made from an agar slant by pouring into a test-tube a 
few c.c. of a 0.85 salt solution, and emulsifying the bacteria by means of a platinum 
loop. A small amount of this emulsion, 0.1 or 0.2 c.c., is injected into an animal. 
If the organisms are those which kill the animal rapidly, they should first be killed 
by heating for a short time to 52° C. In order to obtain precipitating sera, the blood 
is allowed to coagulate and from 0.5 to 1.0 c.c. of the separated serum is used for the 
injection. It is often not necessary to repeat this injection, but if this must be done, 
the reinjection should be made within forty-eight hours.1 
The Method of Adaptation of Animals to Alien Substances. 
Bibliography on Studies of Immunity. 
For an early admirable resumtS of immunity, consult Weigert, Lubarsch-Ostertag, 
Ergebn. d. allg. Path., 1897, iv, 107; for a good later summary see Muller, Infection 
and Immunity, 1912. Consult also Metchnikoff, Immunity in Infectious Diseases, 
1905, in which much lore is gathered and many ingenious points of view of the author 
are set forth. Kolle and Wassermann's Handbuch d. path. Mikroorganismen, 2d ed., 
1912-13, contains excellent summaries of various phases of immunity; as does also in 
more compact form the Experimentelle Bakteriologie of Kolle and Hetsch, 3d ed., 
1911. Many valuable reviews are contained in the Jahresb. ii. d. Ergebn. d. Immuni- 
tatsforschung, Stuttgart. See also Kraus and Levaditi, Technik u. Methodik d. 
Immunitatsforschung; Much, Immunitatswissenschaft, 2ded., Jena, 1914,and Pfeiffer, 
Eiweissanaphylaxie, 1911. 
The records of the researches just summarized in cytolysis and the application of 
Ehrlich's "side-chain" hypothesis are widely scattered through the German, French, 
and English technical periodicals. The most important of the studies of Ehrlich and 
his associates in this field are collected by Ehrlich, Gesammelte Arbeiten zur Im- 
munitatsforschung, English Transl. by Bolduan, 2d ed., New York, 1910; see also 
Bordet, Studies in Immunity, translated by Gay, New York, 1909 and Muir, Studies 
in Immunity, London, 1909. 
The summary of Aschoff, Die Seitenkettentheorie und ihre Anwedung auf die 
kunstliche Immunizierungsprozesse, Ztschr. f. allg. Physiol., 1902, i, 3, is most com- 
plete and contains a full bibliography. The monograph of v. Dungern, Die Antikbrper, 
1903, contains much valuable material. 
1 For further details and many interesting data, consult Nuttall, Blood Immunity and Blood Rela- 
tionship, London, 1904; Kolle and W assermann, Handbuch d. path. Mikroorganismen, 2d ed., and 
Kraus and Levaditi, Handbuch d. Immunitatsforschung, 1914; and Kolmer, Infection, Immunity, and 
Specific Therapy, 2d ed., Philadelphia, 1917. THE RELATIONS OF MICROORGANISMS TO DISEASE 
225 
In English, the Huxley Lecture by Welch (Recent Studies of Immunity, Medical 
News, October 18, 1902) is admirable, and deals with especial fulness with toxins and 
their relationship to various important pathological processes. 
Ritchie's discussion of the subject (Jour. Hyg., 1902, ii, Nos. 2, 3, and 4) treats 
in a clear and philosophical fashion the facts and hypotheses involved. 
See also Nuttall, Blood Immunity and Blood Relationship, 1904; Bolduan and 
Koopman, Immune Sera, 5th ed., New York, 1917; and Hektoen, Resume of Immunity, 
1905. 
For study of transmission of immunity to offspring see Theobald Smith, Jour 
Med. Research, 1907, N. S. xi, 359. 
For most recent reviews, see Zinsser, Infection and Resistance, 2d ed., New York, 
1918; and Kolmer, Infection, Immunity and Specific Therapy, 2d ed., Philadelphia, 
1917. 
For a studv of the local specific therapy of infections see Flexner, Jour. Am. Med. 
Assn., 1913, Ixi, 447, 1872. CHAPTER IX. 
THE INFECTIOUS DISEASES. 
General Considerations. 
In the study of the infectious diseases it is especially important to 
bear in mind that the abnormal processes through which the disturbances 
incited by microorganisms are manifested are processes of the body-cells 
and not processes of the microorganisms. The microorganisms do, 
indeed, incite the train of phenomena by which the disease is mani- 
fested, and the nature or "species" of the microorganisms may largely 
influence the character of the phenomena, but the stored-up energy 
which is released in this manifestation is body-cell energy and not that 
of microbic metabolism. The microbes are excitants of disease, but 
the disease is a performance of the body-cells. If these obvious con- 
siderations be held in view, it will be convenient, in considering certain 
of the infectious diseases, to use the familiar and much abused term 
"specific" as indicative of those phases of abnormal body-cell per- 
formance which are apt to occur in characteristic ways in response to 
special forms of microbic stimulus. Thus the poisonous substances 
which the tubercle bacillus builds up out of the organic material upon 
which it feeds are in part such as exert a peculiar influence upon con- 
nective-tissue cells, leading to their proliferation and the temporary 
formation of new tissue-the tubercle. This, together with associated 
action of the same or other metabolic products of the living bacillus, 
forms a group of lesions and disturbances which is characteristic of the 
action of the tubercle bacillus in the body. In this sense tuberculosis 
is a "specific" disease. On the other hand, the poisons eliminated by 
the tubercle bacillus may incite responses on the part of the body-cells 
which are practically identical with those which many other toxic sub- 
stances, both of bacterial and of other origin, induce-fever, degeneration, 
etc. These manifestations of the action of the tubercle bacillus upon the 
living body-cells are not "specific." 
In our study of the individual infectious diseases we shall encounter 
many examples of this variety in the effects which pathogenic bacteria 
induce-the more characteristic, on the one hand, and, on the other, the 
more general responses which the body-cells make to deleterious agents. 
Classification of the Infectious Diseases.-It is common to group dis- 
eases from either the clinical or the morphological or the etiological 
standpoint. But a complete rational classification of disease is not at 
present possible, because in very few conditions have we even an approxi- 
mately complete knowledge of the symptoms, the excitants, or the 
morphology of the lesions. 
226 THE INFECTIOUS DISEASES 
227 
In the infectious diseases as we now define them, the excitant is 
definite and in many cases known, but a classification based upon the 
character of the excitants alone would be, as Martins has urged, a classi- 
fication of the microorganisms and not a classification of the diseases. 
If every microorganism capable of exciting disease always met in the 
body a similar response, the matter would be comparatively simple. 
But the fact that the responses of the body-cells to bacterial invasion are 
exceedingly varied, and that dissimilar organisms may evoke similar 
responses, renders a simple etiological classification even of the infectious 
diseases unsatisfactory, if not impracticable. Thus it is that it is con- 
venient to consider the infectious diseases in part together, in part in 
connection with the special organs in which their more common and 
characteristic lesions are manifested. Such a classification of the in- 
fectious diseases as is here made is based in part upon similarity of 
lesions, in part upon the relationships of the microorganisms concerned, 
and may wisely be regarded only as a convenient form of catalogue. 
Groups of Bacterial Disease-Excitants.-One of the interesting results 
of the later studies of bacteria and their associations with the infec- 
tious diseases is the discovery that many microorganisms which have 
been proved to be excitants of disease in men or in lower animals are 
closely related to forms which are not pathogenic. So that we now 
recognize many bacterial groups which we are wont to characterize 
by the name of the pathogenic representative. Thus there are staphy- 
lococcus and streptococcus groups of closely similar organisms, most 
of them harmless to man. There is the colon-bacillus group, embrac- 
ing many closely related forms difficult to identify. The tubercle-bacil- 
lus group, the diphtheria-bacillus group, the actinomyces or strepto- 
thrix group, are other examples of this relationship. The more these 
related forms are studied, the more evident it becomes that in very 
slight physiological variations may lie the difference between patho- 
genic and non-pathogenic forms, and that equally slight variations in 
the susceptibility of the host may be of corresponding significance. 
In the arrangement and associations of the infectious diseases con- 
sidered in this section, the existence of these bacterial groups will be 
frequently recognized. 
SUPPURATIVE AND ALLIED FORMS OF INFLAMMATION. 
We have seen in an earlier part of this book that in various kinds of 
injury in the living tissue there may be a series of responses on the 
part of the body-cells which constitute or give rise to the phenomena and 
lesions of inflammation. One of these forms of tissue response to in- 
jury is called suppuration or suppurative inflammation. 
We have seen that the characteristic feature of suppurative inflam- 
mation is the collection, at or near the seat of injury, of leucocytes, mostly 
of the polymorphonuclear type. These leucocytes, attracted through 
chemotaxis, emigrate from the smaller vessels and gather in the tissues. 
Here through their phagocytic powers they may directly or indirectly de- 228 
THE INFECTIOUS DISEASES 
stroy living microorganisms; by lytic substances which they elaborate 
they may soften and remove dead tissue (see page 119); or they may 
themselves succumb to the action of poisons or other local conditions 
inimical to their life. While, to a limited extent, a suppurative inflam- 
mation can be incited by chemical agents, such as ammonia, turpentine, 
etc., in most cases it is incited and sustained by microorganisms or by 
poisons which these microorganisms set free as the result of their own 
metabolism or by the decomposition of substances in the tissues or the 
tissue fluids. 
Before considering in detail the characteristics of the various forms 
of microorganisms which may act as excitants of suppurative inflam- 
mation, it is necessary for us to survey the various phases which this 
process presents under different conditions. 
Phases of Suppurative Inflammation.-In the first place while the 
emigration, proliferation, and gathering of leucocytes are the most char- 
acteristic features in this form of inflammation, these are always associ- 
ated with the accumulation of more or less fluid transudate from the 
blood-vessels and often with the formation of fibrin. These, the leu- 
cocytes, the serum, and the fibrin, constitute the exudate. Further- 
more, associated with the accumulation of the exudate there may be 
albuminous degeneration and necrosis of cells and tissue of the affected 
part or of the formed elements of the exudate itself. Finally, a pro- 
liferation of the fixed cells of the affected region, connective-tissue 
cells, endothelium, etc., frequently accompanies the exudative phases 
of inflammation and may dominate the process when regeneration 
and repair are under way (see page 87). 
Although the processes involved are essentially the same, it has been 
found convenient to attach special names to various topographic forms 
of suppurative inflammation, the differences depending largely upon the 
origin, situation, extent, and complications of the primary lesion, some- 
what, however, upon the qualities, fixed or variable, of the infecting 
microorganism. Thus a suppurative inflammation involving the serous 
surfaces and resulting in the accumulation of a purulent exudate in the 
serous cavities, such as the pleural and the pericardial, is called em- 
pyema. An exudative inflammation of the mucous membranes with a 
marked emigration of leucocytes from the vessels of the submucosa is 
called a purulent catarrh or blennorrhea. 
Pustules are superficial collections of purulent exudate in the skin. 
Furuncle.-A furuncle is an acute, circumscribed, suppurative, and 
necrotic inflammation of the skin, the necrosis commonly involving a 
central plug or core. Furuncles are usually incited by Staphylococcus 
pyogenes aureus, rarely by Streptococcus pyogenes. They are common 
on the neck, back, buttocks, perineum, and axilla. Diabetes, marasmus, 
and obscure nutritional disturbances, often associated with worry and 
overwork, seem to predispose to this form of infection. The invasion 
of the staphylococcus is usually through the sebaceous glands and hair 
follicles. Furuncles may be experimentally induced by rubbing cul- 
tures of staphylococcus over the intact skin. THE INFECTIOUS DISEASES 
229 
From the seat o infection the inflammation extends outward and 
in depth to a varying extent. The tissue becomes hard from infiltra- 
tion of the tissue interstices with fluid and leucocytes, by the swelling 
of the stroma and connective-tissue cells (Fig. 120). The vessels are 
congested and the central portions become more or less necrotic, with 
gradual liquefaction of the tissue and the development of pus. Lym- 
phangitis and hyperplasia of the associated lymph-nodes may accompany 
furuncles. 
Carbuncle.-If the infection of several contiguous hair follicles, 
either immediately or in rapid succession, takes place, so that several 
centers of necrosis, with surrounding areas of exudative inflammation, 
On the left the connective-tissue cells are swollen and proliferated and the lymph-spaces are dis- 
tended with fluid. Nearer the center of the boil the connective-tissue spaces are infiltrated with pus 
and the fibrils of the stroma swollen. 
Fig. 120.-Section of a Boil-Furuncle. Showing the Red and Swollen Area. 
merge, the resulting lesion is called carbuncle. The process is essentially 
similar to that involved in furuncle, but usually more severe and ex- 
tensive. Carbuncle is common on the neck, back, and face. 
A diffuse infiltration of the subcutaneous or deep fibrous tissue, 
muscle tendon, periosteum, or of the interstitial tissue of the viscera, 
with exudate, is called phlegmon. If in this phlegmonous inflammation 
there be much serous fluid associated with the cell accumulation, as is 
commonly the case in the earlier stages of the process, the condition is 
often named purulent edema. When, on the other hand, there is a 
more or less circumscribed collection of purulent exudate in the depth 
of the tissues or organs, associated with necrosis and fluidification of 
the tissues involved, it is customary to call the result of the process an 
abscess 
In some cases of exudative inflammation, particularly those in- 
volving the serous surfaces, the exudates often occur together in the 
most variable proportions; they are formed under the influence of 
the same agents, and frequently an exudate at first simply serous in 
character becomes fibrinous or purulent or both together. 230 
THE INFECTIOUS DISEASES 
Pus and Pus Cells.-It will thus be seen that the exudate which is 
formed in suppurative inflammation varies considerably in its composi- 
tion and structure. Primarily, pus consists of an albuminous fluid 
containing leucocytes, of which some are mononuclear, but the majority 
polymorphonuclear (Fig. 121). While the 
exudate is in the tissue and the conditions 
are favorable, these cells may be alive 
and without structural abnormalities. 
But in accumulations of pus they present 
various phases of degenerations-albumin- 
ous, glycogenic, or fatty-or of necrosis 
and disintegration. It is on account 
of their relative frequency and abun- 
dance in purulent exudates that the 
leucocytes are regarded par excellence as 
pus cells. But other cells, as we have 
seen, may be present in pus; thus in in- 
flammation of the serous membranes, such 
as the peritoneum, pleura, etc., the exfoliated and proliferated meso- 
thelial cells may furnish no small part of the cellular content of the 
exudate. Red blood-cells, detached and young connective-tissue cells 
formed from the old and capable of emigration, and endothelial cells 
may be present in considerable num- 
ber. In inflammation of the mucous 
membranes, also, the epithelial cells, 
either new-formed or simply exfoliated, 
may be abundant. Furthermore, pus 
may contain a variety of chemical sub- 
stances and formed elements depend- 
ing upon the place of its formation or 
accumulation. Thus mucus, fibrin, 
cell and tissue detritus, fat, and micro- 
organisms may be intermingled with 
the pus cells. 
Ulcers-in whatever way originat- 
ing (page 69)-may be the seat of 
suppuration, the exudate passing off 
upon the free surfaces. 
The bacteria which are found in the 
various phases of suppurative inflam- 
mation may lie free in the interstices of 
the tissue with the exudate, or they 
may be in part within the cells which 
have gathered about them (Fig. 122). 
Both within and without the cells the bacteria may present those 
structural alterations which denote their death and degeneration in 
the struggle for existence to which the two forms of living beings, the 
microbes and the body-cells, are subjected under the conditions which 
Fig.121.-Pus Cells in Suppurative 
Inflammation. 
Some of the cells show the marks of 
necrosis and disintegration with frag- 
mentation of the nuclei, etc. 
Fig. 122.-Staphylococcus Pyogenes 
Aureus, in and Among the Pus Cells, 
from an Abscess of the Kidney. THE INFECTIOUS DISEASES 
231 
mark infection. The local and systemic reaction, on the other hand, 
and the cell necrosis which so frequently follows the growth of microbes 
in the body are expressions of an unfavorable environment to which the 
body-cells as individuals and the body as a composite organism are sub- 
jected, and to which they may successfully react or under unfavorable 
conditions may succumb.1 
In the softening of tissue involved in the development of abscesses, 
as well as in the removal of exudates by absorption, it is probable that 
the solution of the formed elements of the tissues is accomplished by 
the development of lytic substances derived from the bacteria and also 
from proteolytic ferments set free by the destruction of the leucocytes 
(page 117.)2 
Fig. 123.-Focal Necrosis in the Liver in Pneumonia. 
Showing the local eSect of a toxin circulating in the blood in toxemia. 
Toxemia.-While the various forms of exudative inflammation are 
more or less circumscribed, the soluble toxins which are formed at the 
seat of local bacterial growth may, without the dispersion of the germs 
themselves, be diffused through the blood and the other fluids of the 
body, giving rise to the symptoms and lesions of toxemia-fever (see 
page 501) and various other forms of functional disturbance, albuminous 
degeneration of the viscera, focal necroses, petechial hemorrhages, hemo- 
lysis,3 thrombosis, leucocytosis, chromatolysis of the ganglion cells, etc. 
1 For an exhaustive review of suppurative inflammation, with bibliography, consult Janowski, 
Zieglers Beitr., 1894, xv, 128. 
2 For a fuller reference to removal of exudates by autolysis see page 122. 
3 For a summary of facts relating to the hemolytic power of various species of bacteria see Pribram, 
Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1913, ii, 1328. 232 
THE INFECTIOUS DISEASES 
Of these alterations in the body, which are of frequent occurrence in 
many forms of toxemia, whether induced by bacterial or other kinds of 
poisons,1 the only ones which demand special notice here are the focal 
necroses. These usually small, often sharply circumscribed areas of 
dead tissue2 may be present in any of the viscera, but are often most 
abundant and conspicuous in the liver (Fig. 123). They vary con- 
siderably in appearance, depending upon the stage of the tissue in- 
volvement. The cells in the affected area may be swollen, the cyto- 
plasm more transparent than normal, while the nuclei may remain 
unstained with the usual dyes or show various phases of fragmentation 
or disintegration; or they may disappear altogether. Again, the cells 
in the involved areas may become more coarsely granular than is nor- 
mal, may undergo a change similar to that seen in coagulation necrosis, 
and with destruction of the nucleus may form deeply staining, irregular 
clumps or masses, or may disintegrate. 
Associated with or following these changes there may be a gathering 
of leucocytes about and within these necrotic areas, so that the foci 
may present the appearance of little abscesses or masses of lymphoid 
tissue. Finally, these necrotic areas may undergo repair and be re- 
placed by small, spheroidal, young connective-tissue cells, granulation 
tissue, or finally by small masses of cicatricial tissue.3 
Septicemia and Pyemia.-Bacteria as well as their toxins may be 
distributed from a local portal of entry or an infected region throughout 
the body, not only inciting general functional and structural changes, 
but, when the bacteria lodge in various situations, giving rise by new 
local proliferation to fresh foci of inflammation. 
It is customary to designate a pathological condition in which 
bacteria as well as their toxins are distributed through the body by the 
blood- and lymph-channels, as septicemia * When fresh suppurative 
foci develop as the result of this distribution, the condition is called 
pyemia. 
The terms septicemia and pyemia are survivals of a nomenclature 
adapted to the period before the nature of the excitants of infectious 
disease was definitely known. The manifestations of septicemia were 
then attributed to the presence of putrid material in the blood. Pyemia 
expressed the belief that the lesions characterizing this condition were 
due to the presence of pus in the blood. The term bacteriemia is some- 
times and more correctly used to indicate the presence of bacteria in the 
1 See for effects of abrin and ricin intoxication, Flexner, S., Jour. Exper. Med., 1897, ii, 197; also 
Muller, F., Zieglers Beitr., 1900, xxvii, 331 (bibl.). 
2 It seems probable that this marked localization of the action of a soluble poison in the tissue 
fluids may be due to some local vulnerability or susceptibility induced, perhaps, by limited vascular 
disturbance or by nutritional defects otherwise induced. In some instances local necrotic foci may be 
due to agglutinative thrombi (see p. 33). 
3 For a comprehensive study of focal necrosis and other associated lesions in certain forms of toxemia 
consult the excellent study of Flexner, The Pathology of Toxalbumin Intoxication, Johns Hopkins 
Hosp. Rep., 1897, vi, 259 (bibl.). 
4 The mere presence of a moderate or even of a large number of bacteria in the blood does not of 
itself indicate septicemia, since the protective mechanism of the body suffices, under usual conditions, 
for the disposal of such an invasion. See discussion on page 176. THE INFECTIOUS DISEASES 
233 
blood, but the old words with their new implications and limitations are 
still commonly employed.1 
The term pyemia, as will be seen, indicates a clinical and anatomical 
phase of septicemia. 
The new foci of suppuration in pyemia are called metastatic ab- 
scesses, and in distribution these may bear an obvious relationship to 
the seat of the primary lesion. Thus, in suppurative processes in the 
intestinal tract, metastatic abscesses are liable to occur in the liver. 
From suppurations in the skin, bones, muscles, etc., infectious emboli 
may be transmitted to the lungs and lead to infarction and abscess; 
or, passing these organs, the germs may induce multiple abscesses in 
the kidneys and in other viscera. 
It should be remembered that the point of introduction into the 
body of the offending germs may be wholly concealed and not associated 
with any form of demonstrable external lesion. This is often called 
cryptogenetic pyemia or septicopyemia. 
After death from septicemia and pyemia there is a considerable 
variety in the post-mortem appearances. 
There are cases in which there are no recognizable gross lesions. 
There are cases characterized by early post-mortem decompositions; 
post-mortem staining of the tissues; congestion of the lungs, stomach, 
intestines, and kidneys; extravasations of blood in the serous mem- 
branes; swelling of the solitary and agminated lymph-nodules in the 
small intestine; swelling of the spleen and albuminous degeneration of 
the liver and kidneys; chromatolysis of the ganglion cells of the brain 
and cord. 
Fig. 124.-Micrococci in Masses in the Fibrinous Exudation of Pyemic Pleurisy. 
1 It has long been known that persons who have received injuries or wounds may suffer from con- 
stitutional symptoms, among the most marked of which may be fever, and develop local or disseminated 
lesions. To designate the condition of these patients the terms pyemia, septicemia, septicopyemia, 
pyosepticemia, ichoremia, inflammatory fever, surgical fever, traumatic fever, suppurative fever, puerperal 
fever, and purulent infection have been used. 234 
THE INFECTIOUS DISEASES 
There may be localized inflammations. The joints and the tissue 
about them, the pleura, the pericardium, the endocardium, the perito- 
neum, the pia mater, and the connective tissue in different parts of 
the body may be inflamed. These local inflammations are usually puru- 
lent, except in the serous membranes, where the principal inflammatory 
product may be fibrin (Fig. 124). The veins in the neighborhood of the 
wound may contain softened, purulent thrombi, without infarctions in 
the viscera, while there may be inflammation of the joints and serous 
membranes. On the other hand, with the venous thrombosis there may 
be infarctions and abscesses in the viscera; acute inflammations of the 
joints and serous membranes may be present or absent. While thrombi 
are often formed in the veins near the wound, they may be situated in 
veins at a distance, and sometimes, although infarctions and abscesses 
be present, no thrombus can be discovered. The veins may be distended 
by the thrombi or contain only small coagula. The different kinds of 
thrombi, and the varieties of emboli and infarctions which they produce, 
are described in the section on Thrombosis (page 31). Leucocytosis 
usually accompanies pyemia and septicemia as well as the suppurative 
process with which they are associated. Studies of the blood in various 
forms of septicemia are numerous and instructive, but we cannot consider 
them here.1 
Various lines of research on minute changes in cells which bacterial 
and other poisons may induce, justify the expectation that more and 
more we shall be able to associate characteristic groups of symptoms in 
toxemia and septicemia for which there is now no morphological basis, 
with well-defined cell alterations. Among the most striking of the 
toxic cell lesions thus far studied in septicemia and bacterial toxemia 
are those involving the cytoplasm of the ganglion cells (see Nervous 
System). 
While many species of microbes are capable under favorable condi- 
tions of inciting suppuration and other forms of 
exudative inflammation and may, when they or 
their toxins are disseminated in the body, give rise 
to toxemia, septicemia, and pyemia, there are 
two forms which, on account of their early dis- 
covery and their relative frequency, are commonly 
considered as par excellence "pyogenic" bacteria. 
These, which are called Staphylococcus and Strepto- 
coccus, we shall consider first. 
THE PYOGENIC BACTERIA. 
Fio. 125.-Staphylo- 
coccusPyogenes 
Aureus. 
From a bouillon culture. 
Characters of Staphylococcus Pyogenes. 
The Staphylococcus pyogenes aureus (Micrococcus pyogenes aureus) (Fig. 125) is a 
relatively small coccus, the individuals varying, however, considerably in size (0.4 to 
1.2 u in diameter). In its growth it does not show a characteristic grouping, but 
grows in irregular masses and heaps (the somewhat crude resemblance, when studied 
1 Consult White, F. IF., Jour. Exper. Med., 1899, iv, 425 (bibl.); and Warren, M., and Herrick, 
W. IF., Am. Jour. Med. Sc., 1916, cli, 556. THE INFECTIOUS DISEASES 
235 
under a cover-glass, to a bunch of grapes gave rise to the generic name); sometimes, 
however, pairs and groups of four or short rows of the cocci are seen. The germ is 
readily stained by the aniline dyes, and does not lose its color in Gram's method of 
staining. It does not show spontaneous movement, and, like other spheroidal forms, 
does not appear to develop spores. It is quite tenacious of vitality, surviving long 
drying and degrees of heat and cold and an exposure to chemical bactericides to which 
many pathogenic germs readily succumb. It grows well at ordinary room tempera- 
ture in such artificial culture media as nutrient-gelatin, agar, beef-tea, and milk, and 
on potato, forming somewhat voluminous masses of culture. It rapidly fluidifies 
gelatin through the formation of a ferment, it coagulates milk, and in the various 
media develops a yellowish white or a deep golden yellow color, whence its specific 
name, aureus, and its common name, "golden coccus." Its color-producing capacity 
is subject to wide variation. Staphylococcus pyogenes aureus forms in old cultures a 
hemolytic substance 1 which may be demonstrated in plate cultures mixed with red 
blood-cells (Fig. 126) or in tubes containing the washed corpuscles to which filtrates of 
old bouillon cultures have been added. 
Fig. 126.-Infective Embolus of Staphylococcus Pyogenes Aureus in the Kidney. 
Rabbit-Experimental. 
Effects of Staphylococcus Pyogenes in the Body.-The virulence of 
cultures of Staphylococcus pyogenes obtained from different sources 
varies considerably, but, in general, suppuration is not readily induced 
in the lower animals by its subcutaneous injection. Liability to sup- 
puration is greatly increased by mechanical or chemical injury to the 
tissues with which the germ is brought in contact. Injection of a viru- 
lent culture into the ear vein of the rabbit is usually followed by multi- 
1 For a study of the bacterial hemolysins see Pribram, Kolle and Wassermann, Handbuch d. path. 
Mikroorganismen, 2d ed., 1913, ii, 1328. 236 
THE INFECTIOUS DISEASES 
pie abscesses in the kidneys and muscles, by suppuration of joints, etc. 
(Fig. 126.) 
In man this coccus grows readily and rapidly, and may cause necrosis 
and exudative inflammation, especially the suppurative phases (Fig. 127). 
The lesions which it induces are apt to be circumscribed, but septicemia 
and pyemia may result as well as pustules, boils, and abscesses, and 
various suppurative inflammations of the visceral and serous membranes, 
joints, bones, endocardium, etc. These effects may be induced by the 
staphylococcus alone or by it in association with other species of germs. 
It is frequently associated with Streptococcus pyogenes. 
Fig. 127.-Masses of Micrococci in a Blood-vessel of the Kidney, Inducing a Small Abscess. 
From a case of pyemia. Around the dilated and partially necrotic blood-vessel in which the bacteria 
lie is an area of necrotic tissue and a small-cell infiltration or zone of pus. 
Staphylococcus pyogenes aureus incites these changes in the body 
in virtue of certain toxins or toxalbumins which are produced as the 
result of its metabolism, and which are either at once set free or stored 
up in the body of the germs-endotoxins-until their release by dis- 
integration after the death of the germs. The special power of the 
staphylococcus to cause the gathering of leucocytes is apparently due 
to the marked chemotaxic powers of some of the protein substances in 
its protoplasm. In its growth in the body staphylococcus may lead to 
the development of hemolytic, agglutinative, leucocidal, leucolytic, and 
opsonic substances. 
Portals of Entry.-It may enter the body through wounds, small or 
large, of the skin or mucous membranes, through sweat and sebaceous 
glands and hair follicles, and sometimes through uninjured surfaces. 237 
THE INFECTIOUS DISEASES 
In many cases its mode of access is not evident.1 While usually this germ 
dies in the body, it may remain for a long time alive. 
Sources.-It is widespread in inhabited regions, especially in towns, 
being frequently found on the surface of the body, and in the saliva, par- 
ticularly of those with acute or chronic catarrh of the upper air pas- 
sages. As the result of the filthy habit of indiscriminate public spitting 
and unguarded sneezing, it is common in the dust of hospitals, houses, 
towns, public conveyances, and places of public assembly.2 It is proba- 
ble, however, that the larger part of the acute staphylococcus infections 
are incited by organisms derived directly or indirectly from others 
already infected. 
Susceptibility.-In man there may be a susceptibility to Staphy- 
lococcus pyogenes associated with a general disease, diabetes for example 
On the other hand, local susceptibility in man is of frequent occurrence. 
In chronic furunculosis and in carbuncle, local areas of inflammation 
may develop and persist for long periods, fresh foci developing as the 
older ones heal. In some instances this local vulnerability is apparently 
associated with minor local injuries, such as the friction of garments at 
the back of the neck, or pressure and friction in the gluteal regions. 
Sometimes, however, the local vulnerability appears to arise from disturb- 
ances in the sebaceous and sweat glands and hair follicles, leading to 
stagnation of secretions in which the bacteria long persisting on the sur- 
face find lodgment and conditions favorable to their development. 
The studies of Wright have indicated that in cases of carbuncle and furunculosis 
the opsonic index3 for the special strain of staphylococcus concerned may be low, and, 
further, that by the injection of emulsions of the dead bodies of these organisms- 
vaccines of Wright-a rapid immunization of the individual, marked by a rise in the 
opsonic index of his serum may be produced with a speedy decline of the local inflam- 
matory reaction. 
Not all the yellow staphylococci found in dust and on the person are pathogenic. 
These may be indistinguishable from the infective forms by the usual culture methods. 
They may, however, be differentiated not only by their innocuousness to animals, 
but in their failure to develop in these either agglutinative or leucolytic substances. 
Staphylococcus pyogenes albus.-This appears to be a variety of the Staphylo- 
coccus pyogenes which does not develop the yellow color in cultures. It is of frequent 
occurrence both in connection with the aureus and alone. Its action on the body is 
similar, but it has seemed to many observers to be in general less virulent. 
Staphylococcus epidermidis albus.-This coccus has been described by Welch as of 
frequent occurrence in the epidermis, and, although of rather feeble pyogenic power, 
yet seems frequently to cause small stitch-abscesses and moderate suppuration along 
drainage tubes. It has been regarded as possibly a variety of Staphylococcus pyo- 
genes albus. 
Other forms of staphylococcus have been described-S. salivarius pyogenes, S. 
cereus albus and flavus-but they are apparently of little pathological significance.4 
Other Forms of Staphylococcus. 
1 For a r6sum6 of the role of S. pyogenes aureus in skin disease, with bibl., see White, Boston Med 
and Surg. Jour., 1899, cxli, 235. 
2 For bibliography of S. pyogenes aureus consult article by Neisser, Kolle and Wassermann, Hand- 
buch d. path. Mikroorganismen, 2d ed., 1912, iv, 355. 
3 See p. 213. 
* For a study in differentiation between pathogenic and saprophytic staphylococci see Geisse 
Ztschr. f. Hyg., 1913, Ixxvi, 282. 238 
THE INFECTIOUS DISEASES 
Characters of the Streptococcus Pyocenes 
Streptococcus pyogenes is distinguished by the marked tendency of the individuals 
to hang together in longer or shorter chains (Fig. 128). It is immobile and its staining 
reactions are like those of Staphylococcus pyogenes. The organism grows readily on 
ordinary culture media, the optimum temperature being 37.5° C., although at 15° to 
to 20° C. growth still takes place, a useful point in differentiating streptococci and 
pneumococci. It does not liquefy gelatin. On the surface of agar plates after twenty- 
four hours at 37° C. the small grayish colonies show, under the microscope, loops and 
fringes of chain-like cocci along the borders. In broth the organism forms delicate, 
flocculent masses, which cling to the sides of the 
tubes, leaving the fluid clear; but occasionally the 
masses are dense and compact; or growth is diffused 
throughout the broth, rendering it turbid. 
Streptococci are most conveniently divided on the 
basis of their growth on blood agar plates into two 
broad groups of <8. hemolyticus and <8. viridans. 
When the colonies are surrounded by a clear hemo- 
lyzed zone, the organism is put in the hemolytic 
group; when they show a definite green color with- 
out a well defined zone of hemolysis, it is classed as a 
viridans. When neither hemolytic zone nor greenish 
color appears the organism may be considered of in- 
definite type. Holman1 has proposed a classification 
on the basis of carbohydrate fermentation reactions of the two groups of hemolytic 
and non-hemolytic, comprising eight subgroups. The fermentation reactions have 
also been used to distinguish the pathogenic and the saprophytic types.2 Brown3 has 
classified the organisms into three groups: Alpha, producing brownish or greenish 
coloration, but no hemolysis; Beta, producing a zone of marked hemolysis; and 
Gamma, producing neither hemolysis nor coloration. An Alpha prime type, inter- 
mediate between Alpha and Beta, has also been distinguished. 
Fig. 128.-Streptococcus 
Pyogenes. 
From a broth culture. 
Effects of Streptococcus Pyogenes in the Body.-Streptococci which 
give evidence of little virulence in animal inoculation are very common 
in the mouths of healthy persons. The significance of these germs in 
healthy mouths is not yet clear. 
The results of animal inoculation with the Streptococcus pyogenes 
are in general similar to those with the Staphylococcus pyogenes aureus. 
The streptococcus is very frequently associated with the staphylococcus 
in its distribution outside the body, in healthy persons, and in disease. 
In general it may be said that the streptococcus incites those forms of 
suppuration and fibrinopurulent inflammation which tend to spread 
both locally and through metastasis. 
Streptococcus pyogenes has been found either alone or in association 
with staphylococcus in a large number of suppurative and other in- 
flammatory processes in various parts of the body; the condition in some 
cases receiving special names, in others not. Thus, in boils and car- 
buncles, in abscesses and phlegmons, in herpes, impetigo, and panaritium, 
1 Holman, W. L., Jour. Med. Research, 1916, xxxiv, 377. 
2 Hopkins, J. G., and Lang, A., Jour. Infect. Dis., 1914, xv, 63. 
8 Brown, J. H., The use of blood agar for the study of streptococci, Monograph No. 9, Rockefeller 
Institute, New York, 1919. THE INFECTIOUS DISEASES 
239 
in phlebitis and lymphangitis, in erysipelas, in suppurative inflamma- 
tion of various mucous and serous membranes, especially of the throat 
and the gastrointestinal canal, and of the bones and joints, in some 
forms of bronchitis and pneumonia, in puerperal and other forms of 
septicemia, in the pustules of smallpox, one or other or both of these 
germs are frequently concerned.1 
One of the most important features of the relationship of Streptococ- 
cus pyogenes to man is the frequency with which it enters as a concur- 
The streptococcus was grown in a culture medium with which red blood-cells were mixed. Around 
each colony the color has left the red blood-cells and is diffused through the plate. 
Fig. 129.-Hemolysis by Streptococcus. 
rent pathogenic agent in already established infectious diseases due to 
other forms of microorganisms. Thus, some of the most serious com- 
plications to which the victims of scarlatina, diphtheria, typhoid fever, 
and pulmonary tuberculosis are liable are due to the action of the strep- 
tococcus in a body rendered unusually vulnerable by the existence of 
another form of infection. 
The serum of individuals adapted (immunized) to streptococci may 
agglutinate the homologous microorganisms.2 
Streptococci, which upon their isolation from the body in suppurative 
or other infectious processes are very virulent, usually, and sometimes 
1 Anaerobic streptococci have been found by various observers in abscesses and other forms of 
suppuration of which they are apparently the excitants. 
2 For a study of agglutination of streptococci see Moser and v. Pirquet, Centralbl. f. Bakteriol., 
Orig. I., 1903, xxxiv, 560 and 714: also Neufeld, Ztschr. f. Hyg., 1903, xliv, 161: also Weaver, Jour. 
Infect. Dis., 1904. i. 91. 240 
THE INFECTIOUS DISEASES 
very quickly, partially or wholly lose this virulence under artificial 
cultivation. On the other hand, cultures of streptococci which have 
largely lost virulence under artificial cultivation, or whose initial viru- 
lence was slight, may experience a great exaltation of virulence by a 
long succession of inoculations from animal to animal.1 
In streptococcus infections hemolytic, agglutinating, and opsonic 
substances may be formed in the body. 
Artificial Immunity.-The metabolic products formed by virulent 
streptococci growing in nutrient broth have been found to induce in ani- 
mals the symptoms of toxemia. The results of preliminary experiments 
on immunization with these toxic products, and the dead and living 
bodies of the germs and the use of the blood-serum of the immune 
animal for therapeutic purposes, are complex, and along the present 
lines of work apparently not very promising. 
SEPTIC SORE THROAT. 
There have been known for some time in England, and recently have 
occurred in several localities in the United States, serious epidemics of 
inflammation of the throat and tonsils associated with particular milk 
supplies. The milk apparently is contaminated by a streptococcus from 
the inflamed udder of cows or from the throats of the milk handlers. 
This organism closely resembles Streptococcus pyogenes and has been 
called Streptococcus epidemicus.2 
ERYSIPELAS. 
Erysipelas is a diffuse inflammation of the skin and subcutaneous 
tissue which tends to spread, and is characterized locally by swelling of 
the tissue and a bright red color of the integument. It is usually accom- 
panied by constitutional disturbances, the most marked of which is 
fever. The morphological changes at the seat of lesion, as we see them 
after death, vary considerably in different cases and in different stages 
of the disease. The redness of the skin usually disappears after death. 
But the tissues may be swollen by the accumulation of serous fluid. 
This fluid may be nearly transparent, or turbid from admixture with 
pus cells (Fig. 130). Pus cells may infiltrate the tissues either sparsely 
or in dense masses. Fibrin may be present, abscesses may form. Some- 
times vesicles or scabs are found on the surface, or the affected region 
may become gangrenous. Aside from the local lesions, there may be 
toxemia marked by petechiae in the serous membranes, swelling of the 
spleen, focal necroses, and albuminous degeneration in the kidneys and 
liver. 
i For bibliography of streptococcus consult the article by ». Lingelsheim, Kolle and Wassermann, 
Handbuch d. path. Mikroorganismen, 2d ed., 1912, iv, 453; for a study of the action of the toxin on 
various parts of the body, see Homen and others, Zieglers Beitr., 1899, xxv, Iff. 
2 For a summary of such epidemics and a study of the streptococcus, see North, C. E., Jour. Infect. 
Dis., 1914, xiv, 124. THE INFECTIOUS DISEASES 
241 
The most common excitant of erysipelas is Streptococcus pyogenes.1 
This organism may be present in large numbers in the lymph-vessels, 
especially in the borders of the inflamed region. The reasons for the 
clinical peculiarities of this phase of inflammation are not yet very clear. 
INFECTIOUS PSEUDOMEMBRANOUS INFLAMMATION OF MUCOUS MEM- 
BRANES. (Pseudodiphtheria; Diphtheroid Angina; Membranous Angina.) 
Under a variety of conditions, as during scarlatina and measles, 
whooping-cough, typhoid fever, etc., or entirely apart from any compli- 
cating disorder, an acute exudative inflammation of the mucous mem- 
Fig. 130.-Erysipelas of the Skin. 
Showing streptococci in the lymph-spaces. 
branes, especially of the upper air passages, occurs, which is associated 
with and is apparently induced by the growth of Streptococcus pyog- 
enes.2 There may be much or little fibrinous exudate; there may in 
early stages, or even throughout, be none at all. The pellicle when formed 
may be loose or adherent, sharply circumscribed or tending to spread. 
The submucous tissue may show little change, or may be congested and 
edematous, or may be the seat of suppurative inflammation (see Fig. 131), 
necrosis, or gangrene. The process may be confined to the tonsils. 
While under these varying conditions the inflammatory process is usually 
a local one and runs its course with or without the symptoms of septice- 
mia, occasionally the streptococcus which enters the blood may induce 
the lesions of pyemia. On the other hand, it may by aspiration gain 
access to the lungs and induce varying phases of complicating broncho- 
pneumonia. The Staphylococcus pyogenes is not infrequently associated 
with the streptococcus in these lesions, but is not apparently of primary 
significance. 
Simulating very closely, as it does in many cases, both the local and 
1 In the early days of modern bacteriology the "chain" coccus which was discovered in the exu- 
date of erysipelas was thought to bear a peculiar relationship to this clinical form of phlegmonous inflam- 
mation and was called by FMeisen Streptococcus erysipelatis, but it has now been definitely identified 
with the S. pyogenes. 
2 Prudden, Med. Rec., 1891, xxxix, 445; Baginsky and Sommerfeld, Berl. klin. Wchnschr., 1900, 
xxxvii, 588, 618. 242 
THE INFECTIOUS DISEASES 
general phenomena of diphtheria, this disorder has formerly been con- 
founded with it, and has only recently been recognized as a distinct 
phase of disease. It is now most frequently called pseudodiphtheria. 
It seems in part to cover the condition formerly known as croup, in part 
those cases formerly thought to be mild diphtheria. In many phases of 
acute angina, and in many cases of follicular tonsillitis, streptococci 
In thia case there is purulent infiltration of the mucosa and submucosa, and of portions of the 
mucous glands, a, False membrane; b, portion of intact epithelium; c, infiltration of the mucosa with 
fibrin; d, portion of mucous gland infiltrated with pus. 
Fig. 131.-Pseudomembranous Inflammation of Trachea. 
have been found in large numbers. Other bacteria, either alone or in 
association with the pyogenic cocci, may be excitants of pseudomem- 
branous as well as simple angina. 
OTHER BACTERIA WHICH ARE FREQUENT EXCITANTS OF SUPPURATION. 
While the Staphylococcus pyogenes and Streptococcus pyogenes are 
the most common excitants of local suppuration with and without 
toxemia and septicemia, such conditions, as we have seen, are not in- 
frequently due to other microorganisms. Among these we may men- 
tion here as the more common and important:-Diplococcus pneumoniae, 
the gonococcus, Micrococcus tetragenus, Bacillus pyocyaneus, the colon 
and the typhoid bacillus, the bacillus of glanders, the tubercle bacillus, 
the pneumobacillus of Friedlander, the diplococcus of cerebrospinal 
meningitis, Bacillus pyogenes foetidus, and actinomyces with its related 
forms. 
In some of these organisms the pyogenic qualities in their relation- 
ships to human infections are most conspicuous; in others, the reaction 
of the body to their presence is such as to justify a special name. The THE INFECTIOUS DISEASES 
243 
latter is particularly noteworthy in the case of the pneumococcus, the 
gonococcus, glanders, typhoid, and tubercle bacilli, Diplococcus menin- 
gitidis, and actinomyces. 
Many other microorganisms may be excitants of suppurative inflam- 
mation in man as well as in the lower animals under experimental 
conditions, but this exceptional reaction of living tissues does not fall 
within the scope of this work, which deals primarily with such tissue 
reactions as may occur under the usual conditions of life. 
The Bacillus Coli Communis and the Colon Group. 
The Bacillus coli communis is an organism so commonly present in the 
intestines under normal conditions as usually to be called the " colon 
bacillus." It is motile, facultative aerobic, asporogenous, considerably 
resembling in general form the typhoid bacillus (see page 265). It grows 
readily in artificial cultures and does not fluidify gelatin. It has been 
repeatedly found in connection with suppurative processes under such 
conditions as to justify the belief that it is often their excitant. 
It has been found in various forms of peritoneal suppuration, both 
with and without such lesions of the intestine as would obviously permit 
of its egress; in appendicitis; in suppuration about the gall-ducts; in 
hemorrhagic pancreatitis; and in inflammatory processes in the genito- 
urinary apparatus; frequently in the bladder, in the pericardium and 
pleura; and it is believed to be concerned in certain types of diarrhea. 
It is often demonstrable in terminal infections. 
Local infection with this organism is often associated with serious 
toxemia and septicemia. Intravascular injections of virulent cultures 
in rabbits are usually followed by symptoms and lesions of septicemia. 
Introduced subcutaneously and intraperitoneally, it may excite local 
suppuration or serofibrinous inflammation, often hemorrhagic in char- 
acter, terminating fatally.1 
It is not possible to indicate very definitely all the conditions under 
which the colon bacillus, an ordinarily harmless intestinal saprophyte, 
may gain access to the tissues and become actively pathogenic. Whether 
it is special strains of the bacillus coming in from without which are 
pathogenic, or whether the ordinary forms assume virulent capacities 
under unknown conditions, we cannot tell to-day. It appears in any 
event that very slight damage to the mucous membrane of the intes- 
tinal tract which may permit the exit of the germs, or the existence of 
damaged tissues elsewhere in the body-in the kidney, ureter, perito- 
neum, etc., for example-favor infection with this organism. To w7hat 
extent a reduction in efficiency of the protective fluids of the body 
may determine infection we cannot say with certainty. Shortly after 
death the colon bacillus may pass from the intestine into the tissues, 
and the possibility of this post-mortem invasion should be borne in mind 
1 For details concerning B. coli, see Conradi and Bierast, Kolle and Wassermann, Handbuch d. path. 
Mikroorganisinen. 2d ed., 1913, vi, 483. 244 
THE INFECTIOUS DISEASES 
in the examination of cultures from the dead body, since it may readily 
and doubtless often does give rise to errors in diagnosis. 
The Colon Group.-There are so many organisms so closely resembling 
the colon bacillus in their morphological and biological characters 
that it has been found convenient to consider them as possible variations 
of one form and to speak of them collectively as the "colon group." 
The differentiation between the individual members of this group and 
between these and the typhoid bacillus has presented many difficulties 
to bacteriologists and given rise to much technical finesse.1 
The Bacillus Pyocyaneus. 
The occurrence of brilliant greenish or bluish pus in superficial wounds 
has been noted for over a century, although the organism causing it was 
unknown until its isolation by Gessard in 1882. The organism was not 
regarded as possessing any special pathogenic qualities until 1898 when 
Charrin published a study of the disease induced by its growth, under the 
name "la maladie pyocyanique." His observations were confirmed by 
Schimmelbusch, and since that time the Bacillus pyocyaneus has been 
recognized as a widespread organism occurring in air, dust, water, and the 
intestinal contents of man and animals, and regularly infesting the skin of 
the human body, especially the axillary and inguinal folds. It is also 
found saprophytically in the external auditory meatus. Its occurrence 
has been noted in purulent otitis media, in acute throat infections, in 
endocarditis and pericarditis, in inflammations of the urinary tract, in 
meningitis, in bronchopneumonia, and in gastrointestinal disturbances in 
infants and adults. A moderate number of cases of general infection with 
isolation of the organism from the circulating blood have been reported.2 
It is frequently found in the blood post-mortem, but its presence is then 
considered to be due to a terminal invasion from the intestinal tract and 
not to a true infection. The infection by the organism of superficial 
wounds, especially abdominal incisions for the drainage of appendical 
abscesses, is frequent; as a rule, however, it merely delays the healing 
process and does not seem to play a more active part. In closed cavi- 
ties, on the contrary, it is highly pathogenic. Among the more marked 
lesions which are usually present in cases of pyocyaneus infection are 
albuminous degeneration of the viscera, focal necroses, hyperplasia of 
the lymph-nodes, hemorrhages, and especially superficial, circumscribed 
or diffuse necrosis and ulceration in the intestinal mucous membrane. 
The most striking characteristic is the hemorrhagic nature of the lesions. 
The Bacillus pyocyaneus is a slender rod, is motile, and is negative to Gram. 
It grows readily on artificial media, liquefies gelatin, and ultimately forms pigment. 
It is highly pathogenic for rabbits and guinea-pigs.3 
Characters of the Organism. 
1 See Hiss, Jour. Exper. Med., 1897, ii, 677; Jour. Med. Research, 1902, N. S. iii, 148; Hiss and 
Russell, Med. News, 1903, Ixxxii, 289. 
2 Brill and Libman, Am. Jour. Med. Sc., 1899, cxviii, 153 (bibl.). 
3 For further details see Voss, Der Bacillus pyocyaneus im Ohr, Berlin, 1906; and Heller and Lepbre 
Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1913, v, 1185. 245 
THE INFECTIOUS DISEASES 
Bacillus Mucosus Capsulatus (^Friedlander Bacillus'). 
In a small proportion of cases of lobar and lobular pneumonia, and 
in a few cases of exudative inflammation of the pleura, pericardium, 
meninges, nose, throat, and middle ear, this short encapsulated bacillus 
has been found. It is sometimes found alone, but in pneumonia is often 
associated either with the pneumococcus or with the pyogenic cocci. It 
has been found in the nasal secretion and mouths of healthy persons and 
in the intestinal contents. While belonging definitely among the bacilli, 
it so frequently occurs in the form of very short rods or ovals or short 
chains that it was formerly thought to belong among the cocci. It is 
readily cultivated on artificial media and is slightly pathogenic for certain 
animals. 
This germ was formerly believed to be of great importance in connec- 
tion with acute lobar pneumonia, and for a time was generally spoken of 
as the pneumococcus of Friedlander. It is now known not to be a coccus, 
and is certainly of subordinate, though occasionally serious, importance 
in inducing inflammation of the lungs.1 In a few instances its presence 
in the spinal fluid and the blood has been proved. 
Micrococcus Tetragenus. 
This organism has been many times found about the mouth and 
respiratory tract, especially in connection with suppurative processes, 
tuberculous cavities, etc. It has been found also in metastatic abscesses. 
While not very virulent it is apparently an occasional excitant, either 
alone or with other organisms, of suppuration. 
Characters of the Organism. 
It is a coccus about 1 M in diameter, usually occurring in groups of four. These 
tetrad groups may be encapsulated. It stains by Gram's method, and is readily 
cultivated on artificial media. It forms a dense whitish growth on gelatin, which it 
does not fluidify. Septicemic lesions with local suppuration may be induced in guinea- 
pigs by subcutaneous injection with cultures. 
The Proteus Group of Bacilli. 
This is a large and, in the economy of nature, an important group of 
bacilli much concerned with the putrefactive processes. 
Characters of the Group. 
The bacilli of this group may be aerobes or facultative anaerobes. They are of 
medium size, asporogenous, and while staining readily with ordinary dyes are apt to 
be decolorized by the Gram method. While the organisms of this group are bacilli, 
they often present considerable variation in form as they grow, sometimes being very 
1 Howard, Philadelphia Med. Jour., 1898, i, 336; and Bull. Johns Hopkins Hosp., 1899, x, 66; 
Stuhlern, Centralbl. f. Bakteriol., Orig. I., 1904, xxxvi, 493; Perkins, Jour. Infect. Dis., 1904, i, 241. 246 
THE INFECTIOUS DISEASES 
short so as to resemble cocci, sometimes forming threads which may be so bent as to 
suggest spirals. Their growth on solid media is especially characterized by the ten- 
dency to send runners from the central growth out into the surrounding media, thus 
establishing secondary growth centers. They are particularly sensitive to environ- 
ment, so that physiological as well as morphological variations are frequent. It is for 
these reasons that the name Proteus has been given to the group and to various 
species. The limitations of the named species are, however, in many cases quite ill 
defined. 
One of the most common forms has been called Proteus vulgaris. 
While this bacillus is very widespread, it is only occasionally the exci- 
tant of pathological processes in man, and then almost always in concur- 
rence with other organisms, usually the pyogenic cocci. Under these 
conditions a suppurative inflammation with foul exudate is apt to de- 
velop. Thus it has been found in purulent peritonitis and endometritis, 
in pleurisy and in phlegmonous inflammation in various parts of the 
body. Although this bacillus is not apt to grow in the human body, 
except in association with other microorganisms which may damage 
the tissues or in tissues already vulnerable from injury, it may in the 
bladder independently incite an exudative inflammation. In animals, 
subcutaneous injection of the pure culture in considerable quantity 
may lead to abscess, while the soluble products of broth culture may 
induce toxemia. 
Several other forms of Proteus, as well as closely related species, 
have been found in human lesions for the most part suppurative and 
necrotic in character, and these, in some cases, have been conclusively 
shown to be the excitants of the pathological processes, but the scope 
of this work does not permit further details. 
OTHER PYOGENIC BACTERIA. 
Among the other bacteria which commonly induce local suppuration, 
with or without toxemia and septicemia, some are of frequent occur- 
rence as excitants of such well-marked and more or less characteristic 
forms of disease as have long been recognized clinically and have re- 
ceived special names, such as pneumonia, gonorrhea, cerebrospinal menin- 
gitis, etc. The tubercle bacillus may also induce suppurative inflam- 
mation. These will be in part considered in the section dealing with 
the organs in which their more characteristic lesions are manifested. 
ACUTE LOBAR PNEUMONIA AND OTHER INFECTIOUS DISEASES INDUCED BY 
THE DIPLOCOCCUS PNEUMONIAE (Pneumococcus Lanceolatus). 
Diplococcus pneumoniae is sometimes spoken of as the " pneumo- 
coccus of Frankel," because its significance and life history in connection 
with acute lobar pneumonia were first demonstrated by him.1 It is 
commonly called simply the "pneumococcus." 
1 It was discovered by Sternberg in saliva, and its pathogenic power demonstrated some years be- 
fore its full significance in connection with pneumonia was understood. THE INFECTIOUS DISEASES 
247 
Characters of the Diplococcus Pneumoniae. 
During active growth these germs are spheroidal; but in their mature condition 
they are apt to become slightly elongated or oval and are often a little broader at one 
end than at the other, assuming a lanceolate form. They are very apt to occur in 
pairs, and frequently are seen in short chains, rarely in long. Very frequently in the 
living animal, the pneumococcus is surrounded by a distinct, homogeneous capsule of 
varying thickness (see Fig. 132). Except in certain media capsule development is not 
well marked. The coccus itself is readily stained by the aniline dyes and retains the 
stain by Gram's method; the capsule is not easily demonstrated except by special 
staining methods.1 
The pneumococcus has no spontaneous movement. No growth is obtainable 
at 20° C., but at 37° C. there is a fairly abundant yield, forming on the surface of 
blood-serum or on very slightly alkaline glycerin-agar plates faint grayish, dewdrop 
like, inconspicuous colonies, somewhat similar to those of 
Streptococcus pyogenes, but usually more delicate. As a 
rule, the cultures soon lose their virulence and die off, but 
the virulence may be maintained by successive inoculations 
in suitable animals. The pneumococcus may remain viable 
and virulent for many days when dried in sputum but in 
the form of small particles such as are distributed in cough- 
ing and sneezing it remains alive, for from one to one and a 
half hours.2 In direct sunlight it may die in a few moments. 
The serum of persons suffering from acute lobar pneu- 
monia, as well as the serum of lower animals artificially 
immunized to the Diplococcus pneumoniae, induces agglu- 
tination of the organism in broth cultures. By the use of 
centrifugated cultures of the organism, the reaction of agglu- 
tination can be obtained in much greater dilution than by the 
usual method.3 Precipitins are found in immune sera. 
Cultures which have been reduced in virulence, so as not to cause early death by 
septicemia, may, when introduced into the trachea of rabbits, induce circumscribed 
pneumonic lesions, especially if these animals are made vulnerable by cold or by other 
agencies which impair the integrity of the blood or other tissues. By partially immun- 
izing rabbits to the pneumococcus, so that they do not speedily die from septicemia, 
and then introducing the virulent organism into the lungs through the trachea, diffuse 
pneumonic lesions comparable to the lobar pneumonias of man may be induced.4 
Lesions of lobar pneumonia are readily induced in the dog by intratracheal injections 
of the pneumococcus.5 Blake and Cecil have succeeded in producing in monkeys 
various types of pneumonia which are quite analogous to the forms occurring in man.6 
Whether under natural conditions of infection the pneumococcus is always directly 
introduced into the smaller bronchi or alveoli of the lung by inhalation, as has been 
generally assumed, is still not definitely decided. The idea has been brought forward 
that another route may be of great importance, that is, the lymphatics in the sub- 
mucosa of the trachea and bronchi.7 But the current belief is that in the majority of 
instances the organisms are introduced by inhalation. 
This germ is the ineitant of typical lobar pneumonia in man ana in a 
large proportion, if not in all, cases is present in the blood at some time 
in the course of the disease, though in the earlier stages it can be demon- 
strated in only about 30 per cent.8 In the severer types of the disease, 
pneumococci appear in the spinal fluid, even though no complicating 
Fig. 132. Diplococcus 
Pneumonia Pneumo- 
coccus. 
Showing the stained cap- 
sules. 
1 See Wadsworth, 4-, Jour. Infect. Dis., 1906, iii, 610. 
2 Wood, F. C., Jour. Exper. Med., 1905, vii, 592. 
3 For details of this method see Wadsworth, A., Jour. Med. Research, 1903, N. S. v, 228. 
4 See Wadsworth, A., Jour. Exper. Med., 1912, xvi, 54, 78 (bibl.). 
s Lamar and Meltzer, Jour. Exper. Med., 1912, xv, 133; and Wollstein and Meltzer, ibid., 1912, xvi. 
127. 
6 Blake, F. G., and Cecil, R., Jour. Exper. Med., 1920, xxxi, 403, 445, 499; 1920, xxxii, 401, 691. 
7 Winternitz, M. C., Smith, G. H., and Robinson, E. S., Bull. Johns Hopkins Hosp., 1920, xxxi, 63. 
8 See Rosenow, Jour. Infect. Dis., 1904, i, 280; also Dochez, A. R., Jour. Exper. Med., 1912, xvi, 680. 248 
THE INFECTIOUS DISEASES 
meningitis may occur.1 It induces locally in the lungs an acute exudative 
inflammation associated with an enormous multiplication of the germ 
and a toxemia due to the distribution of soluble toxic products through 
the blood. 
For a more detailed description of the lesions of pneumonia and an 
account of other bacteria which may be present, see page 687. 
Recent studies of the pneumococcus have added much to our knowl- 
edge of its biological characters. Neufeld and Handel2 first showed that 
this group contained a variety of organisms, and their observations, so 
far as the occurrence of groups in the United States is concerned, have 
been confirmed by other investigators by means of precipitin and aggluti- 
nation reactions and by tests on mice.3 The organism may be divided 
into two main groups, the larger of which contains Types I, II, and III, 
comprising from 75 to 80 per cent, of all strains encountered in lobar 
pneumonia, while the smaller contains Type IV, a broad group of less 
virulent organisms all true pneumococci which can not be serologically 
identified with the other three types. Type I is the form which is most 
often the cause of pneumonia in man, and is found in about one-third of 
all cases of lobar pneumonia. Type II is nearly as frequent; Type III is 
responsible for about 15 per cent, of cases, and Type IV for the remainder. 
Type III corresponds to an organism formerly designated Streptococcus 
mucosus capsulatus, but now included among the pneumococci because 
of its solubility in bile, its capacity to ferment inulin, and its pathogenic 
properties. 
In addition to these four types, there are many subgroups, chiefly of 
Type II. Lister, working in South Africa, distinguished a strain which 
he called Type A; but this has not yet been identified in the United 
States.4 It seems probable that in addition to these type variations 
in different parts of the world, there are also great fluctuations in viru- 
lence and possibly also in precipitin and agglutination reactions of the 
organisms found in the same locality, so that slight differences in group- 
ings will probably occur from year to year. For example, in the 1917-19 
epidemic in the United States war hospitals, Type IV was found to be the 
infecting organism more often than all the other types combined, and 
similar accidental fluctuations will no doubt be observed in different 
populations and under different conditions. 
The rapid identification of the organisms, which is important for 
therapeutic reasons since a scrum seems to be of value in the treatment of 
infections with Type I, may be made by the examination of smears or by 
precipitin or agglutination tests. For technical methods of differentia- 
tion the standard textbooks should be consulted.5 
' Rohdenburg, G. L., and Vander Veer, A., Jour. Am. Med. Assn., 1915, Ixiv, 1227. 
2 Neufeld and Hdndel, Arb. a. d. k. Gsndhtsamte, 1910, xxxiv, 293. 
* Dochez, A. R., and Gillespie, L. J., Jour. Amer. Med. Assn., 1913, Ixi, 727; Avery. O. T., Jour. Exper. 
Med., 1915, xxii, 804; Avery, O. T., Chickering, H. T., Cole, R., and Dochez, A. R., Acute lobar pneu- 
monia: Prevention and Serum Treatment, Monograph No. 7, Rockefeller Institute, New York, 1917. 
4 Lister, F. S., Publications of the South African Institute for Medical Research, 1913, No. 2; 1916, 
No. 8; 1917, No. 10. 
5 Hiss and Zinsser, Textbook of Bacteriology, 5th edition, New York, 1922; Wood, Vogel, and Famu- 
lener, Laboratory Technique, 2d edition, New York, 1922. THE INFECTIOUS DISEASES 
249 
In addition to its more common effect in inducing lobar pneumonia, 
the pneumococcus is frequently the excitant of exudative inflammation 
in other parts of the body, either with or without a primary lobar pneu- 
monia. Thus it has been repeatedly found in pleuritis, otitis, menin- 
gitis, empyema, pericarditis, endocarditis, and peritonitis. It has been 
found in abscesses of the viscera and in exudative inflammation of the 
joints. It may induce pseudomembranous inflammation of the mucous 
membranes, and is a frequent cause of corneal ulcer. Leucocytosis 
usually accompanies infection with the pneumococcus. 
Sources of Pneumococcus.-The pneumococcus has been found in 
the mouths of a large proportion of healthy persons. In more than half 
such instances the organism belongs to Type IV which is apparently 
usually less virulent than the other strains. Type III is the organism 
present in about one-third of the cases, and Type II-x, a special subdivi- 
sion, in about one tenth.1 The organism is thrown off in the sputum in 
lobar pneumonia, and no doubt from this source, to a certain extent in the 
dried condition, as dust, but more often in the droplets of sputum ejected 
in the coughing of pneumonics or in the fine spray formed in sneezing,2 
furnishes the infectious agent which in favoring conditions of the body 
lights up the inflammatory process in the lungs.3 Convalescents or per- 
sons who have been in contact with pneumonic patients may act as 
carriers4 of Types I and II. The occurrence of house epidemics due to 
one or the other of the types described has demonstrated that pneumonia 
must to a certain extent be regarded as a communicable disease. 
Toxic Products of the Pneumococcus.-Although clinically pneumonia 
bears many marks of toxemia, investigators have not thus far succeeded 
in finding evidence that, either in artificial cultures or in the infected body, 
very potent soluble toxins are given off through the metabolic activities 
of the pneumococcus. There is evidence, on the other hand, that the 
toxic effects may be induced by endotoxins which are set free when in the 
course of the disease the organisms die and suffer lysis.5 
The Crisis in Pneumonia.-The dramatic character of the crisis in 
many cases of pneumonia has led to much conjecture as to the changes 
in the body fluids or the bacteria which may occur at this time. There 
appears to be no marked development of bactericidal power of the serum 
alone; antitoxic substances are not demonstrable. It has been con- 
jectured that the study of the opsonins might throw light upon the role 
1 For a consideration of the pneumococcus of the mouth in healthy persons, and for a study of 
varieties or strains of pneumococci, see studies carried on under the auspices of the Medical Commission 
for the Investigation of Acute Respiratory Diseases of the Department of Health of the City of New 
York, by Park and Williams: Collins: Longcope and Fox: Norris and Pappenheimer: Duval and Leuis: 
Buerger: Hiss: and Longcope: Jour. Exper. Med., 1905, vii, 401, 626; also Eyre and Leathern, Jour 
Path, and BacterioL, 1906, xi, 246. 
2 See Wood, F. C., Jour. Exper. Med., 1905, vii, 592. 
3 For study of communicability, see Edsall and Ghriskey, Tr. College of Phys., Philadelphia, 1904, 
xxvi, 6. For a study of disinfection of the mouth and of sputum, see Wadsworth, Jour. Infect. Dis., 
1906, iii, 610. 
4 See Kolmer and Steinfield, Jour. Am. Med. Assn., 1918, Ixx, 14, on disinfection of pneumococcus 
carriers; also Jour. Infect. Dis., 1918, xxii, 220. 
6 See Cole, R., Jour. Exper. Med., 1912, xvi, 644. 250 
THE INFECTIOUS DISEASES 
of phagocytes. But in spite of much research no very decisive data 
have as yet been elicited. 
While the crisis in pneumonia is a striking feature in its symptomatol- 
ogy it is only an accentuation of phenomena which occur in recovery from 
all infections. In pneumonia, as in other infections, two phases of the 
bacterial action are to be recognized: first, the capacity to proliferate in 
the host, and, second, the potency of the toxic substances elaborated and 
set free in the body during the disease. Thus far in most of the experi- 
mental and critical studies of pneumonia the reactions of the cells of the 
host resulting in the production of protective substances have received 
chief attention. Many believe with Neufeld that bacteriotropic or 
opsonic substances play an important role. Others, as Romer, think 
that the chief factors in recovery from pneumonic infection are bactericidal 
substances of unknown nature in the serum. But it is not definitely 
known at present what the substances are upon which recovery depends.1 
Although both of these agencies may be important, the capacity for 
growth of the pneumococcus in the body, and the mechanism for the 
neutralization of the poisons developed in infection are also important, 
and the consideration of both classes of factors is necessary in an adequate 
survey of pneumonia. 
For in this as in every other infection, the reaction of the microorgan- 
ism as well as that of the host is decisive in the destruction of the invasive 
germs, as in the neutralization of the poisons, whether these are derived 
from the bodies of the bacteria, or in ways apparently more subtle because 
less clearly understood.2 
While it has been assumed that the crisis in pneumonia is associated 
with the beginning of active autolysis, it has only recently been shown 
that the latter probably depends on an alteration in the ferment-anti- 
ferment balance of the blood. In this connection it has been demon- 
strated that the crisis is usually accompanied by a decrease in the serum 
antiferment with a concomitant mobilization of specific proteases in 
the serum and an increase in the serum lipase. The fibrin and leucocytic 
debris of the exudate must be regarded as one of the potential sources 
of the toxic substance giving rise to the clinical phenomena of the disease. 
The rapid autolysis which sets in at the crisis is accompanied by a de- 
crease in the non-coagulable nitrogen and of the proteoses in the blood- 
serum, which is synchronous with a great increase in the nitrogen ex- 
cretion in the urine.3 
Staining Reactions.-For staining the pneumococcus with its capsule the following 
method of Hiss4 gives good results. Mix the exudate or culture containing the 
organism on the cover-glass with a drop of blood-serum spread thin, dry and fix by 
heat. Add a few drops of the following stain: 5 or 10 per cent, solution of gentian 
violet (5 c.c. saturated alcoholic solution of gentian violet plus 95 c.c. distilled water). 
1 See Cole, R , Harvey Lecture, Arch. Int. Med., 1914, xiv, 56; also Hektoen, L., Jour. Am. Med. 
Assn., 1914, Ixii, 254 (bibl.); and Dochez, A. R., Jour. Exper. Med., 1912, xvi, 665. 
2 For studies on pneumococcus infection and the mechanism of recovery, see Wadsworth, A., Jour. 
Exper. Med., 1912, xvi, 54, 78 (bibl.). 
sJobling, Petersen, and Eggstein, Jour. Exper. Med., 1915, xxii, 568. 
' See, on methods of staining encapsulated pneumococci, Hiss, P. H., Jour. Exper. Med., 1901-5, 
vi, 317; also Wadsworth, A., Jour. Infect. Dis., 1906, iii, 610. THE INFECTIOUS DISEASES 
251 
Heat gently until steam rises. Wash off the stain with a 20 per cent, solution of 
cupric sulphate. Dry and mount in balsam. 
If the material containing the organisms already contain serum, the preliminary 
mixing with this is unnecessary. Pneumococci in sputum, which without the addition 
of serum are often stained, with it not infrequently give better results. 
The method of Welch1 gives good results, but annoying precipitates often form. 
After drying and fixing the specimen upon the cover-glass in the usual way, it is 
treated with glacial acetic acid, which is at once drained off and replaced by aniline- 
gentian-violet solution, this being drained off and renewed several times until the 
acetic acid is displaced. The specimen is now washed with a 2 per cent, solution of 
sodium chloride, in which it may be covered and studied. The pneumococcus 
may be stained in sections by Weigert's modification of Gram's method with 
preliminary contrast stain. By this method the fibrin in pneumonic exudate is also 
stained.2 
GONORRHEA AND OTHER INFLAMMATORY LESIONS INDUCED BY THE 
MICROCOCCUS GONORRHCEA2 (Gonococcus). 
The Micrococcus gonorrhoea (gonococcus) is most commonly found in 
the exudate of gonorrheal inflammation of the mucous membranes, 
especially of the urethra. It may be free or inclosed in leucocytes or 
other cells (Fig. 133), or within or between the epithelial cells. The 
organism may be distributed from 
the seat of primary lesion, giving 
rise to gonorrheal arthritis, to ma- 
lignant endocarditis, to exudative 
inflammation of the pleura, and to 
inflammatory processes in other 
parts of the body.3 
The gonococcus may in the pri- 
mary as well as in the secondary 
lesions be associated with the pyo- 
genic cocci, the colon bacilli, or 
other microorganisms. These as- 
sociations have been observed in 
cases of pyemia following gono- 
coccal infection. The gonococcus is 
usually most abundant in the urethra during the acute stage of the 
inflammation. But long after the organisms have disappeared from 
the urethral discharge they may be present in small numbers in the 
deeper portions of the urethra or in the prostatic secretions whence, 
under favoring conditions, a fresh infection may arise. In the female 
the inflammation develops in the urethra and cervix, and, through the 
transportation of the gonococci, may extend along the mucous mem- 
brane to the uterus and into the Fallopian tubes. The germs may 
enter the peritoneum, inducing exudative inflammation. Hyperplasia 
and suppuration of lymph-nodes near the inflammatory region may 
Fig. 133.-Micrococcus Gonorrhce^ in 
Cells.-Specimen from the Urethra. 
1 Welch, Bull. Johns Hopkins Hosp., 1892, iii, 128. 
2 For a full r6sum6 of studies on the pneumococcus, see Neufeld and Htindel, Kolle and Wasser- 
mann, Handbuch d. path. Mikroorganismen, 2d ed., 1912, iv, 513. 
3 Consult, for cases and bibliography, Young, Welch Anniversary Contributions to the Science of 
Medicine, 1900, p. 677; also, Elting, Albany Med. Ann., 1900, xxi, 144 (bibl.). 252 
THE INFECTIOUS DISEASES 
occur. Gonorrheal conjunctivitis is similar in origin and character to 
the inflammation of the urethra. In the gonorrheal vaginitis of children 
the organism, although highly transmissible, is frequently of such low 
virulence that conjunctival inoculation does not result in a blenorrhea. 
Characters of the Gonococcus. 
The gonococcus is apt to occur in pairs, the apposed sides being more or less dis- 
tinctly flattened (Fig. 134). It stains readily with the aniline dyes, and differs from 
most known cocci which might be mistaken for it in'that it is decolorized by the iodine 
solution in the Gram method of staining. It is well after the decolorization by this 
method, and before mounting in balsam, to make a contrast stain with a dilute aque- 
ous solution of Bismarck brown. Then the gonococci will be of 
light-brown color, while most other germs of similar morphology 
will retain the violet color. 
The gonococcus is non-motile and does not grow at ordinary 
room temperatures nor on the ordinary solid or fluid culture 
media. It may, however, be cultivated at the temperature of 
the body on human blood-serum, on a combination of this with 
agar, or on starch agar.1 
In serum-agar the surface growth of the gonococcus is in the 
form of small circular, sharp-edged, slightly raised, nearly trans- 
parent colonies, coarsely mottled in the central portion, finely 
granular toward the borders. The life of the colonies under artificial culture is 
short, but by frequent transference to fresh media it may be maintained indefinitely 
and gradually adapts itself to the artificial environment. 
The gonococcus is readily killed by heat and light and drying and is very vulnerable 
in the presence of many common disinfectants, especially silver, either as nitrate or in 
loose organic combination. 
It is probable that the organism has no natural habitat outside the bodies of 
human beings. The lower animals are not, as a rule, susceptible to inoculations of 
the mucous membranes with the gonococcus, but suppurative inflammation has been 
induced in mice and guinea-pigs by intraperitoneal injections. In man there are at 
least ten strains, immunologically speaking, which, however, do not differ appreciably 
in culture.2 
Inoculations of pure cultures of the gonococcus upon the urethral 
mucous membranes of man have been repeatedly made and are followed 
by a characteristic catarrhal inflammation. Thus the evidence is com- 
plete that the gonococcus is an excitant of the inflammation with which 
it is so constantly associated. But in what measure this germ, in what 
measure others which may be associated with it, are responsible for the 
complicating inflammations, is yet to be determined. The gonococcus 
appears to act rather through its endotoxins or, more correctly, decom- 
position products, than by soluble substances set free in its growth. 
Inasmuch as one or more forms of cocci and diplococci occurring in 
the normal and in the inflamed urethra are morphologically similar to 
the gonococcus, great caution should be exercised in doubtful cases in 
deciding upon the nature of suspicious microorganisms in urethral 
discharges or other exudates. But the pronounced tendency of the 
Fig. 134.-Micro- 
coccus Gonorrhce.e 
Gonococcus). 
From culture. 
1 Vedder, E. B., Jour. Infect. Dis., 1915, xvi, 385. 
2 Torrey, J. C., Jour. Med. Research, 1907, N. S. xi, 329; Teague and Torrey, ibid., 1907, N. S. 
xii, 223. THE INFECTIOUS DISEASES 
253 
gonococcus to gather within cells; the sometimes conspicuous but often 
ill-defined flattening of the apposed sides of the gonococci; the decolor- 
ization by Gram's method, which leaves most other germs apt to be 
associated with the gonococcus still stained, and whenever practicable 
the artificial-culture characters-these all should be considered in the 
summary of evidence.1 
Recently the technique of a complement fixation test has been suc- 
cessfully developed.1 In acute cases, the fixation test does not become 
positive until about six weeks have elapsed; indeed, with an uncompli- 
cated anterior urethritis it may never appear. With deeper lesions, 
such as vaginitis in children, cervicitis, or salpingitis, or in invasion 
of vesicles or prostate, the reaction is positive in a large proportion 
of cases. In arthritis 100 per cent, of positive reactions have been 
reported. The diagnostic and medicolegal importance of the test is thus 
very great.2 
ACUTE CEREBROSPINAL MENINGITIS. 
This is an acute infectious process of which the characteristic lesion 
is an exudative inflammation of the pia mater of the brain and cord. 
As a rule the inflammation of the pia mater results in the production 
of serum, fibrin, and pus, which infiltrate the pia mater and accumulate 
in the ventricles, so that the gross appearance of the brain is character- 
istic. The exudation is often especially abundant at the base of the 
brain and over the posterior surfaces of the cord. In children the dis- 
tention of the lateral ventricles with purulent 
serum may be a marked feature, while in 
adults the quantity of serum is apt to be 
small. (For details of the lesions in exudative 
meningitis see Nervous System.) 
While the above are characteristic lesions 
of this disease, there are a number of secondary 
or associated septicemic or toxemic lesions in 
different parts of the body. There may be 
subserous punctate hemorrhages in the endo- 
cardium; petechise in the skin; acute arteritis; 
hyaline and granular degeneration in the voluntary striated muscle; 
occasional multiple abscesses in various parts of the body; suppurative 
inflammation of the joints; albuminous degeneration of the heart, 
liver, and kidneys; and hyperplasia of the gastrointestinal lymphatic 
apparatus and of the spleen. 
Cerebrospinal meningitis may occur by itself or in connection with 
some other acute infectious disease, such as acute lobar pneumonia, 
mycotic ulcerative endocarditis, pyemia, multiple suppurative arthritis, 
otitis media, puerperal fever, typhoid fever, etc. 
Fig. 135.-Diplococcus Intra- 
CELLULARIS -MENINGOCOCCUS. 
From fluid obtained by spinal 
puncture in case of epidemic 
cerebrospinal meningitis. 
1 For summary of studies on the gonococcus with bibliography, consult Koch and Bruck, Kolle and 
Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1912, iv, 655, 721. 
2 For details of the technique, see Schwartz and McNeil, Am. Jour. Med. Sc., 1911, cxli, 693; 1912, 
cxliv, 369, 815; and Kolmer, Infection, Immunity, and Specific Therapy, 2d ed., Philadelphia, 1917, p. 
503. 254 
THE INFECTIOUS DISEASES 
It may be epidemic, the lesions, however, being essentially similar to 
those in the simple acute form. 
The bacterial excitants of simple sporadic cerebrospinal meningitis are 
most commonly the pneumococcus and Streptococcus pyogenes. Of less 
frequent occurrence in the lesions are the influenza bacillus,1 the typhoid 
bacillus, and the gonococcus. Other bacteria have been recorded. 
Epidemic Cerebrospinal Meningitis.-This form of exudative inflam- 
mation of the meninges of the brain and cord is induced by an organism 
named by Weichselbaum Diplococcus intracellularis meningitidis (menin- 
gococcus) because of its form and its frequent presence within cells of the 
Fig. 136.-Acute Endarteritis and Arteritis in Epidemic Cerebrospinal 
Meningitis. 
The endothelium is raised from the membrana elastica by an accumulation of cells-shown in the 
next figure. The muscularis is also involved. 
exudate (Fig. 135). While often occurring in epidemics, infection 
with the meningococcus may be sporadic. 
The lesions are in general similar to those above described in exuda- 
tive inflammation of the meninges with other excitants, but, in distri- 
bution and type, present some moderately characteristic appearances. 
The exudate, which is purulent, seropurulent, or fibropurulent, is 
usually most marked at the base of the brain and on the posterior 
surface of the cord. In death at an early period there may be simple 
hyperemia with little exudate. The purulent exudate consists largely 
of polymorphonuclear leucocytes, but there may be large polyhedral 
■See Moore, Brit. Med. Jour., 1913, ii, 10,56 (bibl.). 255 
cells mingled with them. These large cells, apparently derivatives of 
endothelium, are phagocytic and may contain leucocytes, red blood- 
cells, etc. At later periods these large cells may preponderate in the 
exudate. The exudate may be present in the superficial layers of the 
brain and may involve the cranial nerves and the spinal nerve roots. 
There may be proliferation of neuroglia cells.1 Acute arteritis with 
the accumulation of leucocytes and the formation of new cells beneath 
the endothelium of the small arteries of the brain and cord (Figs. 136 
and 137) is often present in this disease. 
In the prolonged, so-called chronic cases there may be edema and 
thickening of the pia mater and degeneration of the pus cells. 
THE INFECTIOUS DISEASES 
Characters of Diplococcus Intracellularis Meningitidis. 
It is a diplococcus, considerably resembling the gonococcus, the 
pairs and tetrads being often flattened on the apposed sides. It is non- 
motile, not staining by Gram's method. It grows readily though not 
voluminously on appropriate culture media at body temperature. It 
is readily killed by exposure to sunlight, and by drying as well as by 
heat, cold, and the common disinfectants. There are a number of 
varieties separable by their serum reactions. 
While the meningococcus is most abundant in the meningeal exudate, 
and is obtained on lumbar puncture, it has been found in the blood2 
Fig. 137.-Endarteritis in Cerebrospinal Meningitis-Epidemic. 
Leucocytes and polyhedral cells have gathered between the endothelium and the muscularis 
in this small artery. 
and in the nasal passages. Agglutinative substances are formed during 
the infection. 
Pathogenicity.-Inoculations of cultures into various animals, mice, 
rabbits, guinea-pigs, etc., show that it is moderately pathogenic, the 
effects seeming to be due largely to an endotoxin. Flexner has induced 
in monkeys lesions almost identical with those of man.3 
Source.-The frequent occurrence of the meningococcus in the 
nasal passages both in those suffering from epidemic cerebrospinal 
1 For an epitome of lesions, see Councilman, Jour. Am. Med. Assn., 1905, xliv, 997. 
2 Elser and Huntoon, Jour. Med. Research, 1909, N. S. xv, 377 (bibl.); Davis, Jour. Infect. Dis., 
1907, iv, 558; and Baeslack, F. IF., and others, Jour. Am. Med. Assn., 1918, Ixx, 684. 
3 See Flexner, Tr. Assn. Am. Phys., 1906, xxi, 378; also Jour. Exper. Med., 1907, ix, 105 and 142. 256 
THE INFECTIOUS DISEASES 
meningitis at an early period and in those closely associated with them,1 
while it is usually absent in well persons not exposed to the disease, 
leads to the conclusion that the infectious material may be transmitted 
by the nasal secretion directly, or through the air in the spray caused by 
sneezing. Recent English statistics have shown that 10 per cent, of 
contacts may become carriers for from four to six weeks; in exceptional 
instances, the condition may persist for a year or more.2 There is reason 
for believing that entrance is gained through the nasopharyngeal mucous 
membrane,3 and through the pharyngeal tonsil. This is obviously pos- 
sible through the direct connections which exist between the meninges 
and the nasal mucosa by lymphatics which pass the cribriform bone 
with branches of the olfactory nerve. But the possibility of origin 
through the blood is to be held in mind.4 
Serum Therapy.-By the immunization of horses with dead and 
living cultures of various types of meningococcus, and with extracts of 
the bodies, polyvalent curative sera have been prepared.5 Such sera 
injected intraspinously have been found after critical tests on a large 
number of cases to be extremely valuable curative agents.6 
Micrococcus Catarrhalis. 
Diplococci resembling the meningococcus and called M. catarrhalis have been 
found on respiratory mucous membranes. Their cultural characters are quite similar 
to those of the meningococcus, for which they may be easily mistaken. They are 
believed to be incitants of catarrhal inflammations. They are often associated with 
pneumococcus and the influenza bacillus. Micrococcus flavus is also a frequent in- 
habitant of the nasopharynx, and as it is gram-negative, like the meningococcus and 
the Micrococcus catarrhalis, must be carefully distinguished by culture.7 
GLANDERS. 
Glanders is an infectious disease incited by the presence and growth 
in the body of the Bacillus mallei. 
It is most common in the horse, affecting the mucous membrane of 
the nose (when involving the skin the disease has been called farcy), 
and can be communicated to man and to certain other of the domestic 
animals by direct or accidental inoculations. 
Man is quite susceptible to glanders infection, and the disease is 
most frequent in those who come much into direct contact with horses. 
The seat of primary local infection is most often the skin, more rarely 
the mucous membranes about the nose and mouth. 
The local lesions are similar in man and the lower animals. In the 
1 See Weichselbaum and Ghon, Wien. klin. Wchnschr., 1905, xviii, 625; Goodwin and v. Sholly. 
Jour. Infect. Dis., 1906, Suppl. No. 2, p. 21; also Elser and Huntoon, Jour. Med. Research, 1909, N. S, 
iv, 377 (bibl.). For study of carriers, see Chapin, Sources and Modes of Infection, 2d ed.. New York, 
1912. 
2 See, for general review, Flexner, Jour. Am. Med. Assn., 1917, Ixix, 639. 
8 Westenhoeffer, Berl. klin. Wchnschr., 1905, xlii, 737. 
4 For a study of cases with bibl., consult Councilmann, Mallory, and Wright, Special Report of the 
State Board of Health of Massachusetts, 1898; also Elser, Jour. Med. Research, 1906, N. S. ix, 89. 
For agglutinative reaction, see Jaeger, Ztschr. f. Hyg. u. Infectionskrankh., 1903, xliv, 225. 
6 Kolle and Wassermann, Deutsch, med. Wchnschr., 1906, xxxii, 609; Jochmann, ibid., 788, who 
first reported good results from infraspinous injections; Flexner and Jobling, Jour. Exper. Med., 1908, 
x, 141. 
' Flexner, Jour. Am. Med. Assn., 1909, liii, 1443; 1912, lix, 1371. 
6 For methods, see Flexner, Jour. Am. Med. Assn., 1917, Ixix, 639. THE INFECTIOUS DISEASES 
257 
presence of the Bacillus mallei there is usually a circumscribed or more 
rarely a diffuse infiltration of the tissue with leucocytes and young con- 
nective-tissue cells. These whitish foci of cell accumulation may be 
small and to the naked eye resemble miliary tubercles, or they may be 
larger and nodular. The tissues about them may be infiltrated with 
blood. But the accumulated cells are apt, in the presence of the bacilli, 
to become necrotic and disintegrate and thus lead to smaller and larger 
abscesses, or, if near the surfaces, to ulcers. If they occur on mucous 
membranes these lesions are often accompanied by intense diffuse 
catarrhal inflammation. 
As the glanders nodules soften, the bacilli are apt to diminish in 
number or in the capacity to stain, so that it may be possible to detect 
their presence only by inoculation or culture methods. 
The disease may begin at a single point, so that it may be mistaken 
for a carbuncle or gangrenous erysipelas. But the infection is apt not 
to remain local; the bacilli, finding their way along the lymph-channels 
into various parts of the body, set up fresh foci of inflammation and 
necrosis. Then the skin may be covered with a pustular eruption; 
furuncles, carbuncles, and abscesses may form beneath the skin and in 
the muscles. Nodules are found in the nasal mucous membrane, the 
lungs, kidneys, testes, spleen, and liver. The joints may be inflamed, 
and there may be osteomyelitis. Leucocytosis may accompany infection 
with the Bacillus mallei. 
The glanders infection may, however, pursue a more chronic course, 
with hard, persistent nodules and sluggish ulcers. Under these condi- 
tions the detection of the bacillus in the tissue by a simple morphological 
examination may be difficult. 
While some forms of glanders nodules somewhat resemble in gross 
and microscopic appearance certain forms of miliary tubercles, the 
absence in the former of coagulation necrosis and of giant cells, and 
the tendency to rapid disintegration and softening in the latter, will 
usually suffice for the distinction between the two sets of lesions. But the 
demonstration of the bacilli characteristic of each is in all cases decisive. 
Characters of the Bacillus mallei.-The Bacillus mallei is a slender bacillus pro- 
portionately thicker than the tubercle bacillus, with rounded ends, occurring singly 
or in pairs (Fig. 138). It stains easily with the aniline dyes, but readily gives up the 
color in presence of even feeble decolorizing agents such as 
dilute alcohol or acids. It is left decolorized by Gram's method. 
It is non-motile, does not form spores, and frequently shows 
vacuoles and various involution forms. 
In the tissues the bacilli may be stained with Loeffler's 
alkaline methylene blue. 
The glanders bacillus grows readily on almost all of the 
ordinary artificial culture media, and best at blood heat. The 
growths on solid media are apt to be viscid. On potato it 
forms in two or three days an abundant yellowish pellicle which 
in a few days darkens and finally becomes brown in color. It gradually loses its 
virulence in successive generations of artificial cultures. The germ is easily killed by 
moist heat, by sunlight, drying, and the several germicidal chemicals.1 
Fig. 138.-Bacillus 
Mallei. 
1 For a r^sumS of characters of the glanders bacillus see Wladimiroff, Kolle and Wassermann, 
Handbuch d. path. Mikroorganismen, 2d ed., 1913, v, 1063. 258 
THE INFECTIOUS DISEASES 
Field mice and guinea-pigs are very susceptible to infection with the Bacillus 
mallei, and develop highly characteristic local and general lesions. 
Toxic Products and Immunity.-The toxic product of B. mallei is chiefly stored in 
the body of the organism as an endotoxin. On extraction by methods similar to those 
used in the preparation of tuberculin (page 294), a substance called mallein has been 
produced, and has been found useful as a means of diagnosis in glanders, affected 
animals showing local reactions and a sharp rise of temperature, and marks of toxemia. 
Immunity is not apparently secured by glanders infection and while antibodies- 
agglutinins-are formed, effective curative sera have not been prepared. 
Diagnosis.-In cases in which an early diagnosis is imperative it is well, in 
addition to the morphological examination and cultures of the suspected exudate, to 
inject a small amount into the peritoneal cavity of a male guinea-pig. If the virulent 
glanders bacilli be present, within two or three days the testicles will swell and 
develop an intense suppurative inflammation. 
Other Bacilli Related to Bacillus Mallei. 
Several bacilli, apparently related to the B. mallei, have been found in various 
lesions in men and lower animals. Thus an organism called Bacillus pseudotuberculo- 
sis has been found in certain nodular lesions somewhat resembling tubercles which are 
especially frequent in rodents. B. pseudotuberculosis liquefaciens has been described 
in a series of cheesy nodules of the peritoneum, pancreas, and liver in man. In this 
group also belong organisms which have been found in noma. 
Soft chancre or chancroid is an acute inflammatory lesion usually of the genital 
regions, at first pustular, then ulcerative. The infective agent is communicated by 
contact. Neighboring lymph-nodes are apt to suffer an acute hyperplasia passing into 
abscess. 
In the lesion of soft chancre and the discharge from it a small oval bacillus ("Du- 
crey's bacillus") has been frequently found either clustered or in chains. It stains 
readily with methylene blue, although it easily loses the color. It usually occurs 
with other microorganisms, and has been found, though not commonly, in the buboes. 
It has been obtained in pure culture in rabbit-blood agar and in human blood, and 
inoculation experiments in man and in monkeys indicate its pathogenicity.1 
Chancroid (Soft Chancre). 
ANTHRAX. (Splenic Fever; Malignant Pustule; Charbon; Carbuncle.) 
This disease, which is much more common in the lower animals, 
especially the herbivora, than in man, is widely prevalent in Europe. 
It is comparatively rare in the United States, but in certain regions is 
more common than formerly. 
It is induced in man by accidental inoculation with the Bacillus 
anthracis, which also incites the disease in the lower animals. Inocu- 
lation may occur through the skin by the agency of flies and other 
insects which have been feeding on animals infected with this disease, 
through abrasions or slight wounds on the hands of those handling 
their carcasses or hides, or in other ways. Following this skin inocula- 
tion a pustule is apt to develop-"malignant pustule"-and varying 
phases of an acute exudative inflammation, which may be hemorrhagic, 
serofibrinous, purulent, or necrotic, accompany the local proliferation 
of the germs (Fig. 139). Anthrax bacilli in large numbers may be pres- 
ent in the local lesion. From this local source a general infection may 
ensue. General infection may occur without evident external lesion. 
1 See Davis, L., Jour. Med. Research, 1903, N. S. iv, 401 (bibl.). THE INFECTIOUS DISEASES 
259 
Infection with anthrax may occur through the lungs, most often 
among those who handle infected wool or hides, the dust from which is 
inhaled ("wool-sorter's disease"). Under these conditions there may 
be edema and lobular pneumonia with involvement of the pleura, medias- 
tinum, and other adjacent structures. Infection through the gastro- 
intestinal canal takes place by the ingestion of food containing anthrax 
spores, and is apt to be accompanied with inflammatory and necrotic 
changes, which are described in detail among lesions of the intestine. 
This is a common mode of infection in animals. 
Fig. 139.-Anthrax-Malignant Pustule-of the Skin. 
From a man who had been handling foreign hides in New York. Bacilli stained. 
Fig. 140.-Bacillus Anthracis Growing in the Blood-vessels of the Liver of a Mouse In- 
oculated with a Pure Culture of the Bacillus. 
When general anthrax infection occurs the post-mortem appearances 
vary. Decomposition, as in other acute infections, generally sets in 
early. The blood is frequently not much coagulated and dark in color. 
Hemorrhages and ecchymoses are frequently found in the serous and 
mucous membranes and in various other parts of the body. 260 
THE INFECTIOUS DISEASES 
The lungs may show small hemorrhages and edema, and the bron- 
chi may be deeply congested. The pleural cavities may contain serum. 
The intestines may exhibit the lesions of the so-called intestinal mycosis. 
The bronchial and other lymph-nodes may be swollen. The spleen may 
be swollen, very dark in color, and soft, sometimes almost diffluent. 
The bacillus may be found, usually in large numbers, in the spleen 
and in the capillary blood-vessels, especially in the liver (see Fig. 140), 
lungs, kidneys, and intestines.1 A serum which has some therapeutic 
value has been prepared ;2 but the use of normal beef serum has apparently 
yielded equally good results.3 
The Bacillus anthracis is from 5 to 20/x long and about 1 to 3 // broad, and is often 
uneven along the sides. The ends of the bacilli are square or slightly concave, and 
the bacilli often hang together end to end, forming thread-like structures (Fig. 141). 
While the bacilli in the vegetative condition are easily killed, they develop spores 
outside the body only, and these are very invulnerable to the ordinary germicidal 
agents and to heat, resisting often for many days the action of from 2 to 5 per cent, 
carbolic acid and defying for some minutes the action of live steam. Anthrax bacilli 
are immobile, sometimes capsulated, and are easily stained by the aniline dyes. They 
grow readily on artificial culture media at ordinary room temperatures, fluidifying 
gelatin. 
Subcutaneous inoculation of cultures of the anthrax bacillus into various species of 
animals induces characteristic lesions. White mice and guinea-pigs are especially 
susceptible, usually succumbing to the anthrax septicemia in from two to four days. 
Serous exudations, often bloody and with many bacilli, develop at the seat of inocula- 
tion, while in the blood multitudes of the bacilli are found. 
Immunization.-If cultures of the anthrax bacillus be made at a temperature of 
about 42° C., growth occurs, but it is meager. Spores are not formed as they are at 
body temperature, and the virulence of the germ dimin 
ishes day by day, so that at last the most susceptible 
animals are not affected by large inoculations of the 
living organisms. If fresh cultures of these organisms 
be made in various stages of their diminishing virulence 
and maintained at their optimum temperature, spores 
will again form, the growth will become vigorous, and 
in morphology quite characteristic; but the physiolog- 
ical qualities which determine virulence will remain 
more or less in abeyance. 
By inoculation of animals with anthrax cultures, 
first with those which had been kept at 42° C. for from 
fifteen to twenty days, and thus had but feeble virulence, 
then passing to those cultivated at 42° C. for a shorter time and which were thus more 
virulent, Pasteur secured immunity from anthrax in a series of the lower animals (see 
p. 187). Based upon these experiments a method of protective inoculation has been 
practised on a large scale among sheep and other animals in some parts of Europe 
which has been of great economic value. The death rate from anthrax has by these 
methods been reduced in sheep from 10 per cent, to about nine-tenths of 1 per cent., 
and in cattle from 5 per cent, to less than four-tenths of 1 per cent.4 
Little is known of soluble toxins or endotoxins of the anthrax bacillus. 
Characters of the Bacillus Anthracis. 
Fig. 141.-Bacillus Anthracis 
Containing Spores. 
From a culture. 
1 For bibliography and r6sum6 of anthrax see Sobernheim, Kolle and Wassermann, Handbuch d. 
path. Mikroorganismen, 2d ed., 1913, iii, 583. 
2 Brown and Simpson, Jour. Am. Med. Assn., 1917, Ixviii, 608. 
' For a review of this method of treatment, see Hyman, C. H., and Leary, T., Boston Med. and Surg. 
Jour., 1918, clxxviii, 318. 
4 For a study of opsonic substances in dog serum favoring phagocytosis of anthrax bacilli, see 
Hektoen, Jour. Infect. Dis., 1906, iii, 102. THE INFECTIOUS DISEASES 
261 
ACTINOMYCOSIS. 
This disease, which is of occasional occurrence in man, but is more 
common in the domestic animals, especially in cattle and in horses, is 
most frequently characterized by a slow suppurative and proliferative 
process, often leading to the formation of large fungous masses w'hich 
may become calcareous. 
In cattle, the new-formed tissue, which develops with especial fre- 
quency in the jaw, is apt to extend beyond the original site and to slough, 
so that not only may the tissues of the tongue, pharynx, larynx, etc., 
be involved, but secondary nodules of similar character may form in the 
lungs, gastrointestinal tract, and skin. 
(The bulbed ends of the filaments are seen in the borders of the colony. The bronchus, cut lengthwise, 
contains purulent exudate, and its wall is becoming involved.) 
Fig. 142.-Actinomyces Growing in Human Bronchus. 
In man, suppuration with necrosis and the formation of abscesses, 
ulcers, and fistulae, are the most marked lesions in parts near the surface 
of the body. In the lungs the lesions may be essentially those of an 
acute general bronchitis or in the form of bronchopneumonia (Fig. 142), 
with the formation of new tissue.1 
Abscesses and cavities may form which extend into adjacent parts. 
In intestinal actinomycosis nodular masses of new tissue with ulceration 
may develop in the mucosa and submucosa. Metastases have been 
described. The excitant of this disease-now most commonly called 
1 For a detailed description of the lung lesions in actinomycosis, see Hodenpyl, Med. Rec., 1890, 
xxxviii, 653 (bibl.). 262 
THE INFECTIOUS DISEASES 
Actinomyces bovis-is a microorganism which seems to be more closely 
related to the moulds than to the bacteria. It is, however, considered 
here because its botanical position is not yet clearly established, and it 
may be one of the so-called pleomorphous bacteria (see page 161). 
The organism often grows in the tissues in the form of little rounded 
masses from a size so small as to be invisible to that of a pin's head. 
They may be transparent or grayish white or yellow or dark in color. 
Under the microscope these masses often appear in the form of a dense 
group of radiating filaments with more or less bulbous ends; hence the 
common name "ray fungus." 
Characters of Actinomyces. 
The organism when freed from other bacteria is readily cultivated at 37° C. It 
grows in delicate branching threads which show segments resembling bacilli and cocci 
besides bulbous or club-shaped forms, probably "involution forms." Successful 
inoculations of cultures have been made in animals. 
The organism is usually conveyed from one animal to another by inoculation or by 
contact of the growth with a wound or an abrasion of the mucous membrane. 
In the examination of sputum, feces, pus, etc., for the presence of actinomyces 
the naked-eye appearances may be of value, since the yellowish white granules are 
often quite visible, especially on a black background. Suspicious masses may be 
teased and studied unstained, or stained by Gram's method. Blocks of tissue may 
be hardened in alcohol, and sections stained by Gram's method with contrast eosin 
stain. 
Other Organisms Resembling Actinomyces. 
Many forms of microorganisms of similar general characters to actinomyces have 
been described, some occurring in connection with infective processes in man and the 
lower animals, of which they seem to be the excitants, others living as saprophytes in 
various situations. Among the apparently pathogenic forms we may mention the 
following: 
An organism somewhat resembling actinomyces and found in connection with a 
disease commonly called mycetoma or " Madura foot," frequent in the tropics and 
characterized by nodular growths associated with suppuration and necrosis most 
often affecting the foot.1 
Another form has been described in connection with a peculiar form of erysipela- 
tous inflammation of the skin; another in the so-called farcin de boeuf, a disease of 
cattle in Guadeloupe; this has been called Streptothrix and now Nocardia. 
Several times organisms of this general character, but differing considerably from 
actinomyces, have been found in inflammatory and necrotic lesions of the lungs. 
Whether these are variants of that species or independent species, and how many such 
there are it is impossible at present to say.2 Many attempts have been made to 
classify these organisms but knowledge of them is still too incomplete to permit 
accurate distinctions. 
1 Consult Wright, J. H., Jour. Exper. Med., 1898, iii, 421 (bibl.); Jour. Med. Research, 1905, N. S. 
viii, 349; and Osler's Modern Medicine, 1907, i, 327; and Babes, V., Kolle and Wassermann, Handbuch 
d. path. Mikroorganismen, 2d ed., 1913, v, 365. 
2 For a description of two such cases, with a selected bibliography, see Norris and Larkin, Jour, 
Exper. Med., 1900, v, 155; also case by Tuttle, Med. and Surg. Rep., Presby. Hosp., New York, 1904, 
vi, 147. 
For a critical summary of this group of organisms, with a full bibliography, see Lachner-Sandoval, 
Ueber Strahlenpilze, Strasburg, 1898; also Petruchsky, Kolle and Wassermann, Handbuch d. path. 
Mikroorganismen, 2d ed., 1913, v, 267; Schlegel, ibid., p. 301; and Musser, Pearce, and Gwyn, Tr. Assn. 
Am. Phys., 1901, xvi, 208. THE INFECTIOUS DISEASES 
263 
Sporotrichosis. 
In the last few years a considerable number of cases of a chronic fungoid process 
involving the skin and mucous membranes, and occasionally resulting fatally, have 
been described. Several types of organism, growing on ordinary media, have been 
isolated. The condition is known as sporotrichosis.1 (See also page 173.) 
Pharyngomycosis Leptothrica. 
Certain filamentous microorganisms called Leptothrix, whose botanical affiliations 
are not yet clear, are of common occurrence in the mouths of healthy persons. Occa- 
sionally, however, a persistently recurrent attack of "sore throat, " with local tender- 
ness and sometimes cough and fever, is associated with the growth of masses of lepto- 
thrix in the crypts of the tonsils, at the base of the tongue, on the walls of the pharynx, 
or in the nose or superior portion of the esophagus. The leptothrix masses or colonies 
form thick whitish'pellicles or patches which may be superficial, or in tonsils may 
extend deep into the crypts. These masses are usually firmly adherent, often leave 
bleeding surfaces when removed, and the growth is apt persistently to recur. 
Microscopic examination of removed portions of the growth show tufts and bun- 
dles of the thread-like microorganisms, growing among or directly out from flat epi- 
thelial cell masses and mingled with various other forms of microorganisms, mostly 
cocci and short bacilli. There may be overgrowth of epithelium and collections of 
leucocytes in and about the leptothrix masses.2 
INFLUENZA. (Epidemic Catarrhal Fever; La Grippe.) 
This is an infectious disease characterized by fever, physical and 
mental prostration, and exudative inflammations in different parts of 
the body. Thus there may be exudative inflammation in the respiratory, 
digestive, and nervous systems, either singly or together. Sometimes, 
however, these local inflammations may be absent, when the disease may 
be marked by the characteristic prostration and symptoms of toxemia. 
None of the lesions appear to be characteristic. The lesion of the 
lungs is usually of the bronchopneumonic type and is apt to involve the 
interstitial tissue. The cut surface is smooth, the exudate is soft and 
contains relatively little fibrin. The lung resembles that of "purulent 
infiltration." 
The numerous bacterial studies which up to 1892 had been made on 
epidemic influenza had failed to reveal any microorganism which could 
fairly be regarded as of etiological significance, although some of the 
complicating inflammations of the lungs had been shown to be very 
frequently associated with the pyogenic cocci-Staphylococcus pyogenes 
and Streptococcus pyogenes and the Diplococcus pneumoniae. 
Early in 1892, Pfeiffer, Kitasato, and Canon described the occurrence 
in the bronchial exudate and in the blood of influenza patients of a very 
small bacillus, hitherto unknown or possibly noted earlier by Babes. 
This bacillus-B. influenzce-is sometimes present in the bronchial 
exudate in enormous numbers, and often with little or no contamina- 
tion with other germs. It is found at the seat of other local lesions, 
and the pus cells often contain many bacilli. It has been found to 
persist in the body long after the active processes have ceased.3 
1 de Beurmann and Gougerot, Traite des sporotrichoses, Paris, 1912. 
2 For further details, and bibliography, consult Campbell, Med. News, 1896, Ixviii, 371; also Pearce, 
Bull. Univ. Pennsylvania, 1901, xiv, 217; and Davis, J. D., Jour. Infect. Dis., 1914, xiv, 144. 
3 For a full resume of the characters of the influenza bacillus and its relation to various forms of the 
disease, with bibliography, see Scheller, R., Kolle and Wassermann, Handbuch d. path. Mikroorgan- 
ismen, 2d ed., 1913, v, 1257. See also, Vaughan, W. T., Influenza, Amer. Jour. Hygiene, Monographic 
Ser., No. I, July, 1921; and Winternitz, M. C., Wason, I. M., and McNamara, F. P., The Pathology of 
Influenza, New Haven, 1922. 264 
THE INFECTIOUS DISEASES 
Characters of the Influenza Bacillus. 
The influenza bacillus is very small-about 0.5 /z long by 0.2 to 0.3 /z in width- 
with rounded ends, non-motile, and does not form spores. It stains with some 
difficulty with simple aniline dyes; but by Ziehl's solution, or by warmed Loeffler's 
methylene blue it is readily colored. It does not retain the stain well by Gram's 
method. The organism apparently dies after a few hours' drying in the air and soon 
in water and is readily killed by heat or cold or chemical germicides. 
This bacillus grows best at body temperature, on glycerin-agar whose surface has 
been smeared with blood-human, rabbit, or pigeon. It forms very small, scarcely 
visible, dewdrop-like colonies, which, although growing close together, do not tend to 
coalesce, as those of many microorganisms do. It has been cultivated through several 
generations, but usually dies soon. 
Animal inoculations have given diverse and not very marked results, most of the 
lower animals being apparently quite insusceptible except to very large doses of 
cultures which may have a toxic action upon them. In monkeys, however, influenza- 
like symptoms have been induced by application of cultures to the nasal mucosa. 
The evidence that the organism described above is the excitant of 
epidemic influenza rests largely upon its apparently constant presence, 
especially in the exudates of the nasal and bronchial mucous membranes, 
where it may be present in enormous numbers and almost free from 
admixture with other germs. 
Cases of sporadic influenza are of frequent occurrence, especially in 
towns. These are often mixed infections, the influenza bacillus being 
associated with pneumococcus, streptococcus, etc. 
That the organism should have been occasionally found under other 
conditions,1 as in chronic pulmonary tuberculosis, does not at all militate 
against its significance in inciting the manifestations of influenza, since 
many parallel instances are known in other infectious diseases. The 
frequent discrepancy between the clinical and bacterial diagnosis in 
influenza is largely due to its varying and often obscure clinical manifes- 
tations which render possible and convenient the use of the name for 
many phases of catarrhal and other forms of inflammation. 
Immunity in any marked degree does not appear to be conferred by 
influenza. 
Source.-Material containing the influenza bacillus is readily and 
doubtless frequently conveyed from the victims of influenza or from 
those harboring the organism to the well, in droplets and spray dispersed 
through the air by unguarded coughing and sneezing, as well as by 
direct personal contact and the use of contaminated utensils for food 
and drink. 
Other Organisms of the Influenza Bacillus Group. 
There are several organisms in the influenza bacillus group which considerably 
resemble it, some of which appear to be pathogenic, others not so. Thus several 
observers have found in exudates from various sources, but especially in the respira- 
tory passages, small immobile asporogenous bacilli growing best under conditions 
similar to those favorable to the influenza germ, the colonies being similar. They are 
somewhat larger than the influenza bacillus, and tend to form threads. This organism 
1 See Park and Williams, Pathogenic Microorganisms, 6th ed., New York, 1917, p. 411; see also 
for studies of this organism Lord, Boston Med. and Surg. Jour., 1905, clii, 537, 574; Auerbach, Ztschr 
f- Hyg. u. Infectionskrankh., 1904, xlvii, 259; and Davis, Jour. Infect. Dis., 1906, iii, 1. 
For a study of the influenza bacillus in inflammations of the respiratory tract in infants, see Woll- 
stein, M„ Jour. Exper. Med., 1906, viii, 681. THE INFECTIOUS DISEASES 
265 
has been called the pseudoinfluenza bacillus-B. pseudoinfluenzoe. Its pathogenic 
capacities are not clear, but it evidently differs in this respect from the genuine influ- 
enza bacillus. In stained specimens of exudate the pseudobacillus may be mistaken 
for its relative. It seems probable that there may be several forms of organisms not 
distinguishable at present from each other and from the influenza bacillus, which 
have been grouped under the name B. pseudoinfluenzse, so that the use of the name 
is of doubtful value. 
Another bacillus of this group, B. conjunctivitidis-Koch-Weeks bacillus-has 
been found in conjunctival catarrh by several observers in various countries and is 
doubtless the inciting factor in a readily communicable form of conjunctival inflam- 
mation. This bacillus, resembling the influenza bacillus, is somewhat longer and 
grows on blood-free media. It may be differentiated by cultural characters. Animal 
inoculations have been negative. A similar organism has been found in trachoma.1 
TYPHOID FEVER. 
Typhoid fever is an acute infectious disease incited by the Bacillus 
typhosus. The reaction of the body to this bacillus is usually mani- 
fested by characteristic lesions, especially by hyperplasia and necrosis 
in the lymphatic structures of the intestines and the mesenteric lymph- 
nodes, and in the spleen, as well as by the more general alterations 
incident to toxemia and septicemia; but the infection is occasionally 
of the septicemic type without characteristic local lesions in the intes- 
tines, or mesenteric nodes, or other viscera.2 
The Bacillus of Typhoid Fever. 
The presence of a bacillus, called Bacillus typhosus, in various parts 
of the body in typhoid fever, in a considerable proportion of the cases 
examined, has been well established. This bacillus does not occur in 
the body, so far as is known, except in connection with this disease, 
although it may persist in the gall-bladder or intestine for years after 
convalescence. 
Characters of the Bacillus Typhosus. 
The typhoid bacillus is usually about three times as long as broad, being about one- 
third as long as the diameter of a red blood-cell. It is rounded at the ends, motile, 
aerobic, facultative anaerobic, and asporogenous. 
It grows readily at room temperature on the ordi- 
nary media. In cultures the bacilli often cling 
together end to end, forming threads (Fig. 143). 
It is readily killed by heat, is fairly resistant to 
chemical germicides, and remains alive for some 
time frozen in ice. 
The inoculation of lower animals with the 
typhoid bacillus may result in various lesions, and 
prove fatal, but typical typhoid fever is not 
induced.3 
The typhoid bacillus in its growth in cultures 
does not seem to produce soluble toxins of 
marked potency in very considerable amount though there is evidence that some 
such poison is formed.4 On the other hand, there is stored up in the bodies of the 
bacilli a virulent endotoxin which has been largely used in artificial immunization. 
Fig. 143.-Bacillus Typhosus. 
1 Williams, A. W., Proc. New York Path. Soc., 1912, xii, 17. 
2 For studies on various phases of typhoid infection, see Johns Hopkins Hospital Reports, 1900, viii. 
3 For a study of experimental typhoid, see Atlassoff, Ann. Inst. Pasteur, 1904, xviii, 701 (bibl.). 
4 For a study of the soluble poisons of the typhoid bacillus, see Rodet, Lagriffoul, and Aly Wahby, 
Arch, de med. exp^r., 1904, xvi, 397. 266 
THE INFECTIOUS DISEASES 
It is probable that the more characteristic symptoms and lesions of 
typhoid fever are largely due to the absorption of toxic substances which 
are produced as the result of the life processes of the bacteria at the 
point of their greatest accumulation and activity. It should be borne 
in mind that the typhoid bacillus, as is the case with many other bac- 
teria, may induce local changes by means of its endotoxins, which are 
set free as the organisms disintegrate after their death in the body.1 
Primary Characteristic Lesions. 
We shall first consider the lesions which are most common and char- 
acteristic of typhoid fever. 
The Intestines.-The lesions of the intestines consist of an inflamma- 
tory enlargement (hyperplasia) of the solitary lymph-nodules and of 
the agminated lymph-nodules (Peyer's patches). Necrosis of the nod- 
ules with ulceration frequently follows the hyperplasia. 
The process appears to begin with a catarrhal inflammation of the 
mucous membrane, accompanied or immediately followed by changes in 
the lymph-nodules. The lesions in the lymph-nodules begin early; 
Fig. 144.-Hyperplasia of Peyer's Patches in Typhoid Fever. 
they have been observed in persons who have died forty-seven hours 
after the commencement of the disease. The increase in size of the 
agminated and solitary nodules may be rapid or gradual. The nodules 
may be only slightly enlarged, or may project far into the lumen of the 
intestine. The enlargement is usually more marked in the agminated 
than in the solitary nodules. Usually the whole of a Peyer's patch is 
enlarged, but sometimes only a part of it. If the enlargement be 
gradual the different nodules which make up a Peyer's patch may 
enlarge, while the septa between them remain but little changed, thus 
giving the patch an uneven appearance. 
The patches which are only moderately enlarged are of reddish or 
reddish gray color, and soft and spongy, and their edges blend gradually 
with the adjoining mucous membrane. The patches which are more 
markedly affected are of grayish color, of firm consistence, and rise 
abruptly from the surrounding mucous membrane (Fig. 144) or even 
1 For a study of the typhoid bacillus with reference to the pathology, diagnosis, and hygiene of the 
disease, see Hiss, Med. News, 1901, Ixxviii, 728. 267 
overhang it like a mushroom. The largest patches are sometimes 
more than three-eighths of an inch thick. 
The enlargement and infiltration may spread from the patches to 
the surrounding mucous membrane, so that the patches appear very 
large; a number of them may become fused together, and there may 
even be an annular infiltration entirely around the lower end of the 
ileum. The infiltration, limited at first to Peyer's patches, may extend 
outward into the muscular coat, and appear in the peritoneal coat as 
small, gray, rounded nodules. This condition is usually found only 
with a few patches in the lower end of the ileum; sometimes in the 
cecum and appendix vermiformis. 
The solitary nodules are affected in the same way as Peyer's patches. 
They may be hardly enlarged at all, or be quite prominent, or may be 
affected over a larger portion of the intestine than are the patches. 
Very rarely the solitary nodules are enlarged, while the patches are not 
at all or but slightly affected. 
The inflammation and enlargement of the agminated and solitary 
nodules may be followed by a healing process. The character of this 
process varies according to the intensity of the previous inflammation. 
If the reaction be slight and the enlargement of the nodules moderate, 
the enlargement gradually disappears, and they resume their normal 
appearance (resolution). In moderate enlargements of Peyer's patches 
resolution proceeds first in the nodules, leaving the septa between them 
for a time still swollen and prominent. This gives to the surface of a 
patch a reticulated appearance. After a time, however, the entire 
patch becomes flattened and uniform. On the other hand, the solitary 
nodules or the separate nodules of a patch may soften and break down, 
and their contents be discharged 
with some attendant hemorrhage. 
This leaves a bluish gray pigmenta- 
tion, due to altered hemoglobin, in 
the situation of each nodule, and this 
may remain for years. 
In more severe types of the disease 
the enlargement of the nodules and 
Peyer's patches ends in ulceration. 
This takes place in two ways: 
(a) The enlarged nodules or 
patches become necrotic, soften, 
break down, and discharge into the intestine. In this way are formed 
small ulcers (Fig. 145). These ulcers increase in size by the same 
softening process, which gradually extends at their edges, and in this 
way ulcers of large size may be formed.1 The ulcers may extend out- 
ward to the muscularis or to the peritoneal coat, or they may involve 
the peritoneal coat also and perforate. 
THE INFECTIOUS DISEASES 
Fig. 145.-Hyperplasia of Peyer's Patch 
in Typhoid Fever, with Small Ulcers. 
The separate small ulcers are extending and 
have in part coalesced. 
1 Owing to the frequent involvement of Peyer's patches, the larger intestinal ulcers in typhoid 
fever are apt to have their longest diameter lengthwise of the gut in contrast to spreading tuberculous 
ulcers, which, owing to the extension of the local inflammation along the encircling lymph-channels, 
are apt to have the longest diameter crossing the gut. But exceptions to this general rule are common. 268 
THE INFECTIOUS DISEASES 
(6) In the severest forms of the disease considerable portions of the 
enlarged patches may slough and become detached, leaving large ulcers 
with thick, overhanging edges (Fig. 146). The slough may involve 
only the nodules, or it may involve also the muscular and peritoneal 
coats, and perforation may occur. These ulcers also may afterward 
increase in size, and several of them may be joined together. When 
the ulceration leads to perforation, peritonitis and death are the usual 
result. In rare cases, however, the patient recovers and the perforation 
is closed by adhesions. 
If the patient recover, the ulcers are covered by granulation tissue, 
their edges become flattened, the granulation tissue becomes firmer and 
denser, and this new connective tissue is gradually covered with cylin- 
drical epithelium. 
Fig. 146.-Ulceration of Peyer's Patches and Solitary Lymph-nodules in Typhoid Fever. 
The swollen patches and nodules are necrotic except at their edges, the central portions forming a 
ragged slough. 
The minute changes which take place in the development of the 
intestinal lesion are as follows: 
At first the blood-vessels around the nodules are dilated and con- 
gested, while the nodules are swollen and the epithelium may fall off. 
Then the nodules increase in size, largely from a growth of new cells. 
This cell growth is essentially a hyperplasia of normal elements of 
the lymphatic tissue, namely, the lymph cells and the endothelium of 
the trabeculae and sinuses. There are thus two main types among the 
new-formed cells: first, small cells with relatively large and deeply stain- 
ing nuclei; and second, larger polyhedral or rounded cells with more 
or less vesicular nuclei. The larger cells may contain foreign substances, 
such as red blood-cells or leucocytes (Fig. 147). The occurrence of 
mitotic figures in the endothelial cells while these are in situ, and the 
position and grouping of the large cells, appear to prove their endothelial 
origin. The production of new cells is not confined to the nodules, but 
extends also to the adjacent mucous membrane and underlying tissue. 
In many cases also little foci of similar new-formed cells are found in 
the muscular, subserous, and serous coats. 
In this stage resolution may take place; then the new-formed cells 
degenerate and gradually disappear. In severer forms of the disease 
necrotic changes are apt to supervene, leading to the large and small THE INFECTIOUS DISEASES 
269 
ulcers above described. The factors which determine the death of the 
hyperplastic tissues are not yet fully understood. It is believed by some 
to be directly due to toxic substances formed by the typhoid bacilli 
which kill the tissue cells; others are inclined to attribute it to the pres- 
sure which the new-formed cells exert on the nutritive blood-vessels. 
Fig. 147.-Endothelial Cells in Hyperplasia of Peyer's Patch in Typhoid Fever. 
These exfoliated and newly formed cells contain various foreign substances-leucocytes, red 
blood-cells, fragments of nuclei, etc. Some of them are necrotic and are degenerating. A mitotic figure 
is seen in one. 
Fig. 148.-Phagocytes in the Perifollicular Sinuses of a Mesenteric Lymph-node in 
Typhoid Fever. 
The large cells in the sinuses contain red blood-cells and blood pigment. 
The conclusions on this point which Mallory draws from a long and 
interesting series of studies would indicate that a proliferation of the 
endothelial cells of the blood-vessels may lead to their occlusion. This 
observer describes the formation of occluding thrombi in the lymph- 270 
THE INFECTIOUS DISEASES 
vessels and smaller veins. These are composed of the proliferated 
endothelial cells which have degenerated, together with fibrin whose 
formation these degenerating cells induce. The accumulation of serous 
and fibrinous exudate about these thrombi, and the necrosis of tissue 
which may now ensue may soon be followed by necrosis of the super- 
ficial epithelium and the development of ulcers. The accumulation of 
polymorphonuclear leucocytes may, according to Mallory, now occur, 
and, in cases which go on to recovery, healing follows by the formation 
in the usual way of granulation tissue with the ultimate restitution of 
the surface epithelium. Mallory lays great stress upon the phagocytic 
nature of the new-formed cells of the veins and lymph-vessels (Fig. 148 
and Fig. 149). For the significance of this process and other interesting 
details we refer to the original paper.1 
Fig. 149.-Phagocytic and Necrotic Cells in Lymph-vessel near Peyer's Patch in the Wall 
of the Intestine in Typhoid Fever. 
The lesions which we have described are found most frequently and 
are most pronounced in the lower part of the ileum. They are not 
always, however, confined to this situation. Enlarged and ulcerated 
nodules may be found over the entire length of the ileum and even in 
the jejunum. They may also extend downward and be found in the 
colon, even as far down as the rectum. Similar changes may take 
place in the appendix vermiformis.2 A few cases are recorded in which 
local nodular foci of new cell production, necrosis, and ulceration are 
limited to the colon. Clusters of typhoid bacilli may be found in these 
nodules. These are usually irregularly scattered, are not limited to a 
hyperplasia of the lymph-nodules, and should be distinguished from 
simple nodular hyperplasia with ulceration.3 
Mesenteric Lymph-nodes.-The mesenteric nodes undergo changes 
similar to those in the nodules of the intestines, and are usually affected 
in a degree corresponding to the intensity of the intestinal lesion. 
The nodes are at first congested and succulent; then there is a pro- 
duction of lymphoid cells and large cells as in the intestinal nodules, 
and the node becomes enlarged. When the enlargement has reached 
its full extent, congestion diminishes, and the cells begin to degenerate. 
The degeneration may take place slowly, and then the node gradually 
1 Mallory, F. B., Jour. Exper. Med., 1898, iii, 611. 
2 For a study of the distribution of typhoid ulcers, see Baer, J. W., Am. Jour. Med. Sc., 1904, cxxvii, 
787. For record of cases in which the infection and the symptoms seemed to be confined to the 
appendix, see Wolfsohn, Berl. klin. Wchnschr., 1915, lii, 872. 
3 See Whipple, Bull. Johns Hopkins Hosp., 1906, xvii, 281. THE INFECTIOUS DISEASES 
271 
returns to its normal condition; or more rapidly, and then little foci of 
necrotic, purulent material are formed. If the patient recover the 
small foci are absorbed, leaving a fibrous cicatrix; the larger foci may 
become dry, necrotic, and inclosed in a fibrous capsule. Intense exu- 
dative inflammation may occur in the nodes, which may be densely 
infiltrated with serum, fibrin, and pus. 
The Spleen.-In nearly every case of typhoid fever the spleen is 
enlarged. This enlargement begins, as a rule, soon after the commence- 
ment of the disease, increases rapidly until the third week, remains 
stationary for a few days, and then diminishes. The organ is congested, 
of dark red color, and of firm consistence while it is increasing in size. 
After it has reached its maximum size, its consistence becomes soft, and 
there is a considerable deposit of brown pigment. The enlargement 
appears to be due to congestion and hyperplasia. 
Mallory describes proliferation of endothelial cells, especially in the 
blood-vessels and pulp spaces, and the formation of venous thrombi. 
In rare cases the softened spleen ruptures, with an extravasation of 
blood into the peritoneal cavity. There may be infarctions of the 
spleen, which sometimes soften and may apparently lead to peritonitis. 
The Liver.-The liver may present no apparent lesion. It is, how- 
ever, frequently large, pale, and flabby, and in this condition the liver 
cells may be the seat of simple albu- 
minous degeneration. 
Less frequently there are present 
in the liver very small, soft, grayish 
nodules (Fig. 150). These focal 
lesions are sometimes too small to be 
distinguished by the naked eye. 
They may be situated about the 
branches of the portal vein or within 
the lobule. Some of these nodules 
consist of masses of small spheroidal 
cells, which may form a diffuse in- 
filtration along the small veins. 
Mallory distinguishes two distinct 
varieties of these focal lesions: one 
formed in the lymph-spaces and -vessels in the capsule of Glisson by 
a proliferation of the endothelium (Fig. 151); the other due to obstruc- 
tion of liver capillaries, in part by the proliferation of endothelium 
on the spot, in part by emboli of endothelial-cell origin, which are 
derived through the portal circulation from the vessels of the spleen 
and intestine. Necrotic changes may develop in and about these focal 
cell accumulations. 
Simple focal necroses of the liver and of other viscera, due to the 
action of toxic substances in the body fluids, may occur in typhoid fever 
as in many other infectious diseases.1 
Fig. 150.-Focal Area of Endothelial- 
cell Proliferation in the Liver in 
Typhoid Fever. 
1 For fuller details of studies on these focal lesions in typhoid and other infectious diseases, con- 
sult Mallory, Jour. Exper. Med., 1898, iii, 611; Reed, Johns Hopkins Hosp. Rep., 1895, v, 379; and 
Flexner, ibid., 1897, vi, 259. 272 
THE INFECTIOUS DISEASES 
While small foci of cell proliferation may be present in the kidneys 
as well as in other viscera, their occurrence is neither so frequent nor so 
characteristic as in the liver. 
In typhoid fever as in other infectious diseases toxemia may be mani- 
fested by disturbances in the circulatory, respiratory, and heat-regu- 
lating mechanism, and in general metabolism, as well as by manifest 
lesions, such as albuminous or other degeneration of parenchyma cells 
throughout the body, and alterations leading to leucocytosis. 
Secondary Lesions. 
In addition to the more characteristic lesions of typhoid fever which we have 
described, there are several of secondary or complicating nature. These are of suffi- 
ciently frequent occurrence in the disease to require brief mention. They are in part 
due to the direct action of the typhoid bacillus or its soluble poisons; in part, how- 
ever, they are brought about by secondary bacterial infections.1 
The Digestive Organs.-In the intestine there may be gangrene, sometimes 
involving the tissues about the ulcers, sometimes apart from these. There may be 
croupous inflammation of the intestinal mucous membrane of either the large or small 
intestine. A slight peritonitis sometimes accompanies the intestinal lesion. A severe 
peritonitis is usually due to perforation, less frequently to ulcers which reach the 
serous coat, but do not perforate. When there is infiltration of the serous coat with 
the new cell growth, described above, peritonitis may be associated with a produc- 
tion of little gray nodules of the same character throughout the peritoneum. In- 
Fig. 151.-Hyperplasia of Endothelium in the Liver in Typhoid Fever. 
Thia cut shows a more highly magnified portion of the focal lesion in Fig. 150. 
farctions of the spleen, inflammation of the ovaries, and perforation of the gall- 
bladder are sometimes the inciting factors in peritonitis. 
Hemorrhage from the intestines may be slight and due to the inflammatory 
swelling and congestion of the mucous membrane; or it may be due to the ulceration 
of the follicles and opening of the blood-vessels, and is then often profuse. 
There may be hyperplasia of the tonsils and of the lymphoid tissue at the base of 
the tongue. Gangrenous ulcers of the sides and floor of the mouth may be present. 
Catarrhal and croupous inflammation of the pharynx may be associated with super- 
1 For bibliography of the extra-intestinal lesions induced by the typhoid bacillus, see Howard, 
Philadelphia Monthly Med. Jour., 1899, i, 402. THE INFECTIOUS DISEASES 
273 
ficial or deep ulceration. Inflammation of the parotid leading to suppuration is not 
infrequent. The submaxillary gland may be similarly affected. Enlargement and 
induration of the salivary glands and of the pancreas in typhoid fever have been 
described and are believed to be due to hyperplasia of the gland cells with accumula- 
tion of their secretion. This may be followed by degeneration. 
The Circulatory Organs.-The heart in many cases is the seat of albuminous, 
fatty, or hyaline degeneration, or of pigmentation. Myocarditis, endocarditis, and 
pericarditis are of occasional occurrence. Thrombi may form upon the valves or in the 
heart cavities, and detached fragments of these may be lodged as emboli in various 
parts of the body. The arteries may be the seat of acute inflammation. If this in- 
volve the intima, an occluding thrombus may be formed which may lead to gangrene 
of the part supplied by the vessel. Thrombosis of the veins is common, and especially 
frequent in the femoral vein late in the disease.1 
The Respiratory Organs.-The larynx is frequently the seat of catarrhal 
inflammation, with or without superficial erosions. Less frequently there is croupous 
inflammation, followed in some cases by destructive ulceration; edema of the glottis 
occasionally occurs. 
The Lungs.-Catarrhal inflammation of the large bronchi is very common. Bron- 
chopneumonia occurs in two forms. There may be a severe inflammation of most of 
the bronchi of both lungs, with cellular infiltration of the walls of the bronchi and 
zones of peribronchitic pneumonia; or there may be an intense general bronchitis, 
with lobules of the lung corresponding to obstructed bronchi, either collapsed or in- 
flamed, or both. 
From the long-continued recumbent position of the patients, the posterior por- 
tions of the lungs become congested, dense, and unaerated. Sometimes, in addition 
to this, irregular portions of the lungs become hepatized. Less frequently there is 
acute lobar pneumonia. Infarctions are not uncommon, and gangrene occasionally 
occurs, either associated with lobular pneumonia or with infarctions, or as an indepen- 
dent condition. Fibrinous pleurisy and empyema are not infrequent.2 
The Genitourinary Organs.-The kidneys are occasionally the seat of an acute 
inflammation. Catarrhal and croupous and nodular inflammation of the bladder may 
occur. Hemorrhage and gangrenous inflammation in the ovaries have been recorded; 
the uterus may be involved. Orchitis and epididymitis may develop during 
convalescence.3 
The Nervous System.-In addition to chromatolytic changes in the ganglion 
cells, which are common to many infectious diseases,4 there may be thrombosis of the 
venous sinuses and obliterating endarteritis. Acute meningitis is rare.5 Degenera- 
tion and inflammation of the peripheral nerves may occur. 
Suppurative inflammation may occur in almost any part of the body in typhoid 
fever. This may be in the form of boils or of deep abscesses. Postpharyngeal sup- 
puration is often one of the most serious of these complications. Posttyphoid bone 
lesions are often important.6 
Septicemic Forms of Typhoid Fever Without Characteristic 
Local Lesions. 
Typhoid fever may occur without the characteristic intestinal and 
associated lesions. In this septicemic type of the disease there may be 
no demonstrable lesions other than those which are due to the toxemia.7 
1 See an analysis of forty-two cases of venous thrombosis in typhoid fever, Thayer, Tr. Assn. Am. 
Phys., 1904, ix, 164. 
2 For pulmonary complications, see Robinson, Proc. Path. Soc., Philadelphia, 1905, viii, 141. 
3 See Kinnicutt, Tr. Assn. Amer. Phys., 1901, xvi, 145. 
4 For a study of ganglion cells in cases of typhoid fever, see Nichols, J. L., Jour. Exper. Med., 1899, 
iv, 189 (bibl.). See also Ewing, JArch. Neurol, and Psychopath., 1898, i, 263. 
5 For study of typhoid meningitis, see Cole, R., Johns Hopkins Hosp. Rep., 1904, xii, 379. 
6 Parsons, Johns Hopkins Hosp. Rep., 1895, v, 417. For a study of bone-marrow in typhoid and 
other infections, see Longcope, Proc. Path. Soc., Philadelphia, 1905, viii, 49. 
7 Consult in this connection, for cases and bibl., Chiari, Ztschr. f. Heilk., 1897, xviii, 5; and Ophills, 
New York Med. Jour., 1900, Ixxi, 728 (bibl.). 274 
THE INFECTIOUS DISEASES 
On the other hand, inflammatory processes in the viscera-lungs, kid- 
ney, spleen, etc.-may be dependent on the presence of the typhoid 
bacillus. The lesions in such cases are not, so far as we yet know, 
characteristic, and the post-mortem diagnosis depends largely upon the 
identification of the bacillus.1 
Distribution of the Typhoid Bacillus in the Body in Typhoid 
Fever. 
In the early stages of the disease the bacillus may be found in the 
lymphatic structures of the intestines and in the mesenteric lymph- 
nodes and the spleen. It may be present in lesions involving the bone- 
marrow, kidney, liver, lungs, pleura, uterus, 
and testicle, and in the rose spots of the skin,2 
as well as in the blood, where it may be 
found in a large proportion of cases.3 
In at least 20 per cent, of cases in the third 
and fourth weeks, typhoid bacilli have been 
found in the urine, usually accompanied by 
albumin, and in the bile, and they may 
persist in both of these and in the feces 
long after the establishment of convales- 
cence.4 They may be found, though not 
in such abundance as was formerly as- 
sumed, in the intestinal contents after 
the disease has become well established.5 
Their abundance here appears to depend 
somewhat upon the degree of intestinal 
ulceration. In the viscera they are apt 
to occur in larger and smaller masses or clusters (see Fig. 152). The 
typhoid bacillus may be transmitted through the placenta to the fetus. 
Typhoid bacilli may be present alone or in association with other 
germs in the foci of suppuration which so frequently complicate typhoid 
fever, also in the exudate in inflammations of the serous membranes 
and in the endocardial vegetations.6 
Mixed Infection.-Some of the inflammatory complications which 
occur in typhoid fever are due to the growth of the bacillus in unusual 
places in the body; but many of them are due to a secondary infection 
with other germs, notably with the pyogenic cocci,7 and also with the 
colon bacillus and the pneumococcus.8 
Fig. 152.-Cluster of Typhoid 
Bacilli in the Spleen. 
1 For summary of studies on the typhoid bacillus and typhoid fever, with bibl., consult Dunbar 
L. O., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1896, i, 605; Kutscher, Kolle and Wassermann, Hand- 
buch d. path. Mikroorganismen, 2d ed., 1913, iii, 717; and Gay, Typhoid Fever, New York, 1918. 
2 See Pratt, Jour. Boston Soc. Med. Sc., 1899, iii, 170. 
'See Coleman and Buxton, Jour. Med. Research, 1909, N. S. xvi, 83. 
*Gwyn, Bull. Johns Hopkins Hosp., 1899, x, 109; also Curschmann, on typhoid cystitis, Munchen 
med. Wchnschr., 1900, xlvii, 1449. 
6 Hiss, Med. News, 1901, Ixxviii, 728. 
6 See Flexner, Jour. Path, and Bacteriol., 1895, iii, 202, and Johns Hopkins Hosp. Rep., 1897, v, 
343; also Mace, Traits de Bacteriologie, 1901. 
7 For full consideration of the pyogenic powers of the typhoid bacillus, consult Dmochowski and 
Janowski, Zieglers Beitr., 1895, xvii, 221. 
s Keen, Surgical Complications of Typhoid Fever, Philadelphia, 1898; Hare and Beardsley, Medical 
Complications of Typhoid Fever, Philadelphia, 1909. THE INFECTIOUS DISEASES 
275 
Modes of Infection with the Typhoid Bacillus. 
Infection with the typhoid bacillus seems usually to occur through the 
gastrointestinal canal. In very many cases the bacilli are conveyed by 
means of food, especially of milk and drinking-water, which have been 
polluted with the excretions-feces and urine-of persons suffering or 
convalescent from the disease. Many serious epidemics of typhoid fever 
have been traced to pollutions of milk and drinking-water from such 
sources.1 
Oysters which have been taken from grossly polluted waters, as near 
sewer openings, have been the means of conveying the germs.2 There 
is abundant evidence that flies convey the infectious material from 
undisinfected discharges.3 
In milk the typhoid bacillus not only remains alive for long periods, 
but undergoes active multiplication. It may remain long alive in water 
but in steadily diminishing numbers.4 In the soil and when dried it 
may remain alive for months. Frozen in ice it has been found alive after 
more than three months, but here also the bacilli are gradually reduced 
in number and finally die out. It is readily killed by exposure to strong 
sunlight. 
Typhoid Carriers.-While the presence of typhoid bacilli in the bile 
and gall-bladder, and even very exceptionally in the blood of healthy 
persons, has been recognized for some time, it is only comparatively 
recently that it has become definitely and widely known that the typhoid 
bacilli may remain in the gall-bladder for many years. Park states 
that from 1 to 5 per cent, of typhoid convalescents may continue to pass 
typhoid bacilli for years.5 In these cases the bacilli may be continually 
discharged in the feces, or in some instances in the urine. Such persons 
are called "typhoid carriers" and if they are of uncleanly habits or are 
engaged in handling foods as cooks, milkmen, etc., may lead to the infec- 
tion of many persons. Attempts have been made to remove the source 
of infection by excision of the gall-bladder, but this procedure is justified 
only when gall-stones are present. Vaccines also have been employed 
with only fairly satisfactory results. 
Immunity and Preventive Inoculations. 
One attack of typhoid successfully overcome gives a certain measure of protection, 
though this is not absolute, against another. Animal experiments have shown that 
it is possible to secure immunity against deadly doses of typhoid bacilli, either by the 
1 Anderson, J. F., Med. Rec., 1908, Ixxiv, 909; also Vaughan, Jour. Am. Med. Assn., 1902, xxxviii 
979. For rSsumfi with bibl. of viability of typhoid bacillus under various conditions, see Wheeler 
Jour. Med. Research, 1906, N. S. x, 269. 
2 Freeman, R. G., Albany Med. Ann., 1897, xviii, 135 (bibl.); Brooks, P. B., Jour. Am. Med. Assn. 
1916, Ixvi, 1445. 
3Graham-Smith, Flies in Relation to Disease, Cambridge, 1913; Howard, U. S. Dept. Agriculture 
Bureau of Entomology, Bull. 78, 1909; and Ficker, Arch. f. Hyg., 1903, xlvi, 274; also report on typhoid 
fever in U. S. Military Camps during Spanish War of 1898, by Reed, Vaughan, and Shakespeare, 1900. 
4 See Jordan, Russell, and Zeit, Jour. Infect. Dis., 1904, i, 641; also Russell and Fuller, ibid., Suppl. 
No. 2, 1906, p. 40. 
5 For typhoid carriers, see Park and Williams, Pathogenic Microorganisms, 6th ed., New York 
1917, p. 339; Ledingham, Carrier Problem in Infectious Diseases, 1912 (bibl.); Chapin, Sources and 
Modes of Infection, New York, 1912; Stone, Am. Jour. Med. Sc., 1912, cxliii, 544; and Gay, Typhoid 
Fever, New York, 1918. 276 
THE INFECTIOUS DISEASES 
inoculation in increasing amounts with sensitized living typhoid-bacillus cultures, or 
by the injection of suspensions of the bodies of the dead bacilli. 
Preventive inoculations have been practised on a large scale in man by the method 
of Haffkine with very favorable results. In this method emulsions of the bacillus 
are killed by heating to 53° C. for an hour; tricresol is added to insure sterility; and a 
known number of organisms are injected intramuscularly. A number of different 
types of vaccine have been employed, even live bacilli.1 
There is a slight and temporary local and general reaction which may be mani- 
fested with diminished intensity on the subsequent injections made after a few days' 
interval. 
By comparing the records of thousands of persons inoculated with dead 
typhoid bacilli, with an equal number not inoculated and exposed to the same 
conditions, it has been found that practically no cases of typhoid fever occurred in 
the inoculated group, and that in the few instances in which the disease was present 
it was of a much less severe type than that which occurred in the uninoculated group. 
In the United States this method of preventive inoculation has been practised 
on a large scale in the army with extraordinarily favorable results.2 
We have seen in an earlier section of this book (page 206) that in the adaptation 
of a living body to certain alien organic substances, among which are bacteria and their 
toxins, the serum of the adapted-or in the case of microorganisms, of the immunized 
-individual may contain substances which are agglutinative for the particular species 
of microorganism involved. By the use of this phenomenon of agglutination, a 
method of clinical diagnosis of considerable value has been devised and much employed 
especially in typhoid fever.3 
Specific precipitins also are formed in the adaptation of the organism to the typhoid 
bacillus.4 
Opsonins are formed in animals artificially immunized to the typhoid bacillus and 
also in man during typhoid fever. But determination of the opsonic index is difficult 
owing to the rapid lysis of the bacilli in the serum and in the phagocytes. 
Agglutinins, Precipitins, and Opsonins. 
The Typhoid and Colon Bacillus. 
Much difficulty has been encountered in separating the typhoid bacillus from 
various forms of the colon bacillus when they occur together, as may be the case in 
contaminated water or in the dejecta of persons suffering from typhoid fever. The 
more actively growing colon organisms obscure the few small typhoid colonies which 
may be present. A large number of special plating media have been devised, many 
of them employing the different color reactions induced in aniline dyes by the growth 
of the two types of organism. 
Hiss demonstrated that by a slight modification of the common methods the 
growth of each form is quite characteristic, so much so that pure cultures may be made 
from the mixed plates without difficulty.5 When once the two forms are separated, 
distinguishing characters are readily demonstrable.6 
The bacilli from artificial cultures stain readily with the ordinary aniline dyes, such 
as fuchsin and methylene blue. In sections, however, they do not stain so readily. 
Method of Staining the Typhoid Bacillus. 
1 See for a review of this method, Wright, Brit. Med. Jour., 1904, ii, 1343. 
2 See Russell, Harvey Lectures, Philadelphia, 1912-1913, also Am. Jour. Med. Sc., 1913, cxlvi, 803. 
For a study of the efficiency of the various types of vaccines, see Sawyer, Jour. Am. Med. Assn., 1915, 
ixv, 1413. 
3 For further details of agglutination we refer to the works on clinical pathology, and for bibliography 
to Craw, Jour. Hyg., 1905, v, 113. 
♦ Norris, Jour. Infect. Dis., 1904, i, 463. 
8 Hiss, Jour. Exper. Med., 1897, ii, 677; Jour. Med. Research, 1902, N. S. iii, 148; also Hiss and 
Russell, Med. News, 1903, Ixxxii, 289. See also the standard bacteriological text-books. 
6 For a study of agglutinative reactions of the colon-typhoid group, see Bruns and Kayser, Ztschr. 
f. Hyg. u. Infectionskrankh., 1903, xliii, 401. THE INFECTIOUS DISEASES 
277 
They are decolorized by Gram; and in sections, may be stained by Ziehl's solution. 
Stain for half an hour, decolorize in alcohol, clear in oil of cedar, mount in balsam. 
The decolorization in alcohol should be carefully done to avoid the removal of too 
much color. Flexner recommends Loeffler's methylene-blue solution for two hours; 
then acetic-acid solution 1:1,000 for several minutes; dehydrate in absolute alcohol; 
clear and differentiate in oil of cloves; mount in balsam. The aim in both of these 
methods is to leave the cell nuclei faintly colored, but not so much so as to conceal the 
clusters of more deeply stained bacilli. 
PARATYPHOID. 
The study of a number of cases of disease resembling typhoid fever 
has revealed a class of organisms of the colon-typhoid group which are 
pathogenic for man and of which three types, separable by their cultural 
and agglutination peculiarities, have been recognized. The organism 
most frequently found is distinguished as paratyphoid B; this incites a 
disease closely resembling typhoid fever, but running usually a some- 
what shorter clinical course. In another group of infections, usually 
following the eating of spoiled food, the symptoms are those of an acute 
gastroenteritis; while in still a third type the symptoms more closely 
resemble those of cholera. In all cases the bacilli are usually found in 
the blood. The agglutinative reactions of these organisms show to a 
high degree the so-called group agglutinins, the organisms of groups other 
than that causing the infection being agglutinated by the patient's serum 
in ordinary dilutions, and the specific agglutination for the invading 
organism appearing only when very high dilutions are used. 
The disease is not very common in the United States except in the 
military camps. In these situations it has not infrequently occurred in 
persons who have been vaccinated against typhoid fever, and in conse- 
quence at the present time the soldiers are vaccinated also against both 
paratyphoid A and paratyphoid B organisms. The protection offered 
does not seem to be as lasting or as complete as that conferred by typhoid 
vaccination. 
As the organisms do not form a distinct group and the clinical 
symptoms of the disease differ so greatly, it is to be expected that the 
pathological findings are not wholly characteristic. The lesions are 
frequently very small in extent, but occasionally there is swelling and 
ulceration of the Peyer's patches, enlargement of the spleen, Zenker's 
degeneration of muscle fibers, and other changes which are usually seen 
in cases of typhoid fever.1 
DYSENTERY. 
This form of infectious colitis is regularly associated with and doubt- 
less incited by bacilli of the colon-typhoid group. One of these is the 
1 Schottmuller, Deutsch, med. Wchnschr., 1900, xxvi, 511; Wells and Scott, Jour. Infect. Dis., 1904, 
i, 72; Saltykow, Virchows Arch., 1913, ccxi, 467; Uhlenhuth and Hubener, Kolle and Wassermann, 
Handbuch d. path. Mikroorganismen, 2d ed., 1913, iii, 1005 (bibl.); and Gay, Typhoid Fever, New 
York, 1918. For bacteriological studies of paratyphoid bacilli and methods of differentiating organisms 
of the paratyphoid-enteritidis group, see Proescher and Reddy, Jour. Am. Med. Assn., 1909, lii, 470, 
Arch. Int. Med., 1910, v, 263 (bibl.); and Krummede, Pratt, and Kohn, Jour. Med. Research, 1916, 
N. 8. xxix, 355; 1916-17, N. 8. xxx, 55, 357; 1917, N. S. xxxi, 509; 1918, N. S. xxxiii, 89. 278 
THE INFECTIOUS DISEASES 
organism originally described by Shiga1 which has long carried his name; 
in addition, three other types have been described,2 which are separated 
by their fermentation reactions. The organisms are found also in cases 
of summer diarrhea among children. The infection is often severe, 
with a high degree of intoxication. 
The lesions of the disease vary from a slight catarrhal inflammation 
to a diffuse pseudomembranous or gangrenous inflammation of the wall 
of the gut (see page 769).3 
The disease is transmitted probably through contamination of food 
and water. Healthy and convalescent carriers have been found, even 
up to 50 per cent, of those who suffer from an attack of the disease. 
Good therapeutic results have been reported from the use of polyvalent 
sera. The diagnosis of the type can as a rule be made by agglutination 
reactions, but as these are often not very strong it is sometimes neces- 
sary to fall back upon cultural methods.4 
ASIATIC CHOLERA. 
Asiatic cholera is a disease incited by the growth and proliferation 
in the intestines of a slightly curved or spiral-shaped bacterium, which 
is called the cholera spirillum-Spirillum choleras, asiaticce {Vibrio choleras 
asiaticoe). This organism in the early and active stages of the disease 
may be present in enormous numbers in the contents of the small intes- 
tine, often penetrating the mucosa. It is usually confined to this situa- 
tion. Its deleterious effects upon the body appear to be largely due to 
the production of toxic substances, which on absorption, in addition to 
serious intestinal irritation or lesion, may incite those systemic disturb- 
ances which characterize profound toxemia. 
In addition to the action of the toxins the extraordinary desiccation 
of the body due to the enormous loss of fluid from the bowel and made 
evident by the polycythemia which exists, seems to play a very important 
part in the symptomatology and course of the disease. The passage 
of large quantities of alkaline fluid also increases the alkali deficit of the 
body with the production of an acidosis. Very successful therapeutic 
results have been reported from the use of intravenous infusions of large 
quantities of normal saline and of 4 per cent, sodium bicarbonate solu- 
tions. The first replaces the fluid lost, the second neutralizes any excess 
of acid. The benefits of the alkaline treatment have been especially 
evident in persons approaching the uremic stage in cholera.5 
Lesions of Asiatic Cholera. 
In some cases of cholera there are no definite changes to be found 
after death, and in no case are the lesions distinctive of this disease. 
1 Shiga, Centralbl. f. Bakteriol., Orig. I, 1898, xxiii, 599; xxiv, 817, 870, 913; Deutsch, med. 
Wchnschr., 1901, xxvii, 741, 765, 783. 
-Flexner, Bull. Johns Hopkins Hosp., 1900, xi, 39; Hiss and Russell, Med. News, 1903, Ixxxii, 289; 
Strong and Musgrave, Report, Surgeon General, U. S. Army, Washington, 1900. 
3 Lentz, O., Kolle and Wassermann, Handbuch d. path. Mikroorganisman, 2d ed., 1913, iii, 899 
(bibl.). 
4 Hiss, Jour. Med. Research, 1904-05, N. S. viii, 1. 
• Rogers, Lancet, 1917, ii, 745: see also Seilards, The Principles of Acidosis, Cambridge, 1917, p. 54. THE INFECTIOUS DISEASES 
279 
If death occur during the invasion of the disease or in the stage of 
collapse, the appearances in the more pronounced cases may be summar- 
ized as follows: 
The body may remain warm for some time, and the temperature 
may rise for a short time after death. The rigor mortis usually begins 
early and lasts for an exceptionally long time. The muscles sometimes 
exhibit a peculiar spasmodic twitching before the rigor mortis sets in, 
especially the muscles of the hand and arm. 
The skin is of a dusky gray color; the lips, eyelids, fingers, and toes 
are of a livid purple. The ends of the fingers are shrivelled, and 
the cheeks and eyes sunken. 
The Brain.-The sinuses of the dura mater are filled with dark, thick 
blood. The pia mater may be normal, or edematous, or ecchymotic. 
or infiltrated with fibrin. The brain is usually normal, but may be dry 
and firmer than usual. 
The lungs are retracted and anemic, the pleura may be dry or coated 
with fibrin. The heart is normal. The peritoneum may be dry or coated 
with a layer of fibrin. 
The stomach is usually unchanged, but may be the seat of catarrhal 
inflammation. In the small intestine there may be ecchymoses in the 
mucous membrane; the mucous membrane may be soft and edematous; 
there may be general congestion, or the congestion may be confined to 
the peripheries of the solitary and agminated nodules, and these nodules 
may be swollen; or there may be croupous inflammation and superficial 
necrosis. All these changes are usually most marked at the lower end 
of the small intestine. There is apt to be post-mortem desquamation of 
the epithelium. The characteristic rice-water fluid may be found in the 
intestines after death, or, instead of this, dark-colored, bloody fluid. 
The large intestine is usually normal, but in some epidemics croupous 
inflammation occurs in a considerable number of cases. 
The spleen may be soft, and normal in size or enlarged. The liver 
may show small areas of granular or fatty or hyaline degeneration. 
The kidneys are often increased in size, with white and thickened 
cortex and congested pyramids. The epithelium of the cortical tubes 
may contain coarse granules and fat globules, or be necrotic. The tubes 
may contain casts and disintegrated epithelium. The uterus and ovaries 
may be congested and contain extravasated blood. 
If the patient does not die until the stage of reaction, the body does 
not present the same collapsed appearance, and there are often inflam- 
matory changes in different parts of the body, especially in the larynx, 
the lungs, the stomach, and the intestines. 
Characters of the Cholera Spirillum. 
The cholera spirillum, which was discovered by Koch in IBS'S, is a curved rod with 
rounded ends, from 0.8 to 2.0 /z long, asporogenous, aerobic, and motile. When grow- 
ing under suitable conditions these rods are apt to cling together by their ends, forming 
S-shaped structures or spirals, often of considerable length (Fig. 153). The organism 
stains readily and grows abundantly on the ordinary culture media. The life period is 
short and various degenerative " involution" forms are apt to be present in old cultures. 280 
THE INFECTIOUS DISEASES 
It grows best at about blood heat, growth ceasing at about 16 C., but it may survive a 
reduction of the temperature to -10° C. It is quickly killed by drying or by the tem- 
perature of boiling water. Acids are inimical to its growth. It may retain its vi- 
tality for a considerable time in water. On moist surfaces, 
such as damp linen, earth, or vegetables, or in milk, it may 
rapidly proliferate. 
Pathogenesis.-The results of animal experiments 
with the cholera germ are not in themselves decisive in 
determining its relationship to this disease, since animals 
do not react in its presence as man does. However, the 
constant occurrence of this organism in Asiatic cholera, 
its absence from the body under other conditions, and 
the accidental laboratory infections which have several 
times occurred in men handling pure cultures of the 
germ, leave no doubt as to its significance as the excitant of this disease. 
Bacterial Diagnosis.-It is often of the highest importance to determine, at 
the earliest possible moment, whether or not a suspected case be one of Asiatic cholera 
or some other form of acute intestinal disorder, so that in the former case the proper 
measures may be instituted to prevent the spread of the disease. The characters 
which are developed in cultures of the cholera bacillus enable an expert bacteriologist 
to distinguish this organism from all other known forms. But the scope of this work 
does not permit a detailed description of the cultural peculiarities of the germ; and 
the responsibility of such determinations should not be assumed without adequate pre- 
liminary laboratory experience. By taking together the morphological and biological 
characters, it is possible, usually on the second or third day, to determine whether the 
intestinal contents in a suspected case do or do not contain the bacillus of Asiatic 
cholera.1 
Fig. 153.-Spirillum Chol- 
ER® ASIATIC.®. 
From a culture. 
Communicability.-Through milk or water or other uncooked food 
contaminated with the dejections of those suffering from Asiatic cholera, 
epidemics are lighted up and maintained. After drying, there appears 
to be relatively little risk from cholera discharges. Individual sus- 
ceptibility plays an important r61e in this as in many other infectious 
diseases. For during cholera epidemics the spirillum has been found 
in many instances in the stools of apparently healthy persons. Such 
"cholera carriers" seriously complicate the problems of public sanita- 
tion and quarantine. The elements of susceptibility to Asiatic cholera 
are not yet understood, though it is commonly assumed that dietetic 
indiscretions and gastrointestinal disorders may be significant factors 
in the acquired disposition to the disease. 
A certain degree of temporary immunity is acquired through recovery 
from the disease. 
Toxic Products and Preventive Inoculation. 
Toxic Products.-The toxic substances formed by the cholera spiril- 
lum are apparently set free to some extent in soluble form, but are 
largely such as are stored in the bacterial cell itself-endotoxins. 
Pfeiffer has shown that the spirillum of Asiatic cholera, put into the 
peritoneal cavity of an artificially immunized guinea-pig, is quickly 
immobilized, swells and becomes granular, and soon disappears. A 
similar effect can be secured in tubes by a mixture of the immune serum 
1 For characters of the cholera organism, methods of diagnosis, etc., see Kolle and SchUrmann, 
Kolle and Wassermann, Handbuch d. path, Mikroorganismen, 2d ed., 1912, iv, 1. THE INFECTIOUS DISEASES 
281 
and fresh serum to which the spirilla are added. This lytic effect of 
the immune serum upon the bacteria may be used as a test of the specific 
character of a suspected spirillum; and, on the other hand, with a defi- 
nitely known spirillum the lytic action of the serum in a suspected case 
of disease may be valuable as a diagnostic aid. 
This bacteriolytic action of specific sera is not peculiar to the so- 
called anti-cholera serum, but has been observed in other cases-for 
example, in typhoid serum with the typhoid bacillus. Its nature and 
its bearing on immunity have been considered in an earlier section of 
this book (page 196). 
Agglutinative substances which may be of value in diagnosis, are also 
developed in Asiatic cholera. 
Preventive Inoculation.-A large amount of work has been done 
rooking toward artificial immunization of man against Asiatic cholera 
in the East, and preventive inoculation practised by the method of 
Haffkine appears to have given encouraging results. This method con- 
sists in the subcutaneous injection of cultures of the cholera bacillus; 
first, those whose virulence has been diminished, and then, those in 
which the virulence has been exalted by artificial means. 
But the Haffkine preventive inoculation with living cultures has 
been in a large measure superseded by the injection of a small amount 
of a fresh agar culture killed by heat. The dose is repeated after a few 
days. There is moderate local and general reaction to the injections. 
The serum of persons thus twice injected, after two or three weeks, may 
show the development of bactericidal substances exceeding in efficiency 
those present during convalescence from the disease. Such an active, 
artificial immunity may last for many months. The practical result 
of this form of preventive inoculation on a large scale in Japan has been 
a considerable reduction in the proportion of cases in the protected 
groups, as compared with others similarly exposed, as well as a reduction 
in the mortality of those who in spite of the protective attempt contracted 
the disease.1 
Other Spirilla Resembling the Cholera Spirillum. 
There are several fairly distinct forms of spirilla, some of which appear to be 
related to the cholera organism, which have been occasionally found in various situa- 
tions. One of these is the so-called Vibrio proteus or spirillum of Finkler and Prior. 
This organism was found by these observers in the dejecta of persons suffering from 
cholera nostras, shortly after the discovery by Koch of the cholera spirillum, which 
at first it was thought closely to resemble. The cultural characters, however, abun- 
dantly suffice to differentiate the organisms. The Vibrio proteus is slightly pathogenic 
for certain lower animals, but not for man. 
Several forms of spirilla of somewhat similar general characters have been found 
in various situations; thus in cheese, by Denecke, S. tyrogenum; in a chicken epidemic 
and in sewage, by Gamaleia and by Pfuhl, Vibrio metschnikovi; in the dejecta during 
a cholera epidemic at Massawah, Vibrio massawah, etc. 
1 For a study of protective inoculations against Asiatic cholera, see Hetsch, Kolle and Wassermann, 
Handbuch d. path. Mikroorganismen, 2d ed., 1912, iv, 110. 282 
THE INFECTIOUS DISEASES 
Tuberculosis is an infectious disease characterized by inflammatory 
and necrotic processes in the body and incited by the presence and 
growth of the Bacillus tuberculosis (tubercle bacillus). The most dis- 
tinctive morphological feature of tuberculosis is the development under 
the influence of the tubercle bacillus of larger and smaller, gray or white 
or yellow, firm or friable masses of tissue called tubercles. 
The effect on the body-cells of the presence and growth of the tubercle 
bacillus varies considerably, depending upon the number and virulence 
of the germs present, the character of the tissue in which they lodge, 
and the vulnerability of the individual. In general, it may be said 
that tubercle bacilli may stimulate the connective-tissue cells in their 
vicinity to proliferation; or they may excite emigration of leucocytes 
from blood-vessels and lead to the production of other exudates; or 
they may cause death of tissue. Thus the phases of inflammation 
which are excited by the tubercle bacillus are productive, exudative, 
and necrotic. The tubercle bacillus may incite these changes separately 
or simultaneously, in the sequence just indicated or in some other; 
and now one, now another of them may preponderate. 
TUBERCULOSIS.1 
Morphology of the Lesions of Tuberculosis 
Tuberculosis manifests itself most often in the form of an inflamma- 
tion affecting some one part of the body, as the lungs and bronchial 
lymph-nodes (the parts most frequently involved in adults), the gastro- 
intestinal tract, or the skin-"localized tuberculosis." In a considerable 
proportion of cases the local lesions induced by the tubercle bacillus 
are in the form of circumscribed nodules or masses of new-formed cells 
or tissue which are called tubercles, or, if small, miliary tubercles.2 
Such a localized tuberculosis may retain throughout the characters 
of a local inflammation, or it may be accompanied by the clinical evi- 
dences of systemic infection. It may give rise through metastasis to 
the successive development of tuberculous inflammations in other parts 
of the body, or to a sudden development of small foci of tuberculous 
inflammation in many parts of the body at the same time-general 
miliary tuberculosis. 
A general infection may occur by the diffusion through the body of 
bacilli derived from a local tuberculosis, such as tuberculous phlebitis 
1 Some authors are disposed to class together, under the name Infectious Granuloma, lesions in- 
duced by microorganisms, certain phases of which are characterized by a localized, usually slow, nodular 
growth tending to necrosis. The more important of these are tuberculous, leprous, syphilitic, and 
actinomycotic. It may be doubted whether it is wise to group together, under a name suggesting 
tumor relationships which do not exist, lesions of such diverse origin and clearly of infectious character. 
2 The term miliary tubercle, which arose from the coincidence in size between small foci of tubercu- 
lous inflammation and some forms of millet seed, is now very liberally applied to tubercles which are 
very much larger as well as to those which are very much smaller than millet seeds. It is convenient 
to designate a small mass of new tissue formed under the influence of the tubercle bacillus, whatever its 
minute structure, as a tubercle granulum (see Fig. 155). Very frequently two or more tubercle granula 
are joined together by a more diffuse formation of tubercle tissue to form larger or smaller miliary 
tubercles-conglomerate tubercles (see Fig. 156). THE INFECTIOUS DISEASES 
283 
or arteritis, or tuberculous inflammation of the thoracic duct (Fig. 154), 
or from the breaking into a vessel of a tuberculous lymph-node. It is 
probably seldom that tubercle bacilli enter the blood-channels at one time 
in sufficient quantity to account for the enormous numbers of tubercles 
which are sometimes found in acute general miliary tuberculosis; but it 
is not unlikely that, from the newly formed tubercles which develop in 
the walls of the smaller blood-vessels, new distributions of bacilli may take 
Fig. 154.-Tuberculosis of the Thoracic Duct. 
From a case of generalized miliary tuberculosis. 
place from time to time as the tubercles mature. This probability is 
sustained by the frequent occurrence of miliary tubercles on the intima 
of the small arteries in the lung for example, as well as by the evidence 
of differences in age of the individual tubercles in generalized miliary 
tuberculosis.1 
Diffuse Tuberculosis.-In many cases, however, the lesion is not focal 
or circumscribed but diffuse, and more or less widely infiltrates or re- 
places the tissues involved. This is called diffuse tuberculous inflammation. 
Miliary Tubercles.-Miliary tubercles are small nodules of irregular 
shapes (Plates VI, VIII, and IX), the smallest hardly visible to the 
1 It is well, in the endeavor to understand the occurrence of general miliary tuberculosis or of the 
less striking instances of distribution of the bacilli, to remember that two varying factors are constantly 
active and significant: first, the virulence of the bacilli, which may be slight or extreme; and, second, the 
vulnerability of the infected individual-i.e., his "predisposition"-which also may be slight or ex- 
treme. Thus the distribution of bacilli, be these few or many, from an infective focus, may be in dif- 
ferent individuals or at different times in the same individual of quite different significance. For a 
r6sum6 of the discussion as to the sudden or gradual origin of miliary tubercles see Ribbert, H., Deutsch, 
med. Wchnschr., 1906, xxxii, 5. Silvergleit, H. (Virchows Arch., 1905, clxxix, 283), was able by careful 
searching to find a vascular tubercle, most frequently in the pulmonary veins, occasionally in the thor- 
acic duct, aorta, and other vessels, in about 95 per cent, of the cases of miliary tuberculosis examined 
by him. 284 
THE INFECTIOUS DISEASES 
naked eye. The smaller tubercles are gray and translucent; the larger 
are usually, especially in the central parts, opaque and white or yellow 
on account of the necrosis which is apt to commence here. 
In studying the reaction of the living tissues to the tubercle bacillus 
it should be always borne in mind that while, as a whole, the lesions 
produced are quite characteristic, there is still no one structural feature 
or combination of features of tubercles or tuberculous inflammation 
which is absolutely distinctive of the action of this bacillus. In doubtful 
cases the demonstration of the presence of the germ itself may be neces- 
sary for the establishment of the character of the lesion.1 This is espe- 
This is growing in the liver and is composed mostly of new-formed polyhedral cells closely packed 
with little intercellular stroma. At the center, coagulation necrosis is commencing. 
Fig. 155.-A Small Miliary Tubercle. 
cially true in certain hypertrophic tuberculoses of the large intestine, and 
the procedure may be necessary also when the number of tubercle bacilli 
present is so small that a very slight and quite uncharacteristic reaction 
takes place. 
The experimental studies in animals, as well as the morphological 
data gathered from the examination of tuberculosis in man, show that 
when tubercle bacilli in moderate numbers lodge and develop in the 
living body one of the early local effects is a proliferation of the connective- 
tissue, endothelial, and reticular cells.2 These become larger and poly- 
hedral, with conspicuous nuclei (Fig. 155). 
A new reticulum or stroma may form hand-in-hand with the growth 
1 The term tubercle tissue, which is in common use, indicates a tissue formed under the influence 
of the tubercle bacillus rather than a tissue which is morphologically characteristic of tuberculosis in 
distinction from other forms of new tissue. 
2 The studies of W echsberg indicate that in some cases, at least, the first effect of the tubercle bacillus 
upon the living tissue is destructive, so that the characteristic cell proliferation which follows may not 
be altogether due to a direct formative stimulus to cell proliferation furnished by the bacillus. See 
Wechsberg, F., Zieglers Beitr., 1901, xxix, 203; also Herxheimer, G., ibid., 1903, xxxiii, 363 (bibl.), and 
Herxheimer and Roth, ibid., 1916, Ixi, 1. THE INFECTIOUS DISEASES 
285 
of these new cells, or the old stroma may persist, adapting itself in form 
and arrangement to the new conditions. 
Either after the connective-tissue cell proliferation or hand-in-hand 
with it, or preceding it, or altogether independently of it, emigration of 
leucocytes and extravasation of serum may take place from blood- 
vessels in the vicinity of the germs. During the more or less active 
cell proliferation which occurs under the influence of the tubercle bacillus, 
multinuclear cells-giant cells-may be formed (Fig. 156), either by 
persistent nuclear division in growing protoplasmic masses which do 
not divide into separate cells; or by the coalescence of the bodies of cells 
already formed. The former view of giant-cell formation is the one now 
most generally accepted.1 Such cells may be produced with great rapid- 
This tubercle is of the conglomerate type, made up of four granula, the larger one showing coagu- 
lation necrosis in the central portion. From the peritoneum. 
Fig. 156.-A Miliary Tubercle with Giant Cells. 
ity, only thirty-six hours being required to form a miliary tubercle with a 
giant cell and surrounding epithelioid cells in experimental tuberculosis 
in the rabbit's liver. In this situation giant cells form from the so-called 
Kupffer cells lining the sinusoids. Within half an hour after the inocu- 
lation of tubercle bacilli, cellular reactions have been found in the inter- 
lobular capillaries. The polymorphonuclear leucocytes contain relatively 
few bacteria, but many of the Kupffer cells contain organisms. The poly- 
morphonuclear leucocytes disappear at the end of half an hour and by 
this time mitotic figures are frequent in the Kupffer cells. 
More or less new tissue with numerous small spheroidal mononuclear 
cells and little stroma may form in and about the tuberculous foci. 
Blood-vessels are not apt to develop under the influence of the tubercle 
bacillus. Old blood-vessels are, on the other hand, usually obliterated 
as the new tissue forms. 
Sooner or later under the influence of the tubercle bacillus, there is 
usually a damage of cell and tissue, which may lead to coagulation 
necrosis in the new-formed as well as in the old tissue of the infected 
1 Herxheimer and Roth, Zieglers Beitr., 1916, Ixi, 1; Evans, Bowman, and Winternitz, Jour. Exper. 
Med., 1914, xix, 283. 286 
THE INFECTIOUS DISEASES 
region. This necrosis is more apt at first to manifest itself in the central 
portions of the tuberculous foci (Fig. 157) and may progress outward; 
the nuclei may become fragmented or disappear, or fail to stain in the 
usual way, the protoplasm may become more homogeneous; and cells 
and stroma may form at last an irregularly granular mass of tissue detritus 
which tends to disintegrate (coagulation necrosis, cheesy degeneration, 
caseation, see page 69), forming cavities or, if on free surfaces, ulcers. 
Showing polyhedral cells, small spheroidal cells, and giant cells, with coagulation necrosis at the center. 
Fig. 157.-A Miliary Tubercle in the Lung. 
As coagulation necrosis progresses, the tubercle masses lose the gray 
translucent appearance which in their early stages they are apt to pre- 
sent to the naked eye and become more opaque and of yellowish white 
appearance at the centers. 
Finally dense fibrous tissue may form in and about foci of tuberculous 
inflammation, encapsulating or sometimes entirely replacing the more 
characteristic new-formed structures.1 It is in this way-by the forma- 
tion of connective tissue-that such repair as is possible after local tuber- 
culous inflammation is brought about (Fig. 429, page 710). 
Forms of Tubercles.-Before the discovery of the tubercle bacillus 
and while knowledge of the lesions of tuberculosis was largely limited 
to their morphology, it was natural that much stress should be laid upon 
the variety in structure which the nodular growths called tubercles 
1 Langhans' original paper contains interesting observations on the morphology of tubercles, and 
especially on the type of giant cell which bears his name. See, Langhans, Th., Virchows Arch., 1868, 
xlii, 382. THE INFECTIOUS DISEASES 
287 
present, and that elaborate classifications and groupings of tubercles 
were often deemed important. 
With an exact knowledge of the excitant of the new growths and of 
the varying phases of their development in the body, the morphological 
peculiarities of tubercles are not now to be regarded as of such extreme 
significance, since they for the most part indicate simply variations in 
the local effect of a definite poison. These variations are due, as we have 
seen, to differences in the amount and intensity of the poison, to the degree 
of susceptibility of the individual, to the structure of the particular 
tissue or organ involved, and to the extent and variety of local complica- 
tions caused by other agencies. 
Fig. 158.-Exudative Form of Tuberculous Inflammation Showing Tubercle Bacilli. 
From the lung of a child. The size of the bacilli has been slightly exaggerated in the cut. 
It is, however, usually convenient and sometimes important to recog- 
nize structural types in miliary tubercles. Thus they may be composed 
wholly of small spheroidal cells-"lymphoid tubercles," or of larger poly- 
hedral cells-"polyhedral-cell tuberclesor of both forms of cells 
together and with or without a new-formed stroma; or of any of these 
combinations with giant cells. Then coagulation necrosis, which may 
occur in tubercles of any type; development of new dense connective 
tissue; association with various phases of simple exudative inflamma- 
tion-all of these contribute to the variety in the structural types of 
miliary tubercles. 
Diffuse Tuberculous Inflammation (Diffuse Tubercle).-1. If the 
infection with tubercle bacilli be extensive, or if step by step the bacilli 
are distributed in the tissues about the primary seat of infection, con- 
siderable amounts of tubercle tissue of one or other form may develop 288 
THE INFECTIOUS DISEASES 
and pass into the condition of coagulation necrosis, so that at length 
large necrotic masses, with a comparatively small amount of well- 
defined tubercle tissue, either diffuse or in the form of granula, may alone 
remain to indicate the character of old and slowly progressive local 
infection. This form of lesion is found in the large tuberculous masses 
in the brain, in the mucous membrane of the bronchi, in large flat masses 
on the serous membranes, and in the diffuse, cheesy infiltration of the 
lymph-nodes, kidneys, ureters, bladder, prostate, testicle, and uterus. 
These large areas of tuberculous inflammation are apt to be white or 
yellow in the central and necrotic portions, which are sometimes dense, 
compact, and hard, sometimes soft and friable. These areas are not 
infrequently surrounded by an irregular gray zone of tubercle tissue or 
by a dense fibrous-tissue capsule. 
2. In marked contrast with the phase of diffuse tuberculous inflam- 
mation just described, though often associated with it, is that in which 
the formation of inflammatory exudates is a prominent feature. This 
exudative form of tuberculous inflammation is best exemplified in the 
Fig. 159.-Tubercle Bacilli in Sputum from a Case of Pulmonary Tuberculosis. 
Showing the bacilli stained with fuchsin, and pus cells stained for contrast with methylene blue. 
lungs by some of the forms of acute phthisis (page 714). The tubercle 
bacillus is under certain conditions markedly pyogenic, and when it 
rapidly develops in the air spaces of the lungs or suddenly gains access 
to them in large quantities, pus, serum, fibrin, and exfoliated or pro- 
liferated epithelial cells may collect in and largely fill the air spaces, and 
then the whole new exudate and the old lung tissue may, over larger or 
smaller areas, rapidly undergo coagulation necrosis (Plates X and XII). 
Thus in one phase of tuberculous inflammation the intensity and 
rapidity of the local poisoning by the bacillus do not permit of the 
formation of organized new tissue at all, but only of exudative products 
which are apt soon to become necrotic (Fig. 158). Less intense degrees 
of exudative inflammation are liable to develop in the vicinity of miliary 
tubercles anywhere in the body. 289 
THE INFECTIOUS DISEASES 
The Bacillus tuberculosis is a long, slender bacterium varying in length from 2 to 
4 /i (from one-quarter to one-half the diameter of a red blood-cell) and in breadth from 
0.2 to 0.5 fi. It is frequently more or less curved, and the individual bacilli may cling 
together end to end, forming threads or chains. It may occur in branching forms? 
The bacillus (Fig. 159) is stained with difficulty by the aniline dyes (see below), and 
when stained often presents an irregular beaded or knobbed appearance, due to an 
unevenness in the coloring of the protoplasm, or to involution changes. It is immobile, 
and spores have not been demonstrated in it. 
Characters of the Tubercle Bacillus 
Fig. 160.-Culture of Tubercle Bacillus 
on Glycerin Agar. 
Fig. 161.-Culture of Tubercle Bacillus 
on Glycerin Agar. 
From tuberculosis in man. 
From tuberculosis in bird. 
At the temperature of the body it can be grown on many of the artificial culture 
media. The growth of the tubercle bacillus in cultures is very slow in comparison with 
that of most of the pathogenic microorganisms. After several weeks' growth it forms 
dry, scaly masses or thin, wrinkled pellicles on the surface of the media (Fig. 160 and 
161). It requires a certain amount of oxygen for its growth, and thrives best in the 
dark. 
1 Branching forms of the tubercle bacillus have been frequently seen, and while their significance 
is not yet altogether clear, the tendency at this time is to separate this organism with the diphtheria 
bacillus and the so-called streptothrix or actinomyces forms into a group called higher bacteria. 
Whether, as many think, they are more closely allied to the moulds than to the bacteria, or whether, 
they should be considered in a class by themselves, is a problem still unsolved. For the present, we 
may wisely consider the tubercle bacillus as one of the bacteria. 
For studies and bibliography on this subject consult Schulze, Ztschr. f. Hyg. u. Infectionskrankh, 
1899, xxxi, 153; and Lubarsch, ibid., p. 187. 290 
THE INFECTIOUS DISEASES 
When brought in direct contact with various chemical disinfectants it is readily 
killed, but when inclosed in mucus, as in sputum, it may be quite resistant. If in a 
thin layer and not protected by glass, it is killed by an exposure of a few minutes to 
direct sunlight. If in dust, however, and protected from light, individual bacilli 
may retain their viability for a long time.1 In the moist condition, the bacilli may be 
killed by an exposure of ten to fifteen minutes to 70° C. 
Cultures can be continued indefinitely from generation to generation with a slowly 
diminishing virulence which finally is largely lost. Under certain conditions the 
virulence may be restored or enhanced by successive inoculations into susceptible 
animals. 
The tubercle bacillus does not, so far as we know, grow in nature outside of the 
bodies of men and certain warm-blooded animals. It is thus apparently strictly 
parasitic. 
Inoculation of various animals, especially of guinea-pigs, rabbits, and monkeys, 
may be followed by lesions similar to those of man. 
Methods of Staining the Tubercle Bacillus. 
In Fluids.-For the examination of fluids, such as sputum,2 etc., the material 
should be spread in a thin layer on a cover-glass, dried in the air, and then passed thrice 
through the flame 
While, as has been said above, the tubercle bacillus is stained much less easily with 
the aniline dyes than are most bacteria, it can be deeply colored by the use of accessory 
agents which intensify the stains or render the protoplasm of the bacilli more accessi- 
ble to them. But when once stained the tubercle bacillus clings with great tenacity to 
its color in the usual decolorizing agents. 
A variety of methods are in vogue for staining the tubercle bacillus, Ziehl's 
solution being the most useful. This is made by adding to a 5 per cent, aqueous 
solution of carbolic acid about one-tenth its volume of saturated alcoholic solution 
of fuchsin. This carbolic fuchsin will keep unchanged for a long time. 
The prepared cover-glass is floated in a watch-glass or porcelain capsule-speci- 
men side down-on this coloring fluid, and gently heated almost to boiling for from 
three to five minutes. 
The entire specimen is thus completely stained, tubercle bacilli, tissue elements, 
and other bacteria which may be present, all in the same way. The next step is to 
remove the color with acid from all the structures which may be intermingled with 
the tubercle bacilli; the latter, owing to the tenacity with which they retain the stain, 
being but slightly affected. This is done by dipping the cover-glass into an aqueous 
or alcoholic solution of 5 per cent, sulphuric acid, and shaking it about for a few 
seconds. Under the influence of the acid the specimen on the cover-glass loses its red 
color and becomes gray or colorless. It is then thoroughly rinsed in three or four suc- 
cessive portions of alcohol, and finally in wrater. By this manipulation the red color 
may be to a slight extent restored. 
Care should be taken not to expose the specimen too long to the action of the acid, 
because then the bacilli also may be partially or completely decolorized. A little 
experience will enable the experimenter to judge of the proper time for the action of 
the acid. The specimens may be studied immediately after drying with the use of 
an oil immersion lens, or they may be mounted in balsam before examination. 
Inasmuch as some bacteria besides the tubercle bacilli not infrequently retain a 
slight red color, it is well, after the specimen is rinsed in water, to float the cover-glass 
for a few minutes in a dilute aqueous solution of methylene blue, which will replace 
the red color in all of the bacteria except the tubercle bacilli. There is thus secured 
a marked contrast between the tubercle bacilli, which are red, and other bacteria, 
which are blue. The contrast stain should not be intense. 
1 For a study of the viability of the tubercle bacillus, see Rosenau, Bull. No. 57, Hyg. Lab., U. S. 
Pub. Health and Mar.-Hosp. Serv., Washington, 1909. 
2 It is well in obtaining sputum for examination in cases of suspected pulmonary tuberculosis to 
secure that which has been raised during several hours, including the early morning discharge. THE INFECTIOUS DISEASES 
291 
Pappenheim's Method.-After staining in the hot carbol-fuchsin as above, the 
specimen is immersed, without washing, in a solution of 1 per cent, rosolic acid in 
95 per cent, alcohol saturated with methylene blue, to which 20 per cent, of glycerin 
has been added. After ten minutes in this solution the specimen is washed in water, 
dried, and mounted. By this method the tubercle bacilli are stained red, and the 
smegma bacilli (page 300), blue. 
In Sections.-Thin sections of tuberculous tissue which has been hardened in 
alcohol are stained in the same way, except that instead of drying and fixation by heat 
the sections are fixed to the cover-glass by means of the albumen fixative (see page 
1234), and then cover-glass and section are manipulated together. 
When differentiation is complete, the section is cleared in oil of origanum and 
mounted in balsam. 
For purposes of simple recognition of the bacilli in sections it seems to the writer 
usually better to have no color in the preparation other than that which the tubercle 
bacilli possess. But it is often convenient to demonstrate the nuclei of the cells at the 
same time, and this may be accomplished by staining lightly afterward with a dilute 
solution of some color which will contrast with that of the bacilli, such as methylene 
blue. 
In the examination of urine for the presence of the tubercle bacillus it is well to 
collect the sediment by means of a centrifugal machine. In the examination of milk 
or other fat-containing fluids for tubercle bacilli, it is well, after the film has been 
formed upon the cover-glass and before staining, to rinse with chloroform followed by 
alcohol, and this by water. 
Occasionally one finds in urine acicular crystalline bodies considerably resembling 
the tubercle bacillus in size and shape, and retaining a red color after the decolorization 
of the specimen. A careful study of the form, however, will suffice to prevent mistakes. 
The only other bacilli which are liable to be mistaken for the tubercle bacilli are 
the bacillus of leprosy and the so-called smegma bacillus which sometimes occurs be- 
neath the prepuce. The lepra bacillus may be distinguished from the tubercle bacillus 
by the following differential staining process: If the lepra bacillus be stained for ten 
minutes in a dilute alcoholic solution of fuchsin (five drops of saturated alcoholic solu- 
tion of fuchsin to 3 c.c. of water), and then rinsed for a few seconds in a solution of 
nitric acid (one part) in alcohol (ten parts), it will retain a red color, while under the 
same treatment the tubercle bacillus remains uncolored. 
Antiformin in Sputum Examinations.-Antiformin is a patented preparation 
containing sodium hydroxide and sodium hypochlorite. When mixed with sputum 
in such proportion that the antiformin is present in about 15 per cent, the sputum is 
softened and most bacteria except the tubercle bacilli are killed. After the softening 
of the sputum it is diluted with water or alcohol and spun in the centrifuge, the sedi- 
ment is gathered and respun, and the final sediment is used for smears and stained in 
the usual way. By the use of antiformin and centrifugation a "concentrate" of the 
bacilli from sputum may be secured for diagnostic inoculation of guinea-pigs or for 
culture, if the use of alcohol as a diluent is avoided. 
Varieties of Tubercle Bacilli. 
While many of the lower animals are susceptible to inoculation with human tubercle 
bacilli, the organisms obtained from such animals may present noteworthy biological 
variations from the human type. Even so long ago as 1868, Villemin called attention 
to the fact that none of the rabbits inoculated with human tubercle presented so 
rapid and generalized a disease as that which was noticed when tuberculous material 
from the cow was used. More recently, Theobald Smith again called attention to 
the marked biological peculiarities which separate the bovine bacillus from the human 
type.1 
1 See Smith, Th., Jour. Med. Research, 1905, N. S. viii, 253; also Wolbach, S. B., and Ernst, H. C., 
Jour. Med. Research, 1903, N. S. v, 313 (bib!.); and Cobbett, The Causes of Tuberculosis, Cambridge, 
1917 (bibl.). 292 
THE INFECTIOUS DISEASES 
At present three groups are well recognized: the human, the bovine, and the avian 
types of organism,1 the last of which plays but a small part in human pathology. A 
fourth group, that known as the fish tubercle bacillus or tubercle bacillus of cold- 
blooded animals, is still somewhat doubtfully classed with the group of tubercle 
bacilli which occur in the mammalia. In other words, it has not yet been satis- 
factorily demonstrated that these tubercle bacilli of cold-blooded animals are the cause 
of certain pathogenic lesions with which they are associated. 
Of considerable importance in human pathology is the differentiation of the human 
and bovine types, as such determination not infrequently leads to a more or less com- 
plete demonstration of the source of the infection. The morphological characters 
of the two groups are quite similar. The tubercle bacilli of both types vary a great 
deal in length and diameter, and no constant difference has been determined which is 
of any value. There are, however, marked differences in the growth rate on suitable 
culture media. The human type of tubercle bacillus is eugonic, that is, it grows 
easily on suitable soil, while the bovine bacillus is dysgonic and grows very poorly 
as compared to its human relative. Nevertheless, after long cultivation on suitable 
media, the growth rate of the two approach each other, and the difference may be 
marked only in the primary culture. On blood serum to which 2 per cent, to 5 per 
cent, of glycerin has been added, the human strain grows very well, while the bovine 
strain grows with difficulty. This is probably due to the difference in their capacity 
for making use of glycerin. The same variation is observed with glycerin-agar on 
which the human type of bacillus ultimately grows very luxuriantly, while the bovine 
type never does. Glycerin-egg and glycerin-potato media also afford valuable means 
of differentiating the organisms, the same variations being shown. 
While these cultural differences are sufficient to enable an expert to distinguish 
the two types of organisms, a check is usually employed by the inoculation of an animal 
of differing susceptibilities to the two types. The most convenient is the rabbit, 
which is fairly resistant to infection with the human tubercle bacillus and very sus- 
ceptible to that with the bovine type. After intravenous injection of organisms of the 
latter form, the animal will often be studded with large and small tubercles, the size 
depending somewhat upon the length of time which it has been allowed to live after 
the injection; and this result can be obtained by the intravenous injection of not over 
0.01 mg. of tubercle bacilli from a pure culture. If a smaller quantity of human 
organisms is injected, the result may be minimal, and the animal will probably not 
die. Intraperitoneally 1 mg. of pure culture may be employed in this differential 
inoculation. 
Toxic Products of Tubercle Bacilli. 
While there is evidence that some soluble toxic substances are given 
off from the tubercle bacillus in its growth.and activities, it is to its 
specific body protein that its chief poisonous capacities seem to be 
linked.2 
It has been found that tubercle bacilli which have been killed by 
boiling or otherwise, when introduced into the body of the rabbit either 
beneath the skin, or into the serous cavities, or into the blood-vessels 
and the air spaces of the lungs, are capable, as they slowly disintegrate, 
of stimulating the cells of the tissues where they lodge to proliferation, 
and to the production of new tissue morphologically similar to tubercle 
tissue in its various phases3 (Fig. 162). Necrosis of the new-formed 
1 For bibliography of animal tuberculosis, see Eber, A. Lubarsch u. Ostertag, Ergebn, d. allg. Path., 
1917, xviii,2 1 (bibl.). For a study of avian tuberculosis, see Hastings, Halpin, and Beach, Jour. Infect. 
Dis., 1913, xiii, 1; also Himmelberger, Centralbl. f. Bakteriol. I. Abt., Orig., 1914, Ixxiii, 1. 
2 For a study of certain toxic products of the tubercle bacillus, see White, B., and Avery, 0. T., Jour. 
Med. Research, 1912, N. S. xxi, 317. 
3 For further details concerning the effects of dead tubercle bacilli in the body, see Prudden and 
Hodenpyl, New York Med. Jour., 1891, liii, 637, 697; and Prudden, ibid.,liv, 617. See also Herxheimer, 
Zieglers Beitr., 1903, xxxiii, 363 (bibl.); and Miller, J., Jour. Path, and Bacteriol., 1905, x, 351 (bibl.). THE INFECTIOUS DISEASES 
293 
cells may occur, but this differs in some respects from the coagulation 
necrosis induced under the usual conditions. Dead tubercle bacilli 
are also markedly chemotactic and capable of causing local suppuration 
and abscess. 
It would seem probable then that while the power of the tubercle 
bacillus to induce necrosis and the fever which, in many cases, indicates a 
systemic intoxication, may be due to metabolic products of the living 
germ, the local lesions characteristic of exudative and productive inflam- 
mation may be due to a peculiar bacterial protein which is set free by 
the disintegration of the bacilli in the tissues. But the products of 
autolysis in the necrotic tissue cells may contribute to the toxemia. 
It is not improbable that, in addition to the protein of the tubercle 
bacillus, the waxy substance which the cell body contains plays an im- 
portant part in determining the morphology of the lesion produced by 
the organism.1 
Fig. 162.-Inflammatory Nodule (Pseudotubercle) in the Liver of the Rabbit Induced 
by the Intravenous Injection of Dead Tubercle Bacilli. 
Most of the dead bacilli have disintegrated, setting free the bacterial protein which has stimulated the 
new cell growth. A few fragments of the bacilli, however, still remain. 
Agglutinating Substances. 
The serum of tuberculous animals and men may contain agglutinating substances. 
The reaction, however, frequently fails and is not at present of much diagnostic value. 
Complement Fixation. 
The use of the method of complement fixation2 has been developed recently as a 
means of diagnosis, and is of great value as indicating only an active and fairly ex- 
1 Morse, P. F., and Stott, E., Jour. Lab. and Clin. Med., 1916, ii, 159. 
2 Craig, C. F., Jour. Am. Me4- Assn., 1917, Ixviii, 773; Miller, H. R., ibid., 1916, lxvii, 1519; Jour. 
Lab. and Clin. Med., 1916, i, 816; and Burns, Slack, Castleman, and Bailey, Jour. Am. Med. Assn. 
1917, Ixviii, 1386. Brown, L., and Petroff, S. A., Amer. Rev. Tuberculosis, 1918, ii, 525. 294 
THE INFECTIOUS DISEASES 
tensive process. Reactions are not given in the case of latent foci as with the allergic 
tests, which are so sensitive as to be of but little value except as excluding tuberculosis. 
A good deal of the success of the method seems to depend upon the choice of a 
proper antigen. The most efficient so far obtained appears to be that prepared by 
grinding the tubercle bacilli with table salt in a suitable container until the organisms 
are thoroughly disintegrated, and then adding distilled water to isotonicity. 
When the tubercle bacillus is grown on glycerinated nutrient broth certain meta- 
bolic products are formed and pass into solution in the fluids. If after some weeks of 
vigorous growth the germs are separated by filtration and the broth is concentrated 
by evaporation, a dark brown fluid results which is called tuberculin. This substance 
-at one time believed by many, and still by a few observers, to possess distinct cura- 
tive properties in certain forms of tuberculosis-has assumed great economic impor- 
tance on account of its value as a diagnostic agent in bovine tuberculosis. For if 
administered subcutaneously in small quantity to cattle a marked temperature re- 
action follows in tuberculous animals, while those which are sound are unaffected. 
The existence of even very slight lesions may be detected in this way. In man also 
tuberculin has proved of value in cases in which the efforts to establish a diagnosis 
by the usual methods have failed. The new tuberculin "T. R." contains the dead 
bodies of tubercle bacilli.1 
The cutaneous tuberculin test of von Pirquet2 consists in the application of a small 
quantity of Koch's original tuberculin to a superficial abrasion of the skin. The skin 
of the forearm is cleansed with alcohol and dried, and three abrasions are made, about 
two inches apart. A drop of undiluted tuberculin is then placed on the upper and 
the same amount on the lower abrasion, the excess being wiped off with cotton at the 
end of ten minutes. The middle abrasion serves as a control. In a negative reaction, 
which indicates that the patient has no tuberculosis, there is no change in the color 
of the treated areas as compared with the control. If the patient is tuberculous a 
reddening appears in twenty-four to forty-eight hours, which in a very severe reaction 
may go on to vesiculation. In persons with very active tuberculosis the reaction 
may be only infiltration with but little or no redness. 
Tuberculin. 
Immunity and Therapeutic Use of Tuberculin in Tuberculosis. 
The fact that so large a percentage as from sixty to ninety of human beings dying 
from all causes have been shown by autopsies to have been at some period and in 
some measure affected with tuberculosis, while the mortality from tuberculosis as com- 
pared with death from all other causes is not far from fourteen per cent, indicates 
that man enjoys a marked degree of natural immunity to the incursions of the tubercle 
bacillus. The clinical data are not very convincing as to the acquirement of increased 
immunity after successfully coping with the disease. However, experiments on 
animals, those of Trudeau and others, showed that by the repeated inoculation of 
small doses of tubercle bacilli of attenuated virulence, rabbits may be largely pro- 
tected, though not rendered wholly immune, from the full effect of later injections of 
virulent bacilli. By intravenous injections of some product or derivative of the tuber- 
cle bacillus, Behring has apparently succeeded in rendering young cattle highly, and 
it is claimed permanently, immune. Similar results have been obtained by others.3 
Many attempts have been made to secure artificial immunity in man either by 
the injection of products of the growth of the tubercle bacillus, or by the use of the 
dead bodies of the bacilli. Wright and his followers have reported marked success in 
the use of a form of tuberculin which contains the bodies of the dead bacilli, especially 
1 For a r6sum6 of various tuberculin preparations, see Hiss and Zinsser, Text-book of Bacteri- 
ology, 5th ed., New York, 1922, 
2 von Pirquet, Berl. klin. Wchnschr., 1907, xliv, 699. 
3 See review of animal immunization against tuberculosis, Pearson, Second Ann. Rept. of the Phipps 
Inst., 1905, p. 311. THE INFECTIOUS DISEASES 
295 
in localized tuberculosis. This is administered in accordance with the indications 
of a rise or fall of the "opsonic index" of the serum (See page 213), determined by the 
degree of phagocytosis, the opsonic index marking the immunizing effect of the in- 
jection. Trudeau also obtained favorable results from artificial immunization with 
dead bodies of the bacilli, "T. R.," controlling the administrations of the very potent 
agent by careful clinical observations. 
Altogether, then, it appears that a certain measure of active artificial immunity to 
tuberculosis may be secured in man. Attempts to secure passive immunity in tuber- 
culosis by alleged antitoxic sera do not seem to have been notably successful.1 
Complex Factors in the Tuberculous Process. 
It is well in studying the characters of tuberculous inflammation to remember 
that in its progressive phases there are two factors at work: first, those which lead 
to cell proliferation and new tissue formation, which is apparently a reparative and 
conservative process; second, those which are inhibitory or damaging or destructive; 
and, also, that both sets of factors are commonly active together. It may still be 
considered doubtful whether the tubercle bacillus furnishes a direct formative 
stimulus, or whether such is furnished by damaged cells, or whether the cell pro- 
liferation may not be an expression of reparative activity in the presence of damaged 
tissue made possible by disturbed organic control (see page 383). In any event the 
new tissue which forms under the influence of the tubercle bacillus apparently owes 
its morphological as well as'biological characteristics to impulses toward tissue forma- 
tion which are exerted in the presence of agencies-doubtless poisons-restraining 
within narrow bounds the new connective-tissue growth, no matter how extensive or 
persistent this may be, and tending constantly to its destruction. 
It is interesting in this connection to note that when lesions in many respects 
similar to those of the ordinary tuberculosis are induced experimentally in animals 
with dead tubercle bacilli (see above), the poisonous substances leading to necrosis 
are not produced continually and for indefinite periods, as is the case in infection 
with living bacilli, but are soon exhausted, so that after a certain amount of initial 
necrosis the new tissues go on to develop in the usual reparative wray, blood-vessels 
are formed, and healing by a cicatrix under favorable conditions regularly takes place. 
It is probable that effective healing in tuberculosis in man takes place only after 
the local production of destructive poison ceases through the death or complete lysis, 
or, at any rate, the diminished virulence of the tubercle bacilli present. 
On the other hand, it is important to bear in mind that while the formation of 
new cells and tissue on the part of the body in tuberculosis marks a protective adapta- 
tion to new and harmful conditions, the tubercle bacilli themselves are also subject to 
adaptive changes which on their side are protective. Thus, through what has been 
called selective adaptation of both host and microbe, a condition of balanced para- 
sitism may be brought about in which there may be a reduced mortality, but not a re- 
duced morbidity, since in the processes of adaptation the microbe has won capacities 
for harm which may be very potent and significant in individuals not adapted to it.2 
The Number of Tubercle Bacilli in Lesions. 
The number of bacilli which are present in the lesions of tuberculosis 
is subject to great variation. They are usually abundant in the walls 
and contents of phthisical cavities, and in tubercle tissue which is under- 
going cheesy degeneration and disintegration. In these situations they 
may be found in myriads, forming sometimes a large part of the disin- 
1 See for the bearing of the parasitism of the tubercle bacillus on infection and immunity Th. Smith 
Jour. Am. Med. Assn., 1906, xlvi, 1247. 
For an admirable review of our knowledge of some problems of tuberculosis, see Th. Smith, Jour. 
Am. Med. Assn., 1917, Ixviii, 669. 
2 For a consideration of the mutual relationship of microbe and host, see Th. Smith, Jour. Am. Med. 
Assn., 1906, xlvi, 1247. 296 
THE INFECTIOUS DISEASES 
tegrated mass. They are found in cells and scattered among them. 
Sometimes they are present in considerable numbers in the giant cells of 
miliary tubercles. In the acute general tuberculosis of children they 
are often present in large numbers, particularly in the lungs (Fig. 158). 
They may be found in tuberculous inflammation in any part of the body, 
and are occasionally demonstrable in the blood. The demonstration 
of tubercle bacilli in the circulating blood can be made in a small propor- 
tion of cases of tuberculosis other than those of the miliary type.1 In 
the latter, tubercle bacilli can be found in about 65 per cent, of cases.2 
The bacilli are constantly discharged in the sputa of patients suffering 
from pulmonary tuberculosis, often in enormous numbers-from one 
to four billion in twenty-four hours, according to Nuttall's estimate- 
and their presence sometimes affords valuable diagnostic aid in early 
stages or in obscure forms of the disease. 
The number of bacilli required to infect man is not known; but in 
the case of a susceptible animal, such as a small guinea-pig, for instance, 
the inhalation of from five to twenty bacilli is sufficient to set up a tuber- 
culous process. On the other hand, the feeding of as many as 20,000 
bacilli has failed to cause an infection in the same animals.3 
Under a variety of conditions, especially in the older tuberculous 
lesions, the bacilli may not be demonstrable. This apparent occasional 
absence of the bacilli is probably due either to their disappearance as 
the process grows older or to some unknown changes which interfere 
with the ordinary staining procedures. Much has introduced a special 
modification of Gram's staining method by which granules may be demon- 
strated in tubercle tissue not showing bacilli with the ordinary technique.4 
On the other hand, tuberculous lesions of characteristic morphology 
containing easily demonstrable bacilli may not give rise to infection when 
injected into animals nor yield bacteria to culture, the organisms evidently 
being dead. This occurrence is most frequent in the cervical and peri- 
toneal lymph-node tuberculoses of children, due very often to the bovine 
type of bacillus. The bronchial nodes usually give positive results after 
animal inoculations and the organisms so obtained are of the human 
type. 
Frequency of Tuberculosis in Man and the Lower Animals. 
Tuberculosis is a very common disease not only of man5 but also of 
many of the lower animals, especially of cattle, and inasmuch as the 
1 For a study of tubercle bacilli in the blood, see Anderson, Bull. No. 57, Hyg. Lab., U. S. Pub. 
Health Serv., Washington, 1909: KlopstocK and Seligmann, Ztschr. f. Hyg., 1913, Ixxvi, 7; and Klemp- 
erer, Berl. klin. Wchnschr., 1914, li, 436. 
2 Clough, M. C., Bull. Johns Hopkins Hosp., 1917, xxviii, 363. See, however, Austrian, C. R., and 
Hamman, L., ibid., 1915, xxvi, 293. 
3 See Findel, Ztschr. f. Hyg. u. Infectionskrankh., 1907, Ivii, 104; and Pfeiffer and Friedberger, 
Deutsch, med. Wchnschr., 1907, xxxiii, 1577. 
4 Much, H., Berl. klin. Wchnschr., 1908, xly, 691. See, also, Hiss and Zinsser, Text-book of Bac- 
teriology, 5th edition, New York, 1922, p. 588 
6 Carefully prepared statistics show that tuberculous lesions are present in more than 90 per cent, 
of bodies examined at autopsies. See for a thorough and suggestive analysis of five hundred autopsies 
Naegeli, O., Virchows Arch., 1900, clx, 426; also Keeker, Verhandl. d. deutsch. path. Gesellsch., 1904, 
viii, 129. For a study of frequency of tuberculosis in children, see Winkler, Verhandl. d. deutsch. path. 
Gesellsch., 1904, viii, 118. 297 
THE INFECTIOUS DISEASES 
victims of this disease, both men and animals, are apt, as stated above, 
to throw off enormous numbers of the bacilli in the sputum and other 
excreta, the germ is widely dispersed in inhabited regions, especially in 
buildings frequented by uncleanly tuberculous persons or by infected 
cattle. 
Among the lower animals, guinea-pigs, rabbits, monkeys in confine- 
ment, and cattle are particularly susceptible to the action of the tubercle 
bacillus. Although tuberculosis is widespread in man, he is not, as 
compared with some of the lower animals, particularly susceptible. 
While the tuberculous process presents some differences in different 
animal species in rate of development, amount of necrosis, tendency to 
softening, calcification, etc., the fundamental effects are similar in man 
and in the lower animals. 
Portals of Entry, Distribution of Lesions, and Sources of the 
Tubercle Bacilli. 
Portals of Entry and Distribution.-The question of the chief portals 
of entry of the tubercle bacillus has given rise to much discussion and 
much experiment. So far as concerns the lungs, in which tuber- 
culosis is common, it has been assumed that infection is most frequently 
direct, the bacilli gaining access through the respiratory passages to 
the alveoli. Others have contended that lung infection is most often 
secondary to the entrance of the bacilli through the gastrointestinal 
canal with or without local lesions. Still others believe that tuber- 
culosis of the lung is commonly secondary to tuberculous lesions of the 
bronchial lymph-nodes, or that the bacilli may enter through the tonsils, 
or that they often enter through the placenta. To the advocates of 
the latter views the blood-vessels and lymphatics play a predominant 
rdle in the distribution of the infective agents. 
While it is probable that all of these portals of entry are of importance, 
it would seem well established that direct inhalations are the most 
frequent occurrence, while entrance through the intestinal mucosa is 
very common, especially in infancy.1 
We may assume, then, that the tubercle bacillus most frequently 
enters the body through the respiratory organs, including tonsils and 
pharynx, and through the gastrointestinal canal. Traumatic infection 
through the skin is of relatively infrequent occurrence, as is apparently 
the congenital transmission.2 
1 For a full discussion of this subject, see Lubarsch, Fortschr. d. Med., 1914, xxii, 669, 701. For 
experimental tuberculosis in young guinea-pigs with reference to portals of entry, see Bartel and Spieler, 
Wien. klin. Wchnschr., 1905, xviii, 155; 1906, xix, 25. For a resumS of studies on the tubercle bacillus 
and its portals of entry, see Baumgarten, Verhandl. d. deutsch. path. Gesellsch., 1906, ix, 5; Aufrecht, 
Pathologic und Therapie der Lungenschwindsucht, Vienna, 1908; Ravenel, Am. Jour. Med. Sc., 1907, 
cxxxiv, 469. For mode of tubercle bacillus infection in young, see Westenhoeffer, Berl. klin. Wchnschr., 
1904, xli, 153 and 191. For intestinal origin of pulmonary tuberculosis, see Calmette and Guerin, Ann. 
de 1'Inst. Pasteur, 1905, xix, 601; and Calmette, Med. Rec., 1908, Ixxiv, 741. For a study of mode of 
infection of the lungs by way of the mouth and pharynx, see Beitzke,,H„ Virchows Arch., 1906, clxxxiv, 1. 
2 For a study of placental and congenital tuberculosis, see Warthin and Cowie, Jour. Infect. Dis., 
1904, i, 140. 298 
THE INFECTIOUS DISEASES 
In adults the lungs, in children the bronchial lymph-nodes, are the 
most frequent seat of tuberculous lesions.1 
Many observations on the occurrence of tuberculous bronchial, 
cervical, and mesenteric lymph-nodes in persons exhibiting no appre- 
ciable tuberculous lesions elsewhere would indicate the frequency of 
access of the bacilli to the lymph-channels without primary lesion at 
the portal of entry in the pharynx, tonsils, respiratory passages, intes- 
tinal mucosa, or elsewhere (see page 675). A considerable percentage 
of persons dying from other diseases have been found to have tuberculous 
lesions, often healed, in the lungs or bronchial lymph-nodes. 
Sources of Tubercle Bacilli.-Tubercle bacilli are frequently trans- 
mitted to the well from the victims of tuberculosis by means of the 
sputum which is cast off and allowed to dry, and becoming pulverized 
is then inhaled as dust. 
But this source of infection is perhaps not as significant as was 
formerly believed from analyses of material gathered from walls and 
floors of contaminated rooms. For it has become clear that not all the 
infectious material which may be cast out of the body as sputum is 
always readily and speedily transformed into dust. In the drying of 
the mucus with which much of this material is mingled, a process ordi- 
narily rather slow, the bacteria are closely imprisoned so that only 
under certain conditions, such as the rubbing and beating of soiled 
clothing, the shuffle and tread of feet over contaminated floors, dry 
sweeping, and the like, is the excretion sufficiently comminuted to float 
in the air as dust. Even when this is the case, it has been found that a 
large part of such pulverized excreta is still in too large particles to 
remain long suspended in the air. 
This condition of affairs was not appreciated in the earlier studies 
on dust infection, and in many instances the material called dust, col- 
lected in various places for analysis, was evidently not in such form as 
would have remained long in suspension. Thus it is that while the 
earlier identification of various pathogenic microorganisms in the dust 
of rooms was correct, the inference as to the constant risk of dust infec- 
tion in such places was frequently at least somewhat overestimated. 
On the other hand, Fliigge and others2 have found that not only in 
sneezing and coughing, but also in ordinary speech, the secretions 
of the nose, mouth, and throat may be cast forth in considerable quantity 
for a distance of several feet, not only in the form of visible droplets, 
but as a more or less abundant, invisible spray, which may remain sus- 
pended for from half an hour to several hours, and may be carried for 
long distances on such slowly moving air currents as are common in 
inhabited rooms. 
Thus, fully virulent, infectious material may be transmitted directly 
through the air in coughing and sneezing, indirectly through dried 
1 For studies in the frequency, localization, and modes of dissemination of tuberculosis, with special 
reference to its occurrence in the lymph-nodes and during childhood, see Harbitz, Jour. Infect. Dis., 
1905, ii, 143 (bibl.). For a study of localization in infants and young children, see Wollstein, Arch. 
Int. Med., 1909, iii, 221. 
2 For the studies of Fliigge and his assistants, see Ztschr. f. Hyg. u. Infectionskrankh., 1899, xxx, 
107; 1901, xxxviii, 1. THE INFECTIOUS DISEASES 
299 
infectious sputum ground to dust and floating in the air. Less fre- 
quent is the conveyance of tubercle bacilli through soiled utensils. 
The transmission of this germ through contaminated milk1 and the 
meat of tuberculous cattle2 is a mode of infection of great importance, 
especially when such contaminated milk is taken by young children. 
Whichever way the tubercle bacilli enter the body, whether directly into the 
lungs, or by the pharynx or tonsils, or through the intestinal mucosa, or in rarer cases 
through wounds or through the placenta, they are transported by the blood- and 
lymph-vessels to lymph-nodes or to the tissues, where they lodge and grow and incite 
the formation of tubercles. These, again, if in the blood- or lymph-vessels when 
they soften and set the bacilli free by ulceration into the channels, afford fresh foci of 
distribution. So that in cases of disseminated tuberculosis the process of distribution 
is more or less gradual. In the meantime the progress of the lesions dependent in their 
topography upon the fortuitous character of the distribution of the infective agent is 
marked by the protective adaptation of the body-cells expressed by the formation of 
the tubercles and the development of immunizing substances; while, on the other 
hand, the bacillus itself is undergoing these adaptative modifications of its own bio- 
logical characters which are expressed in what we call its virulence. 
Statistics show, as we have seen, that in the majority of cases in man the pro- 
tective agencies of the body suffice to localize the lesions, surround the bacilli by 
necrotic masses in which they do not flourish, or inclose them in a fibrous envelope. 
Thus it appears that it is largely the chances of a wide or a continued distribution of 
the infective agent, or an unusual susceptibility of the host, or exalted virulence of the 
bacilli, or the occurrence of fresh infection, that makes tuberculosis now and then so 
formidable a malady to man. 
While it is not impossible that future research may lead to the development of 
effective methods of artificial immunization to tuberculosis, it is to preventive meas- 
ures that we must look for the largest success in the suppression of this scourge of the 
human race. By proper disposal of the sputum; by providing against aerial disper- 
sion of infective material through unguarded coughing and sneezing; and by such intelli- 
gent methods of cleaning and disposal of dust as shall safeguard the respiratory organs; 
together with an enlightened supervision of the supplies of meat and milk, it should 
be possible even in crowded communities largely to reduce both the morbidity and 
the mortality of tuberculosis.3 
Concurrent Infection in Tuberculosis. 
A concurrent infection with the tubercle bacillus and the pyogenic 
microorganisms is of extreme significance in that phase of tuberculous 
inflammation of the lungs commonly called phthisis.4 While the so- 
called cold abscesses may be caused by the tubercle bacillus alone, this 
1 Many cases of infection of human beings, especially of children, with bovine bacilli, have been 
reported and in children abdominal tuberculosis and tuberculosis of the cervical lymph-nodes are most 
frequent. Park estimates that about 10 per cent, of tuberculosis in children under five years is due to 
bovine infection. See, for tables of observation, Park and Williams, Pathogenic Microorganisms, 6th 
ed., New York, 1917, p. 377-8; for a most comprehensive study of the question of types of organism 
and portals of infection, Cobbett, The Causes of Tuberculosis, Cambridge, 1917; and for study of bovine 
and human types of tubercle bacilli, Pork, W. H., and Krumwiede, C., Jour. Med. Research, 1910, 
N. S. xviii, 205; 1912, N. S. xxii, 109. See also Lewis, Jour. Exper. Med., 1910, xii, 82; Mitchell, P., 
Brit. Med. Jour., 1914, i, 125; and Fraser, Jour. Exper. Med., 1912, xvi, 432. 
2 See Kober, Am. Jour. Med. Sc., 1903, cxxvi, 684 (bibl.). For the intercommunicability of human 
and bovine tuberculosis, see Ravenel, Proc. Path. Soc., Philadelphia, 1902; also r6sum6 by Bovaird, 
Med. Rec., 1905, Ixvii, 283. 
3 For a study of tubercle bacilli on books, see Mitulescu, Ztschr. f. Hyg. u. Infectionskrankh., 1903, 
xliv, 397. 
For a study on flies and tuberculosis, see Lord, Boston Med. and Surg. Jour., 1904, cli, 651. 
4 See Spengler, Ztschr. f. Hyg. u. Infectionskrankh., 1894, xviii, 343 (bibl.); and Prudden, New 
York Med. Jour., 1894, lx, 1. 300 
THE INFECTIOUS DISEASES 
germ is not infrequently found under these conditions to be associated 
with other pyogenic microorganisms, especially the streptococcus and 
staphylococcus. In addition to the concurrent infection of the tissues, 
organisms of the streptococcus, staphylococcus, and pneumococcus groups 
may occasionally be demonstrated in the circulating blood of persons 
suffering from active pulmonary tuberculosis.1 
Bacteria Resembling the Tubercle Bacillus. 
There are several species of bacteria which after deep staining resist the decoloriz- 
ing action of dilute acids. These have been called, collectively, acid-resisting or 
acid-proof bacteria.2 We shall consider only two of these. 
The Smegma Bacillus.-This organism is often present and sometimes in large 
numbers in the preputial smegma and elsewhere about the external genitals. It so 
closely resembles the tubercle bacillus in size, shape, and staining reactions that it is 
liable by morphological examinations alone to be mistaken for it. It has been culti- 
vated on artificial media and is not pathogenic. The smegma bacillus, when stained as 
above recommended for the tubercle bacillus, resists the decolorizing action of the 
acid; but it is usually decolorized by prolonged exposure to alcohol, thus differing 
from either the tubercle bacillus or the leprosy bacillus. But this color reaction is not 
certain; individual bacilli not infrequently remain unstained. Various special 
methods for differentiation have been suggested.3 In doubtful cases, and when 
serious operative procedures are dependent upon the bacterial diagnosis, recourse 
should be had to animal inoculations. 
The "Hay Bacillus."-This resembles the tubercle and smegma bacilli in form 
and staining peculiarities. It is called the " hay bacillus " or " grass bacillus " because 
of its common occurrence upon grass-heads in the fields. It is not pathogenic and is 
readily cultivated. 
Similar organisms have been frequently found in milk and butter, also in the 
sputum in gangrene of the lung. 
Lupus and Other Forms of Tuberculosis of the Skin. 
Local tuberculous inflammation of the skin may occur in the form of small nodules 
or wart-like thickenings, as the result of accidental inoculation. Local skin infection 
may occur about the orifices of the body in tuberculous persons from contact with 
secretions or excretions containing the tubercle bacilli, or about sinuses leading to 
tuberculous abscesses, joints, etc., or in the vicinity of tuberculous lymph-nodes. 
A chronic form of tuberculous inflammation which presents special clinical features 
has long been known under the name of lupus. 
Lupus.-This form of inflammation most frequently occurs in the skin of the face, 
but also in the mucous membrane of the mouth, pharynx, conjunctiva, vulva, and 
vagina. The lesion consists of small, multiple nodules of new7-formed tissue, in the 
cutis or mucosa and submucosa. By the formation of new nodules and a more diffuse 
cellular infiltration of the tissue between them the lesion tends to spread, and by the 
confluence of the infiltrated portions a dense and more or less extensive area of nodular 
infiltration may be formed. There may be an excessive production and exfoliation 
of epidermis over the infiltrated area, or an ulceration of the new tissue. 
Microscopical examination show's the lesion to consist of small spheroidal cells in- 
termingled with variable numbers of larger, polyhedral cells and cell masses, and in 
1 Brown, L., Heise, F. H., and Petroff, S. A., Trans. 9th Ann. Meeting National Assn, for Study and 
Prevention of Tuberculosis, 1913. 
2 See for r6sum6 and bibliography Abbott and Gildersleeve, Tr. Assn. Am. Phys., 1902, xvii, 37; also 
Rosenberger, Proc. Path. Soc., Philadelphia, January, 1904. 
3 For a critical review, see Dahms, Jour. Am. Med. Assn., 1900, xxxiv, 983 (bibl.). Consult also 
Cowie, Jour. Exper. Med., 1900, v, 205 
For the method of Pappenheim, which is said to be more reliable than the alcohol decolorization, 
see p. 291. THE INFECTIOUS DISEASES 
301 
many cases giant cells (Fig. 163). In some cases a well-marked reticulum is present 
between the new cells, and these are often grouped in masses around the blood-vessels. 
In some cases there is, without previous ulceration, a formation of new connective tis- 
sue in the diseased area, and a well-marked cicatrization; in other cases the cells and 
intercellular substance undergo a disintegration which leads to ulceration. Tubercle 
bacilli in small numbers may be found in these lesions. In the clinical group of dis- 
eases called lupus there are other forms of lesion which are not incited by the tubercle 
bacillus 
Fig. 163.-Lupus of Face. 
Bibliography of Tuberculosis. 
The announcement of the discovery of the Bacillus tuberculosis by Koch was made 
in the Berliner klinische Wochenschrift, 1882, xix, 221. A most elaborate and valu- 
able article on the same subject by Koch is contained in the Mittheilungen aus dem 
Kaiserlichen Gesundheitsamte, 1884, ii, 1. 
In the large work of Straus, La Tuberculose, Paris, 1895, the experimental aspects 
of the subject are fully considered. 
In the work of Cornet, Die Tuberculose, Vienna, 1907, together with the general 
and clinical consideration of the disease, the modes of infection and prophylaxis are 
set forth, with bibliography. See also Kolle and Wassermann, Handbuch der 
path. Mikoorganismen," 2d ed., 1913, v., 391-746. An excellent summary of the 
tubercle bacillus and its biological characters is in Kolle and Hetsch, Die Experi- 
mentelle Bakteriologie und die Infectionskrankheiten, 3d ed., Berlin, 1911. An ex- 
tremely important work is the Handbuch d. Tuberkulose, edited by Brauer, Schroder, 
and Blumenfeld, Leipzig, 1914. One of the most valuable recent sources of informa- 
tion on the biology of the tubercle bacillus is Cobbett, The Causes of Tuberculosis, 
Cambridge, 1917. 302 
THE INFECTIOUS DISEASES 
LEPRA (Leprosy). 
Leprosy is characterized by the development of nodular and some- 
times diffuse masses of tissue, consisting of larger and smaller cells of 
various shapes-spheroidal, fusiform, and branched, with a fibrous 
stroma-the whole somewhat resembling granulation tissue. The new 
tissue is most frequently formed in exposed parts of the skin, as the 
Fig. 164.-Tubercular Leprosy. 
face, hands, and feet, but it may occur in the skin of any part of the 
body. It is formed more rarely in the subcutaneous connective tissue, 
in interfascicular connective tissue of nerves, in the viscera, and in the 
mucous membranes. The mucous membranes most frequently affected 
are those of the eye, nose, mouth, and larynx. The nodules may be 
very small or as large as a walnut, and may be single or joined together THE INFECTIOUS DISEASES 
303 
in groups or masses. The tissue of the part in which the new formation 
occurs may be atrophied and replaced by, or may remain intermingled 
with, the leprous tissue, or it may be hyperplastic. The nodules may 
persist for a long time without undergoing any apparent change, or they 
may soften and break down, forming ulcers; but ulceration, except in 
the mucous membranes, is said usually to occur as the result of injury 
or unusual exposure. The leprous tissue may change without ulceration 
into cicatricial tissue, or cicatrization may follow ulceration. 
Various secondary lesions and disturbances of nerve function are 
associated with the formation of leprous tissue in the nerves and central 
nervous system, and lead to various types of neuritis, perforating ulcers 
of the sole of the feet, etc. 
In all the primary lesions of leprosy, bacilli are said to be present, 
mostly in the cells, and particularly in the larger transparent spheroidal 
forms, but sometimes free in the intercellular substance. The bacilli 
have been found in the skin, mucous membrane of the mouth and 
larynx, in peripheral nerves, in the cornea, in cartilage, in the testicles, 
kidney, liver, and in the blood and lymph-nodes. Sometimes the cells 
contain but few bacilli, but they are frequently crowded with them.1 
Characters of the Lepra Bacilli.2 
The bacilli are from 4 to 6 /z long and very slender. They are sometimes pointed 
at the ends and sometimes present spheroidal swellings (Fig. 165). In their-com- 
portment toward staining agents, as well as in 
general morphological characters, they consider- 
ably resemble the Bacillus tuberculosis, but they 
are more readily stained. They may be stained 
with fuchsin or gentian violet by the ordinary 
method, or by the method employed for staining 
the tubercle bacillus (see page 290). 
Cultures and Pathogenesis.-Various reports 
of success in the artificial cultivation of the lepra 
bacillus have been made, the organisms de- 
scribed being separable into four groups: diph- 
theroid bacilli, acid-fast chromogenic bacilli, anaerobic acid-fast bacilli, and acid-fast 
non-chromogenic bacilli. The problem is complicated by the fact that a variety of 
organisms is undoubtedly present in the tissues in leprosy; and the possibility that 
the disease is due to more than one organism in symbiosis must be considered.3 
The structure of the new tissue growth, the absence of coagulation 
necrosis, and the peculiar grouping of the bacilli in the large transparent 
cells are characters which usually clearly distinguish the lesions caused 
by the leprosy bacillus from those of tuberculosis. 
Leprosy is common in India and in other hot countries. It is infre- 
quent in America, but in the Gulf States, in Mexico, among the Nor- 
wegians in the Northwest, and in the eastern British provinces a con- 
Fig. 165.-The Bacilli of Leprosy. 
From a nodule in the skin, showing the 
bacilli free and within cells. 
1 A valuable article on leprosy is that by Sticker, G., Mense, Handbuch d. Tropenkrankheiten, 2d 
edition, Leipzig, 1914, iii, 1. 
2 The Bacillus leprae was first discovered by Hansen in 1874, and reported by him in Virchows 
Arch., 1880, Ixxix, 32. 
3 For a critical review of the'bacteriology of human and rat leprosy, see Wolbach and Honeij, 
Jour. Med. Research, 1913-14, N. S. xxiv, 367 (bibl.). See also Johnston, Philippine Jour. Sc., 1914, 
ix, 3. 304 
THE INFECTIOUS DISEASES 
siderable number of cases are grouped. Isolated cases are, however, 
encountered now and then in various parts of the United States.1 
Communicability.-So long as the leprous tissue is intact the bacilli 
are closely inclosed by it. But when necrosis and ulceration occur, as on 
the skin or the mucous membranes, the bacilli may be widely distributed; 
from ulcerated nodules in the nose and pharynx, for example, in sneez- 
ing and coughing. But even persons exposed to infective exudates are 
so seldom infected that when infection does occur one is forced to assume 
special predisposing factors which we do not understand. Under 
proper sanitary conditions leprosy is not to be regarded as readily 
communicable.2 
SYPHILIS. 
It has been found convenient to consider the lesions of syphilis as 
occurring in three stages, primary, secondary, and tertiary. These 
stages may perhaps mark epochs in the development of the infective 
agent or phases in the protect- 
ive action of the body-cells in 
the course of their adaptation 
to the parasitic organism; or, 
finally, the stages of syphilis 
may bear some relationship to 
the adaptive processes of the 
infective organism itself. 
It may be said in general 
that the characteristic lesions of 
syphilis consist in a more or 
less circumscribed formation of 
new tissue. This may be made 
up largely of small spheroidal 
cells or of these with polyhedral 
cells (Fig. 166), and of occa- 
sional giant cells. The new 
tissue, which may be diffuse or 
in more or less clearly circumscribed masses, contains, as a rule, few 
blood-vessels, and is prone to undergo coagulation necrosis. This 
tendency is most pronounced in the circumscribed masses. 
The endothelial cells of the blood-vessels in and near the inflammatory 
foci in this form of inflammation are not infrequently swollen and may 
proliferate (Fig. 166 and 167, B). The vessels may otherwise undergo 
extensive changes. 
Primary Lesions.-At the point of inoculation in a few weeks a focus 
of inflammation develops-the initial sclerosis. This may be in the 
form of a papule or a vesicle, and in either case erosion of the surface is 
Fig. 166.-New-formed Tissue in Syphilitic 
Inflammation. 
From a hard chancre, showing swollen endo- 
thelium in a small blood-vessel. 
1 See Brinckerhoff, Present Status of the Leprosy Problem in the United States, Pub. Health and 
Marine Hosp. Serv., Washington, 1908. 
2 For bibliography of leprosy, consult Jadassohn, Kolle and Wassermann, Handbuch d. path. 
Mikroorganismen, 2d ed., 1913, v, 771. THE INFECTIOUS DISEASES 
305 
apt to occur and a hardening of the deeper tissues, leading to the so- 
called chancre. In this primary lesion, in addition to more or less 
fluid and cellular exudate, there may be obliterating endarteritis, a 
small spheroidal-cell infiltration of the connective tissue, proliferation of 
connective-tissue cells, especially near the blood-vessels (Fig. 168), 
swelling of the vascular endothelium, and an occasional development 
of giant cells. This new tissue may become fibrous and the initial 
lesion may heal. 
Fig. 167.-Section of a Portion of a Syphilitic Condyloma of the Mucous Membrane. 
A, Edematous papilla; B, swollen endothelial cells in small blood-vessels of a papilla; C, pus cells 
in the submucous connective tissue; D, pus cells in the epithelium; E, disintegration of the epithelium 
in the superficial portion of the mucous membrane. 
Usually in connection with, or following the development of, the 
initial lesion there is a hyperplasia of the lymph-nodes belonging to the 
anatomical district of the lesion, which become hard and swollen. These 
hyperplastic lymph-nodes, called buboes, are not apt to suppurate except 
as the result of concurrent infection with pyogenic bacteria, and the 
swelling gradually subsides. 
Secondary Lesions.-After six or seven weeks the so-called secondary 
stage of syphilis, now called constitutional syphilis, is entered upon. 
This is characterized by various forms of eruption on the skin and 306 
THE INFECTIOUS DISEASES 
mucous membranes-macules, papules, and pustules. Periostitis is not 
infrequent. At this period there often develop on the mucous membranes 
or where these join the skin, circumscribed areas of exudative and pro- 
ductive inflammation of the papillary layers with necrosis and exfolia- 
tion of the epithelium. The papillae are enlarged, the epithelium swollen 
and opaque. These local areas of inflammation and necrosis are called 
mucous patches. Of similar character are the elevated areas of the skin 
common about the generative organs in secondary syphilis, called con- 
dylomata. Here also there is at the base the characteristic cell prolifer- 
Fig. 168.-Section from a Primary Syphilitic Nodule of the Mucous Membrane of thh 
Mouth. 
Showing collections of cells about the blood-vessels in the submucous tissue. 
ation with swelling of the papillae and thickening and exfoliation of the 
epithelium, and there may be an abundant infectious exudate from the 
surface. 
Tertiary Lesions.-One of the most characteristic phases of the 
tertiary inflammations of syphilis is the formation in the periosteum 
or in the viscera, especially in the liver, lungs, heart, brain, and kidney, 
of masses of new tissue called gummata. THE INFECTIOUS DISEASES 
307 
The smaller gummata consist of a mass of small spheroidal and epi- 
thelioid cells (see Fig. 169). As these cell masses grow larger they are 
apt to become necrotic and caseous at the center, and we may then 
have, as seen by the naked eye, a grayish white, usually firm mass, with 
a more or less dense and irregular granular center and a translucent, 
often radially striated border of dense fibrous tissue (see Fig. 170). In 
the early stages, giant cells of the Langhans' type may be present in 
small numbers. 
Fig. 169. 
Fig. 170. 
Fig. 169.-Small Nodule of Syphilitic Inflammation (Miliary Gumma) in the Liver. 
Fig. 170.-Syphilitic Gumma in the Liver. 
Showing necrotic caseous center merging into the new-formed cellular and fibrous tissue in the 
periphery. This gumma was much larger and is much less magnified in the cut than that in Fig. 169. 
Gummata vary in size from those invisible to the naked eye to 
those several centimeters in diameter; they are usually single, but may 
be multiple, and occasionally several coalesce. The border zone of the 
gumma usually consists of granulation or fibrous tissue and may be 
regarded as due to the reparative reaction of the surrounding tissues. 
The necrotic portions of gummata may be absorbed and the whole 
replaced by a mass of cicatricial tissue; or strands of fibrous tissue inclos- 
ing irregular islets of caseous material may long persist at the original 
seat of the gummata. In some instances the syphilitic inflammation 
may be diffuse, with or without marked necrosis. In the lungs, the 
liver, and the walls of the arteries the later stages of syphilitic infection 
may be marked by the diffuse formation of fibrous tissue. 
Congenital Syphilis.-The lesions of congenital syphilis are those of 
the secondary and tertiary stages, and may be present at birth or develop 
at a later period. Various phases of malnutrition are often obvious. 
There may be pemphigus of the hands and feet or elsewhere, with vesicles 
or blebs containing variously colored or bloody fluid. Pustules, usually 
about the buttocks, various erythematous rashes, coryza, inflammations 308 
THE INFECTIOUS DISEASES 
of the bones, joints, and cornea, etc., are frequent. Irregularities in 
the ossification of the long bones (page 1066), gummata and cirrhosis of 
the liver, enlargement of the spleen, various inflammatory and degener- 
ative lesions of the kidney, and obliterating endarteritis are among the 
more common marks of congenital syphilis. 
Diagnosis.-The nodular lesions of syphilis are in many respects 
structurally similar to those of tuberculosis, so that it is sometimes 
difficult to distinguish them on morphological examination alone. But 
the greater variety in the developmental stages of the tuberculous foci 
which may be found in a single individual, the grouping of the lesions 
in a manner indicative of local infections, and in the last resort the 
demonstration of the presence of the tubercle bacillus, will usually suf- 
fice to distinguish the tuberculous from the syphilitic lesion, even with- 
out recourse to the clinical history. 
For further details regarding syphilitic lesions of the viscera see 
Part II. For many details regarding syphilis, its symptomatology and 
lesions, its effects upon gestation and the infant, etc., reference is made 
to special works on the subject.1 
Animal Inoculations.-It has been shown by Metchnikoff and Roux2 
and by Neisser,3 that successful inoculations of apes may be made with 
the virus of syphilis. It has been found that while cutaneous inocula- 
tion with material from primary and secondary lesions gives positive 
results, subcutaneous and intraperitoneal introduction of similar mate- 
rial does not. Rabbits also have been successfully inoculated.4 
Treponema pallidum (Spirochaeta pallida).-In 1905 Schaudinn and 
Hoffmann5 described the occurrence in primary lesions of syphilis of a 
slender, spiral organism (Fig. 171 and 172) of about the length on the 
average of the diameter of a red blood-cell, which they called Spirochceta 
pallida. It is sharply curved, corkscrew like, having from three to ten 
or more curves, and is pointed at the ends. It is mobile, rotating on 
the long axis, and moving in both directions. This organism, at first 
called Spirochaeta, was afterward renamed Treponemal 
The Treponema pallidum is stained with difficulty by the ordinary 
reagents and is thus frequently difficult of detection. It may be mixed, 
especially when on the ulcerating surfaces of syphilides, with coarser 
and more readily stained spiral organisms, particularly Spirochceta 
refringens, and with various other saprophytic bacteria. It was first 
isolated in pure culture from animal and from human lesions by 
Noguchi.7 
1 For critical summary of syphilis with bibl. to date, see Lang and Ullmann, Lubarsch-Ostertag, 
Ergebn. d. allg. Path., 1898, v, 481; and Herxheimer, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1907, 
xi1, i; and 1908, xii, 499. 
For a study of blood-vessel changes in syphilis with bibl., see, Abramow, Zieglers Beitr., 1899, 
xxvi, 202. 
2 Metchnikoff and Roux, Ann. d'Inst. Pasteur, 1903, xvii, 809. 
' Neisser, Deutsch, med. Wchnschr., 1904, xxx, 1369, 1431; and Neisser and Baermann, ibid., 1905, 
xxxi, 48. 
4 Bertarelli, Centralbl. f. Bakteriol., Orig. I, 1906, xli, 320. 
6 Schaudinn and Hoffman, Arb. a. d. k. Gsndhtsamte., 1905, xxii, 527; also Deutsch, med. 
Wchnschr., 1905, xxxi, 711. 
8 For a discussion of the nomenclature of the organism, see Stiles, C. W., Jour. Am. Med. Assn., 
1917, Ixviii, 57; and Pusey, W. A., ibid., p. 139. 
' Noguchi, H., Jour. Amer. Med. Assn., 1911, Ivii, 102; Jour. Exper. Med., 1911, xiv, 99, 1912, xv, 90. THE INFECTIOUS DISEASES 
309 
The Treponema pallidum has been found in condylomata and in the 
primary macules, papules, and pustules, as well as in the internal organs, 
in the lymph-nodes of involved regions, in the spleen, adrenals, and liver, 
and in the blood. 
The organism has been found also in the secondary lesions of syphilis, 
even at a late period, and in tertiary lesions and in the brain in paresis. 
It also occurs, sometimes in large numbers, in the lesions of the skin and 
in the internal organs of the victims of congenital syphilis. 
It has been found possible by inoculating monkeys and rabbits, the 
latter preferably in the testicle, with human syphilitic material, to obtain 
characteristic lesions containing the treponema, 
and also to induce similar lesions with pure cultures 
obtained directly from human tissues. The blood 
of infected monkeys also gives the Wassermann 
reaction. There is, therefore, no longer any doubt 
that the organism is the inciting agent of syphilis. 
Its exact classificatory relationships are as yet a 
matter of discussion, but it is generally regarded 
as a special order of the protozoa.1 
The clinical results of infection with the 
Treponema pallidum have led to the suggestion 
that a number of strains may be included under 
the one name. In some cases there has been 
noted an extremely early involvement of the cere- 
brospinal nervous system, the organisms from 
these cases producing similar symptoms when 
transmitted to other persons. Other strains of 
the spirochete seem to cause extensive local 
lesions without any tendency to incite a cerebro- 
spinal syphilis. Slight differences in cultural characteristics and in the 
type of lesion produced in the testicular substance of rabbits also have 
been noted; but as yet the results cannot be considered as final.2 
Communicability.-The infective agent of syphilis is readily and most 
frequently conveyed in man by direct inoculation with the exudate from 
some lesion of a victim of the disease. This most frequently occurs 
during sexual intercourse, but may take place in many other ways, through 
either direct or indirect transmission of the infective exudate to 
abraded or wounded surfaces. 
Syphilis may also be congenitally transmitted, apparently from either 
the father or the mother. But the transmission of the infective agent 
through the placental blood is the more common. 
Immunization.-Though many attempts have been made to secure 
active and passive immunity, none has been successful. 
Fig. 171.-Treponema 
Pallidum. 
(Spirochaeta pallida.) India 
ink preparation. 
1 For cultural methods, see Noguchi, Jour. Exper. Med., 1912, xv, 90. For a general review with 
bibliography, see Sobernheim, G., Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 
1913, vii, 745; Doflein, Lehrbuch d. Protozoenkunde, 3d ed., Jena, 1911; Levaditi and Roche,(.La syphilis, 
Paris, 1909. 
2 Noguchi, Jour. Exper. Med., 1912, xv, 201; Nichols, H. J., ibid., 1914, xix, 362. 310 
THE INFECTIOUS DISEASES 
The material is most readily obtained from the primary ulcerated lesions by gently 
scraping with a platinum loop after a preliminary cleansing of the surface, or from 
mucous patches by a deep scraping with a sharp spoon. From papules, pustules, and 
roseolae one may obtain material by expressing fluid through a superficial incision; 
from lymph-nodes, by the hypodermic needle. 
Living Organisms.-By the use of the arc light and a special condenser for dark 
field illumination in a fresh preparation, one may see the refractile unstained spiral 
organisms in rapid motion across the dark field. 
Staining.-Smears of the material should be made very thin. After fixation in 
strong methyl alcohol for ten minutes, the Treponema pallidum can be stained by the 
Giemsa method (page 1237) or the azure-eosin method of Wood (page 350). With the 
Giemsa method it is well to stain for from twelve to twenty-four hours; with the 
Wood method a warm preparation can be stained in ten minutes. 
Demonstration of Treponema Pallidum. 
Fig. 172.-Treponema Pallidum. 
Stained by the silver method. Preparation of Dr. Noguchi. Showing enormous numbers of 
spirochetes in the smear of material from syphilitic lesion. 
In tissues, the treponema is best demonstrated by the silver impregnation method 
of Cajal, as modified by Levaditi and others. This is as follows: 
1. Fix slices of tissue not over 2 mm. thick in a solution of 1 part (40 per cent.) 
formaldehyde and 9 parts water, for twenty-four to forty-eight hours. 
2. Harden in 96 per cent, alcohol for twenty-four hours. 
3. Wash in distilled water until the fragments sink. 
4. Impregnate with the following solution: 
Pyridin 10 c.c. 
Silver nitrate, 1 per cent, aqueous sol 90 c.c. 
Tightly stoppered bottles are maintained at a temperature of 50 to 55° C. in a paraffin 
oven for five hours. 
5. Wash in distilled water and reduce in the following mixture at room 
temperature: 
Pyridin 17 c.c. 
Acetone 10 c.c. 
Pyrogallic acid, 4 per cent, in dist. water 90 c.c. 
The tissue should be kept in the dark and reduction carried out for several hours. THE INFECTIOUS DISEASES 
311 
6. Dehydrate in alcohol, embed in paraffin, and cut sections not over 5 micra 
thick. 
If a counterstain is desired, use toluidin blue or Unna's alkaline methylene blue, 
and differentiate with glycerin-ether. 
Noguchi1 states that in the use of the Levaditi method certain modifications are 
necessary if satisfactory results are to be obtained. The preliminary fixation of the 
cerebral tissue in formaldehyde should be very thorough, a period of six months to 
a year giving the best results. Slices of brain tissue, 5 to 7 mm. thick, are placed in 
the following mixture: 
Formaldehyde, 40 per cent 10 parts 
Pyridin 10 parts 
Acetone 25 parts 
Alcohol 25 parts 
Distilled water . . ..» 30 parts 
In this they remain at room temperature for five days. They are then washed in 
distilled water for twenty-four hours; transferred to 96 per cent, alcohol for three days; 
washed in distilled water for twenty-four hours; soaked in 1.5 per cent, aqueous solu- 
tion of silver nitrate for three days at 37° C. or for five days at room temperature; 
washed in distilled water for two hours; reduced in 4 per cent, pyrogallic solution to 
which has been added 5 per cent, formalin, for twenty-four to forty-eight hours at 
room temperature; washed thoroughly in distilled water; transferred to 80 per cent, 
alcohol for twenty-four hours; then to 95 per cent, alcohol with daily renewals for 
three days; and absolute alcohol for two days; and embedded in paraffin. Sections 
should be cut about 3 to 5 micra thick, and should be taken from different portions 
of the block in order that areas may be obtained in which the neuroglia fibers are not 
deeply stained and the treponema is black. 
By this method the spirals are more or less definitely black, the tissues pale yellow. 
Double staining reveals the relationships of the organism to the tissue cells. 
India Ink Method.2-An effective method of demonstrating the syphilis organism 
in smears is as follows: 
The fluid squeezed from a syphilitic lesion on to a slide with as little blood as pos- 
sible is mixed with a drop of India ink (Chin-Chin waterproof ink manufactured by 
Gunther Wagner), and the mixture spread as in making blood smears. After dry- 
ing, which is almost immediate, the specimen, examined directly with an oil immer- 
sion lens shows the organism, if present, as unstained in a black field (see Fig. 171). 
General Considerations.-The principles on which this test is based have been 
considered on page 214 under the heading Fixation of Complement. We have 
there seen that when a substance capable of inciting the body-cells to the formation of 
antibodies, i.e., an antigen, is mixed with its corresponding heated serum, i.e., 
antibody or amboceptor, in the presence of complement, the latter is so "fixed" in 
combination with the antigen that it is no longer free to enter into any other combina- 
tion. This is shown by the fact that if such a mixture be placed in contact with 
the sensitized red blood-cells, no hemolysis is produced. 
If, in the above reaction, the heated serum contained no antibody, the comple- 
ment would not be fixed and hemolysis would take place on the addition of the 
sensitized red blood-cells. 
In this way one may determine the presence in given fluids of specific antibodies, 
on the one hand, or of antigens on the other, if he have at hand the homologous 
antigens or antibodies as the case may be. For antigens one may use bacteria or 
bacterial extracts. 
In Wassermann's test3 it-was assumed that syphilitic organs might contain uncom- 
WASSERMANN'S TEST IN THE DIAGNOSIS OF SYPHILIS. 
1 Noguchi, Munchen, med. Wchnschr., 1913, lx, 737. 
2 Burri, Das Tuscheverfahren, Jena, 1909. 
8 Wassermann, Neisser, and Bruck, Deutsch, med. Wchnschr., 1906, xxxii, 745. 312 
THE INFECTIOUS DISEASES 
bined portions or products of Treponema pallidum, i.e., free syphilitic antigens, and 
thus extracts of organs-spleen, liver, etc.-of a syphilitic fetus were made in salt 
solution or alcohol. But it was discovered later that specific antigens are not necessary 
for the reaction; that extracts of normal organs-liver, spleen, heart, human or animal 
-or lecithin in solution can act as antigens in the tests. 
Recent work has shown that the concept that there is a specific antigen-antibody 
reaction in syphilis must be abandoned. The phenomenon is due to some as yet 
unknown substance produced in the serum of the syphilitic patients, by the reaction 
between the organism and the body. Extracts of cultures of the Treponema and 
emulsions from the testes of infected rabbits do not furnish an antigen for the Wasser- 
mann test as ordinarily performed.1 
The reaction may be obtained not only from the blood but also from the spinal 
fluid, and in the latter, in cases of cerebrospinal syphilis, may be positive when 
negative in the blood. It is obtained in blood taken post-mortem in some 90 per cent, 
of those with syphilitic lesions.2 
The frequency of syphilis in the general population may be inferred from the fact 
that 15 per cent, of the patients admitted to the Peter Bent Brigham Hospital, and 
25 per cent, of those admitted to Bellevue Hospital, give the reaction.3 
The details of the test cannot be given here. Many types of antigen are em- 
ployed by different workers and there is as yet no final agreement as to the method. 
The student is referred, therefore, to special texts for the minute precautions necessary 
to obtain reliable results.4 
Luetin Test. 
Cultures of Treponema pallidum are ground in a mortar, sterilized by heat, and 
suitably diluted, and 0.5 per cent, of tricresol are added. From the solution, cultures 
are made for ordinary bacteria, and rabbit inoculations are carried out so as to deter- 
mine that no spirochetes have survived the sterilization. The skin is cleansed with 
alcohol and the luetin is injected intradermally. In the majority of normal persons 
a very small erythematous area appears after twenty-four hours; in those who have 
been infected with syphilis a large reddish papule, 5 to 10 mm. in diameter, appears 
in twenty-four to forty-eight hours, gradually fading toward the end of a week. In 
more active reactions a pustule may form. The reaction is generally negative in the 
untreated primary and secondary stages; in tertiary syphilis it is from 80 to 100 per 
cent, positive. In congenital syphilis the results vary within wide limits. The test 
is frequently positive when the Wassermann reaction is negative, especially so in 
cases of late syphilis after treatment where the blood and even the spinal fluid are 
negative. 
Colloidal Gold Reaction. 
Another test of great value in cerebrospinal syphilis is a purely physical phe- 
nomenon obtained by mixing spinal fluid in varying dilutions with a colloidal gold 
solution. Various color changes appear in the mixture, which when properly 
checked give valuable differential diagnostic hints in tabes, paresis, and cerebro- 
spinal syphilis.5 
1 Noguchi, Jour. Am. Med. Assn., 1912, Iviii, 1163; Craig, C. F., and Nichols, H. J., Jour. Exper 
Med., 1912, xvi, 336. 
2 Graves, S., Jour. Immunol., 1916, ii, 53. 
8 Walker and Haller, Jour. Am. Med. Assn., 1916, Ixvi, 488. 
4 Wood, F. C., Chemical and Microscopical Diagnosis, 3d ed., New York, 1917; Kolmer, J. A., 
Infection, Immunity, and Specific Therapy, 2d ed., Philadelphia, 1917; Noguchi, Serum Diagnosis of 
Syphilis, 3d ed., Philadelphia, 1912 and Craig, C. F., The Wassermann Test, St. Louis, 1918. 
5 For details of the technique of the test, see Kolmer, J. A., Infection, Immunity and Specific Ther- 
apy, 2d ed., Philadelphia, 1917. For method of preparation of the colloidal gold solution, see Lee, 
0. I., Am. Jour. Med. Sc., 1918, civ, 404. For a discussion of the nature and interpretation of the 
reaction, see Vogel, K. M., Arch. Int. Med., 1918, xxii, 496. THE INFECTIOUS DISEASES 
313 
This disease, which occurs especially in eastern Europe and occasion- 
ally in other parts of the world, is a chronic inflammation of the nasal, 
pharyngeal, and laryngeal mucous membrane. In this inflammation 
a diffuse or nodular formation of new tissue somewhat resembling granu- 
lation tissue, occurs, which tends to assume a dense cicatricial character. 
(Fig. 173.) 
A bacillus called Bacillus rhinoscleromatis is often found in the lesion. 
In most of its morphological and biological characters it closely resembles 
the pneumobacillus of Friedlander (B. mucosus capsulatus), growing 
Rhinoscleroma. 
Fig. 173.-Rhinoscleroma Showing Large Clear Cells of Mikulicz, Filled with 
Bacteria Not Showing in the Photograph. 
readily on the common culture media and developing a capsule, and it 
may be identical with it. The relationship of this bacillus to the lesions 
of rhinoscleroma does not appear to be as yet definitely established, 
since inoculations in men and animals have not given positive results.1 
DIPHTHERIA. 
Diphtheria is an acute infectious disease incited by the Bacillus 
diphtherice (Loeffler), and usually characterized by a pseudomembranous 
inflammation on some of the mucous membranes or occasionally on 
the surface of wounds, and by immediate or remote effects of absorbed 
toxic substances. The mucous membranes which are the most fre- 
quently affected in diphtheria are those of the tonsils, pharynx, soft 
palate, nares, larynx, and trachea; less frequently those of the mouth, 
gums, conjunctiva, esophagus, and stomach. 
1 See Babes, V., Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1913, v, 
1237. 314 
THE INFECTIOUS DISEASES 
The local lesions in mucous membranes may present various phases. 
Thus there may be a simple redness of the affected surfaces which leaves 
no trace after death. On the other hand, in the more marked forms of 
the lesion there may be a fibrinous exudate which infiltrates the mucous 
membrane, or, intermingled with pus cells, epithelial cells, red blood-cells, 
bacteria, and granular material, forms a thick 
or thin pellicle on the affected surfaces (Fig. 
131, page 242). This pellicle may undergo 
coagulation necrosis (Fig. 174), and with this 
there may be superficial or deep necrosis of 
the mucous membrane. The false membrane 
in diphtheria is thus formed by a combina- 
tion of inflammatory products and necrotic 
tissue, the extent of the necrosis and the 
amount of inflammatory products varying 
in different cases. The membrane may dis- 
integrate or exfoliate, with or without loss of 
tissue in the underlying mucous membrane. 
Phlegmon, abscess, and edema are liable to 
occur as local complications. 
Adjacent and distant lymph-nodes are apt to be swollen, and often 
show, on microscopical examination, endothelial-cell hyperplasia with 
small foci of cell necrosis and disintegration.1 Similar foci of cell hyper- 
plasia with necrosis, 
small spheroidal-cell 
accumulation and 
fatty degeneration 
may be found in the 
kidney, spleen, and 
liver. Albuminous 
degeneration in the 
kidney, and acute 
nephritis are not in- 
frequent. Small 
hemorrhagic foci may 
be present in the liver 
and kidneys. Degen- 
eration of the heart 
muscle may occur.2 
The exact nature of 
the nerve lesions which may be associated with the late paralyses of 
diphthera is not yet clear, but degeneration of the peripheral nerves and 
Morphology of the Lesions. 
Fig. 174.-Fibrin in Diphthe- 
ritic Membrane undergoing Coag- 
ulation Necrosis. 
Fig. 175. - Diphtheritic Inflammation of the Tonsil. 
Showing Loeffler's bacilli in the pseudomembrane. 
1 Consult Waschkewitsch, T., Virchows Arch., 1900, clix, 137. 
2 For studies of the lesions of the myocardium in diphtheria, consult Scagliosi, G., Virchows Arch., 
1896, cxlvi, 115; also Thomas and Hibbard, Boston City Hosp. Rep., 1900, p. 204 (bibl.); for a study 
of nerve lesions with bibl. see Batten, Pediatrics, 1899, vii, 97; also Rainy, H., Jour. Path, and Bacteriol., 
1900, vi, 435. Fora comprehensive study of the bacteriology and pathology of two hundred and twenty 
fatal cases of diphtheria, see Councilman, Mallory, and Pearce, Jour. Boston Soc. Med. Sc., 1900, v, 139. THE INFECTIOUS DISEASES 
315 
chromatolysis of the ganglion cells occur, indicating the action of an ab- 
sorbed toxic substance in the body fluids. Leucocytosis may be present. 
Catarrhal bronchitis and bronchopneumonia or simple lobular pneu- 
monia frequently complicate diphtheritic lesions of the upper air pas- 
sages and fauces. 
Bacteriology of the Disease. 
Although bacteria of various forms are commonly present in the 
false membrane, and some of them penetrate deeply into the underlying 
tissue, the primary and specific excitant of this disease is the Bacillus 
diphtheriae of Loeffler. 
In man the diphtheria bacilli are largely confined to the seat of local 
lesion, and sometimes occur here in enormous numbers, especially in 
the older layers of the pseudomembrane (see Fig. 175). But they may 
become widely distributed through the body. This appears to be espe- 
cially the case when the pyogenic cocci are associated with the diphtheria 
bacillus at the seat of local lesion. The systemic effects in diphtheria 
appear to be largely due to the absorption into the body of toxic material 
elaborated locally by the germs. Septicemia or acute visceral inflam- 
mations, particularly of the kidney, may occur without evidence of an 
external local lesion or of the portal of entry of the bacillus.1 
The very frequent association of the pyogenic cocci and other bacteria 
with the diphtheria bacillus gives rise to a series of changes which make 
the clinical picture and the lesions of diphtheria sometimes very com- 
plex. Thus the complicating bronchitis and bronchopneumonia, as 
well as pyemic symptoms and lesions, may be due to the diphtheria 
bacillus alone. But these secondary lesions may be due to the presence 
in the pseudomembrane, and the entrance into the deeper air passages 
and the blood, of Streptococcus pyogenes, Staphylococcus pyogenes, 
Diplococcus lanceolatus, Bacillus coli communis, and other bacteria, 
or of these together with the diphtheria bacillus.2 Diphtheria bacilli 
are frequently found also in the exudate from the throats of children 
with scarlet fever. 
Concurrent Infections. 
Characters of the B. diphtheriae 
This organism, first described and definitely associated with this disease by Loeffler, 
is a slender rod, in general about 3 // long, but sometimes shorter and sometimes grow- 
ing into threads. It occasionally grows in branching forms,3 and is characterized 
1 For a resume and bibliography of studies relating to diphtheritic septicemia, see Braun and 
Thiry, Gaz. d. hop., 1899, xx1, 668. 
2 For a study of the presence and action of the diphtheria bacilli in the lungs, see Flexner and Anderson, 
Bull. Johns Hopkins Hosp., 1898, ix, 72. 
For a summary of the association of diphtheria and tuberculosis, see Councilman, Mallory, and 
Pearce, Jour. Boston Soc. Med. Sc., 1900, v, 139. 
3 The branching forms which are occasionally observed in the diphtheria as well as in the tubercle 
bacillus, together with certain other characters, have led some observers to the belief that these organ- 
isms are related to streptothrix and to the moulds rather than to the bacteria. But, for the present 
at least, it seems wiser to consider them in their more generally acknowledged relationships. 316 
THE INFECTIOUS DISEASES 
morphologically by marked irregularities in its shape (Fig. 176). While the typical 
form is that of a round-end, straight, or slightly curved bacillus, it is very apt-per- 
haps as a result of degeneration-to appear club-shaped or pointed at the ends, and 
irregularly segmented, and to develop at the ends or elsewhere a strongly refractile 
material which stains more deeply than the 
rest of the protoplasm. 
The diphtheria bacillus is immobile, 
asporogenous, grows best at blood heat, 
and thrives on most of the artificial culture 
media. 
In fluids it may be killed by an exposure 
of ten minutes to a temperature of 58° C.; 
or of one minute to boiling, but it may re- 
main alive for weeks, or even months, in 
fragments of dried membrane. It may be 
stained with Loeffler's alkaline methylene- 
blue solution or by Gram's method. 
It is subject to extreme variations in 
virulence, forms occurring which with all the 
usual cultural characteristics are not at all 
virulent.1 It is, therefore, often necessary 
to inoculate suitable animals, the guinea- 
pig being the best, in order to determine the degree of virulence in organisms of 
characteristic morphology, especially those derived from chronic carriers. 
Fig. 176.-B. Diphtherias. 
X 1000. 
Action of the Bacillus in Animals. 
Inoculations of virulent cultures subcutaneously in guinea-pigs are followed by a 
localized hemorrhagic edema with a variable amount of whitish exudate. Death 
usually occurs in from two to five days. In addition to the local lesions there may be 
-but this is not constant-swelling of the adjacent and of the abdominal lymph-nodes, 
serous effusions into the pericardial, pleural, and peritoneal sacs, swollen spleen, 
albuminous and fatty degeneration in the liver, kidney, and, heart muscle, congestion 
and sometimes hemorrhage of the suprarenals. Microscopical examination shows, 
in a considerable proportion of cases, fragmentation of nuclei and other evidences of 
cell death at the seat of inoculation and in the viscera, as well as chromatolysis of gan- 
glion cells in the anterior horn. Animals which survive the inoculations may later 
develop paralysis, and a similar result may follow the injection into rabbits of culture 
fluids. The bacilli do not usually gain access to the body at large, but may be found 
at the seat of inoculation. Inoculation into the mucous membranes of rabbits, 
pigeons, and certain other animals may result in the development of a pseudomem- 
brane somewhat resembling that of the disease in man. 
In its growth under artificial culture some strains of the diphtheria bacillus de- 
velop and set free in the culture media toxic substances whose chemical composition 
is as yet unknown. It is this toxic material which is used in the production of diph- 
theria antitoxin (see page 190). 
Communicability.-While the possibility of the transmission of the diphtheria 
bacillus by domestic animals to man cannot be doubted, the usual source of infective 
material is the exudates of victims of the disease; virulent bacilli may be conveyed 
from the mouths of healthy persons to those disposed to the infection. Infection may 
take place directly by contact, or by coughing and sneezing, or through contaminated 
Diphtheria Toxin and Antitoxin and Diagnosis. 
1 For a study of varieties of the B. diphtheria, see Williams, A. W., Jour. Med. Research, 1902, N. S. 
iii, 83; and Kolmer, Jour. Infect. Dis., 1912, xi, 56. See also for full summary of studies on the diph- 
theria bacillus and its toxins, Neisser and Gins, Kolle and Wassermann, Handbuch d. path. Mikroorgan- 
ismen, 2d ed., 1913, v, 931. THE INFECTIOUS DISEASES 
317 
clothing, bedding, or various utensils, or through "carriers."1 The susceptibility to 
diphtheria is greatest in the young. 
It is important from the prophylactic standpoint to remember that the Bacillus 
diphtheriae may remain alive in the mouth of the human subject for many weeks after 
recovery from the local lesions of the disease, and also that healthy persons when the 
disease is prevalent may harbor the virulent bacilli in their mouths. 
Schick Test.-In the control of epidemics of diphtheria it is important to separate 
those persons who have a natural immunity from those who are susceptible, in order 
that the former may be spared the administration of antitoxin. Schick2 has devised 
a test which consists in the injection of one-fiftieth of a minimal lethal dose of diph- 
theria toxin into the skin. The skin is first cleansed with alcohol, and the injection 
is made with an extremely fine needle. If one-thirtieth of a unit of antitoxin is pres- 
ent in the blood of the person injected, no reaction follows. If there is no antitoxin 
present, a small area of redness and edema appears in twenty-four to forty-eight hours. 
The reaction is very reliable.3 The results of the test show that some 20 to 30 per 
cent, of children between the ages of two and sixteen give a positive reaction and are 
probably susceptible to diphtheria. Children under one year of age gave about 85 
per cent, of negatives. In adults over 50 per cent, gave negative results. Diphtheria 
carriers also give negative results.4 The reaction is of value also in the diagnosis of 
nasal diphtheria when the membrane is invisible and in differentiating doubtful 
throat membranes. 
Other Bacteria of the Diphtheria-Bacillus Group. 
While the diphtheria bacillus varies greatly in the physiological capacities which 
determine its virulence, its general morphological and cultural characteristics are 
fairly constant. There are, however, non-virulent bacilli occurring on mucous mem- 
branes under normal as well as abnormal conditions which considerably resemble 
this, but which differ somewhat in both morphological and biological characters from 
the true diphtheria bacillus and its variants. Such organisms have been called pseudo- 
diphtheria bacilli (Bacillus hoffmanni). These non-virulent forms may be regarded 
as attenuated varieties of the diphtheria bacillus.5 
The so-called Xerosis bacillus, a saprophyte which has been repeatedly found in 
xerosis conjunctivae, is apparently a non-pathogenic member of the diphtheria- 
bacillus group.6 
This disease, which is especially marked clinically by muscular 
spasm, is due to infection by the Bacillus tetani, an organism often 
present in the intestinal tracts of horses and cattle, and occasionally in 
that of man. The bacillus is rather widespread and in some places very 
abundant, occurring with other germs in the soil, especially in manured 
soil, and gaining entrance to the body through wounds, which are often 
very slight. The soil in certain regions appears to harbor the tetanus 
organisms or its spores in especial abundance. Thus in certain districts 
on Long Island and in New Jersey slight injuries are frequently followed 
by tetanus. The liability to infection from the spores is greatly enhanced 
by their association with other organisms or with dirt, splinters, etc., in 
TETANUS. (Lockjaw.) 
1 For a study of diphtheria carriers, see Page, H., Arch. Int. Med., 1911, vii, 16; and Chapin, Sources 
and Modes of Infection, New York, 2d ed., 1912. 
2 Schick, Munchen, med. Wchnschr., 1913, lx, 2608. 
3 Park and Zingher, Am. Jour. Pub. Health, 1916, vi, 431; Zingher, Am. Jour. Dis. Child., 1916, xi, 
269; 1917, xiii, 247; Park, W. H,,'Amer. Jour. Dis. Child., 1921, xxii, 1. 
4 Weaver and Rappaport, Jour. Am. Med. Assn., 1916, Ixvi, 148. 
6 For a study of virulent "pseudodiphtheria" bacilli, see Hamilton and Horton, Jour. Infect. Dis., 
1906, ii, 128. 
6 Graham-Smith, Jour. Hyg., 1904, iv, 306. See, also, Axenfeld, Augenheilkunde, Jena, 1945. 318 
THE INFECTIOUS DISEASES 
the wound. It is of practical importance to remember that gelatin and 
catgut (made from sheep intestine) both may contain tetanus spores. 
Lack of knowledge of this fact has led to a number of deaths following 
the injection of solutions of gelatin to check hemorrhage. 
The Lesions of the Disease. 
The local lesion in tetanus is usually slight and not characteristic, 
often consisting only in a slight suppuration. 
The morphology of the lesions of the nervous system to the existence 
of which the symptoms of tetanus so directly point is yet obscure. Over- 
filling of the blood-vessels, cellular exudate into the perivascular spaces, 
chromatolysis of the ganglion cells of the spinal cord are common. The 
bacillus remains for the most part at the seat of local lesion and induces 
its effects by the elaboration of most intense poisons or toxins, called 
tetanotoxins. The action of this toxic substance appears sometimes to 
continue in the body after the death of the organisms which have elabo- 
rated it. This infectious disease affords a most typical example of 
toxemia. 
Characters of the Bacillus Tetani. 
It is 2 to 5 // long, slender, and motde, often growing in pairs or threads and prone 
to develop a spore in one end (Fig. 177), in which condition the bacillus is larger at 
this end, being club- or racket-shaped. It is readily stained. At room tempera- 
ture it grows on artificial culture media, and is strictly anaerobic, flourishing in an 
atmosphere of hydrogen, but may be artificially adapted 
to other conditions. 
The spores of the tetanus bacillus are very resistant 
to drying, to heat, and to various chemical disinfectants. 
Characteristic tetanic symptoms followed by death 
may be induced in mice, guinea-pigs, and rabbits by 
subcutaneous inoculation of cultures. Man and the 
horse are markedly susceptible to tetanus; birds are, as a 
rule, insusceptible, requiring 360,000 times more toxin 
per kilo of body weight than the horse, for example. 
If the tetanus bacillus be grown in nutrient broth at 
blood heat out of contact with oxygen the toxin is de- 
veloped and mingles with the fluid. This toxin when freed from living germs is capa- 
ble of inducing the symptoms of the disease. Broth cultures may, after some weeks, 
have acquired such an extreme intensity that the dried poisonous material, separated 
from the inert fluids and partially purified, may be fatal to a mouse weighing 15 gm. 
in a dose of 0.00000005 gm. Estimating according to the relative weights of the 
subjects, the minimal fatal human dose would be about 0.00023 gm. This toxin is 
rendered inert by a temperature above 65° C. and by light. 
Fio. 177.-Bacillus Tetani. 
From a culture; showing club- 
shaped ends with spores. 
Tetanus Antitoxin. 
By procedures similar to those described in diphtheria immunization 
(page 190), the tetanus toxin has been used to secure artificial immunity 
in dogs, goats, and horses, and here also the blood serum of the immu- 
nized animals has been prepared and employed in man for therapeutic 
purposes with some degree of success.1 
1 For a critical r£sum6 of tetanus and its treatment with the antitoxic serum, with bibliography, 
see Moschcowitz, Ann. Surg., 1900, xxxii, 219; also Park and Williams, Pathogenic Microorganisms, 
6th ed., New York, 1917. THE INFECTIOUS DISEASES 
319 
The tetanus toxin induces its effects in the body chiefly by its action 
on the central nervous system. It has been shown to reach the nerve 
centers from the seat of growth of the bacillus, by way of the axis-cylin- 
ders of the motor nerves. The tetanus antitoxin, on the other hand, 
which may be injected for protective purposes, is not taken up by the 
nerves, but passes into the blood- and lymph-vessels and tissue fluids. 
The power of the antitoxin to neutralize toxin is apparently limited to 
that portion of the latter which has not been absorbed by the nerves, 
but is still free either at the seat of production or in the blood or lymph. 
The theoretical promise of the tetanus antitoxin for therapeutic 
purposes in man is thus in practice rendered in a large measure futile, 
because the existence of the disease is not recognizable until the tox- 
emia is sufficiently marked to produce the nervous symptoms, at which 
time, union of the toxin with the nerve tissues having been effected, 
the usefulness of the antitoxin is limited to the neutralization of the 
unabsorbed toxin. Statistics are as yet too meager to justify a final 
opinion as to the practical value of tetanus serum therapy, but it appears 
to be definitely useful, especially when it is possible to apply the anti- 
toxin directly to the nerve tissues, or when it is introduced by infraspi- 
nous injection in large amounts. Splendid results have followed prophy- 
lactic injections. 
Diagnosis. 
For purposes of diagnosis it may be necessary to inoculate a white mouse at the 
base of the tail with suspicious material at the same time that morphological examina- 
tion and anaerobic cultures are made. Should tetanus develop in the mouse within 
a few days, control cultures may be made from the exudate at the seat of inoculation.1 
Other Bacilli of the Tetanus Group. 
Several bacterial species are already known which may be classed in the tetanus 
group. While varying in size, these bacilli are in general rather large; spores form in 
their thickened ends; they are facultatiye anaerobes; some do, others do not fluidify 
gelatin; and they retain the stain by Gram's method. They are mostly saprophytes 
and have been found in milk and milk products, in excrement and sewage, etc. None 
is known to be pathogenic in man. The most noteworthy among these is Bacillus 
pseudotetanicus, Sanfelice, which in morphology and growth characters resembles the 
Bacillus tetani, but does not form the toxin. 
This disease, which has been most frequently observed along the shores 
of the Mediterranean and in India, and occurs in South America and the 
West Indies, is characterized by prolonged pyrexia with irregular remis- 
sions. In the rather rare fatal cases there may be considerable enlarge- 
ment of the spleen, and albuminous degeneration in the liver and kidneys. 
Acute nephritis may occur. 
It is said that there are constantly present in the spleen in this disease 
small bacilli so short as to have been mistaken for cocci, staining by 
Gram's stain, and readily cultivated on artificial media. The result of 
MALTA FEVER. 
1 For resume of characters of the tetanus bacillus and its toxin, see v. Lingelsheim, Kolle and Wasser- 
mann, Handbuch d. path. Mikroorganismen, 2d ed., 1912, iv, 737 (bibl.). 320 
THE INFECTIOUS DISEASES 
inoculations of pure culture into monkeys and other animals tends to 
confirm the pathogenic significance of the organism, which has been 
called Micrococcus melitensis.1 
BUBONIC PLAGUE. (Oriental Plague; Black Death.) 
Types of the Disease.-This disease presents three main types-the 
bubonic, the pulmonary, and the septicemic. 
The most common is the bubonic, which is characterized by an intense 
inflammatory hyperplasia of the lymph-nodes, most frequently the 
inguinal or axillary. The surrounding tissue may be involved; hem- 
orrhage, necrosis, or suppuration in the nodes may occur. Coincident 
with these local reactions there may be albuminous degeneration, focal 
necrosis, and leucocytosis from toxemia, or secondary foci of inflamma- 
tion in the spleen or lungs or liver. A second type of the infection is the 
pulmonary, in which larger or smaller areas of the lungs are involved in 
bronchopneumonia with associated secondary involvement of the 
bronchial lymph-nodes. In the septicemic type of bubonic plague 
there may be a general involvement of the lymph-nodes and -nodules of 
the body with the marks of toxemia, without an indication of the point 
of primary infection.2 
In all these various phases of the disease the plague bacillus may be 
present often in enormous numbers in the primary buboes and in the 
secondary lesions and in the viscera; in the consolidated areas and in 
the sputum in the pulmonary type, and, in the septicemic type, in the 
blood. An attack confers immunity. 
Characters of the Bacillus Pestis. 
The plague bacillus was discovered in 1894 by Kitasato and Yersin, and its role as 
the excitant of the disease was soon established. It is a short, thick, motile, round- 
end bacillus, often staining more deeply at the ends than in the middle. It some- 
times grows in chains and may be capsulated, not forming spores; it is decolorized by 
Gram's method. It grows readily though not voluminously on the ordinary culture 
media at blood heat.3 This organism is killed by drying for a few days and by expo- 
sure to sunlight for a few hours. Subcutaneous inoculations into guinea-pigs and 
rabbits is followed by local hemorrhagic and serous inflammation with typical involve- 
ment of the regional lymph-nodes and by septicemia. Death may follow in from one 
to five or six days, with albuminous degeneration of the viscera, hyperplasia of the 
spleen, and petechial hemorrhages. 
Portals of Entry.-The chief portals of entry in man are abrasions 
or wounds of the skin, the lungs, and the intestines. The spread of the 
infectious material in overcrowded and unsanitary districts readily 
takes place by rats, which are very susceptible to the disease and may 
be infected by feeding.4 Through mosquitos, flies, and other vermin, 
1 Consult Birt and Lamb, Lancet, 1899, ii, 701 (bibl.); and Eyre, J. W. H., Kolle and Wassermann, 
Handbuch d. path. Mikroorganismen, 1912, vi, 421 (bibl.). 
2 For a resume of lesions of plague, see Flexner, Trans. Assn. Am. Phys., 1901, xvi, 481. 
3 See Dieudonne and Otto, Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 
1912, iv, 155. 
4 The ground squirrels along the Pacific Coast were widely infected with plague bacilli and were a 
menace to the population of that region; see Pub. Health Repts., U. S. Mar. Hosp. Serv., 1910, xxv, 27. THE INFECTIOUS DISEASES 
321 
also, the bacilli may be conveyed from man to man or from dead rats or 
their dejecta to man;1 but the most important vector is the rat flea, 
which has been definitely proved to be the most usual agent. 
Preventive Inoculation has been largely practised in the East by the 
Haffkine method. This consists in the subcutaneous injection of beef- 
tea cultures of the plague bacillus, which have been killed by heating. 
Moderate local inflammatory reaction and slight fever may follow the 
injection. The statistics seem to indicate that among exposed persons 
the mortality may be considerably reduced by this preventive inocula- 
tion.2 
An antiplague serum, prepared by the immunization of horses, has 
been used by Yersin with at least promising results.3 
HEMORRHAGIC SEPTICEMIA. 
Many of the lower animals are victims of acute infections, septicemic in character, 
often with petechial hemorrhages in the viscera and serous membranes and marked 
intestinal disturbances. These are called hemorrhagic septicemias. 
Associated with these and doubtless their inciting agents are several bacilli which 
may be classed, as is done by Hueppe, Kruse, and others, with the plague bacillus 
under the designation, the hemorrhagic-septicemia group. These are mostly small, 
short, sporeless forms growing readily on the ordinary media as facultative anaerobes, 
not fluidifying gelatin, and decolorizing by Gram. Some of these are motile, others 
not. Among these may be mentioned the bacillus of mouse typhus (B. typhi murium), 
the bacillus of chicken cholera (B. cholerce gallinarum), the bacillus of swine plague 
(B. suisepticus). Several species related to these and to the plague bacillus are 
pathogenic in man; thus the B. hcemorrhagicus septicus of Babes, the B. hcemorrhagicus 
of Kolb, the B. hcemorrhagicus velenosus of Tizzoni and Giovanni. 
The recognition of these and related species may be of especial significance in con- 
nection with the diagnosis of bubonic plague by cultures and animal inoculations.4 
Bacillus ASrogenes Capsulatus (Bacillus Welchii, Gas Bacillus, 
Bacillus Perfringens). 
This bacillus was described in 1891-92 by Welch and Nuttall. Later 
studies of Welch and Flexner and many others have confirmed the orig- 
inal belief that the bacillus is a frequent excitant in man of a serious 
infectious disease, characterized by a local widespread serous and 
emphysematous phlegmonous inflammation, frequently associated with 
gangrene and general symptoms of a profound toxemia. 
The Bacillus aerogenes is rather large, on certain media is spore-form- 
ing, is often encapsulated, and occasionally forms chains. It retains the 
stain by Gram's method. It is anaerobic, growing readily in a variety 
of artificial culture media. 
Rabbits are not susceptible to even large intravenous injections of 
pure cultures. But if the animals be killed soon after inoculation, within 
a few hours, at room temperatures, an abundant development of gas 
1 On insects as plague-carriers, see Herzog, Am. Jour. Med. Sc., 1905, cxxix, 504. 
2 For summary of results of the Haffkine method, see Forsyth, Lancet, 1903, ii, 1646; also Slaughter, 
Bull. Johns Hopkins Hosp., 1903, xiv, 307. 
3 See, for critical summary and bibl., Netter, Arch, de med. exp6r., 1900, xii, 86. 
* For studies on various forms of hemorrhagic infection, see Babes, Verhandl. d. deutsch. path. 
Gesellsch., 1900, ii, 262; also Hutyra, Kolle and Wassermann, Handbuch d. path. Mikroorganism-en, 
2d ed., 1913, vi, 64. 322 
THE INFECTIOUS DISEASES 
occurs throughout the body. On the other hand, the subcutaneous 
injection of a very small quantity of the fresh edematous exudate is 
followed by the typical local and general marks of infection. Guinea- 
pigs are more susceptible than rabbits to inoculation, either with cultures 
or fresh material, and develop characteristic lesions. 
While infection may occur without gas, there is an abundant formation 
of gas in the tissues after death. This is largely hydrogen formed through 
the splitting by the bacillus of either sugar or proteins. While the gas 
may be present hi any of the tissues, in the body cavities, and in the 
blood-vessels, it is especially in the liver after death that the marks of 
its accumulation are most striking. This organ may be riddled with 
small holes, presenting an appearance which has been characterized as 
"foamy liver" (Fig. 535, page 840). Crushing wounds of the extremities 
are often followed by gas gangrene, the bacteria developing in the 
necrotic tissues and spreading along the muscle bundles. The gas 
formed in the dead tissue causes further destruction, through stoppage 
of the capillary circulation either by gas emboli or by pressure, being 
retained by the fascial planes of the muscle. Free incision of the muscle 
to relieve pressure is the only means of preventing further extension. 
Infection may occur through wounds or injuries in any part of the 
body. It has been frequently observed in pregnant and puerperal 
women.1 Ulcers of the stomach and intestine or of the urinary tract 
may be portals of entry. One of the more common forms of local 
infection is the so-called gaseous phlegmon or emphysematous gangrene. 
Pulmonary and pleural lesions, appendicitis, and peritonitis are described, 
as well as gaseous abscesses and purulent meningitis. While the usual 
action upon the tissues is the induction of bloody edema and necrosis, 
this bacillus is also occasionally pyogenic. 
The Welch bacillus produces at least two distinct toxins, one hemo- 
lytic, causing diffuse staining of the tissues, the other purely toxic. An 
antiserum has been produced by Weinberg, and has proved of great 
value in infections with this organism.2 
The natural habitats of the organism are the soil and the intestinal 
canal. This accounts for the relative frequency of infection through the 
intestinal and genitourinary tracts and through wounds contaminated 
with dirt. 
Infection, especially from the intestinal canal, may occur apparently 
during the later hours of life, with or without symptoms and with a 
post-mortem formation of gas. It is often difficult to determine, since 
gas formation occurs so early and so extensively after death, whether the 
entrance has or has not been effected during life. Usually, however, 
when the autopsy is done immediately after death, no mechanical lesions 
due to gas are found in the organs. It seems fair to infer, as the result 
of animal experiments, that when the gas formation, even after death, 
is widespread, ante-mortem infection has occurred. 
1 For a study of B. capsulatus in puerperal infections, see Little, Bull. Johns Hopkins Hosp., 1905, 
xvi, 136. 
2 See Weinberg, MCompt. rend. Soc. de biol., 1914, Ixxvii, 543; and Weinberg, M., and Seguin, P., 
Compt. rend. Acad, de sc., 1917, clxiv, 365; clxv, 199. Bull and Pritchett, Jour. Exper. Med., 1917, 
xxvi, 119. THE INFECTIOUS DISEASES 
323 
Concurrent infection with other organisms, especially the pyogenic 
cocci, the bacillus of malignant edema {Vibrio septique}, and the Bacillus 
oedematiens, is frequent. 
Welch and Nuttall early called attention to the importance of recog- 
nizing the possibility of infection with this bacillus in judging of a cer- 
tain class of cases of alleged air embolism. 
It is probable that the Bacillus aerogenes capsulatus is identical with 
forms which have been described under various names in connection with 
cases of gaseous phlegmon, or so-called malignant edema.1 
Bacillus oedematiens, Bacillus oedematis Maligni 
Malignant Edema.2 
This disease is of occasional occurrence in man and certain domestic animals- 
horses, cattle, sheep-usually following some form of traumatism. It is a septicemia 
with local, often hemorrhagic edema, visceral degeneration, etc. 
The bacillus of malignant edema, Bacillus oedematis maligni, which is frequently 
present in dust, in putrefying substances, and in soil, considerably resembles the 
Bacillus aerogenes capsulatus in both its morphological and biological characters. It 
is, however, more slender, and more apt to form threads; spore formation occurs 
readily in the ordinary media. It decolorizes partially by Gram's method. Other 
differential characters are to be made out in cultures. It is an excitant of hemor- 
rhagic edema, but with slight if any development of gas. 
Other Bacteria which may Induce Hemorrhagic Septicemia. 
Nearly related to the Bacillus aerogenes capsulatus and to the bacillus of malignant 
edema are several other spore-forming anaerobic bacilli occurring especially in the 
earth, in excrement, and in various rotting substances. Some of these appear to be of 
pathogenic significance in the lower animals under both natural and experimental 
conditions. 
Thus the Quarter-evil {Rauschbrand; charbon symptomatique), especially in Europe, 
is a serious infectious disease of sheep, goats, and cattle. At the seat of infection, 
often in the legs, there is a hemorrhagic edema with gas formation, the involved 
region often becoming much swollen and black in color ("black leg"). The bacillus 
which is the excitant of this disease is known, and preventive inoculation has been 
practised. 
Howard has described a group of cases of hemorrhagic septicemia characterized by 
hemorrhages into the skin, serous membranes, and viscera, in which capsulated bacilli 
apparently related to the above-described bacillus of Friedlander (page 245) have been 
found.3 
Meat Poisoning. 
Meat poisoning may be due to some strain of Bacillus enteritidis 
which infects various animals. The meat of these diseased animals is not 
abnormal in appearance or taste but may contain the organism, and if 
1 For an excellent critical resume of this subject, with bibl., see Welch, Bull. Johns Hopkins Hosp., 
1900, xi, 185. See also, Ghon and Sachs, Centralbl. f. Bakteriol., Orig. I, 1904, xxxv, 665; 1904, xxxvi, 
1; Simonds, J. P., Studies in Bacillus welchii, Monographs of the Rockefeller Institute, New York, 
No. 5, 1915; and Weinoerg, M., and Seguin, P., La gangrene gazeuse, Paris, 1918; and Pease, M. C., 
Proc. Soc. Exper. Biol, and Med., 1519-20, xvii, 30. 
2 d. Wert, F., Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 1912, iv. 837 (bibl.). 
3 Howard, W. T., Jour. Exper. Med., 1899, iv, 149; also Blumer and Laird, Bull. Johns Hopkins 
Hosp., 1901, xii, 45. See also Typhus and Rocky Mountain Spotted Fever (p. 333-334). 324 
THE INFECTIOUS DISEASES 
not thoroughly cooked may induce serious gastrointestinal disorders in 
man. The meat of diseased cows and calves most frequently has been 
the source of infection. The infection is most common in summer and 
the infective agent may apparently be conveyed from man to man 
through excreta. 
Several other forms of meat poisoning, some resembling typhoid 
fever, others involving a mild or violent gastroenteritis, others especially 
characterized by toxemic symptoms have been attributed to the pres- 
ence of various bacterial organisms which we cannot consider further 
here.1 
This is a toxemia characterized by chills, giddiness, trembling, headache, and 
sometimes vomiting, followed by symptoms such as loss of accommodation, dilated 
pupils, ptosis, aphonia, etc., referable to the action of some toxic substance.2 Death 
may follow general motor paralysis and dyspnea, due to the action of the toxin on 
the cells of the central nervous system. Visceral hyperemia, petechial hemorrhage, and 
albuminous degenerations may be noted. The disease is due to the toxins formed by 
the Bacillus botulinus, first isolated by van Ermengem from a contaminated ham 
which had poisoned many persons. The bacillus is a spore-bearing anaerobic organ- 
ism, which is, however, aerobic when growing in symbiosis with other organisms such 
as Sarcina or Bacillus subtilis. 
It is believed that the toxins inducing botulism are formed in the contaminated 
food-ham, sausages, and canned meat and vegetables3-before their ingestion, but 
as the poison is rapidly destroyed by heat at a temperature above 80° C., it is obvious 
that only uncooked foods are dangerous. 
Botulism 
RELAPSING FEVER. (Typhus Recurrens; Famine Fever; Spirillum Fever; Seven- 
Day Fever.) 
This disease is common in India, Africa, and many tropical countries, 
and has occurred in Russia and in the United States.4 It is characterized, 
apart from the fever and associated symptoms, by the presence in the 
blood at certain periods of a spiral organism discovered by Obermeier in 
1873. Some six closely related species of spirochetes inducing the dif- 
ferent forms of the disease have been described, of which the Spirochaeta 
obermeieri and the Spirochaeta duttoni are the best known. 
There may be albuminous degeneration in the viscera, leucocytosis, 
catarrhal or croupous inflammation of the mucous membranes of the 
respiratory and digestive organs, and ecchymoses in the skin and in the 
mucous and serous membranes; as well as pneumonia and pleurisy, 
degeneration of the cardiac muscle, and hyperplasia of the mesenteric 
lymph-nodes. The spleen may be large and flabby, this change being so 
extreme that rupture has occurred during life; it may also be the seat of 
infarctions, and these have given rise to peritonitis. 
1 For a brief r6sun>6 of this group, see Hiss and Zinsser, Text-book of Bacteriology, 5th ed., New 
York, 1922, p. 686, 740. 
2 ran Ermengem, Kollo and Wassermann, Handbuch d. path. Mikroorganismen, 2d ed„ 1912, iv, 
909 (bibl.). 
3 Dickson, E. C., .lour. Am. Med. Assn., 1917, Ixix, 966; and Botulism, Monograph No. 8, Rocke- 
feller Inst., New York, 1918, and Dickson, E. C., Burke, G. S., and TFarfc, E. S., Arch. Int. Med., 1919, 
xxiv, 581. 
J Carlisle, Jour. Infect. Dis., 1906, iii, 233 (bibl.), describes two cases. THE INFECTIOUS DISEASES 
325 
In the blood of all parts of the body during the febrile attacks may be found, in 
very large numbers, a long, slender spiral called from its discoverer Spirochaeta ober- 
meieri (Sp. recurrentis) (Fig. 178). The organisms dis- 
appear from the blood during the afebrile intervals, and 
it has been shown that at this time they accumulate in 
the spleen, where they are destroyed in large numbers, 
apparently through the action of phagocytic cells. The 
organism is in general from 7 to 9 p in length, some- 
times longer, and performs rapid, undulating movements. 
The inoculation of healthy men and of 
monkeys with the blood of relapsing-fever 
patients which contains the organism induces a 
similar disease. Successful inoculations of 
white rats have been made with a spirochete 
believed to be of this species or a closely related one, Spirochaeta 
novyi.1 Pure cultures of these organisms have been obtained through 
several generations,2 and for the reasons indicated, and since the 
organism has never been found except in connection with the disease, 
there is every reason for believing that the Spirochaeta obermeieri is the 
excitant of relapsing fever.3 The organisms are considered to be protozoa 
by many observers, though Novy regards them as definitely bacterial in 
nature. It is probable that Spirochaeta obermeieri is transmitted by 
lice, especially Pediculus vestimenti and Pediculus capitis, and possibly 
also by the bedbug. The spirochetes are not carried directly into the 
skin by the bites of the insects, but when the lice are crushed, as in 
scratching, the organisms enter through the abrasion of the skin.4 
When the fingers are contaminated, the infection may be carried to 
the eyes by rubbing, and may then become general through the 
conjunctiva. 
Characters of the Spirochaeta Obermeieri. 
Fig. 178.-Spirochaeta 
Obermeieri. 
TICK FEVER. 
This is a disease of Uganda, Abyssinia, and the Congo region in 
Africa. The parasite has been studied by Novy and Knapp,5 and 
designated by them Spirochaeta duttoni. The pathological changes 
induced in the body by the parasite are the same as those caused by the 
presence of the Spirochaeta obermeieri. The organism is transferred by 
the bite of the Ornithodorus moubata, a tick in which it can live for a 
long time. The disease has been induced in monkeys by causing these 
animals to be bitten by the infested ticks.6 
Morphologically the parasite resembles very closely the Spirochaeta 
obermeieri, except that it is somewhat thicker. 
1 Norris, Pappenheimer, and Flournoy, Jour. Infect. Dis., 1906, iii, 266. 
2 Noguchi, Jour. Exper. Med., 1912, xvi, 199. 
3 See for resumd, Novy and Knapp, Jour. Infect. Dis., 1906, iii, 291; also Miihlens, P., Kolle and 
Wassermann, Handbuch d. path. Mikroorganismen, 2d ed., 1913, vii, 864 (bibl.). 
* Nicolle, Blaizot, and Conseil, Compt. rend. Acad. d. sc., 1912, cliv, 1636; civ, 481; Nuttall, Para- 
sitology, 1912-13, v, 262. 
i Novy and Knapp, Jour. Infect. Dis., 1909, iii, 379; Todd and Wolbach, Jour. Med. Research, 1914, 
N. S. xxv, 27. 
* Dutton and Todd, Brit. Med. Jour., 1905, ii, 1259; Ross and Milne, Brit. Med. Jour., 1904, ii, 1453. 326 
THE INFECTIOUS DISEASES 
VINCENT'S ANGINA.1 
This is an inflammation of the mouth, pharynx, and tonsils, often 
associated with a pseudomembrane and sometimes leading to ulceration. 
There is usually but moderate systemic disturbance. While in the 
lesions there are frequently many bacteria, two forms usually associated 
are most commonly found, one spindle-shaped resembling a bacillus, 
the other spiral-shaped, longer than the first, with shallow irregular 
curves, and staining with difficulty. 
These two organisms have been cultivated under anaerobic conditions.2 
YAWS (FRAMBCESIA TROPICA). 
This disease of tropical and subtropical countries is characterized 
chiefly by a papular eruption, with ulcerations suggestive of a relation- 
ship to syphilis. Castellani in 1905 demonstrated in the lesions spi- 
rochetes resembling Treponema pallidum; and his observation has been 
repeatedly confirmed. The infective agent can be transmitted to mon- 
keys and to rabbits by inoculation of material from the lesions.3 It 
seems clear that though the inciting agent of yaws, Spirochaeta pertenuis 
(Treponema pertenue) resembles the syphilis organism, the diseases are 
entirely distinct. Salvarsan, however, is therapeutically beneficial. 
HYDROPHOBIA. (Rabies.) 
Morphology of the Lesions. 
This is an infectious disease occurring most frequently in the car- 
nivora, and especially common in dogs and wolves, and usually com- 
municated to man by bites of the rabid animals. 
The lesions are not constant nor are they characteristic. Though 
well marked in some cases, in others they are but very slightly developed. 
Changes, when present, are apt to be most pronounced in the medulla 
oblongata and pons, but they may be observed in the spinal cord. They 
consist of small hemorrhages, of accumulation of leucocytes in the peri- 
vascular lymph spaces about the blood-vessels (Fig. 179) and around 
the ganglion cells, of thrombi in the smaller blood-vessels, and finally of 
chromatolysis of the ganglion cells.4 
Changes have been described in the intervertebral ganglia and in 
the plexiform ganglia of the pneumogastric nerve, which, although not 
limited to rabies, are yet so frequently present as to be apparently of 
value in diagnosis. The lesions consist in degeneration or atrophy or 
destruction of the ganglion cells with a proliferation of the endothelial 
cells lining the capsule.5 
1 Vincent, Ann. de 1'Inst. Pasteur, 1899, xiii, 606; and Lancet, 1905, i, 1260. 
2 For a study of fusiform bacilli, see Dick, Jour. Infect. Dis., 1913, xii, 191; Krumwiede and Pratt, 
ibid., 1913, xii, 199; 1913, xiii, 438, and Larson and Barron, ibid., 1913, xiii, 429. For cultures of spiro- 
chetes, see Noguchi, Jour. Exper. Med., 1912, xv, 81; ibid., 1912, xvi, 194. 
3 See, for a study of experimental yaws in the monkey and rabbit, Nichols, H. J., Jour. Exper. Med., 
1910, xii, 616. 
4 Bailey, F. R., Jour. Exper. Med., 1901, v, 581. 
6 See Ravenel and McCarthy, University Med. Mag., 1901, xiii, 766. THE INFECTIOUS DISEASES 
327 
Animal Inoculations. 
Since the infective agent of rabies is present in the central nervous 
system of victims of the disease, this material, i.e., brain and spinal-cord 
tissue, especially the latter, is used in experimental work. This is 
called the "virus" of rabies. Rabbits and guinea-pigs, as well as vari- 
ous other animals, are susceptible to subdural injections of a small amount 
of emulsion of the infective nerve tissue. After an incubation period 
varying in different animals, these succumb with characteristic symptoms 
and lesions.1 
Showing accumulation of leucocytes and proliferation of connective-tissue cells in the adventitia of 
the vessels. 
Fig. 179.-Hydrophobia. Transverse Section of Small Blood-vessels in the Spinal Cord. 
The Excitant of the Disease. 
The infective agent appears to be carried especially along the nerves 
from the point of inoculation to the central nervous system, where it 
seems to develop. It is not present in considerable quantity in either 
blood or lymph. 
It is known that the infective agent is in the saliva and salivary 
glands of rabid animals, and that it may be present in the saliva of the 
dog from three to five days before the symptoms of the disease appear. 
It seems to be especially concentrated in the central nervous system. It 
is readily rendered inert by corrosive sublimate and other germicides. 
It resists cold even to -20° C. but loses virulence after one hour's 
exposure to 50° C. It is preserved for some time in glycerin. 
1 For further data, see epitome in Kolle and Hetsch, Die experimentelle Bakteriologie, 3d ed., Berlin. 
1911. 328 
THE INFECTIOUS DISEASES 
It has been found that the rabic virus may pass the pores of an un- 
glazed porcelain filter not pervious to ordinary bacteria, so that some 
form or developmental phase of the organism must be extremely minute. 
Negri Bodies.-In 1903 Negri announced that he had seen in sections 
of the central nervous system of rabic animals within the ganglion 
cells, rounded bodies from 1 /z to 23 long, containing vacuoles and 
granules often grouped around a larger central structure. These bodies 
he regarded as parasites belonging among the protozoa and believed 
them to be the specific inciting factors in hydrophobia. These intra- 
cellular structures, now called "Negri bodies," have been the object of 
many careful researches, and the observations of Negri have been in 
general confirmed and extended. 
Fig. 180.-Negri Bodies. 
In smears from Cornu Ammonis of rabic dog. 
The Negri bodies are, as a rule, most abundant in the large ganglion 
cells of the hippocampus major (Cornu Ammonis), but occur in ganglion 
cells of the cerebral cortex and elsewhere. They are readily stained and 
appear to consist of a rounded or oval homogeneous basement substance 
containing a central body surrounded by variously shaped granules (Fig. 
180). They occupy central or peripheral positions in the ganglion cell 
and vary greatly in number in different cases of rabies. 
Similar cell inclusions have been found in animals inoculated with 
"fixed virus" (see below), but they are smaller and more difficult of 
detection than in street rabies and in animals inoculated with the street- 
rabies virus. Negri bodies have been found in nearly all cases of street 
rabies examined for them, and in no disease other than rabies. Their 329 
THE INFECTIOUS DISEASES 
constancy in street rabies has led workers in this field to regard them 
as of the utmost diagnostic value. While their nature is not yet defi- 
nitely established, their morphology and staining qualities seem to be 
consistent with the assumption of their protozoan character. They 
have indeed been named by Williams Neuroryctes hy dr ophobice. Their 
uniform presence in street rabies and the frequent presence of smaller 
similar structures in fixed virus and in animals inoculated with this, 
together with their absence in diseases other than rabies, seems to 
justify the tentative assumption of a specific etiological relationship to 
hydrophobia.1 
Preparation and Staining of "Negri Bodies." 
Williams-Lowden Method.-While the earlier studies were made on sections, 
Williams and Lowden have shown that in stained smears of the nerve tissue made 
upon slides, which is much simpler than sectioning, the "bodies" are more clearly 
demonstrated, and that this method for diagnostic and other purposes is to be 
preferred. The technique of making and staining smears as devised by Williams and 
Lowden is in outline as follows: 
On a clean slide a small bit of the gray matter is placed, and a cover-glass is lightly 
pressed upon it, spreading it into a thin layer; the cover-glass is then moved along the 
slide, leaving a uniform thin smear of the substance. The smears are dried in the air. 
Staining may be done by the Giemsa solution (page 1237) or by the eosin meth- 
ylene-blue stain of Mallory. The latter is effected as follows: 
Fix smears in Zenker's fluid for one-half hour; rinse and place in iodinized, 95 per 
cent, alcohol for fifteen minutes; in 95 per cent, alcohol and absolute alcohol, succes- 
sively, one-half hour each; aqueous eosin solution, twenty minutes; rinse in water; 
place in Unna's alkaline methylene-blue solution (methylene blue, 1; carbonate of 
potash, 1; water, 100) diluted 1 to 5 or 1 to 10 for fifteen minutes; differentiate in 95 
per cent, alcohol from one to five minutes; dry with filter paper; balsam. By this 
method the cytoplasm of the Negri bodies is magenta in color, the central bodies and 
associated granules dark blue, the ganglion cell-body light, and its nucleus a darker 
blue.2 The red blood cells are a brilliant eosin pink. 
Frothingham's Impression Method.-To avoid the distortion of the ganglion cells 
and the disturbance of their relationships inevitable in the "smear" method, and 
to enable the operator to recognize the topography and thus select for examination 
the larger cells lying just outside the hilus in which Negri bodies are more commonly 
found, the following procedure has been recommended for rapid diagnosis.3 Dissect 
out the cornu Ammonis, removing extraneous tissue from the edges. With scissors 
cut out a small disc at right angles to the long axis of the organ from any part desired 
and place it upon a board near its edge so that one of the flat surfaces of the disc rests 
upon the board, the other being exposed. The grouping of nerve cells may now be 
seen in distinct white lines. 
Place a thoroughly cleaned slide upon this disc of tissue, press it gently and lift sud- 
denly. The disc adheres to the wood, and an impression of its upper surface is left 
upon the glass. Repeat, using a new portion of the slide and a little more pressure. 
Make a third impression, using still more force, and a fourth, using sufficient pressure 
to flatten the disc almost completely. Before these impressions have dried, place 
slide in methyl alcohol for one-half to two minutes or longer. Remove from the alco- 
1 For a r6sum6 and study of "Negri bodies" see Williams and Lowden, Jour. Infect. Dis., 1906, iii 
452 (bibl.); and Watson, E. N., Jour. Exper. Med., 1913, xvii, 29. For the preliminary announcement 
of a study of rabies with a special culture medium in which granular and larger nucleated bodies were 
found, see Noguchi, Jour. Exper. Med., 1913, xviii, 314. 
2 For the details of the Giemsa staining and stain for Negri bodies suggested by Van Gieson, see 
Williams and Lowden, Jour. Infect. Dis., 1906, iii, 452, and foot-note p. 461. 
3 See Frothingham, Jour. Med. Research, 1905-06, N. S. ix, 471; also Am. Jour. Pub. Hyg., 
1908, xviii, 4. For a study of virus freed from cells of host, see Poor and Steinhardt, Jour. Infect. Dis., 
1913, xiii, 263. 330 
THE INFECTIOUS DISEASES 
hoi and cover with Van Gieson stain. Warm gently for one-half to two minutes till 
a light vapor rises. Wash in water, dry with filter paper, and examine without cover, 
first with low power to locate best cells, then with an oil immersion. 
The stain may be modified by the use of water 20 c.c.; saturated alcoholic solution 
of fuchsin, 3 drops; saturated aqueous solution of methylene blue, 1 drop, prepared 
fresh each day. The Negri bodies are stained pale pink to pinkish red, the ganglion 
cells are bluish. 
Preventive Inoculation. 
Notwithstanding his total ignorance of the microorganisms con- 
cerned in inciting hydrophobia, his genius in wise experiment enabled 
Pasteur to establish a method which has proved most beneficent for 
artificial immunization against the disease. 
He first obtained a virus of high and definite intensity. This was 
accomplished by a series of inoculations beneath the dura mater in 
rabbits of portions of the spinal cords of rabid animals. This was called 
"virus fixe"-fixed virus. It was found that by drying in the air, 
spinal cords of rabbits having definite and high virulence-fixed virus 
-with due protection against aerial contamination, the virulence 
diminished day by day. With virus thus obtained of virulence ranging 
from that which is practically inert to that of the utmost potency, it 
has been found possible, by subcutaneous injections, safely to accustom 
both animals and men to the presence of amounts of hydrophobia virus 
contained in the spinal cord emulsion, which under ordinary conditions 
would prove speedily fatal. In other words, it has been found possible 
to confer artificial immunity against the disease. 
This process occupies several weeks, and immunization must be com- 
pleted before the disease has begun to manifest itself; but as the incu- 
bation period in hydrophobia is fortunately a long one-the average 
is about forty days-it has been possible, in a large and increasing 
number of cases, to save the lives of persons bitten by rabid animals.1 
This work is now done in laboratories maintained for the purpose 
and requires care and experience in the preparation of the virus as well 
as in diagnosis. 
Diagnosis. 
In view of the importance of diagnosis in animals which have died 
or have been killed under suspicion of rabies, the brain, spinal cord, 
medulla, and ganglia should be saved. 
The presence of Negri bodies is believed to be diagnostic for rabies, 
so that these should be sought for in the fresh tissue by the methods 
indicated above. But considerable experience is required for this work. 
The examination of the plexiform and other ganglia, and of the 
perivascular tissue and ganglion cells in hardened tissue for possible 
changes, may be useful in cases of doubt, though not in themselves 
positively diagnostic. Finally, it may be necessary to have recourse 
'See, for details of preventive inoculations, Park and Williams, Pathogenic Microorganisms, 6th 
ed., New York, 1917, p. 569; also for general summary and bibl. Stimson, Bull. 65, Hyg. Lab., Pub. 
Health Ser., Washington, 1910. 331 
THE INFECTIOUS DISEASES 
to the biological test, that is, subdural inoculation of susceptible animals 
with fresh material from the medulla of the suspect. Portions of the 
fresh medulla in watery emulsion are inoculated beneath the dura mater 
of three healthy rabbits or guinea-pigs, and the development of rabic 
paralysis and other symptoms awaited. This operation for diagnostic 
purposes should be done only by one experienced in this subject.1 
It is always wise not to kill animals suspected of rabies, but to keep 
them under observation in confinement. Rabies being always fatal, 
recovery from a suspicious disease excludes it, so that further pro- 
tective measures may be clearly unnecessary. On the other hand, the 
carefully observed symptoms of a suspected animal may even in the 
event of a fatal termination afford valuable evidence. If the laboratory 
for diagnosis be accessible, it is well, if the suspected animal should die 
or be killed, to send the whole animal or the head cut off low down, 
packed in ice. Cold does not rapidly diminish the virulence of the 
rabic virus. If the material is to be transmitted for a long distance, 
after the preparation of impressions or smears from the gray matter of 
the cornu Ammonis, the brain of the animal with the medulla, carefully 
removed to avoid contamination, may be sent in a sterilized bottle con- 
taining a mixture of equal parts of glycerin and water, which has been 
sterilized by boiling and cooled. 
It has been found that by cauterization with fuming nitric acid of 
the wounds made by rabid animals, the infective agent may be destroyed 
even after the lapse of several hours. 
ACUTE ANTERIOR POLIOMYELITIS. (Infantile Paralysis.) 
Acute anterior poliomyelitis is an infectious disease occurring in 
epidemic and sporadic forms, affecting especially young children, and 
definitely, though apparently not readily, communicable. 
While before 1907 epidemics of this disease were infrequent in the 
United States, since that time it has widely prevailed. In Europe also 
within the past few years the disease has been of frequent occurrence 
and widespread. It is characterized by an exudative inflammation of the 
meninges, and of the interstitial tissue of the brain, and especially the spinal 
cord, which may lead to destructive changes in the ganglion cells, par- 
ticularly of the anterior horns, and to paralysis, atrophy, and contracture 
of the associated muscles. 
Although a series of earlier studies had shown that the disease could 
be incited in monkeys by the intraperitoneal injection of an emulsion 
of nerve tissue from fatal cases of infantile paralysis, it was not until 
1909 that Flexner and Lewis2 succeeded in carrying the infective agent 
from a human case on through monkeys, by the intracranial inoculation 
of nerve tissue of infected animals, in a series which is now extended 
and apparently may be indefinitely prolonged. Then it was discovered 
'For further details of diagnosis, see Williams and Lowden, Jour, Infect. Dis., 1906, iii, 452; 
Frothingham, Jour. Med. Research, 1905-06, N. S. ix, 471; and Park and Williams, Pathogenic Micro- 
organisms, 6th ed., New York, 1917, p. 564. 
-Flexner and Lewis, Jour. Exper. Med., 1910, xii, 227. 332 
THE INFECTIOUS DISEASES 
that experimental infection can be secured by inoculation into the sub- 
cutaneous tissue, blood-vessels, and nerves, and it now seems probable 
that under all these conditions the course of infection is through the 
nerves. It has been found, also, that the infective material may be 
present, not only in the brain, spinal cord, sensory and sympathetic 
ganglia, but also in the blood, spinal fluid, nasopharyngeal mucous 
membranes, and the lymph-nodes.1 
The infective agent belongs among the so-called "filterable viruses" 
for it passes through the pores of the Berkefeld filter. Its virulence per- 
sists after drying and after long preservation in glycerin-two years or 
more. It is readily killed by 
heat-45° to 50° C. for thirty 
minutes, but sustains prolonged 
cold, though less resistant to 
this than to long immersion in 
glycerin. 
Flexner and Noguchi2 have 
cultivated from the brains of 
human cases of poliomyelitis as 
well as from the brains of ex- 
perimentally infected monkeys, 
a minute organism which in- 
duces characteristic symptoms 
and lesions in monkeys. This 
spheroidal organism occurs in 
masses or pairs or chains, de- 
pending upon conditions of cul- 
ture (Fig. 181). The individual bodies are about 0.2 micron in diameter, 
which is much smaller than any known cocci, and close upon the limits of 
visibility. By appropriate stains these organisms can be demonstrated 
also in the central nervous system.3 
Cultures were at first secured from fragments of infected brain, in 
human ascitic fluid to which had been added a fragment of sterile tissue, 
such as fresh rabbit kidney, for example, oxygen being excluded by cover- 
ing the liquid in the tube with a thick layer of sterile paraffin oil. The 
growth of the organism is manifested by a gradually increasing opales- 
cence of the fluid. After the adaptation of the organism to the above- 
culture medium, it may be transferred and grown on agar and under other 
conditions. Cultures have been carried forward through many genera- 
tions, still maintaining the capacity, under the requisite conditions, of 
inciting the disease in monkeys. 
In addition to the organism described by Noguchi, there have been 
found by Rosenow4 in the brain, cord, mesenteric lymph-nodes, tonsils, 
and elsewhere, irregular, short-chain streptococci or diplococci, usually 
Fig. 181.-Organism Isolated from Case of 
Poliomyelitis. 
From a preparation by Dr. Noguchi. X 1000. 
1 For a study of the distribution of the virus from the blood, see Flexner and .4 moss, Jour. Exper. 
Med., 1914, xix, 411. 
1 Flexner and Noguchi, Jour. Exper. Med., 1913, xviii, 461; Flexner, Noguchi, and Amoss, ibid., 
1915, xxi, 91. 
3 Hektoen, Mathers, and Jackson, Jour. Infect. Dis., 1918, xxii, 89. 
* Rosenow, Wheeler, Towne, v. Hess, and Gray, Jour. Infect. Dis., 1918, xxii, 281-426 (complete bibl.). 333 
THE INFECTIOUS DISEASES 
giving a green halo on blood agar media, and in some cases fermenting 
inulin. Under anaerobic cultivation, the organism becomes filterable 
and appears in every way identical with the organism described by 
Flexner and Noguchi. The agglutination of some of the more sensitive 
strains has been observed when serum of persons who have recovered 
from poliomyelitis has been used. 
In experimentally infected monkeys the symptoms and lesions of the 
disease in man are fairly reproduced. The lesions in the monkey are, 
primarily and chiefly, cellular infiltrative changes in the perivascular 
lymph-spaces of the arteries and of the interstitial substance of the nerve 
tissues (Fig. 787). This leads to temporary occlusion of the vessels, 
focal hemorrhage and edema, and degeneration of the nerve tissues with 
necrosis and disintegration. While the brain may be involved, the lesions 
are especially marked in the spinal cord and medulla. (For details of the 
lesions in man, see page 1156.) 
Communicability.-Clinical evidence of the communicability of 
epidemic poliomyelitis is abundant. Since it has been shown by Flexner 
and Lewis, not only that the nasopharyngeal mucosa in animals arti- 
ficially infected by intracranial injections may contain the infective 
agent, but that on rubbing the virus from an infected animal over the 
scarified nasopharynx of monkeys characteristic paralysis may follow, 
one is led to assume that the discharges from the mouth and nose of 
victims of the disease should be properly cared for.1 The infectious agent 
is present in the nasopharyngeal secretions in mild cases giving no symp- 
toms and in contact carriers; and the occurrence of isolated cases far 
removed from the central epidemic focus is probably due to such 
carriers. 
Immunity.-Flexner and Lewis have shown that a certain immunity 
is secured in monkeys by a successfully weathered artificial infection. 
But the nature of this immunity is not yet quite clear, nor are the pre- 
liminary studies on the production of immunizing sera sufficiently 
advanced to justify prediction of success in the immediate future.2 
TYPHUS FEVER. (Hospital Fever; Spotted Fever; Jail Fever; Ship Fever, etc.) 
The characteristic clinical lesion of the disease is the petechical skin 
eruption. Histologically, the chief changes are thrombosis and striking 
perivascular accumulations of adventitial lymphocytes and polymor- 
phonuclear leucocytes. The vascular endothelium is swollen, and the 
endothelium of the sinusoids in the liver shows similar swelling and hyper- 
plasia. The large vascular trunks often, though not constantly, show 
subendothelial infiltration and minute mural thrombi. Similar lesions 
are seen in the vessels of the central nervous system, heart, kidney, and 
muscles, but no other characteristic changes are found.3 
1 Flexner, Jour. Am. Med. Assn., 1910, liv, 535. 
2 For an interesting resume of the nature, prevalence, and prevention of the disease, see Frost, Pub. 
Health Repts. U. S. Mar. Hosp. Service, 1910, xxv, 1663. See also, Heist, Solis-Cohen, and Kolmer, 
Jour. Infect. Dis., 1918, xxii, 169-188; and Nuzum, J. W„ ibid., 1918, xxiii, 307. 
3 Ceelen, W., Lubarsch u. Ostertag, Ergebn. d. allg. Path., 1919, xix1, 307. 334 
THE INFECTIOUS DISEASES 
It is now generally believed that the infecting agent is Rickettsia 
prowazeki, which is transmitted by means of the louse, Pediculus 
humanus.1 
A form of typhus fever has been described in Mexico under the name 
Tabardillo, and in New York under the name Brill's disease. 
ROCKY MOUNTAIN SPOTTED FEVER. (Tick Fever.) 
This infectious febrile disease, occurring chiefly in the spring in 
Montana and adjacent Rocky Mountain States, is often fatal, not com- 
municable, and without obvious characteristic lesions save petechial 
and other spots of the skin which mark it as one of the group of hemor- 
rhagic septicemias. 
Minute organisms, apparently belonging to the group Rickettsia, 
have been found within the endothelial cells of the vascular lesions.2 
The disease can be transmitted to guinea-pigs, rabbits, and monkeys, and 
is probably conveyed to man by the bite of infected ticks, Dermacentor 
venustus. 
YELLOW FEVER. 
Lesions of the Disease. 
Yellow fever is endemic in tropical America, occurs on the west coast 
of Africa, and occasionally invades the temperate zones of America. 
This infectious disease of man is without characteristic lesions save 
for the hemorrhages and pigmentation in the skin. Such other lesions 
as commonly exist are those common to toxemia. The following con- 
ditions are, however, frequently present after death: 
Rigor mortis is marked and occurs early. 
The brain and its meninges are usually congested. The skin is of a 
yellow color from the presence of bile pigment, and may be mottled 
by ecchymoses. Ecchymoses are frequent in the mucous and serous 
membranes. 
The heart is of a pale or brownish yellow color. Its muscular fibers 
may be the seat of fatty degeneration. The lungs may be congested. 
The stomach often contains a characteristic dark fluid, due to altered 
blood pigment, similar to that which is vomited during life-black 
vomit. Its mucous membrane may be congested and softened, and is 
sometimes eroded. The intestines are dark-colored, often distended 
1 da Rocha-Lima, H., Lubarsch u. Ostertag. Ergebn. d. allg. Path., 1919, xix1, 159; Strong, R. P., 
and others, Typhus Fever, with particular reference to the Serbian epidemic, Cambridge, Mass., 1920; 
Wolbach, S. B., Todd, J. L., and Palfrey, F. IF., The Etiology and Pathology of Typhus, being the main 
report of the Typhus Research Commission of the League of Red Cross Societies to Poland, Cambridge, 
Mass., 1922. 
2 Wolbach, S. B., Jour. Med. Research, 1919-20, xli, 1. 
* Rickets and Gomez, Jour. Inf. Dis., 1906, iv, 141. THE INFECTIOUS DISEASES 
335 
with gas, and sometimes contain blood. The liver in the earlier stages 
of the disease may be intensely congested. More frequently it con- 
tains but little blood and is of a light yellow color, and the hepatic cells 
show the changes of an intense albuminous degeneration, often much 
more marked than are found in any other disease except acute yellow 
atrophy of the liver. Areas of focal necrosis may be present. The gall- 
bladder is apt to be contracted. 
The spleen shows no marked changes. The kidneys present an 
intense albuminous degeneration. The tubules usually contain masses 
of hyaline material. 
The Excitant of the Disease. 
While its mode of occurrence and the characters of its symptoms and 
lesions indicate that yellow fever is an acute infectious disease, none of 
the various studies which have been made upon its etiology has as yet 
revealed the presence of any microorganism which can be confidently 
accepted as its excitant.1 
The Mode of Infection. 
It was shown by Reed and his colleagues, Carroll, Agramonte, and 
Lazear, that the infectious agent in yellow fever may be transmitted by the 
subcutaneous injection into a healthy individual of a small quantity of 
blood drawn from a patient in the early stage-first three days-of the 
disease. It has, furthermore, been shown by repeated and abundantly 
confirmed experiments that yellow fever may be induced in a non-immune 
individual by the bite of mosquitos-Stegomyia fasciata and Aedes 
calopus-which have previously-at least twelve days-bitten a patient 
in an early stage of the disease. Practical sanitary procedures, based 
upon the hypothesis that these insects act as intermediate hosts in 
which the (unknown) yellow-fever parasite passes one of its develop- 
mental cycles, have furnished strong evidence that it is through the 
intervention of these mosquitoes, and thus only, that the disease is con- 
veyed. For it has been possible, by the prevention of access of them to 
yellow-fever patients through the use of netting and other precautionary 
measures, practically to suppress the disease in Havana, where it was 
formerly endemic, and to stifle epidemics elsewhere.2 It has been further 
demonstrated in the most conclusive way that the infectious agent in 
yellow fever is not conveyed directly through the air or by fomites.3 
1 The various studies of Sternberg, who isolated a bacillus which he called Bacillus x, and of Sanarelli, 
who found a bacillus which he named Bacillus icteroides, are the most noteworthy earlier contributions 
to the subject. A later study and references to the bibliography of this subject may be found in an 
article by Reed and Carroll, Jour. Exper. Med., 1900, v, 215. 
2 For a summary of observations relating to the mosquito as an intermediary host of the infectious 
organism in yellow fever, see Reed, Carroll, Agramonte, and Lazear, Philadelphia Med. Jour., 1900, vi, 
790; also Jour. Am. Med. Assn., 1901, xxxvi, 431; and Am. Med., 1901, ii, 15; Guiteras, Am. Med., 1901, 
ii, 809; Durham, Thompson Yates' Laboratories Report, 1901, iv, 485; Reed and Carroll, Am. Med., 
1902, iii, 301; also Carroll, Jour. Am. Med. Assn., 1903, xl, 1429. A summary and bibliography by 
Goldberger is in Bull. No. 16 of the Yellow Fever Institute, 1907, U. S. P. H. S. 
3 For a brief r6sum6 of the reasons for the belief that the mosquito is the sole agent in the conveyance 
of the infectious agent in yellow fever, see Carter, Bull. No. 10, of the Yellow Fever Institute, 1902, 
U. S. P. H. S. For a discussion of mosquitos and a general review of the subject, see, also, Howard, 
Dyar, and Knab, The Mosquitoes of North and Central America and the West Indies, Carnegie Institu- 
tion of Washington, Pub. No. 159, 1912. For the bearing of this subject upon quarantine regulations, 
see Doty, Med. Rec., 1901, lx, 649. 336 
THE INFECTIOUS DISEASES 
That it is an extremely minute organism is shown by the fact that it can 
pass through the pores of a Berkefeld filter. 
VARIOLA. (Smallpox.) 
Smallpox is an acute, readily communicable, infectious disease, 
especially characterized anatomically by an inflammation of the skin 
which passes through a series of more or less distinctive phases of papule, 
vesicle, pustule, with a final drying of the exudate and necrotic tissue 
constituting the crust. 
Various phases of the exanthem are used to designate forms of the 
disease. 
Secondary lesions are diffuse suppurative inflammation of the skin, 
congestion, inflammation, and ulceration of the mucous membranes, 
hemorrhages in various parts of the body, swelling and ulceration of 
the lymphatic tissues, albuminous degeneration of the kidney, liver, and 
spleen, and leucocytosis. 
Fig. 182. -A Smallpox Vesicle of the Skin. 
The skin lesion shows in general at first circumscribed areas of inflam- 
mation above the ends of the papillae, with the development of a fluid- 
filled reticulum, so that vesicles more or less umbilicated are formed 
(Fig. 182). These at first contain a clear fluid, but by the gathering of 
pus cells the fluid becomes turbid and accumulates to form a pustule. 
Hand-in-hand with these changes the papillae and adjacent layers of the 
corium may become infiltrated with cells. The contents of the pustules 
and the necrotic tissue above dry and form the crusts. When the 
changes are largely confined to the epidermis, the lesion may leave no 
deformity. But if the changes in the cutis are considerable, cicatricial 
tissue may form, leaving scars. The association of local hemorrhage 
with the above changes gives rise to the hemorrhagic form of exanthem. 
Artificial Immunization in Smallpox. 
Smallpox affords one of the most striking examples of positive and 
prolonged acquired immunity conferred by a successfully weathered 
attack of an infectious disease. THE INFECTIOUS DISEASES 
337 
In the early days attempts were made to mitigate the virulence of 
smallpox acquired by exposure in the usual ways by artificial inoculation 
of material-virus-taken from a smallpox pustule. The usually 
relatively mild form of the disease induced in this way also conferred 
immunity. But the individual was during his immunization a source of 
danger to others. The great discovery of Jenner that by inoculation 
with virus from cowpox, immunity was secured against smallpox need 
not be considered in detail here. The immunity secured in this way, 
while not absolute, is usually effective and involves as a rule but slight 
indisposition. By revaccination after an interval of a few years prac- 
tical protection is secured, so that the occurrence of smallpox epidemics 
to-day is possible only through neglect of simple and positive protective 
measures. 
The more recent view of the immunity conferred by vaccination 
against smallpox is based upon the demonstration that the disease 
variola in man and the disease vaccinia in the bovine species are of 
the same nature and not different, as was formerly believed. This 
has been established by numerous inoculation experiments; by comple- 
ment fixation tests, also, the close biological relationship between variola 
and vaccinia has been demonstrated.1 The disease in the cow is a modi- 
fied form of the human disease. The effect of the passage of the unknown 
microorganisms through the insusceptible bovine-thus runs the rationale 
in the new light-is so to diminish the virulence of the germ that by its 
subsequent inoculation in man immunity is secured without the profound 
disturbance which infection with a germ of unmitigated virulence would 
involve.2 
The Excitant of Smallpox. 
Bacteria.-The large number of studies which have been made of the 
skin lesions of smallpox and of vaccine lymph have shown that bacteria 
of various kinds are frequently present.3 Streptococci and staphylo- 
cocci are especially common in the pustules and may be present in the 
blood in later stages of severe or fatal cases.4 It is probable that the 
pyogenic cocci are of great importance as complicating factors in the 
disease. But there is no evidence at hand that these or any other bac- 
teria are its primary excitants. 
Protozoa.-While it was natural that the most painstaking search 
should be made for bacteria in the lesions of smallpox, there have been 
1 Kolmer, Jour. Immunol., 1916, i, 51, 59. 
2 In diphtheria the perfection of the process of artificial immunization and the establishment of 
a precise and successful curative method are the direct results of a long, patient, logical series of animal 
experiments with a definite end in view, and by the use of the absolutely identified and well-known 
germ which induces the disease. On the other hand, it is not a little curious that in smallpox and in 
hydrophobia effective methods of immunization should have been perfected without precise knowledge 
of the microorganisms which incite the diseases, and yet by procedures which, though somewhat em- 
pirically hit upon, are nevertheless in close accord with those which the most recent studies on immunity 
in general have shown to be effective. Thus in both smallpox and hydrophobia the material used 
for protective inoculation is that which has been artificially reduced in virulence; in the one case-small- 
pox-by its passage through the body of a relatively insusceptible animal; in the other-hydrophobia- 
by drying in the air. 
3 See Huguenin, Lubarsch and Ostertag, Ergebn. d. allg. Path., 1897, iv, 387 (bibl.). 
4 See report by Ewing, Trans. Assn. Am. Phys., 1902, xvii, 213; also Perkins and Pay, Jour. Med. 
Research, 1903, N. S. v, 180. 338 
THE INFECTIOUS DISEASES 
from the first many obvious reasons for the conjecture that this disease 
as well as the other exanthemata might be incited by organisms of a 
different nature. In fact, as early as 1886 and 1887 bodies were found 
in the pustules by Van der Loeff and L. Pfeiffer, which they conjectured 
to be protozoa. It was not until 1892, however, when Guarnieri under- 
took a series of noteworthy experiments in animals, that the nature of 
the suspected structures in vaccine lymph became clearer. Guarnieri 
inoculated vaccine lymph into the cornea of rabbits and after a few days 
noted in the epithelial cells the appearance in increasing numbers of the 
structures which had been previously discovered in the contents of small- 
pox pustules. In some of these bodies he believed that he saw ameboid 
movements. These bodies, which were called "vaccine bodies," he 
regarded as protozoa and named the species Cyloryctes vaccinoe.1 
These observations of Guarnieri on the vaccine bodies found in the 
lesions of both vaccinia and variola were confirmed by Wasielewski2 
and many other observers. 
The vaccine bodies of Guarnieri are spheroidal, oval, or irregular 
structures from 1 y to 4 or even 8 y in diameter, staining readily with 
various dyes, the central portion giving in general the staining characters 
of nuclear substance, a peripheral zone being sometimes differentiated 
by cytoplasmic stains. The bodies often lie close upon the border of 
the nucleus of the epithelial cells, sometimes in a depression of the nu- 
clear border. They may, however, lie in other parts of the epithelial 
cytoplasm. They are frequently surrounded by a clear space, which may 
become of considerable size. They have not been found in the nucleus. 
Hand-in-hand with the increase of these bodies there are progressive 
degenerative processes in the epithelium of the inoculated region, with 
the formation of various structures characteristic of the degeneration 
of protoplasm under a great variety of conditions. 
While many observers following Guarnieri have felt justified, largely 
on morphological evidence, in the belief that the vaccine bodies are pro- 
tozoa, others have been led to the conclusion that many, if not all, the 
appearances presented can be accounted for by protoplasmic degen- 
erations induced by other agencies. Several experimenters, indeed, 
by the introduction into the rabbit's cornea of chemical and other sub- 
stances not at all related to the vaccine virus, have been able to induce 
degenerative protoplasmic structures resembling the vaccine bodies. 
The studies of Ewing on this subject are of especial significance.3 
It is evident that the proof on morphological grounds alone of the 
protozoan nature of such minute structures is a task of extreme difficulty, 
associated as they frequently are with the readily stained products of 
protoplasmic degeneration. 
In April, 1903, Councilman announced the results of a long series of 
studies by himself and his associates, Magrath, Brinckerhoff, and Tyzzer, 
1 This name was given because the bodies frequently lay in small spaces in the cell protoplasm, 
which he assumed to have been formed by the destructive action of the parasite. 
2 Consult for a most admirable summary of the subject, with original studies, photographs, and 
bibliography, Wasielewski, Ztschr. f. Hyg. u. Infectionskrankh., 1901, xxxviii, 212. 
3 See Ewing, Jour. Med. Research, 1904, N. S. vii, 509; 1905, N. S. viii, 233. THE INFECTIOUS DISEASES 
339 
on the excitant of smallpox.1 The observations of Guarnieri, Wasie- 
lewski, and others, on the vaccine body, were in the main confirmed. 
These observers found the vaccine bodies in the lower layers of skin epi- 
thelium before the production of the vesicles and in the advancing 
edges of the young vesicles. They found morphological evidence of the 
segmentation of the bodies and the formation of round, spore-like 
structures about 1 in diameter. Councilman further announced 
the discovery of other bodies, not before described, within the nucleus 
of the epithelial cells in the infected region in man. These intranuclear 
structures are circular, with a central dot, and may be seen singly or in 
clusters. They are from 1 to 1.5 n in diameter. Councilman regards 
them as a later stage and as representing a second complex cycle of de- 
velopment of the smallpox parasite, and believes that they are developed 
from the spore-like bodies resulting from the segmentation of the intra- 
cellular vaccine body, which then penetrate the nucleus. The vaccine 
bodies are found both in the epithelial cells of the smallpox lesion in man 
and in the lesion induced by vaccination of the rabbit and calf; but the 
intranuclear forms have not been found in the latter animals. After in- 
oculation of the monkey with the contents of smallpox pustules, both the 
intracellular and the intranuclear forms were found. It is thought prob- 
able that in smallpox the parasite undergoes complete development, pass- 
ing through two cycles, an intracellular and an intranuclear, while in 
vaccinia only one, the primary, cycle is achieved.2 
Calkins, from an independent study of the material furnished by 
Councilman, is convinced of the protozoan nature of the organisms in 
question and now groups them among the rhizopods.3 
It is clear that final judgment upon the nature and significance of 
these minute structures must be suspended until further experiments 
upon suitable animals shall have furnished fuller biological data than 
are yet at hand, which may sustain the evidence, still largely morpho- 
logical, on which these suggestive conclusions are based.4 
The virus of vaccinia has been cultivated in vitro by the use of special 
methods of tissue culture.5 
SCARLET FEVER. (Scarlatina.) 
This is an infectious, readily communicable disease characterized by 
a diffuse skin eruption, and frequently accompanied by inflammation, 
either catarrhal, or croupous, or gangrenous, of the tonsils, pharynx, 
and larynx. Focal necroses, albuminous degeneration in the viscera, 
and leucocytosis with moderate eosinophilia may occur. 
1 Councilman and others, Jour. Med. Research, 1904, N. S. vi, 1; see also summary by Councilman, 
Am. Med., 1905, x, 689. 
2 For studies on experimental variola and vaccinia in monkeys, see Brinckerhoff and Tyzzer, Jour. 
Med. Research, 1906, N. S. ix, 209 et seq. See also, for studies on reaction of variola virus to external 
conditions, ibid., p. 352. 
3 Calkins, Protozoology, New York, 1909, p. 308. 
4 Consult for general bibb, Freeman, article on vaccination in Cyclopedia of the Diseases of Children, 
vol. v, suppl., p. 263; or Moore, in Twentieth Century Practice, vol. xiii. 
5 Steinhardt, Lambert, Israeli, and Grund, Jour. Infect. Dis., 1913, xiii, 294; 1914, xiv, 87; 1915, 
xvi, 205. 340 
THE INFECTIOUS DISEASES 
There may be acute hyperplasia or suppuration of the cervical lymph- 
nodes. There is very frequently an acute exudative or an acute diffuse 
nephritis.1 The spleen may be enlarged. Bronchopneumonia, endo- 
carditis, and pericarditis may complicate the disease. 
The exanthem or skin eruption in scarlatina is a simple dermatitis, 
as the result of which the papillae and subpapillary stratum become 
infiltrated with fluid or leucocytes, or both, the leucocytes being gathered 
especially about the blood-vessels. There may be small hemorrhages, 
and the acute phase of the inflammation is followed by an increased 
production of epithelium and an exfoliation of the superficial layers. 
These lesions of the skin may be, excepting the hemorrhages, very 
slightly marked after death. 
The Excitants of Scarlatina.-That the disease is due to some form 
of microorganism there can be no doubt; but the exact nature of this 
organism is not yet known. The acute nephritis and the marks of 
degeneration and focal necrosis so often present appear to be due to some 
poison formed in the body during the disease. 
Mallory2 has described bodies in and between the epithelial cells of 
the epidermis and free in the superficial lymph-vessels and spaces of 
the corium in scarlet fever which he believes to be protozoa and to bear 
an etiological relationship to the disease. Most of these bodies are 
from 2 to 7 /z in diameter and stain with methylene blue. A series of 
forms are found, including rosettes, which are said to resemble the series 
in the asexual development of the malarial parasite. Further studies 
will be required to establish the protozoan nature as well as the signifi- 
cance of these structures.3 
One of the most marked features of the disease is the predisposition 
which it entails to the incursions of pathogenic germs other than that 
which we believe to be its excitant. Thus an infectious croupous inflam- 
mation of the mouth, tonsils, pharynx, larynx, and trachea, due to a 
streptococcus (page 241), is a frequent complication. True diphtheria 
due to the Loeffler bacillus is also prone to establish itself upon the vul- 
nerable inflamed mucous membranes. So also the frequently associated 
pneumonia, the inflammatory hyperplasia and suppuration of the lymph- 
nodes, suppurations in various parts of the body, the endocarditis and 
pericarditis which are not uncommon, may all be due to a secondary 
infection with the pyogenic cocci. 
TRACHOMA. 
The inflammation of the conjunctiva, known as trachoma, has long 
been suspected to be of infective nature. But it was hot until 1907 that 
1 For a special study of kidney lesions in scarlatina, see Chapman, Jour. Path., 1906, xi, 276 (bibl.). 
2 Mallory, F. B., Jour. Med. Research, 1904, N. S. v, 483; Mallory, E. B., and Medlar, E. M., ibid., 
1916-17, N. S. xxx, 209; and Williams and Lowden, Studies from the Research Laboratory, Dept, of 
Health, New York, 1907, iii, 42. On the demonstration of the alleged parasites of scarlatina in blister 
fluids, see Duval, C. IP., Uni>. Pennsylvania Med. Bull., 1904, xvii, 298, and Virchows Arch., 1905, 
clxxix, 485; and Field, C. IP., Jour. Exper. Med., 1905, vii, 343. 
'For a study of intraleucocytic inclusions (Dohle bodies), seo Glomset, Jour. Infect. Dis., 1912, xi, 
468. For a study of the alleged incitement of scarlet fever in monkeys, see Draper and Hanford, Jour. 
Exper. Med., 1913, xvii, 517. THE INFECTIOUS DISEASES 
341 
Halberstaedter and v. Prowazek,1 and Greeff2 described the occurrence in 
the epithelial cells of the conjunctiva during the early stages of the 
disease of extremely minute, round or oval bodies, smaller than the 
smallest cocci, and surrounded by a clear mantle which stains blue with 
Giemsa. The bodies do not take the Gram stain, but by the Giemsa 
method stain reddish or violet. They have been called trachoma bodies 
Fig. 183.-Trachoma Bodies. 
Conjunctiva. From a preparation by Dr. Noguchi. The bodies nearly fill the cell near the center 
of the cut and partly surround the nucleus. 
or granules, and because of the mantle have been classed by v. Prowazek 
as Chlamydozoa. They are found in the epithelial cells, often grouped 
in concentric masses close to the nucleus, sometimes filling and dis- 
tending the cell body (Fig. 183). They vary considerably in size, in- 
creasing rapidly within their mantles, which presently they displace, 
but are never very abundant and may soon disappear. Their nature 
and significance is not clear.3 
1 Halberstaedter and v. Prowazek, Deutsch, med. Wchnschr., 1907, xxxiii, 1285; Handbuch d. path. 
Protozoen, Leipzig, 1912, i, 172 (bibl.). 
2Greeff, Deutsch, med. Wchnschr., 1907, xxxiii, 914. 
3 For a study and bibl., see Noguchi and Cohen, Jour. Exper. Med., 1913, xviii, 573; and Wolbach 
and McKee, Jour. Med. Research, 1911, N. S. xix, 259. 342 
THE INFECTIOUS DISEASES 
In various types of inflammation of the conjunctiva, the presence of 
hemoglobinophilic bacilli has been demonstrated and it has been sug- 
gested that the trachoma granules found in these inflammations as well 
as in inflammations of the mucous membranes of other parts of the body, 
such as the vagina and the urethra, may be due to these bacilli.1 
MEASLES. 
This is a readily communicable infectious disease, the most prominent 
features of which are an intense hyperemia with inflammation of the 
skin, associated with catarrhal inflammation of the mucous membrane 
of the air passages. The inflammation of the skin is anatomically of 
the same general type as that in scarlatina.2 Albuminous degeneration 
of the kidney or acute exudative nephritis may occur. Focal necrosis 
in the liver and kidneys has been described.3 
The more common secondary lesions are bronchopneumonia, pseudo- 
membranous inflammation of the pharynx and larynx, suppurative 
inflammation in various parts of the body, and diphtheria. These compli- 
cations, as in scarlatina, are doubtless, in part at least, due to secondary 
infection with germs other than those causing the disease itself. 
The excitant of measles is not known though a variety of organisms 
have been described.4 
Inoculation of Measles.-Although readily conveyed in natural ways 
from one human being to another predisposed individual, the attempts 
at experimental inoculation of the infectious agent in measles in man 
have not led to very definite conclusions. Hektoen succeeded in two 
cases in inducing typical measles by the injection of material derived 
from the blood at an early stage of the disease.5 
MALARIA. 
The Lesions of Malaria. 
The characteristic lesions of acute malarial infection are found in the 
blood, the liver, spleen, kidneys, and brain. 
The alterations in the blood are chiefly confined to the diminution in 
number of the red corpuscles, due to their destruction by the parasites 
developing in them, and to a reduction in the hemoglobin content of 
those which do not contain parasites. These changes are apparently 
due to some toxic agent, for which there is additional evidence in the 
polychromatophilia and granular degeneration of the body of the red 
cell so often present in severe malarial infections. The evidence of some 
poison acting on the protoplasm of the red cells is found, not only in 
1 Park and Williams, Pathogenic Microorganisms, 6th ed., New York, 1917, p. 416. 
2 For a study of epithelial cell changes in measles, see Ewing, Jour. Infect. Dis., 1909, vi, 1. 
3 Freeman, Arch. Pediat., February, 1900, xvii, 721. 
4 For recent studies on the bacteriology of measles, see Tunnicliff, R., Jour. Infect. Dis., 1918, xxii, 
462; and Hektoen, L., Jour. Am. Med. Assn., 1918, Ixxi, 1201 (bibl.). 
6 For attempts at inoculation of measles see Hektoen, Jour. Infect. Dis., 1905, ii, 238. For an 
experimental study of measles in monkeys, see Lucas and Prizer, Jour. Med. Research, 1912, N. S., 
xxi, 181; and Blake, F. G. and Trask, J. D., Jour. Exper. Med., 1921, xxxiii, 385, 413, 621. THE INFECTIOUS DISEASES 
343 
those cells in which the organism is developing, but more abundantly 
in those cells in which no plasmodia are present. 
The leucocytes show slight qualitative changes, there being usually 
present a relative increase in the large mononuclear cells. Pigmented 
leucocytes are often seen, and in very severe infections large macrophages 
loaded with pigment may be seen in the circulating blood. In severe 
cases the pigment, which is derived from the hemoglobin of the blood 
corpuscles and forms the granules in the body of the parasite, may be 
found free in the general circulation, but is usually soon removed by 
the leucocytes and the phagocytic cells of the liver, spleen, and bone 
marrow. The brain in cases of pernicious estivoautumnal fever is 
often much congested, and the smaller capillaries may be thrombosed, 
or filled with enormous numbers of the plasmodia in various phases of 
development; there may also be small punctate hemorrhages in the white 
matter. The deposition of the malarial pigment in the cortex may give 
to the latter a dark reddish brown color, or it may be almost black. The 
spinal cord shows similar changes. 
The liver in acute cases may show focal necroses resembling those 
present in other infectious diseases. The endothelium of the liver 
capillaries may contain much pigment (Fig. 521, page 821), while 
the lumina of the capillaries may be stuffed with plasmodia in various 
stages of development. Thromboses of infected red blood-cells, pig- 
ment, and cell fragments are not uncommon. The kidneys may show 
albuminous degeneration, and while the intertubular capillaries may be 
filled with pigmented leucocytes there is not, as a rule, a great accumu- 
lation of plasmodia in the vessels. A moderate diffuse nephritis is 
occasionally seen. The capillaries of the mucosa of the stomach and the 
intestines may be filled with parasites in cases with choleraic symptoms, 
and there may be a considerable amount of necrosis in the epithelium 
of the mucosa of the intestines. The bone-marrow usually contains large 
numbers of the plasmodia, chiefly segmenting forms. A good deal of 
pigmentation is present, and an active phagocytosis is carried on, mainly 
by the giant-cell macrophages present in the marrow. Crescentic organ- 
isms may be present in the marrow even if these have not been present 
in the blood during life. Hyperplasia of the marrow is not seen unless 
the disease has continued for some time. 
The spleen is increased in size, the pulp is softened and very dark, 
the Malpighian bodies are not well marked and may be necrosed. The 
heart muscle is fatty and capillary thrombi may be present. Microscopic- 
ally, the organ is greatly congested; many of the red cells are invaded by 
the plasmodia which are often in the segmenting stage. There is a very 
active phagocytosis by the macrophages present, often so extensive as 
to include the red cells with their contained parasites. 
In the chronic cases the patient may become extremely anemic with 
nucleated red cells in the blood and a great reduction in the number of 
erythroblasts. The spleen is greatly enlarged, the capsule thickened and 
adherent to the surrounding tissues. The cut section of the organ is of 
a dark brown or slaty black from the deposit of pigment. The Mal- 344 
THE INFECTIOUS DISEASES 
pighian bodies are well marked. The fibrous-tissue trabeculae are 
thickened, as is the reticulum of the pulp; the pulp cells are pigmented. 
The liver shows a marked pigmentation, especially in the endothelium 
of the capillaries and in the cells of Kupffer, while occasionally there is 
a moderate amount of new connective tissue, which, however, does not 
follow, as a rule, the anatomical distribution of the connective tissue in 
the usual atrophic cirrhosis. In chronic poisoning the kidneys may show 
a chronic diffuse nephritis. The bone-marrow may remain fairly normal 
except for the deposition of pigment, or there may be seen a marked 
hyperplasia with replacement of the normal fatty marrow of the shafts 
of the long bones by red marrow containing normoblasts, or even mega- 
loblasts if the disease has been long-continued and severe. 
The Excitant of Malaria. 
The excitant of the disease long known clinically as malaria is a small 
animal parasite, the Plasmodium malarias, which enters the red corpuscles1 
of the blood and in the course of its development destroys them. The 
destruction of the cells is coincident with the maturation of the con- 
tained parasite, a phenomenon which is also coincident with the clinical 
appearance of the chill and its accompanying fever.2 
These parasites of the red cell are protozoa belonging to a spe- 
cial sub-group, the hccmosporidia. For purposes of description these 
hemosporidia of human malaria may be classified into three species 
or types, each of which incites a different clinical form of disease 
and each of which also differs from the other types in its morphology. 
These types are the tertian, the quartan, and the estivoautumnal 
parasites. 
Tertian and Quartan Types.-If the blood of a patient suffering from 
tertian fever be examined shortly after a chill, a number of the red cells 
will be found to contain small, highly refractile, actively ameboid bodies 
which are the early forms of the plasmodia, or merozoites. The latter 
often take the form of small rings surrounding a central clear space 
especially well seen in stained specimens (Plate I., Figs. 1-4). If the 
blood be examined some hours later, the small forms will have grown 
and small brown or black granules will be noted in the body of the plas- 
modium, having a very rapid motion inside the body of the parasite. If 
the blood be examined at the end of forty-eight hours the organism may 
be seen to have grown so large as to occupy nearly the whole of the red 
cell (Plate I., Figs. 5-12), which becomes somewhat swollen and pale, 
the latter effect being due to the destruction of the hemoglobin of the 
cell by the parasite, which thus produces the pigment granules of melanin 
with which it is filled. The pigment now occupies the center of the organ- 
ism, which has ceased its active ameboid motion. Now small pale spots, 
which are the nuclei of the segmenting mature form, become easily visible 
> While it is generally known that a few of the parasites adhere to the outer surface of the red cells 
the theory of Rowley Lawson (Jour. Exper. Med., 1914, xix, 450; 1915, xxi, 584; and 1916, xxiv, 291), 
that the parasites are always external to the red cells, has received little or no acceptance. 
2 For cultivation of the parasite, see Bass, C. C., Jour. Am. Med. Assn., 1912, lix, 936. THE INFECTIOUS DISEASES 
345 
(Plate I., Fig. 16), and finally the red cell bursts, and the small merozoites, 
each containing a nucleus, are set free to enter other red cells and to 
repeat the cycle. A certain portion of the free merozoites are destroyed 
by the phagocytic leucocytes and other cells. The free pigment left after 
the segmentation of the mature forms is also collected by these phago- 
cytes. Thus after severe and prolonged attacks of malaria the leucocytes 
are frequently filled with pigment. 
The quartan organism goes through a cycle similar to that of the 
tertian, except that the time required is seventy-two instead of forty- 
eight hours. There are also a few minor differences in the morphological 
appearance of the two organisms. Thus the small early ameboid 
forms of the plasmodium are much more active in their movements in 
the tertian than in the quartan. The pigment in the tertian is very 
fine; in the quartan it is often in small blocks or rods and is much coarser 
(Plate I., Figs. 22-25). The mass of segmenting merozoites in the 
tertian organism is quite irregular in shape and contains from fifteen to 
twenty individuals, while that of the quartan is a regular rosette in 
shape and the merozoites average from six to twelve (Plate I., Figs. 
26-28). 
Estivoautumnal Type.-The parasite of the estivoautumnal fever 
develops in the blood in much the same way as the other forms, with 
the exception that the ameboid rings are, as a rule, smaller. The 
signet-ring shape is more marked, and the pigment is less abundant 
(Plate I., Figs. 31-34). Another peculiarity of this organism is that 
the development of the larger ameboid forms takes place chiefly in the 
bone-marrow and the spleen, while in the tertian and quartan this is to 
be seen in the blood. Thus as soon as the plasmodium of the estivo- 
autumnal type has grown sufficiently to occupy about one-fourth of 
the red cell, it disappears from the peripheral blood and can be found 
developing in the blood obtained by puncture of the spleen, or, in fatal 
cases, from the bone-marrow (Plate I., Figs. 35, 36). In such prepara- 
tions the mature plasmodia may be found and the segmenting process 
followed (Plate I., Figs. 37-39). The organism is not so large as the 
tertian, as the segmenting form usually occupies only about one-half 
of the somewhat shrunken red corpuscle. The number of merozoites 
formed is about fifteen. The time of the developmental cycle in the 
blood is forty-eight hours. 
In the blood of a patient infected with the estivoautumnal parasite, 
there are always found within a few days after the beginning of the 
disease a moderate number of crescent-shaped bodies with pigmented 
centers and the remnant of a red cell about them (Plate I., Figs. 43, 44). 
They are devoid of ameboid motion. The exact nature of these cres- 
centic bodies was quite unknown until very recently, when it was dis- 
covered that they are cells with sexual capabilities, whose function 
seems to be the prolongation of the species in a cycle outside of the human 
body. It had long been known that certain of the large mature ame- 
boid forms of the tertian and quartan organisms and the crescents of 
the estivoautumnal species did not undergo segmentation into mero- 346 
THE INFECTIOUS DISEASES 
zoites, but remained circulating in the blood. When, however, the 
blood containing these forms was examined in a fresh condition on a 
slide, and especially if the blood before being covered was allowed to 
remain in a moist chamber for a few minutes, changes could be seen to 
take place which had not been observed in perfectly fresh preparations. 
Certain of the mature organisms set free long, actively motile flagella 
which entered other mature forms. In stained preparations it could be 
seen that each flagellum contained some of the nuclear chromatin of 
the organism from which it arose, and that this flagellar chromatin 
united with the chromatin of the body which the flagellum entered. 
The crescentic forms under suitable conditions go through the same 
process, the male crescent giving off flagella, one of which in turn fer- 
tilizes another crescent of slightly different morphology. 
Evidently this is a sexual process, and its occurrence only in blood 
which has been drawn from the body suggested the probability that 
under ordinary circumstances it takes place outside the human host. 
The truth of this conjecture has finally been established, and the proc- 
ess of fertilization and maturation of the fertilized organism has been 
found to occur in the stomach of a particular genus of mosquito, the 
Anopheles. No other type of mosquito is capable, according to our 
present knowledge, of acting as host to the plasmodium of human malaria, 
though the organism which induces malaria in birds can develop in a 
mosquito of the genus Culex. Whether the plasmodium can carry out 
its sexual cycle under other conditions than in the stomach of the 
Anopheles is as yet unknown. If an Anopheles bites a patient with 
malaria, the blood with its contained organisms is drawn into the stom- 
ach of the mosquito, the flagella are given off from the gametes and enter 
other mature forms and fertilize them. The fertilized organism goes 
through a complicated development, and the resulting sporozoite finds 
its way in the course of a few weeks to the salivary glands of the mos- 
quito host, to be injected into the blood of the next person bitten. 
The sporozoites enter the red cells, becoming the small ameboid forms 
or merozoites already described.1 
The details of the process of fertilization and the formation of the 
sexual cells which are capable of carrying on the cycle in the mosquito 
have been best observed in the estivoautumnal fevers, so that the 
stages will be here described in connection with the development of the 
crescent gametes. These crescents are formed chiefly in the bone- 
marrow from the small ovoid, intracellular bodies, which can early in 
their development be distinguished from the ordinary ameboid forms 
by their more abundant coarse pigment and oval outline. 
The adult crescents are quite constantly present in well-developed 
cases, and are often found in the blood after treatment with quinine has 
caused the disappearance of the ameboid bodies, the power of resisting 
the action of drugs being much more marked in the crescents than in 
any other form of the plasmodium. Two types may be distinguished, 
both of which begin as small ameboid forms and gradually mature into 
1 For details of the process, see Schaudinn, Arbeiten a. d. k. Gsndhtsamte, 1902, xix, 169. 347 
THE INFECTIOUS DISEASES 
oval or crescentic organisms. One of these, the microgametocytes, or 
the cells producing the male elements, develops and gives off the flagel- 
lum (microgametes); the other, the macrogametes (female elements), 
neither form nor give off flagella. According to Marchiafava and Big- 
nami1 the microgametocytes are distinguished from the macrogametes 
by the fact that in the former (the male form) the pigment is gathered 
in a fairly compact mass in the middle of the crescent, the chromatin 
is more abundant, and the entire body stains faintly; while in the female 
form, the pigment surrounds the rather scanty nuclear chromatin in 
a ring form, the cell body stains deeply, and no flagella are given off. 
The crescents in the fresh blood show no ameboid motion, and even the 
pigment is motionless. They are either crescentic in form with the 
pigment collected at the center, or they may be spindle-shaped with 
somewhat scattered pigment, or finally short, thick ovoid bodies with 
pigment irregularly scattered or more frequently gathered into a ring 
about the nucleus. They are all contained in red blood-cells (endo- 
globular), the faint remnant of the red cell often being seen as a delicate 
line stretching between the two horns of the crescent. 
The formation of flagella (microgametes) does not take place in 
the circulating blood; it begins only after the blood has remained on 
a slide for a few minutes or has remained for some time in the stomach 
of the mosquito. These flagella, usually about four in number, bud out 
from the periphery of one of the microgametocytes, which has assumed 
a spherical instead of a crescent shape, and grow to a length of three to 
five times the diameter of the red cell. They are either pointed or 
bulbous at their extremities, or they present swellings at irregular inter- 
vals. Their motion in warm-stage preparation is rather rapid, and they 
finally become detached and move about free in the serum (Plate I., 
Figs. 45, 46, 47). The pigment during this process usually remains at the 
center of the spherical microgametocyte and is actively motile, but in 
preparations stained to show the nuclear chromatin the latter may be 
seen to penetrate the flagella in the form of long thin rods which remain 
after the flagella become detached. The shell of the red cell in which 
the crescent has developed can rarely be seen in fresh preparations of 
the flagellate forms. These flagella penetrate the body of one of the 
macrogametes present on the slide and fertilize it. 
This process, which we have followed in an artificial preparation, 
seems necessary for the continuance of the race, and is normally carried 
out in the gastric tract of the mosquito of the genus Anophelos. The 
actual entry of the microgamete (spermatozoon) into the macrogamete 
has been observed by MacCallum2 and others in fresh-blood preparations. 
If a patient in whose blood mature crescents are present is bitten by 
the mosquito, the parasites develop in the stomach of the insect, and at 
the end of two days the fertilized forms may be found adherent to the 
wall of the stomach as small pigmented oval bodies quite similar to the 
early forms of the crescents developing in the human bone-marrow. 
1 Other observers assert that in the male forms the pigment is scattered throughout the plasmodium. 
2 MacCallum, W. G., Jour. Exper. Med., 1898, iii, 117. Description of Plate I. 
Haematozoa of Tertian Malaria. 
Figs. 1 to 4 .. . .Small ring-shaped merozoites of tertian malaria; 2 and 3, multiple 
invasion of a single red cell. 
" 5 to 12.... Ameboid forms of gradually increasing size. 
Fig. 13 Large ameboid form in which the pigment is beginning to collect 
as a preliminary to segmentation. 
" 14 Pigment still more clumped, and the pale areas representing nuclei 
begin to be marked. 
" 15 Segmenting form with an irregular mass of merozoites. 
" 16 More symmetrical type of segmentation with central block of 
pigment. 
" 17 Free merozoites after leaving the red cell. 
" 18 Gamete. 
" 19 Microgametocyte with flagella or microgametes. 
Haematozoa of Quartan Malaria. 
Figs. 20 and 21. .Small ring form of merozoites. 
" 22 to 25.. . . Ameboid forms with coarse pigment. 
" 26 to 28 . . .Segmenting forms. 
" 29 Gamete. 
" 30 Microgametocyte with microgametes in the process of formation. 
Haematozoa of Estivoautumnal Malaria. 
Figs. 31 to 34 . . .Small ring forms, some of them on the surface of the corpuscle; 32 
and 33, multiple invasion of the red cell. 
" 35 and 36.. . Ameboid forms found in the peripheral circulation. 
" 37 to 39. . . Large ameboid forms and segmenting parasites found only very 
rarely in the peripheral circulation, but abundantly in the spleen 
and bone-marrow. 
" 40 to 42 . . . Young crescentic forms not found in the peripheral circulation, 
but chiefly in the bone-marrow. 
" 43 and 44. . Adult crescents or gametes, found abundantly in the peripheral 
• blood. 
" 45 and 46. . Microgametocytes becoming oval and preparing to give off microga- 
metes. 
Fig. 47 Microgametocyte giving off microgametes. 
348  THE INFECTIOUS DISEASES 
349 
Two days later the parasites or oocysts are much larger and have a dis- 
tinct capsule, while by the sixth day they may measure from 60 to 80 
// in diameter. They contain numerous small particles which are nuclei 
due to the frequent division of the original nuclear material, and the 
capsule is much thicker. At the end of a week the parasite contains a 
large number of slender thread-like rods with pointed extremities, each 
one of these rods having nuclear chromatin. The parasite or oocyst 
projects through the wall of the stomach into the coelomic cavity of the 
mos'quito host, and when it ruptures these minute rods or sporozoites 
are carried by the lymph currents to the salivary glands, from which 
they may be injected with the saliva when the female Anopheles bites 
another subject. 
The sporozoites, after entering the circulation of man, attack the 
red cells, and become the small ameboid forms described above. In 
two or three weeks the formation of the gametes takes place, and the 
crescent forms appear in the blood. 
That the infection of man in this way is possible has been abundantly 
proved by allowing mosquitos infected with estivoautumnal organisms 
to bite healthy persons, who, after a period of incubation of about ten 
days, are seized with an estivoautumnal type of fever, and the char- 
acteristic organisms, though not present previously, are then to be 
found in the blood. The mature forms of gametes of the tertian and 
quartan fevers undergo a course of development very similar to that of 
the parasites of estivoautumnal fever, and are derived from the blood of 
the infected patient by the female of the same genus of mosquito, the 
Anopheles (Plate I., Figs. 19 and 30). The sporozoites find their way to 
the salivary glands of the mosquito and while the Anopheles is biting 
enter the blood of the person infected. These sporozoites then enter the 
red cells as the small ameboid forms and carry on the sexual cycle in 
the blood until either the tissues of the body finally overcome the para- 
site, or treatment with quinine destroys the merozoites by means of the 
toxic action of the drug on these immature forms.1 
Methods of Examination of the Blood in Malaria. 
The methods for the identification require considerable training, as the artefacts 
produced by imperfect technique have often been mistaken for organisms. 
The Examination of Fresh Blood.-To examine the fresh blood, a puncture 
is made in the pulp of the finger and a perfectly clean cover-glass just touched to.the 
top of the drop of blood which exudes from the puncture. The cover is then dropped 
without pressure on a clean slide. The diameter of the drop on the cover-glass should 
never exceed 2 mm., because if more be taken the corpuscles cannot spread out in a 
perfectly thin layer, but will overlap each other and the preparation will be useless. 
1 A general bibliography of malaria to 1895 is contained in the excellent monograph of Thayer and 
Hewetson, The Malarial Fevers of Baltimore, Johns Hopkins Hosp. Rep., 1895, v, 1. See, also, 
Marchiafava and Bignami, on Malaria, in Twentieth Century Practice, New York, 1900; Liihe, Cen- 
tralbl. f. Bakteriol., 1900, xxvii, 367, 436; 1900, xxviii, 384; and Eysell, A., Mense, Handbuch d. Tropen- 
krankheiten, 2d ed., Leipzig, 1913, i, 97 (bibl.). For a study of structure and biology of Anopheles, 
see Nuttall and Shipley, Jour. Hyg., 1901, i, 4. For practical directions for the identification and 
study of mosquitos, see Alcock, Entomology for Medical Officers, London, 1911; and Howard, Dyar, 
and Knab, the Mosquitoes of North and Central America and the West Indies, Carnegie Institution 
of Washington, Pub. No. 159, 1912. 350 
THE INFECTIOUS DISEASES 
The search for the organism should be made with a one-twelfth oil-immersion lens and 
a moderate illumination. The organisms are best recognized by the actively motile 
pigment in the clear, highly refractile cell body. This is the older method, and is, 
in the writer's opinion much less satisfactory than the study of stained slides. 
The Examination of Blood After Fixation.-The smear should be made on a 
slide or large cover-glass. It is best fixed in strong methyl alcohol for three minutes. 
The organisms are most satisfactorily demonstrated by stains which color the chro- 
matin as well as the protoplasm. For this purpose a very satisfactory stain is that 
devised by Giemsa.1 The staining solution contains azure eosin and azure II dissolved 
in glycerin and methyl alcohol. It is difficult to prepare and had best be bought from 
dealers. It must be kept in tightly stoppered bottles. 
In order to stain a fixed blood smear, a dilution of the stock solution is made by 
adding 1 drop of the dye to 1 c.c. of distilled water. If the smear is on a cover-glass, 
10 c.c. of the dilution should be placed in a shallow dish and the cover floated, blood 
side down, on the mixture. For staining slides a Coplin jar is convenient. As this 
holds about 50 c.c., 50 drops of the concentrated stain should be added slowly to the 
water with constant stirring with a glass rod. The slides are left for an hour, then 
washed with a strong stream of water, dried in the air without heat, and mounted 
and examined. If intended for permanent preservation they should be embedded in a 
neutral gum dammar dissolved in xylol. Slides more than a few days old do not stain 
well. After a year it is necessary to use a more dilute stain and afterward decolorize 
with distilled water or even methyl alcohol, if necessary with the addition of a trace of 
acetic acid, as the blue component overstains all the cells. 
By adding an equal volume of pure methyl alcohol to the stock solution of the 
Giemsa stain, it is possible not only to shorten the time, but also to avoid separate 
fixation of blood smears.2 
The blood smear is placed in a Petri dish and 10 to 15 drops of this new mixture 
are placed on the slide and allowed to act for half a minute. About 10 to 15 c.c. of 
distilled water are poured into the Petri dish and the whole is agitated until the stain 
is thoroughly diffused through the entire fluid. The slide remains in this mixture for 
five minutes. A longer period increases the intensity of the stain. 
A simpler method,3 which is better adapted for clinical work is as follows: The 
smear is fixed for three minutes in methyl alcohol, then stained for ten seconds with 
a 1 :1,000 aqueous eosin solution, the latter allowed to run off the slide, and the smear 
again covered with a few drops of a 0.25 per cent, solution of methylene azure I. In 
from five to fifteen minutes the staining is complete. The slide should be washed in 
distilled water, dried, and examined directly with an oil-immersion lens, no cover-glass 
being necessary. If the organisms are few, the smears should be made very thick, 
the hemoglobin removed in a mixture of 4 per cent, formaldehyde and 1 per cent, 
acetic acid, and the staining then carried out in the usual manner. 
WHOOPING-COUGH. (Pertussis.) 
Whooping-cough is a readily communicable, infectious disease 
usually associated with catarrhal inflammation of the upper respiratory 
passages. It may be complicated by bronchitis or pneumonia. Hyper- 
plasia of the lymph-nodes of the laryngeal and bronchial districts may 
occur. Increase in the lymphocytes of the blood is frequent in the early 
stages. Immunity is usually secured by an attack. 
The organism described by Bordet and Gengou4 seems most probably 
to be the specific agent. This organism is a small, ovoid, short bacillus 
1 Giemsa, Centralbl. f. Bakteriol., Orig. I., 1904, xxxviii, 308. 
2 Giemsa, G., Munchen ined. Wchnschr., 1910, Ivii, 2476. 
3 Wood, F. C., Medical News, 1903, Ixxxiii, 248. 
4 Bordet and Gengou, Ann. de 1'Inst. Pasteur, 1906, xx, 731. THE INFECTIOUS DISEASES 
351 
showing irregular staining. It stains with some difficulty, requiring the 
use of dilute carbol-fuchsin or other strong stains to color it satisfactorily. 
Mallory1 has shown that the bacilli can be demonstrated in large 
numbers lying among the cilia of the tracheal and bronchial mucosa. 
The disease can be transmitted to young dogs and monkeys, with the pro- 
duction of the same lesions; and a complement fixation can be demon- 
strated between the organs and the blood of infected animals and of 
children suffering from whooping-cough. 
The poles often stain more deeply than the centers. The bacillus is 
negative to Gram. The organism is grown only with difficulty and upon 
a special medium of glycerinated extract of potato to which has been 
added an equal volume of sterile defibrinated rabbit or human blood. 
The organism is strictly aerobic and in ascitic broth may remain alive 
for some months.2 Bordet and Gengou report that a specific comple- 
ment fixation can be obtained in the serum of patients suffering from 
the disease. Protective vaccination has been practised with fair results; 
whether the course of the disease can be influenced is still doubtful.3 
ACUTE RHEUMATISM. 
While the excitant of acute rheumatism is unknown, there is much 
reason to believe that some phases of it at least should be classed among 
the infectious diseases. There are no characteristic lesions; but various 
joints are frequently the seat of slight exudative inflammation, serous 
or fibrinous in character. Albuminous degeneration of the visceral 
cells with hyperplasia of the spleen has been noted. The disease is not 
infrequently complicated by endocarditis or pericarditis, and by exudative 
inflammation of the lungs or pleura. Various microorganisms have 
been found in the body in acute rheumatism; of these the pyogenic 
cocci have been most frequently isolated, but these are probably to 
be regarded only as excitants of the suppurative or other complications. 
It is possible that more than one form of infection is embraced under the 
designation rheumatism.4 
TRENCH FEVER.5 
A febrile, rarely fatal disease, described under this name, was very 
prevalent among the troops during the world war, at some periods 
amounting to one-third of all cases of illness, and occurring chiefly among 
those who had been in the trenches. The incubation period varies from 
six to twenty-two days. In many ways, the disease resembles an abor- 
i Mallory and Hornor, Jour. Med. Research, 1912-13, N. S. xxii, 115; Mallory, Hornor, and Hender- 
son, ibid., p. 391. 
2 W ollstein, Jour. Exper. Med., 1909, xi, 41. 
3 For value of vaccines in pertussis, see Barenberg,! . H., Am. Jour. Dis. Child., 1918, xvi, 23. 
'For summary and studies of etiology of acute rheumatism, see Cole, Jour. Infect. Dis., 1904, i, 
714; Beattie, J., Jour. Med. Research, 1906, N. S. ix, 399; Frissell, Med. Rec., 1906, Ixix, 737 (bibl.); 
Meakins, Med. and Surg. Rep., Presbyterian Hosp., New York, 1908, viii. For a study of the sub- 
miliary myocardial nodules of Aschoff, most frequently found in the walls of the left ventricle in rheu- 
matic infection, see Thalhimer and Rothschild, Jour. Exper. Med, 1914, xix, 417 (bibl.). See also for 
bibl. of infective agents, ibid., p. 429. 
6 Swift, H., Arch. Int. Med., 1920, xxvi, 76. 352 
THE INFECTIOUS DISEASES 
five type of typhoid fever. The temperature curve is a peculiar one, 
rising rapidly to 103° or 104°, often falling to normal by the third day, 
and rising again roughly at five-day intervals. The pulse rate is usually 
slow in relation to the temperature. The symptoms include headache, 
constipation, and pain which is especially frequent over the shins and 
calves of the legs and seems to occur at the point of insertion of the 
muscles. There are no joint involvements. The spleen is not enlarged. 
The urine shows no characteristic change. 
The infectious nature of the disease has been demonstrated,1 both the 
red corpuscles and the blood serum being infective. The virus can be 
passed through a Berkfeld filter. The disease can undoubtedly be 
transmitted by the body louse; but that this is the only means of convey- 
ance has not yet been proved. While some observers have thought that 
it is a type of relapsing fever due to the Spirochaeta obermeieri, others 
have believed that the disease is a special form of spirochetosis, the 
organism of which has not been demonstrated. A variety of bacteria 
and other parasites have been isolated, but none has been proved to be 
the specific etiological factor. 
INFECTIVE JAUNDICE. 
Epidemics of jaundice have been recognized since the Greek period 
in medicine, chiefly among the armies in the field. In recent years this 
type of jaundice has been known as Weil's disease. The clinical symp- 
toms are vomiting and diarrhea, accompanied by high temperature. 
There may be blood in the stools. Shortly after the onset of the first 
symptoms jaundice appears; and there is usually a leucocytosis, and bile, 
albumin, and casts in the urine. The liver is frequently enlarged, the 
spleen rarely to a palpable size. Hemorrhages into the skin, hema- 
temesis, and hemoptysis are not infrequent. On post-mortem exam- 
ination, the mucous membranes of the stomach and intestines may be 
found to be swollen, with submucous and subperitoneal hemorrhages. 
The liver shows fatty changes and some infiltration with leucocytes; 
there is a good deal of biliary stasis in the finer bile capillaries; and occa- 
sionally an extreme lesion resembling acute yellow atrophy is seen. 
The kidneys show hemorrhages into the tubules, inflammatory exudate 
in the interstitial tissue, and swelling and degeneration of the tubular 
epithelium.2 
A spirochete can usually be demonstrated in the urine, especially when 
after centrifugalization of the specimen the sediment is mixed with india 
ink and a smear is made. The organism is the Spirochaeta icterohaemor- 
rhagice (page 139). This is frequently found in rats, which presumably 
are the means of carrying the infection.3 
1 McNee, Renshaw, and Brunt, Brit. Med. Jour., 1916, i, 225; and Byam and others, Jour. Am. Med. 
Assn., 1918, Ixxi, 21, 110, 188. See, also, Trench Fever, Report of Commission, Medical Research 
Committee, American Red Cross, Oxford, 1918; and Bruce. J., Jour. Hygiene, 1921, xx, 258. 
2 Lubarsch, O.,Lubarsch u. Ostertag, Ergebn d. allg. Path., 1919, xix1, 560; Inada, K., Jour. Exper. 
Med., 1917, xxvi, 355. 
3 Dawson, B., Hume, H. E. and Bedson, S. P., Brit. Med. Jour., 1917, ii, 345. For serum treatment 
see Inada, R., and others, Jour. Exper. Med., 1918, xxvii, 283; and Kaneko and Okuda, ibid., 305, THE INFECTIOUS DISEASES 
353 
INFECTIOUS DISEASES OF UNKNOWN ORIGIN. 
Protozoa.-Notwithstanding the great increase in our knowledge of infection 
within the past few years, there are still several diseases obviously of this class whose 
inciting factors are unknown to us. We are now beginning to realize that we must 
not confine our search in this class of diseases to the bacteria alone; but that among 
the protozoa may be found most important infective agents. In this latter group of 
organisms the culture methods applicable to the bacteria do not furnish the necessary 
data for the establishment of etiological relationships. While the pathogenic signif- 
icance of the malarial protozoon was determined without cultures, and the pathogenic 
significance of other protozoa has become probable on morphological grounds, the 
desirability of artificial culture methods in the study of protozoa is daily becoming 
clearer. But it is well to remember that many protozoa pass through complex life 
cycles so that simple cultures cannot be expected to yield as illuminating results as 
do cultures of the more simply organized bacteria and yeasts. 
Ultramicroscopic Microorganisms.-In the search for the inciting agents of 
infectious diseases which have as yet baffled investigation, it should be borne in mind 
that it is quite possible that bacterial and other microorganisms may exist which are 
ultramicroscopic; that is, so small as to be invisible with such microscopic resources 
as we at present possess. In one instance, the infectious pleuropneumonia of cattle, 
Nocard and Roux by a special technique1 have been able to isolate an organism so 
small that its morphological characters could not be learned even with the highest 
available magnification. Experiments with the filtration of infectious material, 
especially from certain communicable diseases of animals, through porcelain filters 
whose pores are so fine as to retain ordinary bacteria, have shown that the infective 
agent may pass these filters and, though revealing no morphological elements, still be 
virulent. Among the more important of the ultramicroscopic infective agents which 
have been found to pass the pores of porcelain filters are those inciting contagious 
pleuropneumonia of cattle, anterior poliomyelitis, yellow fever, foot-and-mouth dis- 
ease, and rinderpest of cattle. The possibility of the existence of ultramicroscopic 
organisms must then be held in mind in our summaries of infectious diseases 
whose inciting factors, though persistently sought, are still unknown.2 
THE INFECTIOUS DISEASES OF ANIMALS. 
The study of comparative pathology is of great and increasing importance, and 
already much light has been thrown on the nature of human diseases by the study of 
the diseases of the lower animals. 
The scope of this book does not permit of more than an occasional reference to 
animal diseases, but the reader may consult: Moore, The Pathology of the Infectious 
Diseases of Animals, 1906; Nocard and Leclainche, Les Maladies Microbiennes des 
Animaux, Paris, 1898; Frieberger and Frohner, Lehrbuch der speciellen Pathologic 
und Therapie der Hausthiere, 1896; also Kitt, Text-book of Comparative General 
Pathology, Eng. Trans, by Smith and Cadbury, 1906. 
BIBLIOGRAPHY OF THE INFECTIOUS DISEASES. 
For a fuller treatment of the themes considered in this chapter the reader may con- 
sult among the larger works: 
Kolle and Wassermann, Handbuch der pathogenen Mikroorganismen, 2d ed., 
1908-13. 
1 For a description of collodion sacs used in the study of ultramicroscopic organisms and agglutina- 
tion, and for other purposes see McCrae, J., Jour. Exper. Med., 1900, v, 635; and Rosenau, Laboratory 
Technique, Bull. 7, Hyg. Lab., U. S. P. H. S., Washington, 1902. For details of method of making sacs 
of standard permeability, see Farmer, C. J., Jour. Biol. Chern., 1917, xxxii, 447. 
2 For a summary of investigations on infectious diseases of unknown origin, see Hektoen, Jour. Am. 
Med. Assn., 1903, xli, 405, 493; Roux, Bull. d. 1'Inst. Pasteur, 1903, i, 7, 49 (bibb); Wolbach, S. B., Jour. 
Med. Research, 1912, N. S. xxii, 1; Lipschutz, B., Kolle and Wassermann, Handbuch d. path. Mikro- 
organismen, 1913, viii, 345 (bibl.). 354 
THE INFECTIOUS DISEASES 
Kolle and Hetsch, Experimentelle Bakteriologie u. d. Infectionskrankheiten, 
1906 (excellent summaries). 
Among the smaller works may be mentioned: 
Hiss and Zinsser, Text-book of Bacteriology, 5th ed., New York, 1922. This 
admirable work presents a concise but comprehensive epitome of modern bacteriology, 
especially in those aspects which are of practical value to students and practitioners 
of medicine. 
Park and Williams, Pathogenic Microorganisms, 7th ed., Philadelphia, 1920. 
Presents important hygienic and public-health aspects of the subject. CHAPTER X. 
MALFORMATIONS. 
General Considerations. 
The classification of malformations is difficult, both because of the 
complexities of development not yet wholly understood, and because 
of our ignorance of many subtle phases of nutrition and inheritance in 
general. We shall here attempt little more than a catalogue of some of 
the more striking or common developmental defects, with a suggestion 
of grouping for convenience rather than for scientific accuracy.1 
The individual may be subject to abnormal conditions during embry- 
onic life which lead to changes analogous to those which the body may 
suffer from injuries after birth. But these various lesions are compli- 
cated in the embryo by the fact that it is in a state of active growth and 
development, so that even slight injuries may result in malformations 
of the most extreme character, especially when inflicted in the earlier 
periods of its life. 
Among the abnormal and harmful conditions to which the embryo 
may be subjected may be mentioned first those which relate to the 
mother, such as infectious or other diseases, disturbances of nutrition, 
severe psychic shocks, etc. To these may be added local interference 
with development, such as pressure upon the uterus, circulatory and 
other disturbances of the placenta and membranes, an abnormal accu- 
mulation of amniotic fluid, adhesions between the embryo and the 
membranes of the placenta, and various forms of trauma. 
On the other hand, there are many abnormalities in development 
which must be referred back to inherited defects transmitted through 
the maternal or paternal cells. 
While one may catalogue in a general way many of the conditions 
leading to malformations, the rationale of the process in many instances 
is still obscure. In recent times much light has been thrown on the 
subject by a host of experimental studies on the ova of the lower animals 
by shaking, dissection, and other mechanical interferences. But into 
this field the scope of this book does not permit us to enter. 
Many malformations are so extreme or involve such vital organs 
that extrauterine life is impossible. Such are some of the malformations 
1 The reader is referred for details to Thoma, Pathology and Pathological Anatomy, English 
translation (bibl.), or to other special works, such as Marchand, Missbildungen, in Eulenburg's 
Real Encylopadie der gesammten Heilkunde, 3d ed., Vienna, 1897, xv, 506; Schwalbe, Die Morphologic 
der Missbildungen des Menschen und der Tiere, Jena, 1906 to 1913; Ballantyne, Manual of Antenatal Pa- 
thology, 1902 and 1904; and Rabaud, La t^ratogenese, Paris, 1914. 
For a discussion of the embryological side, see Broman, Normale and abnorme Entwicklung des 
Menschen, Wiesbaden, 1911. For a study of tissue displacements during embryonic life, see Meyer, R., 
Lubarsch-Ostertag, Ergebn. d. allg. Path., 1905, ix2, 518 (bibl.). 
355 356 
MALFORMATIONS 
of the nervous system or of the circulatory apparatus, occlusions of the 
gastrointestinal canal, etc. Some of the abnormalities of development, 
on the other hand, while not fatal, predispose to disease. Such are the 
embryonal displacements of groups of cells which predispose to tumor 
formation. It is customary to speak of the lesser defects as congenital 
anomalies. Such are congenital angiomata, ruevi, and certain dermoid 
cysts. 
Malformations may involve a single individual or embryo or they 
may concern two or more, which are variously united. 
Malformations Involving Single Individuals.1 
The types of such malformations are various. Thus, there may be 
a failure to develop a part or organ. This is called aplasia or agenesia. 
For example, the upper or lower extrem- 
ities may be absent (Fig. 184). 
When an organ or part is formed, but 
remains small or undeveloped, we speak 
of hypoplasia. A common example of 
this is the hypoplasia of the aorta in 
status lymphaticus (see page 500). 
Sometimes a part of the body re- 
mains at an early developmental stage; 
under these conditions, however, the de- 
velopmental arrest may not involve ces- 
sation of growth. Examples of this form 
of lesion are the various fissures and clefts 
which occur in the median line or other 
parts of the body, due to some interfer- 
ence with the closure of the invaginations 
of the germinal layers which should take 
place at an early fetal period-the med- 
ullary groove, intestinal groove, facial 
and branchial clefts. 
From fissures in the facial region arise 
such malformations as absence of the 
whole or parts of the face (Fig. 185 and 
443), various forms of harelip (Fig. 186), 
etc. Defects of closure in the cervical and 
thoracic region lead to many forms of 
fissures, fistulse, cysts, etc., of the neck 
and chest, such as the branchial cysts, 
branchial fistulas, auricular appendages, 
and tracheal fistulae. The lower jaw may be absent {agnathia}. Under 
these conditions the mouth may be represented by a small opening and 
the ears may be placed low down and near the median line (synotia) 
Fig. 184.-Abrachius. 
The arms are absent. 
1 Many of the developmental defects occurring in a single fetus are considered somewhat more 
in detail in the part of this work dealing with the special organs, to which the reader is referred. MALFORMATIONS 
357 
Fig. 185.-Facial Fissure. 
Owing to imperfect union in the anterior median line of the body, in the facial region the larger 
irregular cleft persists. There is also absence of the vault of the skull-cranioschisis. 
Fig. 186.-Double Harelip. 
There is bilateral fissure extending into the hard palate. 358 
MALFORMATIONS 
(Fig. 187). There may be fissure of the sternum, sometimes with pro- 
trusion of the thoracic viscera, among others the heart-ectopia cardis. 
Fissure of the diaphragm may occur with that of the sternum and per- 
mit displacement of the abdominal and thoracic viscera. The imperfect 
closure of the abdominal wall leads to various forms of lesions. Thus 
Fig. 187.-Synophthalmia, Agnathia, and Synotia. 
The rudiments of two eyes are fused and occupy a common orbit-synophthalmia. A wart-like 
process lies above the orbit. The lower jaw is absent-agnathia. The mouth is small. The ears are 
low and near the middle line between the upper jaw and the neck-synotia. 
there may be a patent urachus, the formation of a Meckel's diverticulum 
(see page 759), umbilical hernia, or, when there is large deficiency of the 
abdominal wall-complete abdominal fissure-there may be prolapse 
of the abdominal viscera (Fig. 188). Fissure of the lower portion of the 
abdominal wall may lead to prolapse of the bladder, and the bladder 
itself may be fissured so that the interior of the prolapsed organ is MALFORMATIONS 
359 
exposed-inversio vesicce. Such fissures in the anterior median line 
may involve the urethra, leading to epispadias or hypospadias. 
A failure of the walls of the medullary groove in the posterior median 
line of the body to fuse properly leads to significant malformations of 
the central nervous system. This failure may be complete-cranior- 
rhachischisis totalis (Fig. 189). There is a wide irregular groove involving 
the dorsal aspect of the head and trunk. In this condition, however. 
Fig. 188.-Abdominal Fissure. 
Prolapse of the abdominal viscera through imperfect closure of abdominal wall. 
the anterior portions of the brain, with the nose and eyes, may be formed, 
though distorted. 
But there may be only a partial failure in the closure of the medullary 
groove, limited to longer or shorter segments, especially in the cervical 
and sacral regions. Thus arise various forms of myelomeningocele, in 
which the pressure from within not being sustained by vertebral arches, 
the skin and underlying soft parts are often forced outward in the form 
of a pouch or sac (Fig. 190). 
A local failure in the closure of the anterior portion of the medullary 
groove may lead to many malformations of the skull-cranioschisis, 
hemicephalia, acrania-and to various forms of meningocele', thus in 360 
fissures of the skull there may be prolapse of parts of the brain and its 
membranes, forming with the inclosing skin pendent pouches of various 
forms-encephalomeningocele (Fig. 191). The vault of the skull may 
be absent, and on the base there may be small amounts of brain substance, 
or this may be entirely absent-anencephalia (Fig. 192). For the 
details of some of these lesions we must refer to the chapter on the 
Nervous System and to special works on malformations. 
In many of the developmental lesions of the brain, the anterior 
parts, especially the optic vesicles and the olfactory bulbs, are often 
MALFORMATIONS 
A failure of the medullary groove to close along a portion of the posterior median line. 
Fig. 189.-Craniorrhachischisis. 
but little affected. But we may note here one of the striking malt 
formations which results in the fusing of the eyes into one placed in 
the forehead near the median line. This condition is called synoph- 
thalmia or cyclopia (see page 1110). 
Finally, there may be an arrest of development, more or less com- 
plete, of the brain or some of its parts-micrencephalia. 
In one phase of malformation involving single individuals, paired 
organs may be grown together, for example in the so-called " horse- MALFORMATIONS 
361 
shoe kidney" (Fig. 193). Or single organs may retain lobular forms 
belonging to an early period of life-lobulated kidney. 
There may be supernumerary parts, such as fingers, toes, etc., or 
organs-spleen, adrenals, lungs, pancreas. There may be fusion of 
fingers and toes, frequently involving all of the extremities. Various 
congenital malformations commonly due to arrest of development are 
exemplified in the diverse phases of "club-foot"-talipes-and "club- 
hand"-talipomanus. 
Fetal structures which in the normal development should make way 
From a partial failure in the closure of the medullary groove this sac is formed, containing fluid and the 
lower portion of the spinal cord. 
Fig. 190.-Myelomeningocele Sacralis-Spina Bifida. 
for adult organs may persist; thus the urachus, the Wolffian ducts, or, 
parts of the branchial clefts, may remain. 
Through adhesions of the membranes or by abnormal winding of 
the umbilical cord about the neck or the extremities (Fig. 194), partial 
decapitation or amputation of a limb may take place (Fig. 195). So 
also by adhesions of the surface of the embryo and the placenta or 
the membranes, various disturbances of growth may occur. 362 
MALFORMATIONS 
Normal and Pathological Conditions in which Two or More Individuals 
Develop Together. 
Two or more individuals may develop together, the bodies being 
separated, as in normal twins, triplets, etc., or the individuals being more 
or less closely joined or merged. This duplication may be evident, so 
that the nature of the complexity is clear; or one of the individuals 
may develop greatly in excess of the other. 
There is a fissure on the posterior aspect of the skull, out of which the imperfect brain and its membranes 
protrude, filling the pouch of the scalp. 
Fig. 191.-Encephalocele. 
Twins, Triplets, etc.-Pregnancies may be complicated by the devel- 
opment in the uterus of two or more embryos. These are called twins, 
triplets, etc. This duplication may arise by the development of separate 
ova or the formation of more than one embryo from one ovum.1 
Twins and triplets developed from one ovum-homologous twins- 
are always of the same sex; and if both develop normally they usually 
1 See Newman, H. H., Biology of Twins, Chicago, 1917. MALFORMATIONS 
363 
closely resemble each other. But the individuals, if born alive, often 
do not develop equally; one may be less well nourished than the other, 
from a disturbance of the vascular supply, for example. 
One of the twins may die early in pregnancy and suffer varying 
degrees of degeneration into a shapeless mass, or may die later and be 
born prematurely or at the delivery of the living twin (Fig. 196). Some 
of these abortive forms are without a heart or have only a rudiment 
of that organ. These are called acardiac monsters (fetus acardiacus). 
They may consist of connective tissue, rudimentary bones, and portions 
of intestine, and be covered by skin with hair-acardiacus amorphus. 
Or there may be a more or less distinctly formed head without a corre- 
The vault of the cranium is absent. There is a small reddish mass at the base representing the rudi- 
ment of a brain. 
Fig. 192.-Cranioschisis. 
sponding trunk-acardiacus acormus. There may be a fairly well 
developed trunk with viscera and a rudimentary heart, but no head- 
acardiacus acephalus. Finally, there may be a relatively well developed 
trunk with defective extremities and a rudimentary heart-acardiacus 
anceps. 
In all of the above duplications the fusion is confined to the placenta 
and its appendages, the bodies of the twins being separate. 
Double Monsters (Monstra duplicia).-The union to any considerable 
extent of the embryos themselves is pathological, and the malformations 
are classified as double monsters. 
In these unions of twins there may be: 1, complete duplication 
of the axis of the germinal area, so that there is a double development 
of the central nervous system, while the remaining parts are more or 364 
MALFORMATIONS 
less fused; or, 2, there may be only a partial duplication of the axis, 
so that there may be double development, either of the head or in the 
sacral region, while at the other extremity the body is single. 
We shall now look briefly at some of the forms of double monsters 
in which the individuals are more or less symmetrically united. 
There may be fusion of the bodies in the thoracic region. The 
ensiform processes are united by cartilage, union of the soft parts extend- 
ing over the umbilical region. The thoracic and abdominal cavities 
Fig. 193.-Horseshoe Kidney. 
The kidneys are in place in the body of the young child. They are tabulated with the large adrenals 
above them. 
are separate. This malformation is called xiphopagus. Such were 
the celebrated Siamese twins who lived to the age of sixty-three. In 
other cases there is a common thoracic cavity, usually with two hearts 
and two pairs of lungs more or less malformed (Fig. 197 and Fig. 198). 
The abdominal cavities may also be united. Parts of the intestine may 
be common to both twins. These monsters are called thoracopagus. 
They do not long survive birth. The fusion may, however, extend 365 
MALFORMATIONS 
upward so that two upper extremities may fuse-thoracopagus tribra- 
chius; or two of the lower extremities may fuse-thoracopagus tripus; 
or, finally, the fusion may embrace the head so that the faces are more 
or less united-prosopothoracopagus. The cephalic and thoracic regions 
may remain separate while fusion takes place from the umbilicus to the 
pelvic region. The spinal column is duplicated while there is a common 
pelvic ring-ischiopagus. 
There may be fusion of the otherwise separate twins in the cranial 
Fig. 194.-Fetus with Umbilical Cord Coiled Around the Neck and Leg. 
region-craniopagus. The union is usually only of the scalp and cranial 
bones. 
The head and the upper part of the body may be single, or the head 
alone may be single while the abdomen and pelvis are separate. There 
may be four or less lower extremities. Such malformations are called 
dipygi. 
There may be union of the head, neck, or chest, so that there are two 
faces more or less symmetrical looking in opposite directions-janiceps 
or janus. 366 
MALFORMATIONS 
In cases in which there is only a partial duplication of the axis, this 
may be most marked at the cephalic or caudal extremity, and there may 
be formed an individual with duplication of the face-diprosopus. Thus, 
depending upon the degree of duplication, arise diprosopus distomus; 
d. diophthalmus; d. triophthalmus; d. tetraophthalmus. But this anterior 
duplication may extend to the whole head. Thus arise the two-headed 
monsters-dicephalus-which according to the degree of duplication 
Fig. 195.-Partial Intrauterine Amputation of the Leg. 
of the upper extremities are called dicephdlus tribrachius; dicephalus 
tetrabrachius. 
Finally, the bodies are united posteriorly in the region of the sacrum 
and coccyx. This malformation is called pygopagus. The individuals 
may live for years. 
In the double malformations which we have thus far considered 
there has been a more or less symmetrical development of the physically 
joined twins. But for various reasons it often happens that one of the 
individuals is arrested in its development, while the other continues. 
This condition is analogous with that already considered in which the MALFORMATIONS 
367 
arrest of development involved an independent acardiac individual 
which was not viable. But in the present case the arrested twin is 
joined to the other as a part of a living organism, and its life is thus 
maintained by the more favored relative. Under these conditions 
the more completely developed twin is called the autosite, the arrested 
embryo, the parasite (Fig. 199). 
The rudimentary structure, the parasite, may be variously developed. 
It may have extremities, various forms of tissue, nerve, muscle, intestine, 
Fig. 196.-Twins. 
The individuals are separate. One died early in atero and is only partially developed and mummified. 
etc. It may be formed of a jumble of tissues with cystic cavities which 
may be lined with epithelium. Its size varies; it may be as large as the 
body of the autosite. Thus may be formed the parasitic thoracopagus, 
attached to the sternum, or the parasitic ischiopagus and parasitic 
craniopagus. So also are formed the epignathus, in which an acardiac 
parasitic rudiment is attached to the autosite in the facial region. The 
rudimentary embryo may be attached in the sacral region, forming 
sacral appendages or tumors-sacral teratomata. 368 
MALFORMATIONS 
Finally, the second individual may be much less developed than 
in the cases which we have thus far surveyed, and may be represented 
only by formless appendages or by inclusions in different parts of the 
body, which are made up of various and often complex tissues-fibrous 
tissue, nerve tissue, bone, teeth, cartilage, muscle, glands. These are 
Fig. 197.-Thoracopagus. 
called teratoids, dermoids, fetal inclusions, congenital teratomata. They 
may occur in the ovaries, or testicles, or about the head, in the medias- 
tinum, or in the sacral region, and elsewhere. They often become 
cystic and may give origin to various forms of tumors (see page 1112). 
The teratomata are apparently derived either from extruded polar MALFORMATIONS 
369 
bodies or, more probably, from blastomeres segregated at an early period 
from the cell complex which goes to form the developing fetus. The 
separated cells may long remain latent, finally beginning to grow with 
the power to form complex tissues and structures, but only in a jumbled 
mass, embraced within or attached to the developed individual. Some 
of the teratomata are comparatively simple in structure. Their nature 
Fig. 198.-Skeleton of Thoracopagus-Pig. 
is often revealed by the heterologous character of their component struc- 
tures. The ectodermal elements are often most conspicuous (see page 
393). 
We thus see, in summary of this brief survey of complex malforma- 
tions in general, that under normal conditions two or more individuals 
may develop together in the uterus-twins, triplets, etc. Under patho- 
logical conditions the individuals may be more or less united, forming 370 
MALFORMATIONS 
double monsters. The duplex individuals may develop more or less 
symmetrically with independent cerebrospinal axes and various degrees 
of union. Or the development may be very unequal, so that one is a 
more or less obvious appendage to the other. Finally, one of the indi- 
viduals may exist as a mere complex rudiment attached to or within its 
more favored mate. 
Fig. 199.-Child with Acardiac Parasite Attached Posteriorly. 
One of the twins, the autosite, has developed; the other only partially. 
TISSUE MALFORMATIONS 
While there is but little question as to the nature of the conditions 
underlying the formation of united twins or even of the complex parasitic 
attachment of a partially developed twin to a normal fetus, there has 
been much doubt cast upon the possibility of the persistence of embryo- 
logically displaced fragments of tissue, the hypothesis upon which Cohn- 
heim years ago based his theory of tumor development. Nevertheless, 
investigations of recent years have thrown much light on the theory that 
inclusions of cell complexes derived from early embryonic existence may 
remain in various portions of the body. Some of the most striking ex- 
amples of the persistence of fragments of organs are offered in the minute 
study of the urogenital system of the female, where the very complexity 
of the organ development makes it possible that cells or groups of cells 
may be left behind in the course of the wanderings of the organs to their MALFORMATIONS 
371 
final position.1 In the literature of the subject a large number of definite 
observations now exist concerning the persistence of the Wolffian or 
Gartner's ducts. The presence of glandular structures from these ducts 
and fragments of adrenal tissue has been frequently noted in the round 
ligament. Analogous displacements are observed of the pancreas, frag- 
ments of which are not uncommon in the stomach wall, duodenum, 
mesentery, and Meckel's diverticulum. Fragments of thyroid tissue 
are found at the base of the tongue and along the thyreoglossal 
duct. Epithelium, both squamous and cylindrical, is not infrequent 
as remnants of the branchial clefts, and may remain as epidermoid 
cysts about the embryonic suture lines of the face. Fragments of the 
adrenal have been found in the kidney and liver, retroperitoneally, in 
the broad ligament and, as just mentioned, in the round ligament 
of the uterus. Such well characterized structures, however, are more 
easily identified than a few displaced cells of the connective-tissue group, 
but the study of complex tumors, especially those of the parotid region, 
the kidney, uterus, and other organs, has led to the belief that even a 
few cells may be displaced and remain viable throughout adult life. Such 
cells are only accidentally found-striated muscle, for example, has been 
discovered in a normal uterus-and, as a rule, they make their presence 
felt only when they undergo the necessary biological alterations which 
result in their obtaining an enhanced proliferative power, in other words 
become the basis for tumor formation. The theory of cell misplacements, 
therefore, seems to be the best explanation of many of the complex 
tumors. For example, the parotid tumors, in which striated muscle, 
cartilage, bone, and squamous epithelium are present, besides a host of 
other tissues, both epidermal and mesodermal, are best interpreted as 
misplaced fragments of highly potent embryonic tissue deposited during 
an early period of development while the gland was as yet imperfectly 
formed. So, too, the complex tumors of the kidney, which contain 
cartilage, striated muscle, and remnants of embryonic kidney structures, 
must be interpreted in this way rather than by having recourse to a 
broad theory of metaplasia, which by breaking down all histological 
boundaries really explains nothing but merely avoids the problem. For 
if connective tissue can be turned into striated muscle, it can be perti- 
nently asked of those who believe in metaplasia why such transformation 
occurs practically only in such portions of the body as the face, kidney 
region, and genitourinary tract, where embryological development is of 
the utmost complexity. The same explanation must be offered for a 
certain portion of the complex tumors developing in the region of the 
postanal gut, described in a preceding paragraph. The still more elabo- 
rate teratomata of the ovary and testicle do not belong in this group 
but are probably derived from cells separated from the ovum at so early 
a date that they retain an histological totipotence. 
1 For an interesting collection of inclusions of embryonic tissue, especially in the female genital 
tract, see Meyer, R., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1911, xv1, 430 (bibh). 
Herxheimer, G., Missbildungen des Herzens und der grossen Gefasse, Schwalbe, Die Morphologie 
der Missbildungen des Menschen und der Tiere, Jena, 1910, iii, iii, Lieferung, 339, ibid., Die Einzel- 
missbildungen, 1913, iii, x, Lieferung, 51. CHAPTER XI 
TUMORS 
General Nature 
The word tumor, originally applied by ancient Greek and Roman 
writers to any swelling, has with the increase in our knowledge in modern 
times become more and more restricted in its use, until it is now employed 
only to designate more or less circumscribed growths of new tissues, or 
neoplasms. But as the formation of such new tissue is of common occur- 
rence under both normal and abnormal conditions it is desirable to fix 
upon some features by which true tumors may be distinguished from 
other tissue growth, either normal or abnormal. 
A tumor, like any other tissue, is produced by the proliferation of 
cells originally of a normal type. During the course of such growth, the 
cells may assume considerable variations from the normal, and finally be 
only with difficulty recognizable as belonging to the group of cells from 
which they sprang; but the definite plan to which all normal cells in the 
body adhere and by which the good of the organism as a whole is assured, 
appears, in the case of a neoplasm, to be abandoned. The cells, in other 
words, have ceased to be functionally important to the body. Thus, 
under normal conditions, epithelium, for example, is constantly replaced 
to compensate for the losses which it daily undergoes, and even the 
formation of large masses of new tissue may occur under some special 
etiological stimulus, as in the lactating mammary gland and the uterus 
during the course of pregnancy, but under such circumstances, even in 
abnormal conditions, like inflammation, the end obtained is for the 
good of the organism as a whole; no more new tissue than the required 
amount is produced, nor is more than is actually required elaborated, 
as in the case of a bone callus; the surplus is usually absorbed with 
comparative rapidity. This is not true for neoplasms. They are charac- 
terized in general by such independence, both in structure and in growth, 
of those laws which govern the body topography that their distinguishing 
characteristics are best indicated by the word autonomy, or perhaps by a 
stronger term, cell anarchy. The autonomous character of tumor tissue, 
manifested primarily by its independent growth, is evident also in its 
tendency to vary in structural type, in the functional aberration of the 
cells, and in the ability of these cells to multiply after transportation into 
another part of the host's body, or even after grafting into the body of 
another individual, as in the case of artificial transplantation of a malig- 
nant tumor from one animal to another. Thus a tumor represents an 
independent group of cells whose only dependence upon the host's body 
372 TUMORS 
373 
lies in the fact that the general blood supply is levied upon for its nutri- 
tion. An excellent example of the disregard shown by tumors for the 
general laws of morphology and nutrition1 is seen in lipomata, tumors 
composed of fat cells, where a large growth may persist and even expand 
in size in a poorly nourished individual whose body fat has otherwise 
practically disappeared.2 While this independence is a striking charac- 
teristic of certain tumors, there are others in which it is not so prominent, 
and it is even impossible, in some instances, to distinguish between tumors 
and other newly formed tissue chiefly because we do not yet possess 
definite criteria for a distinction in all instances between normally growing 
cells and those of tumors. 
Definition.-The most generally accepted definition of a tumor is 
that it is a tissue overgrowth which is independent of the laws governing 
the remainder of the body. It is usual to add as a qualifying phrase to 
separate tumors from reparative processes, such as bone callus, that the 
neoplasm serves no useful purpose to the organism. The fact that in 
extremely rare instances tumors may secrete the hormones characteristic 
of the gland from which they spring does not in the least weaken the 
value of this portion of the definition, for even while a thyroid neoplasm 
may be secreting the hormone which prevents the development of myxe- 
dema, the tumor itself is at the same time destroying the life of its host; 
therefore its functional capacity is only accidental and atavistic and can 
hardly be considered as disproving the statement that a tumor serves no 
useful purpose. 
Continuous growth is also frequently added to the definition of a 
tumor, but this must be eliminated because although the great majority 
of tumors do proliferate indefinitely at least during the life of the host, 
even a highly malignant neoplasm may under very exceptional circum- 
stances undergo partial or complete regression. This extremely unusual 
outcome is most often encountered among the chorionepitheliomata but 
has been observed in many other types.3 Furthermore the successful culti- 
vation of embryonal connective tissue in vitro for a period of ten years4 
shows that these cells also are capable of unlimited proliferation under 
suitable circumstances, and it is also certain that this type of cell grows 
much more luxuriously under these conditions than does the cancer cell, 
or the adult normal cell. Thus the faculty of endless growth is charac- 
teristic not only of neoplasms but also of normal somatic tissues when a 
proper environment is assured. 
Structure.-While tumors in general are composed of the same varie- 
ties of tissues as those normally existing in the body, occasional exceptions 
are found in those neoplasms of complex types derived from congenitally 
displaced tissue. In such instances, for example, myxomatous tissue or 
similar structures, not normally found in the adult body, may be present 
1 For a discussion of diet and tumor growth, see Rous, Jour. Exper. Med., 1914, xx, 433; Woglom, 
ibid., 1915, xxii, 766; and Drummond, Biochem. Jour., 1917, xi, 325. 
2 Hirsch, E. F., and Wells, H. G., Retroperitoneal liposarcoma: report of an unusually large speci- 
men, with chemical analysis, Amer. Jour. Med. Sci., 1920, clix, 356. 
3 Rohdenburg, Jour. Cancer Res., 1918, iii, 193. 
4 Ebeling, A. N., A Ten Year Old Strain of Fibroblasts, Jour. Exp. Med., 1922, xxxv. 755. 374 
TUMORS 
in the tumor. Exceptions like this, however, are infrequent, and most of 
the tumors found in the body are derived from preexisting cells of normal 
type; tumors of the connective-tissue group arising from connective 
tissue elements, while those of the epithelial variety arise from epithelium, 
and so on. Most of the primary tumors originate from structures 
normal to the site where they grow, and are therefore said to be autoch- 
thonous in contrast to those forms arising from congenital displacements 
of tissue which are termed heterochthonous, or in simple English, native 
and foreign. An example of the former is seen in the adrenal tumors 
arising in the suprarenal body; of the latter in growths of undoubted 
adrenal tissue occasionally seen in the broad ligament or liver. While in 
general the tumor cells resemble more or less closely those from which 
they are derived, the statement has been repeatedly made and is even 
now current that the cells of malignant tumors, and particularly of the 
carcinomata, have a characteristic structure and appearance, and that 
by the examination of single cells the nature of the tumor can be deter- 
mined. Inasmuch, however, as all the cells of the neoplasm have their 
source in cells of the normal body, with the exception of the congenital 
group named, there is nothing wholly characteristic in the appearance of 
a single element of the tumor, it is only by the study of the general 
relationship and distribution of cells, and very rarely by the examination 
of the characters of the individual cells themselves that we are able to 
determine the nature of a tumor. In an occasional instance it is neces- 
sary to know something concerning the site of origin of the tumor and 
the clinical history before a definite conclusion can be reached. 
While the cellular morphology and the histological topography of 
different organs are closely dependent upon factors such as mechanical 
pressure, nutritive conditions, relationship to surrounding parts, state of 
secretionary activity of cells, and so on, under the circumstances in which 
tumors develop, however, these influences may be disturbed so that the 
shape, size, structure and the mutual relationship of the cells of the tumor, 
their tissue organizations, and their various functional characteristics as 
reflected in their morphology may be more or less profoundly modified. 
There are also changes in the cells of tumors which have been designated 
anaplasia,1 a term designating the loss of a characteristic differentiation 
which the adult cells undergo. While as has been said the tumor cells 
usually imitate the appearance of those of the structures in which they 
originate, they nearly always fall short of wholly reproducing the normal 
morphology in both histology and function. The cells in other words are 
immature, or poorly developed, being generally less highly differentiated 
than the corresponding mature normal cell. This stage is occasionally 
designated as a return to the embryonic type, but there is no evidence 
that biologically these cells are really related to the cells of the embryo, 
or that the analogy of an atavistic return to embryonic qualities is in any 
way valid. The departure from type may be so slight that even with a 
malignant tumor it may not be possible to determine the true nature of 
the growth, except for the fact that metastatic nodules are found at 
1 v. Hansemann, Berl. klin. Wchnschr., 1909, xliv, 1850. TUMORS 
375 
some distance from the primary growth (Fig. 200). This however, is 
a very exceptional circumstance, and usually there is a sufficient differ- 
entiation to permit of determination of the nature of the tumor. 
In our present state of knowledge concerning the biology of cells of 
tumors, it is well to avoid terms such as embryonal in describing the cells 
of a neoplasm, lest the idea be unconsciously adopted that the cells thus 
described have regressed to their embryonal state. For this assumption 
there is no evidence in fact,1 and it is probable that the elements of a 
malignant tumor appear immature only because of the conditions under 
which they live and t he rapidity of multiplication which they undergo. 
Fig. 200.4.-Section of a Lung Metastasis From a Carcinoma of the Liver. Magnified 250 
Diameters. 
Fig. 200B.-Section of a Liver with a Little Chronic Congestion, Otherwise a Normal 
Organ. Magnified 250 Diameters. 
It will be noticed in the tumor that the liver cells are closely packed together and there are 
none of the sinusoids between the trabeculae as there are in the normal liver. The fixation of the 
two specimens is slightly different also, so that the cells in the liver section are more granular than 
those in the tumor. The very slight difference between the cells of the tumor and the normal organ 
is evident at a glance. 
On the other hand, there is no objection to the terms "mature" and 
"immature," and "differentiated" and "undifferentiated," as applied 
to cells or tumors. They may be assumed to be purely descriptive, and 
not imply anything concerning the biology of the cells themselves. 
The tissues of tumors may be divided into two portions, a charac- 
teristic, usually the more rapidly growing fraction, the parenchyma, and 
a non-specific comparatively inert connective tissue portion, the stroma, 
which supports the parenchyma, and carries blood vessels for its nutri- 
tion. In the carcinomata the stroma is derived from the normal connec- 
1 See for a discussion of this question based on a study of the ferment content of embryonal and 
tumor cells, Buxton and Shaffer, Jour. Med. Res., 1904-05, N. S. viii, 543. 376 
TUMORS 
tive tissue of the organ in which the tumor arises. Its quantity seems to 
depend somewhat upon the nature of the tumor. The epithelial cells 
of some forms seem to stimulate the surrounding connective tissue to 
active growth, and thus, in the long run, the number of epithelial cells 
may be small in proportion to the connective tissue stroma. On the 
other hand, tumors composed almost entirely of epithelial cells with 
a minimal amount of stroma are not infrequent. The same conditions 
apply to the number and nature of the invading wandering cells, some 
tumors seeming to incite the appearance of large numbers of plasma cells 
or lymphocytes;' the stroma of others contains vast quantities of eosino- 
philes,2 while in still other forms neither of these wandering cell types is 
present in large quantities. In some sarcomata the bulk of the stroma 
may be so great that it determines all of the physical qualities of the 
tumor, and a differentiation, even by the microscope, from a fibroma may 
be impossible, while in other types the stroma may be extremely scanty 
or almost non-existent as, for example, in the lymphosarcomata. In the 
angiosarcomata, the stroma is largely composed of blood vessels, which 
give rise to the characteristic gross appearance and microscopic mor- 
phology of the neoplasm. In certain of the sarcomata arising from bone 
the stroma may be of an extremely variable nature. It may contain 
osteoid and cartilaginous material as well as blood vessels and connective 
tissue cells. In the sarcomata therefore the stroma may or may not 
play an important part in determining the growth and microscopic 
characteristics of the neoplasm. 
Functionally the only relation between a tumor and the stroma of the 
host is through the blood vessels. Lymph-vessels are scanty or absent 
from tumor tissue. Nerve fibers also are usually absent, or very scanty, 
those present being filaments left during the invasion of the normal 
structures. 
Terminology.-It is customary to terminate the name of a neoplasm 
with the suffix "oma;" this is preceded in most cases by the name of the 
tissue in which the tumor has originated-as myoma, a tumor originating 
in muscle; glioma, one developing from the glia, etc. The nomenclature, 
however, is badly in need of revision; thus the cylindroma was called by 
this term on account of the hyaline cylindrical structures which it con- 
tains, while the psammoma received its name from the Greek for sand, 
because of the small gritty particles scattered through it. 
It will be noted that neoplasms are named from the tissue-not the 
organ-involved. Hence, the use of such appellations as hypernephroma 
(a tumor of the adrenal), thymoma (a tumor of the thymus),3 hepatoma 
(a tumor of the liver),4 is to be discouraged. 
In the names of neoplasms containing more than one kind of tissue, 
the principal constituent is placed last. An osteochondroma, accordingly, 
1 Da Fano, Ztschr. f. Immunitatsforsch. u. exper. Therap., Orig., 1910, v, 1. 
2 Fischer, WZieglers Beitr., 1913, lx, 1. 
3 Grandhomme, Uber Tumoren des vorderen Mediastinums, Darmstadt, 1900; Thiroloix and Debre, 
Arch, de med. expdr., 1907, xix, 668; Simmonds, M., Ztschr. f. Krebsforsch., 1913, xxi, 280; Ewing, 
Surg., Gynec., and Obst., 1916, xxii, 461. 
* L'Esperance, E., Jour. Med. Research, 1915, N. S. xxvii, 225. TUMORS 
377 
is a chondroma containing some bone, while a chondroosteoma is an osteoma 
containing some cartilage. 
Degenerative Processes in Tumors.-Tumors are subject to the same 
degenerative changes as are other tissues. They often undergo degenera- 
tion from failure on the part of their blood supply to keep pace with the 
rapidly increasing demands upon it, or by themselves shutting off 
mechanically, as they increase in size, a supply which might otherwise 
be sufficient; again, circulation may be restricted in a pedunculated tumor 
by torsion of its pedicle. The results of this deprivation soon become 
evident in the form of fatty or other degenerations, calcification, ulcera- 
tion, gangrene, etc. Indeed, a neoplasm may be largely destroyed in 
such a way. 
Benignancy and Malignancy.-A benign tumor proliferates slowly by 
expansive or central growths. A malignant neoplasm, on the other hand, 
attacks and replaces the surrounding tissues, spreading by infiltrative 
or peripheral growth. Benign tumors do not metastasize, as a rule, nor 
do they recur after removal. 
The three main attributes ordinarily ascribed to malignancy are: 
Infiltration of the surrounding tissue, metastasis, and recurrence after 
removal. Still, infiltrative growth is not entirely characteristic of the 
malignant tumors, since the cells of the normal placenta have this prop- 
erty, invading the uterine wall and its blood-vessels, and sometimes 
actually reaching the lungs in the form of emboli; and the hemangioma, 
Fig. 201.-Tumor Embolus in Capillary of Lung. 378 
TUMORS 
ordinarily a benign tumor, grows nevertheless by infiltration.1 Develop- 
ing glands in the embryo are also able to invade subjacent tissues, 
although here, as in normal placentation, the process finally comes to an 
end; in malignant growth, on the contrary, it continues with but very few 
exceptions until the death of the patient has been brought about. 
Metastasis, or the development of secondary nodules in either proxi- 
mate or remote portions of the body, is a consequence of the transplanta- 
tion of tumor cells through the blood-vessels (Fig. 201 and 202) and 
lymphatics, and their growth at the point where they come to rest. Not 
all tumor cells reaching the circulation, however, survive long enough 
to produce secondary tumors.2 The migrating cells usually travel in 
the direction of the current, although in 
the lymphatics they are occasionally able 
to make their way against it (retrograde 
metastasis'). Metastasis may occur, also, 
by contact,3 as when cells from a tumor on 
the lower lip are transplanted into the 
upper and give rise to a tumor at the 
latter site. Some of the recorded cases, 
however, may have been instances of multi- 
ple tumor or of retrograde metastasis.4 
The way in which metastatic nodules 
develop offers a powerful argument against 
the parasitic hypothesis of tumor genesis. 
In every infectious disease with which we 
are acquainted, the local manifestations 
are produced by a tissue reaction directed 
against the invading microorganism; thus, the cells of a pulmonary 
tubercle are derived from the lung itself, those of an hepatic tubercle 
from cells of the liver, etc. The situation is entirely different, however, 
in secondary tumors, the parenchyma of which is produced solely by the 
proliferation of cells transported from the primary growth.5 Accord- 
ingly, a metastasis in the lung from a mammary carcinoma, say, is com- 
posed, not of pulmonary elements, but of cells from the mammary 
gland, the only portion contributed by the lung being the stroma. 
But not only are daughter tumors made up of cells from the primary 
growth; they even reproduce more or less the architecture of the 
parent neoplasm, so that metastases from an adenocarcinoma of the 
stomach appear as adenocarcinomata, while those from an epithelioma 
reflect the structure of the skin. Even the physiological task of the 
parent organ is undertaken, as when cerebral metastases from an hepatic 
growth discolor the surrounding brain with the bile which they secrete. 
Fig. 202.-A Tumor-cell Embolus 
Growing in a Blood-vessel at a Dis- 
tance from the Primary Carcinoma 
in the Mamma. 
1 Borrmann, Zieglers Beitr., 1907, xl, 372; Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 208. 
2 Schmidt, Die Verbreitungswege der Karzinome, Jena, 1903; Brasche, Virchows Arch., 1914, 
ccxv, 106. 
3 For a review of the subject, see Woglom, The Study of Experimental Cancer, New York, 1913, p. 44. 
* Petersen, Arch. f. Dermat. u. Syph., 1904, Ixx, 313; Tendeloo, Munchen, med. Wchnschr., 1904, 
li, 537. 
6 For experimental verification, see Jensen, Centralbl. f. Bakteriol., Orig. I., 1903, xxxiv, 27; 
Bashford, Murray, and Cramer, Second Sci. Report, Imperial Cancer Research Fund, London, 1905, 
Part 2, p. 24. TUMORS 
379 
As a general rule, sarcomata metastasize by way of the blood stream 
and carcinomata through the lymphatic system, although exceptions to 
these rules are not unknown; therefore, sarcomata usually spread first 
to the lungs and carcinomata to the adjacent lymph-nodes. 
The organs to be involved in metastasis depend in some degree upon 
the situation of the primary growth. Carcinomata of the stomach and 
intestine, for example, are apt to metastasize in the liver, those of the 
prostate in the bones, etc. The fact that any given region offers a site 
of predilection for secondary tumors can often be explained by the ana- 
tomical relationship of the two parts; in other words, it is sometimes 
largely a matter of simple mechanics, as in the case of the vulnerability 
of the liver to infection by secondary growths from gastric carcinoma.1 
Again, the spleen, which is commonly described as a soil practically im- 
mune to metastasis,2 proves to be a favorable location, in animals at least, 
for tumor grafts which have been inoculated into it; whence it appears 
that its freedom is due more to the failure of tumor cell emboli to lodge 
in it3 than to any inherent unsuitability for their proliferation.4 In many 
instances, however, the explanation is not so simple; no perfectly definite 
reason can be advanced to explain why the cells of a prostatic carcinoma 
should prefer the osseous system, and it is most probable that factors still 
unknown are in operation, one of which may prove, after all, to be the 
nature of the soil in which the cells have been sown. At any rate, it is 
asserted that the occurrence of bone metastases cannot be referred 
exclusively to the mechanical deposition of tumor emboli, but must depend 
upon the existence in bone, as such, of conditions favorable to their 
development. Thus, Schmorl5 was able to show that metastasis might 
take place in ossified laryngeal cartilages, while the rest of the body 
remained free from secondary growths. 
When a malignant tumor involves the bone-marrow, either directly 
or by metastasis, the anemia which results is usually much more severe 
than the anemia which occurs when such involvement does not take place. 
Under conditions not yet fully understood, metastases may cause an 
extraordinary hyperplasia of the marrow with discharge of cells into the 
circulation, giving a picture suggestive of a myelogenous or lymphatic 
leukemia or of pernicious anemia. In other instances, an aplastic anemia 
may be induced through extensive destruction of the marrow by the 
tumor without causing a corresponding reaction.6 
Like infiltrative growth, metastasis is not absolutely characteristic of 
malignancy, since even morphologically benign tumors7 (chondroma, 
angioma) sometimes form secondary nodules. See page 403. 
The third feature of malignancy, recurrence after removal, appears 
1 For a brief review of the question, see Woglom, Jour. Exper. Med., 1916, xxiii, 189. 
2 Chalatow, Virchows Arch., 1914, ccxvii, 140 (bibl.). 
3 Kettle, Jour. Path, and Bacterio!., 1912-13, xvii, 40. 
4 v. Hansemann, Deutsch, med. Wchnschr., 1915, xli, 633; Sappington, S. W., Jour. Am. Med. 
Assoc., 1922, lxxviii, 953. 
6 Schmorl, Cited by J ores: The Commoner Diseases, Philadelphia, 1915. 
6 See Wood, F. C., Chemical and Microscopical Diagnosis, 3d ed., New York, 1917, p. 146. 
7 Borrmann, Zieglers Beitr., 1907, xl, 372; Shennan, Jour. Path, and Bacterio!., 1914-1915, xix, 139. 380 
TUMORS 
only when extirpation has been incomplete. There is no knowing how 
long tumor cells may persist in the tissues before giving rise to a visible 
metastasis, but it is certain that in exceptional instances as long a period 
as ten or even fifteen years may elapse before the recurrence is noticed. 
Still, this may be regarded as somewhat unusual, and the best surgical 
judgment inclines to accept five years as the shortest interval which must 
elapse before cure can be regarded as reasonably assured. 
Even recurrence after removal is not typical of malignancy, since 
such a benign tissue as adenoid vegetations will return unless the oper- 
ation has been thoroughly performed. 
Cachexia is sometimes added as a fourth sign, but it is extremely 
doubtful whether malignant growths by themselves are able to induce 
malnutrition; certainly no definite harmful product has ever been 
demonstrated in their cells. It is much more probable, on the whole, 
that cachexia is due to the entrance of infection through an ulcerated 
tumor, to interference with an indispensable organ like the stomach 
or intestine, or to some influence exerted on the nutrition of the patient 
by his depressed mental state. So Osler1 relates that he has known a 
patient with gastric carcinoma to be relieved of digestive disturbance 
and to gain eighteen pounds in weight merely as the result of visiting a 
sanguine consultant who denied the presence of a malignant new growth. 
A tumor which is in itself benign sometimes destroys life by pressing 
upon some vital organ; thus, long-continued pressure by a simple fibroma 
may cause perforation of an artery, interfere with respiration, block the 
gastrointestinal tract, etc. In such cases the growth is often said to be 
malignant by position, although it appears better to reserve the term 
malignant for those neoplasms which possess the three characteristics 
discussed above; in other words, to regard malignancy purely as a bio- 
logical and never as an entirely mechanical attribute. 
The microscopical evidences of malignancy, while generally unmis- 
takable, are occasionally difficult of interpretation, and even the most 
expert diagnostician may at times be deceived. This being so, it is neces- 
sary for the pathologist to have fragments from different parts of the 
growth for examination and in particular should he be enabled to investi- 
gate the margin where, of course, any invasive tendency will be most 
clearly shown. But even under the best conditions a decision is reached 
in some instances only with the greatest difficulty, because no exact 
criterion of malignancy is yet known.2 None of the cell inclusions so 
often described is characteristic of malignancy;3 and while it is true that 
the cells and their nuclei are frequently larger in a malignant neoplasm 
than they are in the corresponding normal tissue, that there is a greater 
diversity in the shape and size of the cells and in the amount of nuclear 
chromatin, that the number of mitoses is increased and that they often 
differ widely from the normal type, it is equally true that all these anoma- 
lies may exist in conditions other than malignancy. 
1 Osler. Cited by Weil, Jour. Am. Med. Assn., 1915, Ixiv, 1283. 
2 For a study of mitochondria in tumors, see Porcelli-1 itone, Zieglers Beitr., 1914, Iviii, 237 (bibl)., 
and Goodpasture, Jour. Med. Research, 1918, N. S. xx>iii, 213. 
3Greenough, R. B., Jour. Med. Research, 1904-1905, N. S. viii, 137. TUMORS 
381 
The individual cells thus offering no certain diagnostic criteria, there 
remains only the general structure of the growth on which to base an 
opinion. A tumor of the breast, for example, composed of gland tubules 
in which all the cells are of approximately equal dimensions and in which 
each tubule is surrounded by a basement membrane, would be declared 
benign because it varied but slightly from the normal structure of the 
organ. Another, made up largely of irregular tubules whose cells varied 
in size, in staining qualities, and in the dimensions of their nuclei, the 
epithelium exhibiting in addition to its atypical arrangement a distinct 
power to invade the surrounding tissues, even though in a few areas only, 
would be regarded as malignant because of its wide departure from the 
normal architecture of the breast. Such frank examples as those just 
cited may be accurately diagnosed in the great majority of cases, al- 
though every pathologist encounters from time to time a tumor which, 
Such inclusions, which are very frequent in the cells of ulcerating epitheliomata, have in the past been 
mistaken for intracellular organisms (see also Fig. 204). 
Fig. 203.-Epithelial-cell and Leucocyte Inclusions in Tumor Cells. 
in spite of its typical structure, ultimately destroys the patient; and, con- 
versely, a neoplasm, of .atypical appearance which nevertheless appears 
to be clinically benign. 
It cannot be too strongly emphasized that the natural tendency of a 
malignant tumor to metastasize is often increased by injudicious examina- 
tion, because rough or repeated palpation may readily dislodge masses 
of cells and propel them along the tissue spaces or vessels.1 Metastasis 
may perhaps be hastened, also, by cutting into a growth to remove a 
fragment for microscopical examination, as blood-vessels and lymphatics 
are opened in the process; clinical opinion, however, is not entirely uni- 
form on this point.2 That the danger is not entirely imaginary is shown 
1 Tyzzer, Jour. Med. Research, 1913, N. S. xxiii, 309; Knox, L. C., Massage and metastases: Ann. 
Surg., 1922, Ixxv, 129. 
2 See Etving, New York Med. Jour., 1915, cii, 10; Greenough, Med. Record, 1917, xcii, 749; Ann. Surg., 
1917, Ixvi, 385; and editorials in the Med. Record, 1917, xcii. 728, 1083. For an experimental 
approach to the question, see Tyzzer, Jour. Med. Research, 1913, N. S. xxiii, 309, and Wood, F. C., 
Diagnostic incision of tumors, Jour. Am. Med. Assoc., 1919, Ixxiii, 764. 382 
TUMORS 
by the relative frequency with which malignant neoplasms recur in the 
scar or the suture holes, from cells set free at the time of operation. In 
view of the prevailing uncertainty it is undoubtedly advisable, whenever 
possible, to extirpate the entire tumor for diagnosis; but if this be im- 
possible, it would be better practice to remove a portion for examination 
than to miss the diagnosis entirely. 
Etiology.-The development of tumors has been referred, among 
other causes, to the misplacement and subsequent development of cell 
groups during embryonal life, to a release with advancing age of the 
physiological restraint said to be normally imposed upon all the tissues 
These cell inclusions were formerly considered to be parasites; but this view has been abandoned. 
Fig. 204.-Plimmer's Bodies in Carcinoma of Mamma. 
of the organism, and to parasites; these are the suggestions which have 
been most fruitful in provoking discussion and investigation. Of the 
secondary hypotheses there may be mentioned those that ascribe neo- 
plasia to the development of a specific degeneration and the subsequent 
emergence of a new cell race; to a loss of function with a concomitant 
gain in the power of proliferation; to fertilization of the inculpated cells 
by other elements; to the awakening of "slumbering cells;" to the 
presence of heterotypical mitoses;1 to a reproduction of the asexual 
phase of development (the chorion in mammals and its homologue else- 
where); and to a disturbance of chromosome equilibrium.2 
'Farmer, Moore, and Walker, Proc. Royal Soc., 1903, Ixxii, 499. For a refutation of this hypothesis 
see Bashford and Murray, Third Sei. Report, Imperial Cancer Research Fund, London, 1908, p. 61. 
2 Boveri, Zur Frage der Entstehung maligner Tumoren, Jena, 1914. TUMORS 
383 
Most famous of all these hypotheses is the first, which is usually 
ascribed to Cohnheim,1 although he was not by any means the first to 
suggest the association of neoplasms with embryonic rests. In the 
description of a congenital myosarcoma of the kidney, he suggested that 
the tumor might have originated in primitive muscle cells separated from 
the myotome while the foundations of the urinary organs were being laid 
down, since more cells than are actually necessary may well be produced 
during early embryonal life; the unutilized elements, it was suggested, 
undergo isolation at a very early period in their history, and at a time 
when all their potential power of proliferation remained intact. In 
the undifferentiated embryonal character of tumor cells, as well as in 
the early postnatal occurrence of certain neoplasms, Cohnheim sought 
support for an hypothesis which, he believed, accounted satisfactorily 
for the variety of tissues so often found in tumors, while at the same time 
it explained the observation that epithelial growths are most common 
about the various orifices of the body, the very regions where the embry- 
onal structure is most complicated. Cohnheim made no effort to estab- 
lish the circumstances which initiate malignant growth in an area of cells 
separated from the remainder of the embryo in the manner described, 
though offering the suggestion that one of them might be hyperemia.2 
This hypothesis has been elaborated by Ribbert,3 who believes that 
many carcinomata originate in embryonal remnants, though it is evident 
enough, he says, that all are not able to assume the malignant type of 
growth, since many lie indefinitely quiescent. Hence, although embry- 
onal rests possess, in common with other epithelial cell groups, a normal 
tendency to penetrate underlying connective tissues, these latter struc- 
tures must under ordinary conditions impose some sort of inhibitory 
influence preventing attack on the part of the epithelium. A release of 
the normal invasive power may be accomplished by the presence of in- 
flammation or simple hyperemia in the connective tissues, though it is at 
once apparent that such lesions must be characterized by some special 
attribute, since inflammation and hyperemia in adult connective tissue 
are not always followed by the development of carcinomata. In 
Ribbert's opinion, the process can be best explained on the assumption 
that those changes which precede the inauguration of carcinoma are the 
product of certain agents elaborated by the epithelium itself, or, in other 
words, that the epithelial cells prepare the soil into which they eventually 
penetrate. But as this chain of events would terminate merely in the 
growth of normal epithelium, it is necessary to employ the subsidiary 
assumption that cells which become malignant undergo first a loss in 
differentiation that enables them to proliferate more luxuriantly. Malig- 
nant growths, he believes, can be initiated more readily from embryonal 
rests than from adult epithelium, because the cells of the former are still 
in a condition of incomplete differentiation. 
In criticism of Cohnheim's hypothesis, it has been asked how it is 
1 Cohnheim, Virchows Arch., 1875, ixv, 64. 
2 For a discussion of the relation between heterotopic epithelium and carcinoma, see Lubarsch, 
Verhandl. d. deutsch. path. Gesellsch., 1906, x, 208 (bibl.). 
3 Ribbert, Das Karzinom des Menschen, Bonn, 1911, p. 476. 384 
TUMORS 
possible for embryonal remnants to develop after having lain dormant 
for years, but the objection loses its validity when it is recalled that the 
sexual glands remain quiescent in the body for fourteen or fifteen years, 
as do the hair follicles of the face in males. Much more damaging is the 
objection1 that neoplasms originate wherever the body is exposed to 
chronic irritation, and that if they develop from embryonal rests these 
must be distributed throughout the entire body; hence, that this explana- 
tion is, in fact, no explanation at all. 
As for the hypothesis of Thiersch2 and Waldeyer,3 that carcinoma 
develops in consequence of a disturbance in the restrictions normally 
imposed by the tissues upon one another, it has been suggested4 that if 
tumors were the outcome of a diminution in physiological restraint 
during later life, they would occur more commonly than they do, and 
would never arise in young persons. 
The view of Hauser5 and his followers is directly opposed to that of 
Ribbert. Hauser believes that carcinoma can originate only through a 
fundamental change in the biological properties of the cells implicated, 
an assumption which he supports by the occurrence of such changes as 
loss of physiological function, increase in the size of the cell and its 
nucleus, the higher chromatin content of the latter, the presence of 
abnormal mitotic figures, and, finally, the enormous capacity for multi- 
plication. All these characteristics indicate, in his opinion, the appear- 
ance of an entirely different type of cell-the emergence of a new cell 
race-the process being, in short, a specific cancerous degeneration. In 
a transformation like this, a weakening of the defenses said to be erected 
by connective tissue against epithelium can play but a subordinate role. 
While Ribbert and many other authorities hold that a neoplasm can 
increase only through the multiplication of its own cells, Hauser and his 
associates maintain that it spreads by a wave of malignant degeneration 
which attacks successively the normal structures at its margin. 
v. Hansemann,6 who has exhaustively investigated the types of mitosis 
found in tumor cells, describes three varieties, distinguished according 
to their chromatin content as hypochromatic, normal, and hyperchromatic. 
He explains the increased growth energy of the tumor cell by a gain in 
the power of independent proliferation and a coincident loss of differentia- 
tion; this condition he calls anaplasia. He does not regard it, however, 
as the prime cause of malignant proliferation, since a growth stimulus 
is required in addition. When such a stimulus acts upon a normal cell, 
the outcome is hyperplasia; upon an anaplastic cell, malignant growth. 
One of the criteria of anaplasia is unequal division of the chromosomes 
during mitosis, which, followed by an asymmetrical division of the cell, 
results in the production of elements biologically different from their 
ancestors. Those mitoses are asymmetrical in which the allotment of 
1 Bashford, Third Sci. Report, Imperial Cancer Research Fund, London, 1908, pp. ix and 24. 
2 Thiersch, Der Epithelialkrebs, namentlich der Haut, Leipzig, 1865, p. 78. 
8 Waldeyer, Virchows Arch., 1867, xli, 470; ibid., 1872, Iv, 67. 
4 v. Hansemann, Die mikroskopische Diagnose der bosartigen Geschwiilste, Berlin, 1902, p. 215. 
r Hauser, Das Cylinderepithel-Carcinom des Magens und des Dickdarms, Jena, 1890, p. 135. 
•». Hansemann, Virchows Arch., 1890, cxix, 299; Studien Uber die Spezificitat, den Altruismus, 
und die Anaplasie der Zellen, Berlin, 1893. TUMORS 
385 
chromosomes to the daughter stars is unequal; but as the actual number 
of chromosomes going to each diaster can seldom be accurately enumer- 
ated, it is necessary to be content with an approximate estimate. Though 
v. Hansemann has suggested that irregular mitoses are fairly character- 
istic of malignant epithelial tumors, they have been found in sarcomata, 
in benign growths, and even in i egenerating normal tissues.1 
None of the various hypotheses has fared so badly at the hands of its 
critics as that one which would refer neoplasia to the intervention of 
some parasite. No definite proof has ever been offered in support of this 
hypothesis, the parasites occasionally associated with tumors (as in the 
cancer of the rectum and bladder which sometimes accompanies bilharzio- 
sis) being regarded merely as the cause of a chronic irritation which, in 
its turn, gives rise to the new growth. The existence of cancer villages, 
cancer streets, and cancer houses, together with much of the other evidence 
so often advanced in support of the parasitic hypothesis, must be viewed 
with absolute scepticism until more cogent proofs have been brought 
forward to sustain the contention. It can often be shown, for instance, 
that a 11 cancer village" is one in which the population is composed 
largely of persons in the cancer age, most of the younger ones having 
migrated to the cities, while those authors who describe "cancer houses" 
take no account of the law of chance. As has been so well said in discuss- 
ing this question2: " . . .by the law of chance, just as one individual 
in a thousand may be of gigantic proportions, so one house in a thousand 
may show a great excess of cases of cancer-or of twin births-over the 
ordinary run of houses." Furthermore, few of the reports describing 
the transfer of a neoplasm from one person to another {cancer a deux) 
are in any way convincing. If large numbers of persons could be experi- 
mentally engrafted with a neoplasm, as mice are engrafted, a certain 
proportion might develop tumors; at any rate, a new growth sometimes 
becomes implanted upon an adjacent area of the patient's own body, and 
there is no reason to suppose that the cells of a malignant growth would 
not proliferate in other persons also, if they could be introduced under 
suitable conditions. But the ordinary contact of a physician or nurse 
with a patient, or between two persons residing in the same house, is 
hardly close enough for the disease to be transferred from one to another. 
And yet, after all, it cannot be categorically declared that neoplasia 
is not an infectious process; it can be said only that it does not resemble 
any of those with which we are at present acquainted.3 
In regard to diet it is possible to be more definite, and it may be 
safely maintained that no relation can be discerned between diet and 
neoplasia, since tumors are discovered with equal frequency in vegetarian 
races and in those living on a mixed diet; nor is there convincing evidence 
of a connection between the occurrence of neoplasms and the character 
of the soil, climate, or other surroundings. 
1 Podwyssozki, Zieglers Beitr., 1886, i, 301; Stroebe, ibid., 1893, xiv, 154. 
2 Adami, Principles of Pathology, 2d ed., Philadelphia, 1910, i, 839. 
3 For a vigorous defense of the parasitic hypothesis, see Emery, W. D., Tumours; Their Nature and 
Causation, London, 1918. 386 
TUMORS 
In order to gain some insight into the cause of malignant growth, 
statistics have been collected and analyzed, though without any definite 
result having been so far achieved. This may, perhaps, be partly be- 
cause the information has been until within a short time incomplete; 
thus, the diagnosis has not always been founded upon microscopical ex- 
amination; the site of the new growth has not been carefully given; the 
occupation of the patient is not always stated, etc. Statistics are being 
constantly improved, however, and there is reason to hope that within 
the next few decades this branch of research may yield valuable informa- 
tion. For example, it cannot be due to chance that workers in aniline 
dyes frequently have tumors of the bladder,1 and that those who handle 
tar develop tumors of the skin. 
The chemical investigation of tumors has so far yielded no informa- 
tion of definite value, except that in their composition tumors do not 
differ widely from the corresponding normal tissue.2 
The production of a tumor by one single trauma3 is extremely 
doubtful. In many cases there can be no question that the association 
is a coincidence, while in others the injury serves only to direct attention 
to a tumor already present. Until the cause of malignant growth is 
definitely understood, however, it will be impossible dogmatically to 
assert that a single injury cannot give rise to a new growth; but the fact 
that by far the greater proportion of injuries is not followed by tumor 
renders the probability infinitesimal. In the case of chronic irritation, 
the evidence is much more definite. Cancers about the mouth in 
smokers or in persons with roughened, carious teeth, z-ray cancers, and 
those originating in scars and ulcers spring at once to mind in this con- 
nection. That the occurrence of neoplasms in the irritated areas is a 
matter of pure chance is rendered improbable by the large number of 
recorded instances, no less than by the observation that the tumors arise 
exactly at the point subjected to irritation. Occupations and racial 
habits together constitute, in reality, an extensive experiment.4 Thus, 
epithelioma of the skin overlying the abdomen is very common among 
the natives of Kashmir, who wear a basket of glowing charcoal under 
their robes for purposes of warmth, and cancer of the mouth is equally 
common in those natives of India and the Philippine Islands,5 who chew 
betel-nut, the neoplasm developing in the former case just where the 
effects of the heat are most intense, and in the latter at the site where 
the betel-nut is retained against the cheek. The importance of these 
observations lies in the fact that cancer in the locations mentioned 
is practically unknown in other races. Moreover, instances suggesting 
1 Hamilton, A., Jour. Industrial Hygiene, 1921, iii, 16; Nassauer, M., Frankfurter Ztschr. f. Path., 
1919-20, xxii, 353. 
2 Wells, Chemical Pathology, 3d ed., Philadelphia, 1918, p. 492#. 
3 Brosch, Virchows Arch., 1900, clxii, 32; Schdppler, Ztschr. f. Krebsforsch., 1911, x, 219; Schepel- 
mann, Med. Klin., 1915, xi, 741 (abstr. in Jour. Am. Med. Assn., 1915, Ixv, 748); Wolff, DieLehre von 
der Krebskrankheit, Jena, 1911, Teil ii, p. 125 (bibl.); Lowenstein. Beitr. z. klin. Chir. (Bruns), 1906, 
xlviii, 780; ibid., 1911, Ixxiv, 715; Unfall u. Krebskrankheit, Tubingen, 1910; Arch. f. klin. Chir., 1895, 
xlix, 1; Graef, Centralbl. f. d. Grenzgeb. d. Med. u. Chir., 1913, xvii, 603; Stern, Uber traumatische 
Entstehung innerer Krankheiten, Jena, 1913, p. 487. 
4 Bashford, Third Sci. Report, Imperial Cancer Research Fund, London, 1908, p. 1. 
5 Davis, Jour. Am. Med. Assn., 1915, Ixiv, 711. TUMORS 
387 
a relation between chronic irritation and the development of neoplasms 
are not limited to man alone.1 In the cow, for example, carcinoma 
of the liver is almost invariably connected with severe biliary cirrhosis 
due to infection with a parasite, and is thus complementary to the 
rectal and vesical cancer which occurs in man in association with in- 
fection by the Bilharzia haematobia (Schistosoma haematobium). The 
two together show the futility of trying to explain cancer as a disease 
of civilization. Both organisms, separated as they are in the zoological 
scale, develop tumors at a point exposed to chronic irritation and appar- 
ently in obedience to a law of wide application, since neoplasia assails 
the entire animal kingdom, at least as far down as the reptiles.2 It 
does not attack man because of his civilization, nor does it show any 
greater preference for cultured than for savage races.3 It is discovered 
oftener in highly civilized people because they live to a more advanced 
age and because they have access to a variety of diagnostic measures 
denied to the inhabitants of less advanced countries, and not because 
it occurs more frequently in them. Similarly, cancer does not attack 
the domestic animals on account of their close association with civiliza- 
tion, sparing wild animals, but develops in the former solely for the reason 
that they attain higher age periods by reason of man's care, and is dis- 
covered in them because they are autopsied with comparative frequency. 
The recent successful experimental production of cancer in animals 
by chronic irritation has shown the importance of this factor in the pro- 
duction of tumors. Carcinoma of the stomach has been produced by 
feeding white rats with the larva of a nematode worm, which on invading 
the mucous membrane produces an extensive chronic hypertrophic lesion 
of the squamous epithelium at the cardia of the organ. After a consider- 
able time has elapsed, a certain proportion of these hyperplasias become 
malignant and may metastasize.4 
The repeated painting of the skin of susceptible animals with gas tar 
over a long period of time, generally a year, has also led to the production 
of a large number of squamous cell epitheliomata, some of which metasta- 
size into the internal organs, or can be transplanted. Injection of the tar 
into the breast has produced carcinomata and a very few sarcomata of this 
organ in animals.5 
Another interesting example of the effect of irritation by a parasite of 
an entirely different type is seen in the sarcomata of the liver produced 
by the infestation of that organ in rats with the cysticercus of Tenia 
crassicollis, the cat tapeworm.6 In a susceptible strain of rats as high 
as 50 per cent, of the animals may ultimately develop sarcoma of the 
1 Bashford, Third Sci. Report, Imperial Cancer Research Fund, London, 1908, p. 1. 
2 Murray, Third Sci. Report, Imperial Cancer Research Fund, London, 1908, p. 41. For a resumd 
of tumors in cold-blooded animals, see Plehn, Ztschr. f. Krebsforsch., 1906, iv, 525. 
3 Bashford, Third Sci. Report, Imperial Cancer Research Fund, London, 1908, p. 1; v. Hansemann, 
Ztschr. f. Krebsforsch., 1914, xiv, 39. 
i Fibiger, J., Jour. Cancer Research, 1919, iv, 367 (bibl.). 
6 Y amagiwa, K., Virchows Arch., 1922, ccxxxiii, 235 (bibl.) and Woglom, W. H., and Murray, J. A., 
Seventh Sci. Rep., Imperial Cancer Research Fund, London, 1921, p. 45 (bibl.); Bloch and Dreifus, 
Schweiz. Med. Wchnschr. 1921, li, 1033. 
6 Bullock, F. D., and Rohdenburg, G. L., Jour. Cancer Res., 1916, i, 87; Bullock, F. D., and Curtis, 
M. R., Proc. New York Path. Soc., 1920, xx, 149 (bibl.); and Borrel, Bull, de 1'Assoc, franc, p. 1'Etude 
du Cancer, 1910, iii, 322. 388 
TUMORS 
liver, a tumor never occurring spontaneously in this site in the rat. With- 
in the highly susceptible strain certain families have given a much higher 
yield of tumors. On the other hand, there are strains in which no tumors, 
or very few tumors, develop, in spite of the fact that the cysts form in the 
regular fashion. This crucial experiment demonstrates the importance 
of tissue susceptibility to an irritant as a factor in the production of a 
tumor. Such susceptibility has long been suspected as occurring in 
various human races. The insusceptibility of the skin of the negro to 
epithelioma, and the great liability of that of the white to the same tumor 
being a concrete example. In spontaneously appearing tumors, the 
exact amount of irritation is not however determinable, but in these rat 
experiments the irritant in both cases is the same, both quantitatively 
and qualitatively. The ages of the animals, their food, housing and all 
other conditions are likewise as nearly as possible the same. Therefore 
the same irritant may produce in one strain a large proportion of tumors 
and in another a few or none. Thus the liability to cancer is hereditary 
at least in certain animals, but this is far from the loose general statement 
so often made that cancer is hereditary. 
Chronic irritation, accordingly, appears to be responsible for the 
inception of certain neoplasms, yet it cannot be the only factor in their 
etiology, otherwise every person subjected to it would develop a tumor. 
This, of course, is not the case, and other causes must, therefore, be 
sought. A second has been discovered by Murray1 who has found that 
the offspring of mice suffering from spontaneous (as distinguished from 
transplanted) carcinoma are about twice as likely to develop such a 
tumor as are mice descended from normal parents and grandparents.2 
This information must be applied to the human subject, however, only 
with the greatest reserve since the cancerous ancestry in the mice of 
these and similar experiments is much more concentrated than ever it 
would be in human beings. A study of life insurance statistics3 shows 
that even among persons whose two parents have died of cancer, the 
incidence of the disease is no higher than the average. Therefore, while 
it cannot be denied that there may be found an occasional family with a 
concentrated cancerous liability, there is, in general, no occasion for 
alarm. 
But the two causes, chronic irritation and predisposition, are in them- 
selves apparently not always sufficient for the inauguration of a neoplasm. 
A third factor seems to be necessary in most cases, and this is age. By 
far the largest number of tumors, both in man and in the lower animals, 
affect individuals who have passed middle life, and in the experiments 
just cited carcinoma did not develop any earlier in the mice of cancerous 
ancestry than it did in the other group. Still, in many cases it seems to 
be not the age of the patient himself that is of importance, but the age 
1 Murray, Proc. Roy. Soc., Ser. B., 1911-12, Ixxxiv, 42. 
2 See also Slye, Jour. Cancer Research, 1916, i, 479, 503; and Slye, Holmes, and Wells, ibid., 1917, 
ii, 1, 401; Tyzzer, Jour. Med. Research, 1907-08, N. S. xii, 199. 
8 Hunter, Address delivered at the Tenth Annual Meeting of the Assn, of Life Insurance Presidents 
at New York, Dec. 15, 1916. TUMORS 
389 
of the tissue in which the neoplasm originates.1 This may explain the 
fact that cancer of the uterus and the gastrointestinal tract appears with 
relative frequency in middle life, cancer of the skin, on the contrary, 
rarely before old age. 
The Transplantation of Tumors.-While it is possible to transplant living normal 
tissues or even whole organs into an animal of the same species {homeotransplantatiori) 
and have them remain viable for a time, their almost invariable fate is sooner or later 
to undergo necrosis. The results are better when an animal is inoculated with its 
own tissues {autotransplantation).2 Transplantation into animals of another species 
{heterotransplantation) is not successful. 
Turning to the neoplasms,3 we find that mouse and rat tumors will grow after 
having been transferred into another animal of the same species, or even into the mem- 
brane of chick embryos,4 and that other information of value is being slowly acquired. 
Thus, many of the new growths encountered in man are found among the lower 
animals, though it is to the neoplasms of tame mice and rats that attention has been 
particularly directed, because of the facility with which these small animals can be 
stored and handled. 
In the mouse, the most common tumor is a carcinoma which originates in the 
female mammary gland and closely follows the clinical course of cancer in the human 
subject. Metastasis is common, taking place generally by way of the blood stream, 
more rarely by the lymphatics, and true infiltrative growth is easily demonstrable. 
In the rat the neoplasm most often encountered is sarcoma of the connective tissue, 
or of the liver at the edge of a tapeworm cyst? 
It has been found that if small particles of a spontaneous animal tumor be inserted 
under the skin of healthy young animals of the same species, the implanted cells will 
grow in a few of them, say about 5 per cent., and within three weeks to several months 
produce new tumors similar in character to the original. So from animal to animal 
the tumors may be propagated through long series to an extent which, so far as is now 
known, is without limit, the percentage of successful inoculations gradually rising in 
most cases. A striking feature of these transplantations is the apparently boundless 
capacity of the cancer cell for proliferation, for it will readily be seen that if a 
few cells can, within a relatively short time, produce a mass as large as the growth 
from which they came, the amount of new tissue would be prodigious almost beyond 
belief6 if all the tumors in every generation were to be transplanted. Yet one should 
not lose sight of the fact that recent experiments on the cultivation of normal embry- 
onic tissues in vitro suggest that somatic tissues also may be capable of unlimited 
growth provided that the environment be suitable. 
The existence of certain hereditary factors tending to make some mice naturally 
more, and others less, refractory to transplanted cancer has been intimated, and 
susceptible and non-susceptible strains have been bred. 
It has been shown7 that the cells of a few carcinomata have the power to transform 
the connective-tissue stroma into a sarcoma, which also is capable of continued 
propagation, and even tends to overgrow the epithelial portion of the tumor. It is 
possible that the combination of carcinoma with sarcoma which is occasionally en- 
countered in human neoplasms, may be the outcome of a similar power on the part 
of the epithelial portions of these growths. 
In contrast to the comparative difficulty of getting spontaneous growths to es- 
tablish themselves in new hosts, is the readiness with which they will succeed in the 
animals that develop them, for almost without exception they will proliferate if 
1 Bash.ford, Berl. klin. Wchnschr., 1909, xlvi, 1677; Deutsch, med. Wchnschr., 1913, xxix, 4; 
Middleton Goldsmith Lecture, delivered before the New York Path. Soc., 1912. 
2 Manley and Marine, Jour. Am. Med. Assn., 1916, Ixvii, 260; Jour. Exper. Med., 1917, xxv, 619. 
3 For a resume of the work which has been accomplished in the field and for bibl., see Woglom, 
Study of Experimental Cancer, New York, 1913. 
4 Murphy, Jour. Exper. Med., 1913, xvii, 482; ibid., 1914, xix, 181. 
5 Bullock and Rohdenburg, Jour. Cancer Research, 1917, ii, 39. 
6 For a calculation of the possibilities of such growth, see Ehrlich and Apolant, Berl. klin. Wchnschr., 
1905, xlii, 871. 
7 Apolant, Arb. a. d. konig. Inst. f. exper. Therap., Frankfort a M., Jena, 1906, i, 48; Haaland, 
Third Sci. Report, Imperial Cancer Research Fund, London, 1908, p. 175. 390 
TUMORS 
reintroduced into the organism in which they are native. This is not because the 
bearer of a spontaneous neoplasm offers a more favorable soil for tumor growth in 
general, but because the cells need make no great effort to adjust themselves to their 
environment, as is necessary for them to do if they are to survive introduction into 
another animal. The same phenomenon has long been familiar to the surgeon in 
the form of metastases or of recurrence in the scar or suture holes at the site 
of extirpation. 
Acquired Immunity to Tumors.-This is brought about in an animal by the ab- 
sorption of cells from another of the same species, and persists for as long as two or 
three months. Whether the cells be derived from normal tissues or from a tumor, is 
immaterial; the only requisite is that they shall be living and intact when they are 
introduced. Thus animals have been rendered refractory to transplantation by the 
inoculation of embryonic tissues, or adult spleen, kidney, etc., as well as by unsuccess- 
ful inoculation with tumors, but it has not been possible to obtain immunity by the 
injection of juices or extracts from a tumor or by introducing serum from animals 
possessed of natural or acquired resistance. Experiments in which this outcome has 
been asserted have been vitiated by lack of care in obtaining such uniform experi- 
mental conditions as a pure strain of animals,1 uniform dosage, etc. Apparently 
nothing short of the living cell is capable of producing resistance, and the reaction 
is so delicate that, as has been said, only tissues of the same species are potent. Those 
of the individual itself, however, are devoid of all immunizing power. The exemption 
thus conferred, which is due to a failure of fibroblasts and blood-vessels from the host 
to penetrate the graft,2 is valid only in the case of a graft which is in the act of estab- 
lishing itself in a new host, and no substance known will influence a more advanced 
tumor; nor does immunity prevent the development of a spontaneous new growth. 
In addition large and unpredictable fluctuations occur even in resistance to implanta- 
tion and it is impossible to produce it against many highly malignant tumors.3 
Hence there is no justification for the treatment by analogous methods of tumors in 
man, which, indeed, would be still less likely to yield since they are composed, not of 
cells foreign to the organism, as is a transplanted mouse tumor, but of native elements. 
It is impossible at present to classify tumors scientifically because our 
knowledge of their derivation is in many respects incomplete. 
None of the schemes proposed is perfect, and they differ from one 
another in many respects; yet almost all contain the two headings: 
connective-tissue tumors and epithelial tumors. If to these there be added 
a third group, embryoid and mixed tumors, a classification is obtained 
which, though admittedly rough, will do for practical purposes. Groups 
I and II may be subdivided into (a) mature and (&) immature growths. 
I. (a) Mature Connective-tissue Tumors.-The mature or benign con- 
nective-tissue new growths include such tumors as fibromata, lipomata, 
angiomata, osteomata, and chondromata. Of them it may be said that 
their morphological resemblance to the tissue in which they originate is 
fairly close. Accordingly the two classes of fibrils characteristic of ordi- 
nary connective tissue can be recognized in a fibroma by means of Mallory's 
stain; the adipose tissue of a lipoma closely resembles normal fat; the an- 
gioma consists of proliferating blood-vessels; and the cells of osteomata 
and chondromata prepare bone and cartilage respectively. In no case, 
however, is the corresponding normal structure exactly duplicated. 
The fibroma, for example, is apt to be more cellular than connective 
Classification 
1 It has been observed that mice and rats of different strains, or obtained from different parts of 
the country, show distinct variations in susceptibility to inoculation with the same tumor. 
2 Russell, Third Sci. Report, Imperial Cancer Research Fund, London, 1908, p. 341. 
3 Bullock and Rohdenburg, Jour. Cancer Research, 1920, v, 119, 129. TUMORS 
391 
tissue, while in the fat composing a lipoma both cells and lobules some- 
what exceed the normal dimensions. The atypical condition of the 
tissues making up a tumor is demonstrated, again, in the incomplete 
state of the blood-vessels, most neoplasms being characterized by the 
scarcity of proper arteries and veins with communicating capillaries, 
and receiving their blood supply through simple thin-walled channels. 
The lymph-vessels, too, are abortive, and nerves are said to be ordinarily 
absent as actual components of the growth.1 
(b) Immature Connective-tissue Tumors.-The malignant connec- 
tive-tissue group contains the sarcomata. Though the members are com- 
posed of unfinished tissue, it is possible to divide them into two classes- 
one in which the material is totally immature, and a second, in which a 
certain amount of differentiation has occurred. Those of the former are 
purely cellular tumors in which the elements produce almost no collagen 
or other intercellular material characteristic of the site where the growth 
originates, and appear to expend all their energy in mere proliferation. 
Such growths, the round-cell and spindle-cell sarcomata, are among the 
most malignant of all neoplasms. They have practically no stroma, save 
for an abundant meshwork of blood-vessels, and as the walls of these 
channels often consist of a single layer of cells, hemorrhages frequently 
occur. For this reason, also, tumor cells readily attain the blood-stream, 
so that the sarcomata metastasize early and extensively by way of the 
circulation. 
The second group is made up of sarcomata showing some effort 
toward differentiation-toward a production, that is, of an adult tissue 
like bone or cartilage. Here belong such neoplasms as the osteoblastic 
and chondr oblastic sarcomata. The attempt is less successful, however, 
than that which characterizes the benign connective-tissue tumors 
arising in similar locations and, it is hardly necessary to state, falls 
still further short of what is seen in the corresponding normal tissue 
itself. 
Differential Diagnosis.-A sarcoma is differentiated from a benign 
connective-tissue tumor by the scarcity or irregular character of the 
intercellular material, by variation in the shape and size of the cells, by 
the presence of an increased number of mitotic figures, and by its invasive 
growth. From an infectious granuloma it can often be separated by the 
fact that its elements are all of one variety, whereas infectious lesions 
contain such dissimilar types as fibroblasts, polymorphonuclear leuco- 
cytes, plasma cells, etc. Yet it must be confessed that the distinction 
between a sarcoma and a benign connective-tissue neoplasm, or between 
a sarcoma (especially if it be infected) and an infectious granuloma, 
occasionally proves to be one of the most difficult which the pathologist 
is called upon to draw. 
II. (a) Mature Epithelial Tumors.-The benign epithelial series em- 
braces the papillomata, adenomata, etc., tumors which reproduce more or 
less faithfully the anatomical features of the structures in which they 
originate. Thus the adenoma, which develops from glands, imitates the 
1 For a study of nerves in tumors, see Young, Jour. Exper. Med., 1897, ii, 1. 392 
TUMORS 
parent organ in the arrangement of its epithelium into tubules bounded 
by a connective-tissue wall, the limits of which its cells have no power to 
transgress. As the epithelial elements are arranged in one layer about 
the lumina of these tubules, the resemblance to the normal structure is 
distinct, though not by any means complete, for there is a larger amount 
of epithelium than there should be in proportion to the stroma, and this 
glandular moiety of the tumor is often separated from the excretory 
ducts of the organ in which the growth is situated. 
Tapering glands may appear to have more than one layer of cells, 
particularly in rather thick sections, because the eye looks down into a 
funnel of which it sees the sloping sides. This source of error may be 
eliminated, however, by careful focussing, which will show that the 
several layers seen are not all in one plane (Fig. 205). 
A B 
Fia. 205.-The sloping sides of a gland in a thick section (A) may at first sight create the impression 
of several layers of epithelium. But careful focussing with high power will show (B) that the concen- 
tric rows of cells are not all in the same plane. 
(b) Immature Epithelial Tumors.-The malignant epithelial tumors 
comprise the various types of carcinoma, characterized by the immature 
condition and arrangement of their epithelium. In these neoplasms, 
the orderly correlation between epithelium and connective tissue seen 
under normal conditions and present, though to a smaller extent, in 
fibroepithelial tumors and the adenomata, is disturbed. The epithelium 
becomes totally emancipated from all restraint and, breaking through 
the restrictions normally imposed upon it, attacks and invades the 
neighboring structures. The more highly differentiated carcinomata 
mimic the normal pattern to some degree, while at the opposite end of 
the scale there may be found others in which the epithelium is utterly 
undifferentiated and arranged in solid masses, making its distinction 
from sarcoma difficult without the employment of special staining 
methods. 
The connective tissues at the edge of a carcinoma are not infrequently 
the seat of an infiltration with small round cells, a condition which is 
regarded by many observers as a defensive reaction on the part of the 
organism against further advances by the tumor; others (and Ribbert in 
particular) regard this as a preliminary change in the connective tissue, 
leading to carcinoma. 
III. Embryoid and Mixed Tumors.-The members of Group III are 
referable to developmental anomalies. Cystic embryomata and embryoid TUMORS 
393 
tumors of the ovary, testis, mediastinum, and brain, and in the sacral1 and 
retroperitoneal regions, appear to originate in unused blastomeres at a 
very early period in the life history of these elements, the period of 
cleavage.2 Hence, these growths contain derivatives of all three germinal 
layers and approach more nearly than any other to the normal archi- 
tecture of the adult organism. Elsewhere in the body there occur neo- 
plasms containing products of the three layers and known as fetal inclu- 
sions or teratomata, which may be analogous with the embryomata of the 
testis and ovary just mentioned. 
A subdivision of Group III comprehends the mixed tumors, simpler 
than those of the preceding class, though still very complex in their 
structure. Under this heading are included mixed neoplasms of the 
kidney, vagina, bladder, vas deferens, ovary, and testis. These also 
have their inception in unused blastomeres, differing from the embry- 
oid tumors only in developing at a somewhat later stage in the life 
history of these elements, that of the three germinal layers. 
The malignancy of the mixed tumors varies, but those of the kidney 
are almost always extraordinarily malignant, and metastasize at an early 
period. 
As a substitute for the term mixed tumor, complex or composite tumor 
has been suggested3 since this more definitely indicates the fact that 
several tissues take part in the formation of such a growth, and because, 
furthermore, a true mixture of the various components does not ordi- 
narily occur. Neoplasms made up of two or more modifications of a tissue 
are not compound, according to this view; a chondrosarcoma is not, 
for example, since cartilage, bone, and sarcoma are all variants of con- 
nective tissue. The constituents must be independent varieties. 
By reason of their frequent occurrence, cystic embryomata of the 
ovary deserve a more extended description than can be given to other 
tumors of this group. Ordinarily from five to ten centimeters in diameter 
and filled with hair and fatty debris, these are known also as dermoid 
cysts, because their walls are lined with epidermis. From the inner 
surface of the wall there projects a nodule covered with hair and fre- 
quently containing bone in which fully developed teeth may be set. 
Section of such a mass will usually demonstrate the presence of skin, 
hair follicles, sebaceous and salivary glands, pharyngeal or nasal mucous 
membrane, and, more rarely, of thyroid, intestine, or brain. In fact, 
these cystic embryomata may contain derivatives of any or all the 
germinal layers, microscopic examination showing their content to be 
more varied than gross examination would suggest. Solid embryomata 
are much less often encountered in the ovary than are the tumors just 
described. 
To sum up these complex congenital growths or teratomata: They arise 
by inclusion of portions of another fetus and are thus rather malforma- 
tions than neoplasms in the limited technical sense. But they may give 
1 For a critical summary of tumors of the sacral region, with bib!., see Borst, Centralbl. f. allg. 
Path., 1898, ix, 449. 
2 For a review of the subject, see Wilms, Die Mischgeschwiilste, Leipzig, 1897. 
3 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 638. 394 
TUMORS 
rise to tumors, some of them malignant, like chorionepithelioma and 
sarcoma. Among them are sometimes classed other and simpler congen- 
ital anomalies, such as epidermoid cysts, congenital angiomata, and the 
so-called pigmented noevi or moles. 
More than one type of tissue is present in a considerable proportion 
of all tumors, and it is customary to indicate complexity by compound 
terms, such as osteosarcoma, adenocarcinoma, etc. But some discrimina- 
tion is necessary in the use of such names, and one should be clear as to 
what is connoted by these expressions. All new growths have a certain 
amount of fibrous stroma which carries the blood-vessels and forms a 
sustaining framework, yet a carcinoma is never referred to as a fibro- 
carcinoma, no matter how prominent a part the stroma may play in its 
composition. It is only when a second component assumes an inde- 
pendent growth that it can be justly indicated in the compound name. 
This may not be easy or always possible to determine, but the desirability 
of so doing should be held constantly in mind. Unfortunately, compound 
names are loosely employed by some writers to indicate the seat of a 
tumor, osteosarcoma, for example, being used for sarcoma of a bone, in- 
stead of to imply the association of osteoma and sarcoma. 
It should also be remembered in this connection that a mixed tumor 
does not always start as such, but may assume this character by meta- 
plasia (page 74) within the limits of a tissue group. Thus the occurrence 
of bone or cartilage in a fibroma is common. The possibility of meta- 
plasia should therefore always be taken into account before assuming 
that a multiplicity of related tissues in a tumor necessarily indicates an 
embryonal origin. 
There are neoplasms which cannot readily be brought into the usual 
general classification, since they are formed of special kinds of tissue; 
they have accordingly received distinctive names. Thus there occur 
peculiar tumors formed of placental tissue called chorionepithelioma; 
of tissue resembling the adrenals, hypernephroma, etc. 
Cysts. 
These structures, for the sake of convenience, are often classed among 
the tumors, although in general character, structure, and genesis they 
are usually of an entirely different nature. They may be divided into 
two classes: 
I.-CYSTS WHICH DEVELOP FROM PREEXISTING CAVITIES. 
1. Retention Cysts.-These are chiefly formed by the accumulation 
of secretion in glands or their secretory ducts, as the result of obstruc- 
tion to the normal discharge, inflammatory contractions, pressure, etc. 
The contents are usually mucous, sebaceous, serous, or mixed. To this 
class belong comedones, milium, atheroma, chalazion, ranula, the ovula 
Nabothi, milk cysts, and certain serous cysts of the ovaries, Fallopian 
tubes, gall-ducts, and uriniferous tubules. TUMORS 
395 
2. Transudation Cysts.-These arise usually, though not always, as 
the result of a chronic inflammatory process in lymph-spaces or serous 
sacs; among them are to be included ganglion, hydrocele, etc. Certain 
hematoceles in which blood is extravasated into closed cavities belong to 
this group. 
II. CYSTS WHICH ORIGINATE INDEPENDENTLY AS THE RESULT OF 
PATHOLOGICAL CHANGES. 
•1. Cysts Formed by the Softening and Disintegration of Tissue.- 
Such cysts may at first be small, with meager contents and no well- 
defined wall. A wall may finally develop, either as an entirely new struc- 
ture, or as the more or less modified capsule of the organ in which they 
occur. The contents are usually the detritus of the tissue by whose 
disintegration they are formed. Such cysts are very apt to occur within 
true tumors, particularly those which are succulent and of rapid growdh, 
since these are very liable to degeneration. Cysts may also appear in 
the slowly growing tumor-like masses involving the bones in osteitis 
fibrosa. Finally, old abscesses may be transformed into well-defined 
cysts. 
2. Cysts Formed around Foreign Bodies.-The inflammatory reac- 
tion induced by the presence of foreign bodies of various kinds, such as 
parasites, extravasated blood, etc., frequently results in the formation 
of well-defined encapsulated cysts. 
3. Cysts Formed by a New Growth of Tissues in Whose Spaces 
Various Kinds of Fluid Accumulate.-These spaces may or may not be 
lined with epithelium and have something of the glandular character. 
Such forms are exemplified in some of the compound ovarian cysts-the 
so-called ovarian cystomata, which are really adenomata. 
4. Congenital Cysts.-These are of various forms, and their mode of 
origin is in most cases but imperfectly understood. Some of them, like 
epidermoid cysts of the subcutaneous tissue (Fig. 206) and the dermoid 
cyst of the ovary, are properly grouped among the teratomata. Epi- 
Fig. 206.-Epidermoid Cyst of Skin. 396 
TUMORS 
dermoid cysts of the skin are probably all formed from an embryonal 
displacement of the epidermal structures. The simplest forms are lined 
with epithelium of the squamous type and largely filled with a mass of 
flat desquamated cells. In the more complicated varieties, hair follicles 
and sebaceous and sweat glands are present in the lining epidermal 
membrane. Certain congenital cysts of the kidney and other internal 
organs are conveniently grouped here, although it is probable that some 
of them, at least, originate during fetal life in one or the other of the 
above-described ways, and hence are not essentially different in nature 
from some of the cysts of other classes. For the mode of formation of 
certain cysts of the neck see page 736.1 For cysts of the viscera see 
Special Pathology. 
There are certain enlargements of the lymph-nodes which are in reality hyperplasias, 
sometimes inflammatory in character and sometimes not, and which are often in- 
cluded among the tumors as lymphomata. They are not true neoplasms, and will 
be discussed under lesions of the lymph-nodes. To the same group are often rele- 
gated enlargements of the lymph-nodes in leukemia and in other general diseases, 
which are considered in another part of this book. Another group of tumors some- 
times called lymphomata are in reality sarcomata. 
There is also a class of nodular new formations, the "infective granuloma la," 
which in earlier days were placed with the tumors. These, which are now known to 
be inflammatory, occur in tuberculosis, lupus, leprosy, syphilis, glanders, actinomy- 
cosis, etc., and probably include also the nodes of Hodgkin's disease (page 556). 
Various Lesions Sometimes Described as Tumors. 
Connective-tissue Tumors-Benign. 
Special Forms of Tumors. 
FIBROMA. 
The fibromata are composed of fibrillar connective tissue2 which, as 
under normal conditions, may be dense, col- 
lagenous, and firm (fibroma durum, Fig. 207), 
or loose in texture, cellular, edematous, and 
soft (fibroma molle). Since fibrous connective 
tissue is universally distributed, these tumors 
may be encountered anywhere in the body. 
The subdivision into hard and soft forms is 
not to be taken too seriously, for the dividing 
line is not distinct and many fibromata con- 
tain both hard and soft areas. Fibromata 
are usually sharply circumscribed and are 
often encapsulated, though they may be 
diffuse and merge imperceptibly into the sur- 
rounding tissues. They are frequently small 
and insignificant, but occasionally grow to enormous size. Some 
Fig. 207.-Dense Fibroma 
of Abdominal Wall-Fibroma 
Durum, 
Some of the bands of con- 
nective tissue fibers are cut 
across; others are cut lengthwise. 
1 Consult, for consideration of ciliated and other cysts, Hess, Zieglers Beitr. zur. path. Anat., 1890, 
vii, 98; Zahn, Virchows Arch., 1890, cxliii, 170. For later general bibl. of cysts, see Aschoff, Lubarsch- 
Ostertag, Ergebn. d. allg. Path., 1895, ii, 456. 
2 For a study of fibroglia, see Mallory, Jour. Med. Research, 1904-05, N. S. viii, 113. TUMORS 
397 
fibromata consist almost entirely of intercellular substance containing 
but few fibroblasts; others contain many. 
The younger, growing regions of the tumor are always more or less 
cellular, but in the older portions, where the cells have had time to mature 
and produce their characteristic product (collagen), the number of ele- 
ments is small, and those which are present resemble the adult fibro- 
blast in their long slender cell body and their rod-like nucleus. Thus 
Fig. 208.-A Nodular Polypoid Tumor-Fibroma-Hanging from the Vulva. 
they differ from those in the more cellular parts, which may be of any 
form, though, on the whole, they appear as plump spindle-shaped elements 
with oval nuclei. The denser fibromata usually contain but few blood- 
vessels, although they are occasionally well supplied; many of the softer 
varieties are very vascular. Both types contain lymph-channels, but 
like the blood-vessels these are more abundant in the soft fibromata. 
Nerves are occasionally present-generally preexisting bundles which 
have been surrounded by the grow'th. 398 
TUMORS 
The course and arrangement of the fibers in these tumors are usually 
regular. They often cross and interlace in a most complex manner, 
conferring upon the cut surface an appearance that has been compared 
to that of watered silk. The fibromata are almost always of slow growth, 
though exceptionally they increase rapidly in size. They are benign 
tumors, yet by pressure on important organs, or by ulceration, they may 
become of serious import. Pure fibromata do not form metastases, but 
they are often multiple and when so are frequently congenital. They 
may recur when not fully removed. 
Differential Diagnosis.-It is often very difficult, and sometimes 
even impossible, to distinguish between a rapidly growing fibroma (espe- 
cially of the soft variety) and a spindle-cell sarcoma. The presence of a 
great number of cells with large bodies and nuclei, and showing occasional 
mitotic figures, is suggestive of sarcoma; and the greater their number in 
proportion to the amount of intercellular substance, the stronger be- 
comes the suspicion of malignancy. 
The presence of multinucleated fibroblasts or giant cells sometimes 
seen in the fibroma molle generally indicates that the tumor is more likely 
to be a fibrosarcoma than a simple fibroma.1 These, however, are not 
often found, and the question must finally resolve itself into which is 
more abundant-cells or intercellular substance. If the former prepon- 
derate, the growth is very like to be a sarcoma, while if the latter be in 
excess the tumor is probably a fibroma. 
It seems probable that in the multiple fibromata of the skin (fibroma 
molluscum) the new growths occur in some special form of connective 
tissue, as that of the nerves, blood-vessels, or glands. Some of these 
neoplasms are congenital. There is often a growth of very cellular tissue 
just beneath the epithelium, and such tumors resemble sarcoma.2 
The cheloid (or keloid), composed of very dense fibrous tissue with few 
cells, often develops rapidly in old skin cicatrices and especially in 
negroes, forming flat or slightly lobulated tumors. Besides this cicatricial 
cheloid, a spontaneous form has been described. But it has been suggested 
that these do not differ in any way from the cicatricial type, merely 
following a trivial or forgotten injury, for in predisposed persons even 
the pressure of a shirt stud or a piercing of the ear lobe may give rise to a 
cheloid. Strong evidence of the existence of special predisposition is 
furnished by those cases in which multiple cheloids develop in the scars of 
acne papules, smallpox pustules, etc.3 Because of this predisposition, 
such tumors are not often cured by operation, for another develops in 
the scar. They can often be removed, however, by compression or by the 
application of radium or z-rays, and sometimes disappear spontaneously. 
Some authorities deny that the cheloid is a true tumor, preferring to 
regard it as a tumor-like hyperplasia. 
Differential Diagnosis.-The cheloid is distinguished from the 
fibroma by its typical coarse bands of glassy intercellular substance, and 
1 See, for example, Kettle, Pathology of Tumors, New York, 1916, p. 67. 
2 Gilchrist, Johns Hopkins Hosp. Rep., 1896, i, 349. 
> Lopez-Silvero, Med. Record, 1917, xcii, 673. TUMORS 
399 
from scar tissue by the possession of large mature cells rich in protoplasm, 
those of a scar having a small darkly staining nucleus and a cell body of 
insignificant size. 
Fibromata are frequently combined with other forms of tissue to 
form complex tumors. The looser, softer varieties not infrequently be- 
come edematous, closely resembling a myxoma (Fig. 209); other changes 
which affect the fibromata are calcification and fatty or mucous degener- 
tion, while by metaplasia a fibroma may become a fibrochondroma, fibro- 
lipoma, or fibro-osteoma. The transformation last-named frequently 
occurs when the tumor develops in the periosteum. 
Originating as they do in the connective tissue, fibromata occur in 
various parts of the body: in the skin and subcutaneous tissue; in inter- 
Fig. 209.-Fibroma Molle; from the Subcutaneous Tissue. 
The strqma is edematous, and in gross appearance the tumor resembled myxoma. 
muscular tissue and fasciae; in periosteum; in nerve sheaths and intra- 
fascicular connective tissue; in the dura mater; in the interstitial tissue 
of organs; and in the mucous membranes. 
A type of hard encapsulated fibroma occurring in the abdominal wall 
has received the clinical name of desmoid. Polypoid forms occur 
(Fig. 208). 
It is often difficult to distinguish between genuine fibromata and 
inflammatory or other hyperplasias of the connective tissue such as 
elephantiasis, and future investigation may perhaps show that the dis- 
tinctions are not so definite as our classifications suggest. 
MYXOMA.1 
A myxoma is a tumor made up of embryonic connective tissue similar 
to that of the umbilical cord. The mucous tissue of which they are com- 
posed is essentially an embryonic structure, for in the normal adult it is 
present only in a very imperfect and atypical form in the vitreous of the 
1 Ribbert, Frankfurt. Ztschr. f. Path., 1910, iv, 30 (bibl.). 400 
TUMOR& 
eye, and perhaps occasionally in small amount about the heart and 
kidneys, and in the medulla of bone. 
Myxomata consist in their most typical forms of a homogeneous or 
finely fibrillated, soft, gelatinous basement substance containing mucin, 
in which are embedded a variable number of spheroidal, fusiform, branch- 
ing, and often anastomosing cells (Fig. 210); they may have few7 or many 
blood-vessels. By the addition of acetic acid, the mucin may be precip- 
itated from the matrix; in sections the former is usually stained blue with 
hematoxylin. The very soft forms, which contain comparatively few 
cells and much translucent intercellular material, are called myxoma 
gelatinosvm or myxoma molle. The presence of many cells, on the other 
hand, renders the growth more consistent and confers a whitish and more 
opaque appearance; such forms are called myxoma medullare. 
Showing the diffuse staining of the mucin-containing stroma with hematoxylin. 
Fig. 210.-Myxoma of Larynx. 
The rarity of pure myxomata has led to the assertion that such a 
growth does not exist; and certainly many of the so-called myxomata 
have been in truth merely the product of extensive mucoid degeneration 
in a fibroma, a lipoma, or other variety of connective-tissue neoplasm. 
Yet there is but little doubt that a true myxoma may occasionally be 
encountered. 
The myxomata may be diffuse, or encapsulated by fibrillar connective 
tissue; they are frequently very large, sometimes multiple, and often 
contain cysts and hemorrhages; the cells are likely to undergo fatty 
degeneration. 
Composed as they are of a type of tissue from which fat is developed 
in the embryo, the relations of the myxomata to adipose tissue are very 
intimate. Thus they are most frequently developed in, and probably 
directly from, fat. They are also found, however, in the subcutaneous, 
submucous, and subserous tissue; in the marrow7 and periosteum; in the 
brain and cord; in the sheaths and intrafascicular tissue of peripheral 
nerves; in intermuscular septa; and in the interstitial tissue of such TUMORS 
401 
glands as the mamma and parotid. Some of the polypi of the mucous 
membranes are apparently myxomata or fibromyxomata. On the other 
hand, many of the so-called mucous polyps, those of the nose, for example, 
are merely edematous hyperplasias of the mucosa, or edematous fibroids;1 
for edematous, loose, and cellular forms of fibrillar connective tissue so 
closely resemble some of the forms of mucoid tissue that certain observers 
consider them identical. 
The pure myxomata are in general benign; yet they sometimes grow 
rapidly and occasionally, though rarely, form metastases. In such a 
case there is an increase in the number of cells and a corresponding 
diminution in the intercellular substance. Myxosarcoma, often an ex- 
tremely malignant growth, is distinguished only with the greatest 
difficulty from a malignant myxoma. Many of these, as has already 
been intimated in discussing the myxomatous degeneration of benign 
connective-tissue tumors, are sarcomata which have undergone myxo- 
matous change. Fortunately, however, the distinction is of no practical 
importance. 
LIPOMA. 
The lipoma is a common tumor formed of adipose tissue and occurring 
in the panniculus adiposus or fatty tissues, in the gastrointestinal canal 
or the peritoneum, or, more rarely, in the dura mater, kidney, liver, and 
Fig. 211.-Lipoma. 
The section shows a small portion of the tumor near the surrounding fibrous tissue. 
lung. These neoplasms are usually single, and are sometimes symmetric- 
ally arranged in relation to the median dorsoventral plane of the body; 
as a rule they are sharply circumscribed,2 and are not infrequently 
pedunculated. The lipomata are benign growths, though like other 
benign neoplasms they may do harm by pressure, ulceration, or gangrene, 
and may recur if incompletely removed. They sometimes attain an 
enormous size. The adipose tissue of which they are composed (Fig. 
211) is arranged in lobules and differs little from normal fat except that 
1 Wright, Med. Rec., 1901, lix, 132. 
2 For a review of the literature of adipositas dolorosa (Dercum's disease), see Herxheimer and Schmidt, 
Lubarsch-Ostertag, Ergebn. d. allg. Path., 1912, xvi1, 621. 402 
TUMORS 
the cells and lobules are usually larger and less regularly arranged and 
that the tumor is paler than normal fat, so that even when such a growth 
is situated in adipose tissue its limits can be readily made out. In 
congenital lipomata, however, there may be no capsule, and the tumor 
may be very finely tabulated; this type, therefore, closely resembles 
normal fat.1 
Occasionally a considerable number of cells resemble those of embry- 
onic or rapidly growing fat. There may be but little connective tissue in 
the tumor, in which case it is so soft as to be almost fluctuating (lipoma 
molle), or there may be so much as to give the tumor considerable firm- 
ness (fibrolipoma); a lipoma may be in part transformed into mucoid 
tissue (myxolipoma'), or may become sarcomatous. In some lipomata 
dilated blood-vessels are a prominent feature (angiolipomaY Cartilage 
formation has been described but calcification and ossification are much 
more frequent. 
CHONDROMA. 
These tumors (Fig. 212) are composed of hyalin and fibrocartilage 
and are usually hard. Fibrous tissue in varying quantity is generally 
present, either as a perichondrial capsule, or running in bands between 
the nodules of cartilage, or passing in fascicles into them.2 
Fig. 212.-Chondroma of Femur. 
Like normal cartilage, these neoplasms contain no blood-vessels in 
their matrix, their nourishment being derived from channels in the bands 
of connective tissue which surround or penetrate them. This may 
perhaps explain the lobulated structure which they often assume, no part 
of the tumor being very far removed from the blood-stream under these 
conditions. 
1 Jacobi, Arch. Pediat., 1884, i, 65; Brickner, Am. Jour. Med. Sc., 1918, civ, 473. 
2 For a study of the minute structure of cartilaginous tumors, see Ernst, Zieglers Beitr., 1905 
xxxviii, 67. TUMORS 
403 
The cartilage may be transformed into mucoid tissue {myxochon- 
droma)', the cells may undergo fatty degeneration; or the tumor may cal- 
cify or ossify {osteochondroma). Cartilage frequently forms a part of 
mixed and complex neoplasms. 
Chondromata originate most frequently in connection with bone or 
cartilage (usually at an epiphyseal line), or in subcutaneous connective 
tissue or fasciae. They are not uncommon in the pelvis, where they may 
interfere seriously with parturition. Chondromata may occur, also, in 
soft parts where cartilage is not normally present, as in the parotid, 
testicle, mamma, and ovary; in such cases, however, the cartilage is apt 
to be mixed with other tissue. Under these conditions, they appear to 
arise from developmental anomalies. They may develop in the lungs 
in connection with the bronchial cartilages or from embryonal displace- 
ments of portions of these. 
The majority of these tumors develop in childhood and early life, 
whence it has been suggested that they originate from islands of cartilage 
misplaced in consequence of irregular ossification, such, perhaps, as that 
which accompanies rachitis. Trauma is said to be an etiological factor, 
and an hereditary predisposition has long been suspected.1 
Chondromata are, in general, benign tumors. 
The malignant chondromata are softer than others and may even be 
of gelatinous consistency. While it has been often said that benign 
chondromata metastasize,2 critical reexamination of some of the reported 
instances shows that the phenomenon has occurred in mixed growths 
containing cartilage rather than in pure chondromata. 
Small hyperplastic growths on the surface of cartilages are called 
ecchondroses, and are thus distinguished from the true chondromata, 
which are known as enchondr omata. 
The chordoma is a rare tumor which originates in remnants of the 
notochord.3 In man this is a transient, though important, embryological 
structure which disappears early in fetal life except for traces remaining 
in the intervertebral discs {nucleus pulposus). The tumor consists of 
large vacuolated cells with swollen cytoplasm, lying in a homogeneous 
or finely granulated, jelly-like matrix; these elements readily break 
down, leaving empty spaces in the intercellular material. The small 
nodules of notochordal tissue which are an accidental finding in about 
two per cent, of autopsies, lying at the base of the brain on the clivus 
just behind the sella turcica, are not regarded to-day as true tumors, but 
rather as masses of notochordal tissue, possibly hyperplastic, which have 
been forced out of the bone during fetal development.4 
Chordomata may occur anywhere along the spinal cord, or develop 
from the sacrum and coccyx. The small masses at the base of the brain, 
CHORDOMA. 
1 Percy, N. M., Surg., Gynec., and Obst., 1915, xx, 619; MUller, Zieglers Beitr., 1914, Ivii, 232 (bibl.). 
2 For a study of metastases in chondromata, see Ernst, Zieglers Beitr., 1900, xxviii, 255. 
3 For a discussion of the embryology of the chorda dorsalis, see Huber, Anat. Rec., 1918, xiv, 217 
(bibl.). 
4 Albert, H., Surg., Gynec., and Obst., 1915, xxi, 766. 404 
just referred to, are usually benign, but a considerable number of cases 
is now on record in which such a nodule has developed into a large tumor 
infiltrating the brain substance,1 or has grown into the roof of the 
pharynx.2 Both benign and malignant growths have been described in 
the sacrum.3 In those tumors which reach a large size and show evidence 
of malignancy, the cells vary considerably from the original type found 
in the chordal tissue (Fig. 213). 
TUMORS 
Fig. 213.-Chordoma, Showing the Large Clear Cells, Many of which have Degenerated 
OSTEOMA. 
Heterotopia, the presence of tissues at sites where they are not nor- 
mally found, is well illustrated by bone, which develops under a great 
variety of conditions and in the most unexpected places. For this reason 
it is not so easy to define the term osteoma (Fig. 214), and it is often 
exceedingly difficult to decide whether or not a given mass of bone con- 
stitutes a true tumor. 
While the true osteoma is rare, bone is often found in tumors of the 
connective-tissue group as a secondary or complicating structure-osteo- 
fibroma, osteochondroma, osteosarcoma, etc. It may occur in muscles and 
fasciae in consequence of the repeated trauma of athletic exercises 
{rider's bone), or as the result of a peculiar inflammatory process {myositis 
'Jelliffe and Larkin, Jour. Nerv. and Ment. Dis., 1912, xxxix, 1. 
2 Linck, Zieglers Beitr., 1909, xlvi, 573. 
* Feldmann, Zieglers Beitr., 1910, Ixviii, 630; Albert, H., Surg., Gynec., and Obst., 1915, xxi, 766. 
Wood, Proc. New York Path. Soc., 1913; Stewart, M. J., Malignant sacrococcygeal chordoma, Jour. 
Path, and Bacteriol., 1922, xxv, 40 (bibl.). TUMORS 
405 
ossificans), or may appear in connection with chronic inflammations in a 
variety of tissues-brain, dura and pia mater, pleura, diaphragm, peri- 
cardium, skin, choroid, air passages, lungs, kidneys, aorta, penis, and 
other places. But in order to constitute an osteoma, the bone must show 
independent growth and must not be of inflammatory origin. 
Bony outgrowths projecting from the surface of a bone, and fre- 
quently of inflammatory origin, are called osteophytes or exostoses, similar 
masses in the substance being known as enostoses. These lesions, how- 
Fig. 214.-Osteoma of Humerus. 
Eburnated type. 
ever, are not true tumors for they do not persist after the exciting cause 
has been removed; in other words, they do not exhibit independent 
growth. 
An osteoma may be loose in texture, consisting of spongy bone {osteoma 
spongiosum), or as hard and dense as ivory {osteoma eburneum). The 
difference between these forms lies chiefly in the varying number and size 
of the vascular and medullary spaces. As a rule, the growth of the 
osteomata is slow. They are benign tumors, not infrequently multiple, 
and usually develop in connection with the bone or the periosteum, 
though they may arise in soft parts. 406 
TUMORS 
ODONTOMA. 
Each tooth develops from a cap of epithelium fitting over a connec- 
tive-tissue papilla, the former giving rise to the enamel organ and the 
latter to the dentine and pulp. From either or both of these, or from the 
connective tissue surrounding them (tooth sac or follicle'), a tumor may 
develop (odontoma, odontoblastoma); hence, the classification of the 
odontomata is intricate and not yet entirely settled. Perhaps the best 
method is that1 which divides them into those arising from the epithelial 
cap (epithelial odontomata'), those springing from cap, papilla, and sac 
(composite odontomata), and those originating from the connective-tissue 
constituents of the tooth or its follicle (connective-tissue odontomata). 
The epithelial odontomata, ordinarily known as adamantinomata, 
will be discussed under the benign epithelial tumors (page 448). 
Odontomata of all three types are cystic growths which may attain 
enormous size, though they are, in all probability, always benign. Those 
of the two latter groups may contain dentine, cement, fibrous tissue, or 
partially formed teeth.2 
GLIOMA. 
Gliomata (Fig. 215), the most common of the brain tumors, are 
developed from the characteristic framework of nerve tissue, the neu- 
roglia. Hence, they consist mainly of astrocytes, small cells with round 
Fig. 215.-Glioma of Brain. 
or oval nuclei (two or three being occasionally found), inconspicuous 
bodies, and numerous delicate branching processes. Variations on this 
type, such as spindle-shaped elements, cells with a large amount of cyto- 
plasm, and polynuclear giant cells, may be present, but the bulk of the 
growth always consists of astrocytes or "spider cells" (Fig. 216). In 
order to demonstrate these cells and their branches, it is usually neces- 
sary, however, to shake sections of the tumor in water, or carefully to 
tease small fragments. The nature of the gliar feltwork is not yet entirely 
clear; for while it was held by Weigert that it is composed of fibrils lying 
'Gabell, James, and Payne, see editorial article in Brit. Med. Jour., 1915, ii, 103. For a discussion 
of the various classifications, see Bonney and Ellis, Surg., Gynec., and Obst., 1917, xxiv, 459; Kaempfer, 
ibid., 1911, xii, 357; Molassez and Galippe, Les debris 6pith61iaux paradentaires, Paris, 1910, p. 233. 
2 A discussion of the odontomata of man and the lower animals may be found in Bland-Sutton's 
Tumors, Innocent and Malignant, New York, 1917, p. 211. TUMORS 
407 
close beside the cytoplasm, rather than of actual cell processes, more 
modern authorities1 believe that much of it represents branches of the 
astrocytes. But the occurrence of some independent fibrils is not denied. 
In certain gliomata the elements are to be found in rosettes, or alveoli, 
produced by arrangement of the cells about lumina. These structures 
imitate the ependyma, the side of the cell toward the lumen being free 
and the other ending in prolongations into the surrounding tissues. These, 
more than any other of the gliomata, most clearly reveal their ectodermal 
origin. The cells constituting these rosettes are identical with the 
spongioblasts, according to Ribbert,2 who calls the tumor composed of 
such elements spongioblastoma. He regards this growth as genetically 
identical with the pure glioma, which is merely a more fully differentiated 
spongioblastoma. In their typical form, consisting, that is, of well- 
developed astrocytes, gliomata are found only in the brain and spinal 
Fig. 216.-Neuroglia or Spider Cells from Glioma of Brain. 
Teased specimen. 
cord and at the roots of the cranial nerves. These tumors often contain 
thin-walled dilated blood-vessels, and since they are liable to interstitial 
hemorrhage may be mistaken at autopsy for apoplectic clots. They may 
be soft or moderately hard and, especially when growing in the substance 
of the brain, are not, as a rule, sharply outlined against the adjacent 
normal tissue; this is because, in spite of the fact that they are benign 
tumors, they grow by invading the surrounding brain. Cysts and large 
areas of necrosis are often found and the tumors may undergo fatty degen- 
eration. Gliomata usually occur singly and are comparatively slow in 
growth. They metastasize in the brain and cord, but not in distant 
organs, perhaps because their cells are too highly specialized to grow 
there.3 
Technically speaking, pure gliomata are benign tumors, but their 
situation in the brain makes them almost always dangerous, for as much 
as an entire hemisphere may be compromised; furthermore, beside 
ultimately destroying life by increasing the intracranial pressure or by 
1 e.g., Stroebe, Zieglers Beitr., 1895, xviii, 405. 
2 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 456. 
3 Jacob, Jour. Med. Research, 1916, N. S., xxix, 95. 408 
TUMORS 
invading some vital portion of the brain, they may cause paralysis 
or sudden death from intracerebral hemorrhage. On the other hand, 
even a large tumor may cause but few symptoms. 
All gliomata do not consist of the relatively mature astrocytes which 
characterize these neoplasms in the brain. Thus, gliomata of the 
retina consist largely of a less differentiated element-a small round cell 
with but a minimal amount of cytoplasm and practically no branches. 
Mingled with these, however, there may be found both mature glia and 
epithelial rosettes resembling those found in gliomata of the brain 
and cord. Thus, as Ribbert1 points out, the cells of a retinal glioma, 
which are descended from neuroblasts of the early retinal anlage, produce 
epithelium, gliar cells, and an indifferent element. 
Retinal glioma is an extremely malignant neoplasm, which has 
occurred in nearly all the cases during the first four years of life. Unless 
the eye be promptly enucleated, the tumor grows forward into it, destroy- 
ing the sight, or backward into the brain, the other eye being often in- 
volved secondarily via the optic nerve. The tendency toward its 
development appears to be hereditary.2 
Gliomata have been described, also, in connection with the sym- 
pathetic nervous system,3 occurring almost without exception in the 
medulla of the adrenal. These growths are made up of small cells with 
deeply staining nuclei, embedded in a fine feltwork, and showing a tend- 
ency to collect about masses of the fibrillar ground substance in the 
form of "rosettes." A number of authorities4 insist that such neo- 
plasms are not gliomata, but neuroblastomata (page 409). 
There arise in the nervous system other neoplasms besides the glioma, 
which, as has just been said, originates from the supporting substance. 
These others, involving embryonal antecedents of the nervous system, 
or more fully developed functional elements such as the ganglion cell, 
have been carefully investigated during the past few years, but they are 
comparatively rare growths and many questions regarding them are still 
open. Since the benign and malignant tumors in this group are not clearly 
separated from one another, it will perhaps be most advantageous to 
discuss both classes here. 
The following diagram5 reproduces current conceptions regarding 
the development of the sympathetic system, in which most of these 
growths originate, and will make clear the relationship of these neo- 
plasms to one another. 
NEUROCYTOMA. 
Sympathoblast -> Sympa- 
thetic ganglion cell. 
Phaochromoblast -> Chro- 
maffin cell. 
Neural ectoderm-> Primary sympathetic cell 
(neurocyte) (sympathogonion) 
1 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 470. 
2Griffith, Brit. Med. Jour., 1917, i, 850; see also Hansell, Am. Jour. Dis. Child., 1915, ix, 485. 
3 Schilder, Frankfurt. Ztschr. f. Path., 1909, iii, 317. 
*e.g., Wiesel, Virchows Arch., 1905, clxxx, 553. 
6 Modified from Landau, Frankfurter Ztschr. f. Path., 1912, xi, 26. TUMORS 
409 
Those embryonal cells which are destined finally to produce the entire 
nervous system are called by Kohn1 and others neurocytes, and by Held2 
neurogliocytes. The sympathetic portion of the nervous system originates 
from a special group of neurocytes belonging to the embryonal spinal 
nerves (Kohn). Sympathetic neurocytes emerge relatively late from 
their surroundings in the form of deeply staining elements with vesicular 
nuclei, gathered into groups which anastomose with other groups by 
means of cell processes; often, however, these cells fuse to form a multi- 
nucleated protoplasmic mass or syncytium. At a somewhat later period 
of intrauterine life they appear as small round cells between which fine 
nerve fibrils can be discerned. 
One tumor composed of neurocytes-a neurocytoma-has been de- 
scribed.3 This growth, discovered in the Gasserian ganglion of a man 
fifty-six years old, consisted of groups of entirely undifferentiated, round, 
oval, or polygonal cells with a homogeneous protoplasm and a vesicular 
nucleus. No fibrils were present, and the elements composing the 
growth thus resembled the neurocyte in its earliest, least differentiated 
state. 
Even by the time that the embryonal sympathetic neurocyte has 
reached its next stage, the primary sympathetic cell, or sympathogonion, it 
has progressed but little toward the form which it is finally to assume as a 
member of the nervous system. The sympathogonion appears, accord- 
ingly, as a neutral or indifferent element, no more characteristic in its 
structure than the lymphocyte; in other words, it is merely a small round 
cell with a deeply staining nucleus, and exhibits none of the features 
associated with fully developed nervous tissue save some slight fibrillar 
differentiation. 
The sympathogonion gives rise to two series of cells-(a) the sympatho- 
blast, characterized by a nucleus larger and more vesicular than that of 
the sympathogonion, and by a proportionately wider cytoplasmic rim; 
and (6) the phaochromoblast, which goes through similar changes, but 
develops in addition an affinity for chrome salts. 
NEUROBLASTOMA. 
The second (sympathogonion) stage in the development of the sym- 
pathetic system is represented by the neuroblastoma,4 a malignant neo- 
plasm that may involve any part of the nervous system, though it is far 
more common in the sympathetic, and usually in the adrenal5 or else- 
where behind the peritoneum, whence it metastasizes most frequently to 
the liver, the skeletal system, and the lymph-nodes. The cases so far 
reported have occurred almost without exception in infants or children, 
and the younger is the child the more immature histologically, and 
malignant clinically, is the growth apt to be (cf. ganglioneuroma').6 The 
1 Kohn, Arch. f. mikros. Anat., 1907, Ixx, 266. 
2 Held, Die Entwicklung des Nervengewebes bei den Wirbeltieren, Leipzig, 1909. 
3 Marchand, Festschrift, f. Rindfleisch, 1907. 
4 For a review of the literature, see Lehman, Jour. Med. Research, 1917, N. S. xxxi, 309; Lambert, 
R. A., Proc. New York Path. Soc., 1917, xvii, 96. 
6 Herxheimer, Zieglers Beitr., 1914, Ivii, 112 (bibl.). 
^Freifeld, Zieglers Beitr., 1915, lx, 347 (bibl.). 410 
TUMORS 
fact that there are only some twenty-five instances in the literature 
should not be interpreted to mean that this neoplasm is extraordinarily 
rare. It is not; for there is a large number of doubtful cases on record, 
Fig. 217.-Neuroblastoma of Kidney. 
Fig. 218.-Neuroblastoma. 
Showing rosettes, one of which is drawn under higher magnification in the upper right-hand corner of 
the plate. 
some of which were in all probability true neuroblastomata, and to these 
must be added all early unrecognized examples described as sarcoma of 
the adrenal. TUMORS 
411 
The neuroblastoma (Fig. 217) is composed largely of sympathogonia 
{sympathetic neuroblasts'), which show a tendency to gather in solid masses 
or in hollow spheres inclosing a mass of fibrils; these latter are the 
"rosettes" (Fig. 218), which, however, do not morphologically resemble 
similarly named structures in the glioma. The tumor contains, also, fine 
fibrils, often arranged in bundles, which are probably embryonic nerve 
fibers, and hemorrhagic and necrotic areas. 
Differential Diagnosis.-The diagnosis is not easy, and until the 
last few years these tumors have been passed over as sarcomata. The 
following features, among others, have been advanced as characteristic:1 
Location in the adrenal or elsewhere in the retroperitoneal region of a 
young child; the presence of cells with small round nuclei rich in chromatin 
and surrounded by an extremely narrow rim of cytoplasm which tends 
to flow out into processes; the tendency of these elements to collect in 
groups, or to gather in rings about masses of fibrillae ("rosettes"); and 
finally, the occurrence of a fibrillar matrix staining neither as collagen 
nor as gliar fibers. 
SYMPATHOBLASTOMA. 
The next stage of the developing sympathetic nerve cell is represented 
by the sympathoblastoma, a malignant new growth occupying a place 
midway between the immature neuroblastoma and the mature ganglio- 
neuroma, and composed of sympathoblasts. One such neoplasm has 
been discovered,2 in the cervical sympathetic of a two and a half year 
old boy. It was made up chiefly of cells not so small as the sympatho- 
gonion and containing a large (8 to 12 micra) oval nucleus. 
GANGLIONEUROMA. 
The ganglioneuroma3 consists mainly of ganglion cells, the most 
mature elements of the series now under discussion. However, it should 
be borne in mind that not only do tumors of the sympathetic division 
merge almost imperceptibly into one another, but that cells in all stages 
of development may occur in the same neoplasm. Thus, Wahl's neuro- 
blastoma contained a whole scale of elements, running from the entirely 
undifferentiated neurocyte at one end, to the fully differentiated ganglion 
(Fig. 219) or chromaffin cell at the other, imitating in miniature, therefore, 
the complete normal development of the sympathetic neurocyte.4 Simi- 
larly, the ganglioneuroma contains elements reminiscent of phases earlier 
than the ganglion cell, although the greater part of the growth resembles 
fully developed nervous tissue more completely than the neurocytoma, 
the sympathoblastoma, or even the neuroblastoma. 
Like most other neoplasms, the ganglioneuroma reflects the compara- 
tive maturity of its cells in clinical benignancy, only those immature 
portions which are occasionally present and which correspond to the 
1 Wahl, Jour. Med. Research, 1914, N. S. xxv, 205; Landau, Frankfurt. Ztschr. f. Path., 1912, xi, 26. 
2 Martius, Frankfurt. Ztschr. f. Path., 1913, xii, 442. 
3 Peters, Frankfurt. Ztschr. f. Path., 1913, xiii, 114 (bibl.); Freund, ibid., 266. 
4 See also Robertson, Virchows Arch., 1915, ccxx, 147. 412 
TUMORS 
neuroblastoma, being malignant. As with the neuroblastoma, the 
younger is the patient bearing a ganglioneuroma, the more undifferen- 
tiated and malignant is the growth apt to prove.1 
The ganglioneuroma may occur at any age, but more commonly 
affects children and young adults, and is rather rare after forty. It 
may arise anywhere in the nervous system, though most of them have 
involved the sympathetic; here they appear most often in the abdominal 
portion,2 frequently in the adrenal. This growth is not quite so rare 
as the neuroblastoma, about fifty cases having been recorded. 
Fig. 219.-Neuroblastoma Containing Ganglion Cells. 
Ganglioneuromata, being comparatively mature, contain nerve 
fibers (usually non-medullated) and ganglion cells-large round, oval, 
pyramidal, or polygonal elements with one or more nuclei. The fibers 
often preponderate over the cellular constituents. But since the whole 
tumor is not always completely differentiated, there may be found an ad- 
mixture of entirely immature small round cells resembling the lympho- 
cyte (sympathogonia), or of somewhat more mature elements with large 
vesicular nuclei (sympathoblasts). Gliar portions, also, derived from 
peripheral glia, are not an uncommon finding (ganglioglioneuroma). 
'Falk, Zieglers Beitr., 1907, xl, 601. 
2Dunn, Jour. Path, and Bacteriol., 1914-15, xix, 456. TUMORS 
413 
PARAGANGLIOMA. 
(Phaochromoblastoma or Chromaffin Tumor.) 
The rare tumor composed of chromaffin cells is known as a para- 
ganglioma.1 The neoplasms of this group are benign growths found in 
the parasympathetic (chromaffin) system, particularly in the medulla of 
the adrenal and in the carotid gland (Fig. 334 and 335). 
Of those involving the adrenal only about a dozen cases have been 
described, though it must be remembered that their nature has been recog- 
nized only within the last decade and, accordingly, they may not be so 
uncommon as this statement seems to imply. They are usually small 
and are discovered, as a rule, in middle-aged and elderly persons, being 
found sometimes accidentally at autopsy; they are not infrequently asso- 
ciated with neurofibromatosis. In such cases they may perhaps be viewed 
as but one manifestation of a general disturbance of the entire nervous 
system. Since the cells of the adrenal paragangliomata resemble in 
appearance the fully developed chromaffin cell, or, in other words, are 
comparatively mature, these growths correspond to the ganglioneuro- 
mata. No tumor occupying an intermediate developmental stage, made 
up solely of phaochromoblasts, and analogous, therefore, with the 
sympathoblastoma, has yet been discovered. 
Like most other growths of the sympathetic division, the adrenal 
paraganglioma contains cells in various stages of differentiation. The 
preponderating elements are large epithelium-like cells, in which adrenalin 
and glycogen can often be demonstrated; these frequently assume a 
characteristic brown stain after fixation in chrome salts, although the 
reaction is not invariably demonstrable, possibly because those cells in 
which it is absent are not yet fully differentiated, being still in the phao- 
chromoblast stage. The characteristic mature chromaffin cell appears 
as a polymorphous or polyhedral element with a finely granular vacuo- 
lated protoplasm, while sympathogonia, transitional forms, multi- 
nucleated giant cells, ganglion cells, and cystic or hemorrhagic areas may 
be encountered; medullated or non-medullated nerve fibers are occa- 
sionally found.2 
The paraganglioma of the carotid3 is about as rare as that of the 
adrenal, but as it has been recognized for a longer time, more cases have 
been recorded; thus, about sixty have been described in the past twenty- 
five years or so. It is usually a slow-growing, benign neoplasm, although 
metastasis or recurrence has been described in some cases (25 to 30 per 
cent.), and reproduces in the main the structure of the carotid gland. 
It consists, therefore, of alveoli separated by capillaries and containing 
cuboidal, round, or oval nuclei and a comparatively abundant cytoplasm 
which may be granular or vacuolated. These cells sometimes show very 
1 For a review of the literature, see Wahl, Jour. Med. Research, 1914, N. S. xxv, 205, and Harbitz, 
Arch. Int. Med., 1915, xvi, 312. 
2 Herxheimer, Zieglers Beitr., 1914, Ivii, 112. 
zPaltauf, Zieglers Beitr., 1892, xi, 260; Monckeberg, ibid., 1905, xxxviii, 1; Keen and Funke, Jour. 
Am. Med. Assn., 1906, xlvii, 469: Callison and Mackenty, Ann. Surg., 1913, Iviii, 740; Balfour and 
Wildner, Surg., Gynec., and Obst., 1914, xviii, 203; Wetterdal, Hygiea, 1916, Ixxviii, 1761 (abstr. in 
Jour. Am. Med. Assn., 1917, Ixviii, 4011; Gronemann, Virchows Arch., 1914, ccxviii, 163 (biblA. 414 
TUMORS 
definitely their chromaffin nature by assuming a yellowish hue after 
fixation in solutions of chrome salts. Giant cells and syncytial masses 
are occasionally found. 
NEUROFIBROMATOSIS. 
Neurofibromatosis (von Recklinghausen's disease, fibromata nervorum)1 
is a disorder characterized by the appearance of multiple tumors of sub- 
cutaneous and other nerves; by areas of pigmentation varying in hue from 
light to dark brown; and, less often, by a condition resembling elephan- 
tiasis (elephantiasis neuromatosa); in some of the cases mental abnormal- 
ities or stigmata of degeneration have been present. The most constant 
change, however, is the presence in the subcutaneous tissues and skin 
Fia. 220.-Neurofibrosarcoma of Musculospiral Nerve. 
of hundreds or even thousands of new growths varying from the size of a 
pinhead to that of an orange. Trauma, even so slight as the pressure of 
the clothing, is said to be followed by the appearance of fresh nodules. 
The tumors are generally soft, freely movable, and not tender. The 
diffuse involvement of an entire plexus produces the plexiform neuroma, 
while a mass of nodules resembling a bunch of grapes, forming a more 
isolated mass with a single pedicle, and without intimate connection with 
a nerve trunk or a plexus, is called a racemose neuroma.2 
An hereditary predisposition often underlies von Recklinghausen's 
disease, which, indeed, may even be congenital. Sarcoma (Fig. 220) 
sometimes develops after the removal of the deep-seated tumors, though 
more frequently following the extirpation of a plexiform neuroma. 
When all forms are considered, this change has been discovered in 12.5 
per cent, of the cases (Harbitz). Furthermore, the coexistence of von 
1 Preiser, S. A., and Davenport, C. B., Am. Jour. Med. Sc., 1918, clvi, 507 (large bibl.). 
s Harbitz. Arch. I nt. Med.. 1909, iii, 32. TUMORS 
415 
Recklinghausen's disease with other neoplasms (glioma, paraganglioma, 
and even carcinoma and sarcoma) is not rare. 
Microscopical examination of the lesions of neurofibromatosis shows 
that all the tumors arise from the connective tissue of the nerves (the 
endo- and perineurium), and that they are accordingly simple fibromata 
(Fig. 221) through or around which the nerve fibers pass. While the 
most generally received opinion is that these growths originate in the 
sheath of Schwann, a few observers1 believe that the lesions are not 
Fig. 221.-Nevkofibboma. 
fibromata, but a product of the proliferation of Schwann's cells or anal- 
ogous elements; since these are regarded as peripheral glia cells, the neuro- 
fibroma would then be comparable to the glioma. For this reason, the 
term neurinoma (= nerve fiber tumor) has been proposed as describing 
the condition more accurately.2 
A condition possibly related to von Recklinghausen's disease, is that 
in which one or more neurofibromata similar to those described in the 
preceding paragraph are found in the nerves, without the existence of 
1 e.g., Verocay, Zieglers Beitr., 1910, xlviii, 1. 
2 Verocay, Zieglers Beitr., 1910, xlviii, 1. 416 
TUMORS 
cutaneous tumors or pigmentation; they involve localized regions such 
as the spinal nerve roots, the arm, the optic and auditory1 nerves, etc. 
The painful subcutaneous tubercle (tuberculum dolorosum) is a single, 
small, hard, subcutaneous fibroma or neurofibroma which is sometimes 
exquisitely sensitive. It is more common in women than in men. 
NEUROMA. 
The term neuroma was attached indiscriminately to all tumors of the 
nerves until Virchow separated the false neuroma (composed largely of 
connective tissue) (Fig. 222, 223, and 224) from the true (consisting 
chiefly of nervous material). The latter he subdivided into three types: 
neuroma gangliocellulare, containing newly formed nerve cells; neuroma 
The fibrous tissue is loose in texture and in places edematous, so that many of the nerve fibers pass 
through the tumor with little structural alteration. 
Fig. 222.-False Neuroma-Fibroma of Lumbar Nerve. 
Fig. 223.-Multiple Fibromata (False Neuromata) of Pneumogastric Nerve. 
From the same case as that from which the photographic reproduction of Fig. 224 is made. One-quarter 
natural size. 
fibrillafe amyelinicum, made up of non-medullated nerve fibers; and 
neuroma fibrillare myelinicum, composed of medullated nerves. His fibril- 
lar neuroma, however, does not satisfy those who regard nerve fibers as 
processes of the ganglion cell and who, therefore, deny that a pure nerve 
tumor can exist, since the axon is unable to proliferate independently. 
This school, which constitutes the majority, will admit to a place among 
the true neuromata only such growths as contain ganglion cells. The 
1 Cushing, Tumors of the Nervus Acusticus, Philadelphia, 1917. TUMORS 
417 
Fig. 224.-Multiple Fibromata (False Neuromata) of the Peripheral Nerves of the Arm 
and Leg. 
A, Nerves of the right arm; B, the left sciatic with its branches; C, the left anterior crural with 
its branches. From the same case as Fig. 223. The nerves of the other extremities were similarly- 
involved. 418 
TUMORS 
opposite and newer school, on the contrary, regards the elements of the 
sheath of Schwann as genetically equivalent to the ganglion cell, and 
asserts that the occurrence of neuromata comprised solely of nerve fibers 
can be readily explained, since it is from the sheath of Schwann, and not 
from the nerve cell, that the axon develops.1 
According to the older school of centralists, von Recklinghausen's 
disease would be an example of multiple false neuromata; but Durante,2 
an adherent of the newer peripheralist view, holds that all growths of the 
nerves are true neuromata and that in proportion as the newly formed 
nerve tissue persists in an immature stage or differentiates out to form 
myelin, the tumor will be amyelinate or myelinate, von Recklinghausen's 
disease would therefore be a true polyneuromatosis, in which the nerve 
tissue assumes a fibrous appearance instead of differentiating into young 
fibers or persisting in a myelinogenous stage as do the cells of other 
neuromata. Myxomata of the nerves would also be true neuromata that 
have undergone myxomatous transformation. 
Pending the settlement of these questions, the true neuromata may be 
conveniently divided into the ganglioneuroma, which has already been 
described, and the fibrillar neuroma. Of Virchow's two subdivisions of 
this latter type, the myelinic variety is the more common and the better 
understood, though both are extremely rare tumors. It is a benign 
growth consisting of medullated nerve fibers,3 intricately curved and 
intertwined, as a general rule, and associated with some fibrous tissue. 
Centralists4 explain the absence of ganglion cells by assuming atrophy 
of those formerly present, or5 by referring the fibers to ganglion cells 
situated outside the growth. On the other hand, it has been suggested6 
that many of the neoplasms described as neurofibromata, under the 
influence of von Recklinghausen's work, may actually have been true 
neuromata; the opposite, however, is more likely to be true-that most 
of the neuromata reported before the appearance of his monograph were 
really fibromata. At any rate, it is significant that since the publica- 
tion of von Recklinghausen's paper, the bibliography contains many 
descriptions of fibromata of the nerves, but almost none of true fibrillar 
neuromata.7 Finally, it is possible that transitions may occur between 
von Recklinghausen's disease and the true neuromata.8 
While the diagnosis of myelinic neuroma can easily be confirmed by 
Weigert's myelin stain, that is, of course, not applicable in the case of 
the amyelinic variety, the identification of which is often extraordinarily 
difficult, since the tumor so closely resembles a fibroma. The non- 
medullated neuroma is a grayish neoplasm usually involving the sym- 
pathetic nervous system. Its fibrils are colored somewhat less intensely 
1 For an account of this controversy, which is not by any means settled, see Bruce and Dawson, 
Rev. Neurol, and Psychiat., 1913, xi, 117. 
2 Durante, Rev. neurol., 1906, xiv, 836; article, Nerfs, in Cornil and Ranvier's Manuel d' histol. 
pathologique, iii, Paris, 1907 (abstr. in Centralbl. f. allg. Path, 1908, xix, 21). 
3 Barile, Lo Sperimentale, 1910, Ixiv, 269 (abstr. in Centralbl. f. Path., 1911, xxii, 410). 
* Beneke, Zieglers Beitr., 1901, xxx, 1. 
6 Adami, Principles of Pathology, 2d ed., Philadelphia, 1910, i, 752. 
• Knauss, Virchows Arch., 1898, cliii, 29. 
7 Borst, Die Lehre von den Geschwiilsten, Wiesbaden, 1902, i, 234. 
* Aschoff, Ergebn, d. allg. Path., 1898, v, 90. 419 
TUMORS 
with eosin than those of connective tissue, showing on cross section as 
small discs; cut in a longitudinal direction they appear in bundles and 
hence may be mistaken for smooth muscle.1 It is said that the axis- 
cylinders in these growths can rarely be stained by those special methods 
which are employed to demonstrate them in normal tissue. This, 
however, may be because most of the neoplasms regarded as amyelinic 
neuromata have really been fibromata, and the attempt should always 
be made in doubtful cases. 
To sum up the fibrillar neuromata, it is the consensus of opinion2 that 
such growths do not exist independently of the ganglion cell, and that 
all growths described as fibrillar neuromata are really ganglioneuromata 
in which the ganglion cells either have disappeared or else occupy a 
position outside the growth. The so-called amputation neuroma, a 
tangled mass of nerve fibers sometimes found in the stumps of amputated 
limbs, is relegated by most authorities to the regenerative processes, no 
longer occupying a position therefore among the true neoplasms. 
MYOMA. 
A myoma is a neoplasm composed of either non-striated or striated 
muscle. 
Leiomyoma: Myoma levicellulare.-The parenchyma of this tumor 
consists of non-striated muscle cells-overlapping fusiform elements 
with long rod-like nuclei. They lie closely packed into bands which 
This is of the smooth-muscle type-leiomyoma-and shows one bundle of muscle cells cut lengthwise, 
others across. 
Fig. 225.-Myoma of Uterus. 
run in various directions and are separated from adjacent bands by a 
variable quantity of more Or less vascular fibrous connective tissue (Fig. 
225). The pure leiomyoma, in which the amount of stroma is minimal, 
occurs principally in the female genital tract, the urinary tract, the 
gastrointestinal canal, the skin,3 and sometimes in the veins.4 
A much more common type is the fibromyoma, a leiomyoma contain- 
1 Henke, Mikroskop. Geschwulstdiagnostik, Jena, 1916, p. 89. 
2 Pick and Bielschowsky, Ztschr. fur die gesamte Neurol, u. Psychiat., 1911, vi, 391. 
3 Lieber, Zieglers Beitr., 1915, lx, 449 (bibl.). 
iSchnyder, Centralbl. f. Path., 1914, xxv, 529. 420 
TUMORS 
ing a large amount of connective tissue; it should be remembered, how- 
ever, that no matter how great the quantity of this material, muscle is 
still the primary constituent of the growth (Fig. 226). This we believe 
because the younger is the neoplasm the smaller is the proportion of con- 
nective tissue, very recent growths being made up almost entirely of 
muscle. Since these tumors, then, are myomata, the term myofibroma 
should not be applied to them, though it often is. 
The muscle cells in a myoma, as well as their nuclei, vary consider- 
ably in shape; both may be long and slender or short and plump, the 
latter form prevailing especially in more rapidly growing tumors, wherein 
The muscle cells are crowded apart by dense fibroma tissue. 
Fig. 226.-Fibroma of Uterus. 
mitotic figures may perhaps be discovered as additional evidence of rapid 
proliferation. Myoglia fibrils are demonstrable, frequently presenting 
considerable variation in size and arrangement.1 
Fibromyomata may occur wherever smooth muscle tissue exists, 
but are most commonly found in the uterus, where they are often called 
fibroids, from their resemblance to the fibroma; here they are not un- 
commonly multiple. They have been found also in the wall of the gastro- 
intestinal canal and in the kidney, bladder, and skin, while a certain 
proportion of the hypertrophies of the prostate are sometimes regarded 
as leiomyomata of the interstitial muscle of that gland. 
As a rule, they grow slowly and are benign, but, especially in the 
uterus, they may be large enough to lead to serious disturbance or even 
to threaten life, without being malignant. In this situation, too, 
they may become edematous by reason of some disturbance in their 
circulation and, owing to their poor blood supply, not infrequently 
1 For methods of staining these fibrils, see Mallory, Jour. Med. Research, 1904-05, N. S. viii, 113. 421 
TUMORS 
degenerate, forming cysts or undergoing gangrene; hyaline degeneration 
and calcification are not rare. 
While leiomyomata are usually benign, as has already been said, 
a few instances are on record in which rapidly growing invasive and 
metastasizing neoplasms of this type have been found in the uterus,1 
gastrointestinal canal,2 bladder,3 etc. In such a growth (malignant 
leiomyoma, myosarcoma, or myoma sarcomatodes) the nuclei of many of 
the muscle cells are round, oval, or irregular, and, like the cell bodies, 
variable in size; mononuclear and polynuclear giant cells have been 
described (see Fig. 611, page 942). On the other hand, the connective- 
tissue portion of a fibromyoma may become sarcomatous.4 
Differential Diagnosis.-It is not always easy to distinguish a leio- 
myoma from a spindle-cell sarcoma or a cellular fibroma, or in a fibro- 
myoma to decide what is muscle and what connective tissue. The 
following general rules, however, may be suggested: The muscle cell is 
sharply outlined and has a long rod-shaped nucleus with rounded ends, 
which lies within the cell body; that of the fibroblast, on the contrary, 
is spindle-shaped, relatively shorter, and lies on the surface. Muscle 
does not show so definitely the wavy striations characteristic of connective 
tissue and is apt to contain more nuclei in a given field. Again, the 
muscle cell usually terminates in a definite pointed extremity, 'while the 
tip of the fibroblast is apt to break up into an arborization of fine fibrils; 
these characteristics are best studied in fresh preparations which have 
been treated with 35 to 50 per cent, sodium or potassium hydroxide 
solution to dissociate the cells from one another. Finally, the tinctorial 
properties of the cells are sometimes of assistance; thus muscle is more 
strongly acidophile than connective tissue and therefore takes a more 
intense red color in sections stained with eosin; where doubt still exists 
Van Gieson's stain (muscle, yellow; connective tissue, red) or Mallory's 
(muscle, red; connective tissue, blue),5 may be employed. 
For a description of adenomyoma of the uterus, see page 941. 
Rhabdomyoma: Myoma striocellulare.-In this extremely rare tumor, 
striated muscle fibers are the characteristic elements. These, however, 
very rarely compose the greater part of the growth, but are intermingled 
with other elements, such as fibrillar connective tissue, and spheroidal 
or spindle-shaped cells which often appear to be incompletely developed 
muscle cells. The fibers differ, as a rule, from those of normal striated 
muscle in their arrangement, which is generally quite irregular, and in 
their size and appearance, being in general smaller than normal fibers, 
although they vary greatly; droplets of glycogen can frequently be 
demonstrated, and the sarcolemma is usually absent or incompletely 
developed. These neoplasms, which do not ordinarily attain a large size, 
are supposed to develop from misplaced embryonal muscle cells. 
Rhabdomyomata arising in muscle are said to be homologous. About 
1 Hoevels, Frankfurt. Ztschr. f. Path., 1911, viii, 477. 
2 Rising, Jour. Path, and Bacteriol., 1903, viii, 233; Ghon and Hintz, Zieglers Beitr., 1909, xlv, 89. 
8Lexer, Deutsch, med. Wchnschr., 1904, xxx, 42; Roder, ibid., 485. 
4 Ricker, Virchows Arch., 1895, cxlii, 211. 
6 Mallory, Jour. Med. Research, 1904-05, N. S. viii, 113. 422 
TUMORS 
twenty cases1 have been recorded in the heart, all in children and often 
associated with multiple congenital cerebral sclerosis; but this type is 
a malformation rather than a true tumor.2 Heterologous rhabdomyo- 
mata originate at sites where striated muscle is not normally found, 
the great majority being confined to the genitourinary organs, where 
they generally form part of a mixed tumor;3 an exceptional case of 
rhabdomyoma occurring in the parotid gland, however, has been recorded 
by Prudden.4 These growths, when not associated with other and malig- 
nant tumors, are usually benign and are of greater theoretical than prac- 
tical interest. Only a few malignant rhabdomyomata have been reported 
in man;5 one has been described in the trout.6 
ANGIOMA. 
Angiomata are neoplasms consisting largely or entirely of blood- or 
lymph-vessels or cavities. It often happens that newly formed or old 
blood- or lymph-channels become prominent in a tumor by reason of 
This section is from a vascular mavus, strawberry mark, of the skin. 
Fig. 227.-Angioma Telangiectoides from Skin. 
their dilatation or their great number, and those of otherwise normal 
tissues maybe of increased caliber as in arterial varices, cirsoid aneurysms, 
hemorrhoids, and various lymphectasiae; none of these, however, is a 
true angioma, because the vessels do not proliferate independently. 
Angiomata are of two kinds: I. Hemangioma} II. Lymphangioma. 
1 The earlier literature has been reviewed by Wolbach, Jour. Med. Research, 1907, N. S. xi, 495. 
Later articles are those of Abricossoff, Zieglers Beitr., 1909, xlv, 376 (bibl.); Bundschuh, ibid., 1912, 
liv, 278; Rehder, Virchows Ar<A., 1914, ccvii, 174; Ribbert, Centralbl. f. allg. Path., 1915, xxvi, 241; 
and Kawamura, Centralbl. f. allg. Path., 1913; xxiv, 801 (bibl.). 
^Fujinami, Virchows Arch., 1900, clx, 203; Stumpf, Zieglers Beitr., 1911,1, 171. 
• Wilms, Die Mischgeschwiilste, Leipzig, 1902; Spuler, Centralbl. f. allg. Path., 1905, xvi, 337; 
Squier, J. B., Rhabdomyoma of prostate, Surg., Gynec., and Obst., 1916, xxiii, 341. 
4 Prudden, Am. Jour. Med. Sc., 1883, Ixxxv, 438. 
* Stoerk, Ztschr. f. Heilk., 1901, xxii, 200: Burgess, Jour. Med. Research, 1913-14, N. S. xxiv, 447; 
Muller, Jour. Cancer Research, 1917, ii, 393 (bibl.). 
• Adami, Montreal Med. Jour., 1908, xxxvii, 163. 423 
TUMORS 
I. Hemangioma.1-Of this there are three types: 1. That variety 
(Fig. 227) formed largely of capillary blood-vessels embedded in a more 
or less abundant connective-tissue stroma, and known as capillary 
angioma, angioma simplex, or angioma telangiectoides; its channels are 
frequently dilated or pouched and usually form an intricate mass of 
curled and intertwined vessels. Such growths occur most frequently 
in the skin or subcutaneous tissues, usually about the face, and may be 
either level with the surface (vascular ncevus, strawberry mark, or port- 
wine stain) or raised above it (blue wart). They are ordinarily congenital 
and either circumscribed or diffuse. Besides the face, they involve the 
mucous membranes, mamma, brain, and bones, and, in fact, any part 
of the body except the cornea and the cartilages (Kornmann, l.c.). In 
themselves these angiomata are benign tumors as a rule, almost never 
forming metastases,2 but they may be associated with sarcoma. Except 
in so far as an angioma is a deformity it is of but little clinical significance, 
save for the rather rare variety found in the pelvis of the kidney, which 
may give rise to fatal hemorrhage.3 
Fig. 228.-Angioma Cavernosum of Liver. 
This section shows the entire small tumor. 
2. The second form of hemangioma (angioma cavernosum) consists 
largely of a series of intercommunicating blood-spaces, irregular in shape 
and size (Fig. 228), lined with endothelium, and surrounded by a variable 
quantity of fibrillar connective tissue which may contain smooth muscle 
cells. It resembles the erectile tissue of the corpora cavernosa and the 
clitoris and is apparently produced by a dilatation of old and newly 
formed capillaries and veins. It is sometimes erectile or pulsating and 
not infrequently multiple. Tumors of this sort may be seated in the skin 
and subcutaneous tissue, where they form the noevus prominens, or in the 
1 For a review of the literature, see Kornmann, Hamangiome, Odessa, 1913; abst. in Centralbl. f. 
allg. Path., 1914, xxv, 526. 
2 See, however, Borrmann, Zieglers Beitr., 1907, xl, 372; Shennan, Jour. Path, and Bacteriol., 1914- 
15, xix, 139. 
3 Kettle, Pathology of Tumors, New York, 1916, p. 124. 424 
TUMORS 
internal organs. They are found often in the liver,1 less frequently in 
the bones, brain, spleen, uterus, kidney, intestine, bladder, and muscles. 
They are usually of little significance, though they may give rise to 
hemorrhage. 
To a place among the true tumors neither the capillary nor the 
cavernous angioma is admitted by some authors,2 who believe that these 
growths possess no power of independent proliferation and include them, 
therefore, among the malformations; thus, E. Albrecht3 regarded the 
cavernoma of the liver as a hamartoma, or developmental error. Others, 
on the contrary,4 assert that they do grow, and sometimes even 
invasively. 
Fig. 229.-Congenital Lymphangioma from Arm of Child. 
3. Only a third class is acknowledged by the former group as a genu- 
ine neoplasm. In this variety, to which the term angioma simplex 
hypertrophicum was applied by Ziegler,5 the capillaries show unmistak- 
able evidences of proliferation in their prominent cubical endothelial cells, 
of which there may be several layers. Since it is the endothelium that 
grows so vigorously, tumors of this group may be, and often are, con- 
sidered endotheliomata. 
II. Lymphangioma.6-All that has been said regarding the doubtful 
right of the hemangiomata to a place among the true tumors, applies 
to the lymphangiomata. These consist of dilated lymph-vessels which 
usually preserve approximately the general shape of the original channels, 
though they may be distinctly cavernous in character (lymphangioma 
cavernosum, Fig. 229), or even cystic (lymphangioma cysticum). The 
1 Roogenbau, Zieglers Beitr., 1910, xlix, 313. 
^e.g., Adami, Principles of Pathology, 2d ed., Philadelphia, 1910, i., 814. For a discussion of the 
controversy, see Fischer and Zieler, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1904-5, x, 815. 
• Albrecht, E., Verhandl. deutsch. path. Gesellsch., 1904, vii, 153; Frankfurt. Ztschr. f. Path., 
1907, i, 221. 
*e.g., Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 200. 
6 Ziegler, Lehrbuch d. allg. Pathologie, Jena, 1905, i, 423. 
•For bibl., see Fischer and 7Aeler, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1904-5, x, 842; 
Herxheimer and Schmidt, ibid., xvii, 636. 425 
TUMORS 
vessels are generally filled with a translucent or milky fluid resembling 
normal lymph and are separated by more or less connective tissue. 
Lymphangiomata are most often congenital, but are sometimes ac- 
quired. The simple lymphangioma usually occurs in the skin as a soft 
swelling, the cavernous type in the tongue (macroglossia) or in the lip 
(macrocheilia), and the cystic in the neck (cystic hygroma).1 All are 
benign tumors, which, however, may rupture and give rise to serious 
lymphorrhea. 
Differential Diagnosis.-1. When the endothelial cells of a heman- 
gioma are prominent and the vessels collapsed and free of blood, it may 
be difficult to distinguish it from an adenoma or a sarcoma. It has been 
pointed out, however, that since angiomata of the skin arise in a net- 
work of blood-vessels surrounding the sweat glands, it is often possible 
to find portions of such a gland included in them.2 
2. It is sometimes desired to distinguish between a hemangioma and 
a lymphangioma. The only method is demonstration of the presence or 
absence of blood in the vessels of the tumor; it is obvious, however, that 
all the blood in a hemangioma may occasionally be drained out at the 
time of operation so that under the microscope the growth will appear 
to be a lymphangioma, or, on the other hand, that a few blood-cells may 
enter the vessels of a lymphangioma during its extirpation and thus sug- 
gest a hemangioma. In such doubtful cases as these it may be impossible 
to distinguish one from the other. 
XANTHOMA. 
(Xanthelasma). 
This is included for convenience among the neoplasms, though by 
many authorities it is regarded simply as a connective-tissue reaction 
following the collection of cholesterin esters (page 53) in the cells of the 
affected site. It is usually a small, flat, yellowish prominence, situated 
most often in the skin about the eye (xanthoma palpebrarum), some- 
times elsewhere on the body surface, and occasionally in an internal 
organ; there may be more than one lesion, and cases of xanthomatosis 
(xanthoma multiplex') have been described.3 Either type may be 
hereditary. 
Under the microscope the xanthoma (Fig. 230) is found to be com- 
posed of large foamy cells, with one or more darkly staining nuclei; in 
preparations that have not come into contact with alcohol it can be 
demonstrated that the spaces in the protoplasm are due to the presence 
of cholesterin esters. Xanthoma appears most often in patients with 
diabetes or jaundice,4 conditions which are said to be associated with 
cholesterinemia. 
1 For a discussion of the surgical aspects of this condition, see Winslow, Surg., Gynec., and Obst., 
1917, xxv, 428. 
2 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 202. 
3 Sikemeier, Frankfurt. Ztschr. f. Path., 1913, xiv, 428; McFarland and McConnell, Jour. Med. Re- 
search, 1904, N. S. vii, 69. 
*Pinkus and Pick, Deutsch, med. Wchnschr., 1908, xxxiv, 1426; Schulte, Zieglers Beitr., 1916, 
Ixi, 570 (bibl.). 426 
TUMORS 
Fia. 230.-Xanthoma of Elbow. 
Showing large foam cells. 
Fia. 231.-Sarcoma of the Forearm. 
A tumor of the tabulated type. TUMORS 
427 
Connective-tissue Tumors-Malignant. 
SARCOMA. 
Unlike the benign connective-tissue tumors, the sarcoma often pro- 
duces but an insignificant quantity of the intercellular material1 char- 
acteristic of the tissue whence it originates or, at the most, elaborates a 
diminished amount of an imperfect product in comparison with the 
normal standard. It tends, therefore, to be composed predominantly of 
cells, whereas the normal connective tissue consists largely of a matrix 
containing only enough cells to prepare and maintain it; between these 
two extremes, however, lie not only the benign connective-tissue tumors, 
of which both cells and intercellular material are prominent constituents 
(see page 398), but a group of sarcomata {fibrosarcoma, osteosarcoma, etc.) 
in which the matrix is nearly as abundant as it is in the benign growths of 
the connective tissues. 
The connective tissue of a sarcoma sometimes forms a network of 
large meshes dividing the growth into alveoli {alveolar sarcoma). What- 
ever its disposition, however, the cells always stand in intimate relation- 
ship with it, as is revealed by the fact that fine fibrils can be demonstrated 
between the individual elements or even in continuity with them. Blood- 
vessels, also, form a constant and important structural element in the 
sarcomata, being in some of them so conspicuous as to give structural 
outline and general character to the neoplasm. Like those of normal 
connective tissue, they are intimately associated with the basement 
substance, but unlike these are rudimentary, their walls consisting 
often of a single layer of endothelium, even when the vessel is of compara- 
tively large size. 
The cells of a sarcoma resemble in appearance such actively growing 
connective-tissue elements as are found in the developing embryo or in 
granulation tissue. In outline they vary from a spheroidal shape to 
that of a spindle or a cylinder, and may be large or small. 
Sarcomata are most frequently found in the skin, subcutaneous and 
subserous connective tissue, fasciae, marrow, periosteum, and choroid. 
They involve also, though more rarely, the dura mater, brain and cord, 
lymph-nodes, adventitia of blood-vessels, nerve sheaths, submucous 
tissue, uterus, ovary, and kidney. In the liver, pancreas, lungs, and heart, 
they may appear, but usually by metastasis. 
Though sarcomata do occur in early life they are not more common 
at this time than in later years, as they are ordinarily said to be; on the 
contrary, they develop more frequently in the higher age periods,2 as 
the carcinomata do (see page 453). 
The cellular character of most sarcomata, their rapid growth, vas- 
cularity, and tendency to recurrence and metastasis, stamp them on the 
whole as malignant tumors. But in this respect they vary greatly, for 
1 For a discussion of this question, see Hulisch, Zieglers Beitr., 1915, lx, 245 (bibl.). 
2 Weinberg and Gastpar, Ztschr. f. Krebsforsch., 1904, ii, 216, 220; 1906, iv, 18; Bashford and 
Murray, Second Sci. Report, Imperial Cancer Research Fund, London, 1905, i, 24; Roger Williams, 
Natural History of Cancer, New York, 1908, p. 322; Weller, Arch. Int. Med., 1915, xv, 518; Jour. 
Michigan Med. Soc., 1915, xiv, 524; Harbitz and Platou, Norsk. Mag. f. Laegevidensk., 1917, Ixxxviii, 
145 (abstr. in Jour. Am. Med. Assn., 1917, lxviii, 1074). 428 
while some varieties belong in every sense to the most malignant of all 
neoplasms, others grow slowly, are very dense, and may remain localized 
and harmless for years. Their tendency in this respect will be mentioned 
under the special forms. 
Intimately related as they are to the blood-vessels, metastasis is 
more apt to occur by way of the circulation than through the lymph- 
channels, and adjacent lymph-nodes are consequently much less apt to 
be involved than by some other types of neoplasm, notably the car- 
cinomata. Richly cellular and vascular sarcomata are especially prone 
to hemorrhage, degeneration, and ulceration. 
TUMORS 
Fig. 232.-Large Spindle-cell Sarcoma. 
A single variety of element is often so conspicuous as to furnish a 
suitable qualifying name for the tumor, though in many cases the cell 
form varies widely in the same growth {polymorphous-cell sarcoma). It 
may be said, in the main, that some tendency is shown by the sarcomata 
to reproduce the special characteristics of the tissues in which they 
originate; thus those of the bones may be osteosarcomata, those of fibrous 
connective tissue fibrosarcomata, and so on. It will be more convenient 
for our present purpose to describe briefly the most common forms one 
after another than to attempt any systematic classification of them; it 
should be remembered, however, that the various types are not sharply 
defined, but are apt to merge into one another and to intermingle in 
various ways. 
Spindle-cell Sarcoma.-The cells of these tumors may be large 
{large spindle-cell sarcoma, Fig. 232 and 233) or small {small spindle-cell 
sarcoma, Fig. 234). The growth may consist almost entirely of cells or, 
on the other hand, contain so much intercellular fibrous tissue that it may 
appropriately be called a fibrosarcoma; but different parts of the same TUMORS 
429 
neoplasm often differ greatly as to the proportion between cells and inter- 
cellular material. The cells are frequently arranged in fascicles which 
surround the blood-vessels and cross and interlace in an intricate pattern. 
Accordingly, almost any section from a spindle-cell sarcoma will contain 
some elements which have been cut at right angles to their long diameter, 
or obliquely, appearing therefore to have a circular or an oval outline. 
Fig. 233.-Large Spindle-cell Sarcoma. 
Showing abundant cell growth near a blood-vessel. 
Care should be taken not to make the diagnosis of polymorphous-cell 
sarcoma in such cases. 
The spindle-cell sarcomata, especially the small cell variety, are, as a 
rule, denser, firmer, and less malignant than other kinds, though to this 
statement there are many exceptions; they may be encapsulated or 
infiltrating. To this class belong those growths formerly described as 
fibroplastic tumors and recurrent fibroids. The spindle-cell sarcoma most 
frequently arises in the periosteum, subcutaneous tissue, and muscles, 
Fig. 234.-Small Spindle-cell Sarcoma of Forearm. 
but it is seen also in the uterus and in various glands, notably the mamma, 
testis, thyroid, etc. It is among the most frequent of the sarcomata. 
Differential Diagnosis.-See Fibroma, page 398. 
Round-cell Sarcoma.-Of this there are two classes: 1, small round-cell 
sarcoma, and, 2, large round-cell sarcoma. 
1. The small round-cell sarcoma consists of elements similar in size 430 
TUMORS 
and appearance to the lymphocytes of the lymph-nodes (Fig. 235) and 
of a variable amount of intercellular substance which, as in the spindle- 
cell variety, may be either irregularly distributed or arranged in a 
network. So small is the quantity of intercellular material in many cases, 
however, that it is difficult of detection without special modes of prepara- 
tion. Tumors of this class sometimes contain many blood-vessels, and 
may be soft and succulent. Their growth is frequently rapid and they 
are often extremely malignant; they are apt to metastasize widely and 
early, perhaps because their cells are so small as to be easily transportable 
from one site to another They occur most commonly in the connective 
tissue of the muscles and fasciae, in the skeletal system, and in the internal 
organs. 
2. The cells of a large round-cell sarcoma (Fig. 236) vary in size, but 
are usually much larger than those of the small-cell variety. Their 
Fig. 235.-Small Round-cell Sarcoma. 
From a metastatic tumor in the lungs. A tumor of the mamma. Mitotic figures in some of the cells. 
Fig. 236.-Large Round-cell Sarcoma. 
nuclei are generally large and contain prominent nucleoli. These neo- 
plasms, like those just described, are often very vascular and contain a 
variable quantity of basement substance; they are occasionally alveolar 
in character. As a rule, they are less soft and less malignant than the 
small-cell type. 
Differential Diagnosis.-A small round-cell sarcoma may be dis- 
tinguished from an inflammatory lymphocytic infiltration by its sharper 
boundary, as well as by the fact that its cells usually exceed the lympho- 
cyte somewhat in size and are often found in process of division; further- 
more, the nuclei are apt to be larger and more vesicular than those of 
lymphocytes. A leukemic infiltration is not so discrete as a sarcoma, and 
does not destroy the invaded tissues as a sarcoma does. Nevertheless, 
an absolute distinction between a small round-cell sarcoma and a lympho- 
cytic infiltration may sometimes be impossible (see also Lymphoblastoma). 
Lymphoblastoma {lymphosarcoma).-There may occur in any part 
of the lymphatic system a tumor composed of lymphocytes {lympho- 
cytoma) or, more generally, of their ancestral element, the lymphoblast 
{lymphoblastoma). This type of growth is often called a lymphosarcoma, 
but as there is an increasing desire on the part of pathologists to reserve 431 
TUMORS 
the term sarcoma for neoplasms of supporting connective tissue, lympho- 
blastoma has been suggested1 as a substitute. 
In metastasizing, the lymphoblastoma characteristically follows the 
lymph-channels at first, spreading along them from one node or follicle 
to the next, but it finally invades the surrounding structures also until 
all are fused into one firm mass. Thus it progresses from one region to 
another though without ever becoming so generalized as leukemia or 
pseudoleukemia. Extensive local metastasis of this sort produces the 
condition known as lymphosarcomatosis.2 Metastasis by way of the 
blood stream is rare, so that secondary nodules in outlying organs are not 
commonly encountered. 
The parenchyma of an affected node is entirely destroyed, its follicles 
and lymph-cords being no longer recognizable, while the capsule and 
surrounding tissues are densely infiltrated by tumor cells, elements re- 
sembling in size, shape, and appearance the large mononuclear leucocyte. 
Since cells of the lymphocyte class produce no intercellular substance, 
the only stroma possessed by the lymphoblastoma is such as may be 
furnished by the invaded tissues. 
Differential Diagnosis.-The cells are larger than those of a small 
round-cell sarcoma. From a large round-cell sarcoma the lympho- 
blastoma may be distinguished by the lack of a proper stroma,3 its early 
limitation to the lymphatic system, the capillary size of its blood- 
vessels, the absence of hemorrhage, and its tendency to metastasize in 
organs ordinarily spared by malignant growths. 
Plasmocytoma4 (plasmoma, plasma-cell myeloma, plasmomyeloma).- 
This growth, composed of plasma cells, is closely related to the lympho- 
blastoma but differs from it in being usually benign. In the bones,5 
however, it may behave as a malignant growth.6 
For a discussion of chloroma, see pages 542 and 1073. 
Myeloma.-The myelomata (see page 1073) include a group of peculiar 
tumors which resemble the sarcomata in many ways, though differing 
from them in histogenesis. They are derived from the bone-marrow 
and are usually multiple,7 appearing as grayish or reddish masses which, 
in their growth, cause absorption of the bone. Metastasis is rare.8 
Oxydase reactions may or may not be given by the cells according to 
the type (myeloblast, myelocyte, lymphocyte, plasma cell, erythroblast) 
from which the growth springs.9 
For a discussion of Bence-Jones' protein, often found in the urine in 
connection with myeloma, see page 1074. 
1 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 364. 
2 Kundrat, Wien. klin. Wchnschr., 1893, vi, 211; Paltau], Lubarsch-Ostertag, Ergebn. d. allg. Path., 
1896, iii1, 652; Sternberg, ibid., 1903, ix2, 481. 
3 For a study of the stroma, see Seelig, Surg., Gynec., and Obst., 1907, iv, 319 (biblj. 
4 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 378 (bibl.); Jessup, Proc. New York Path. Soc., 
1912, xii, 6 (bibl.); Frank, A., Verhandl. d. deutsch. path. Gesellsch., 1913, xvi, 115; Zimmermann, Vir- 
chows Arch., 1914, ccxvi, 214. 
6 Warstat, Zieglers Beitr., 1913, Iv, 225 (bibl.). 
8 Verse, Verhandl. d. deutsch. path. Gesellsch., 1912, xv, 62 (bibl.). 
7 Hoffman, Zieglers Beitr., 1904, xxxv. 317 (bibl.); Christian, Jour. Exper. Med., 1907, ix, 325. 
8 Pepper and Pearce, Jour. Med. Research, 1918, N. S. xxxii, 171. 
9 Vance, B. M., Am. Jour. Med. Sc., 1916, clii, 693 (bibl.t; Forman and Warren, Jour. Cancer 
Research, 1917, ii, 79 (bibl.). 432 
TUMORS 
Melanosarcoma.-These tumors consist most frequently of poly- 
hedral cells of various sizes containing particles of brown or black pig- 
ment (melanin, Fig. 237).1 As a rule, the pigment is quite irregularly 
distributed in patches or streaks and may be found also in the inter- 
Fio. 237.-Melanosarcoma. 
Tumor from foot. 
cellular substance. The growths arise most frequently in the skin (Fig. 
238) where pigmented moles often form their starting point,2 and in the 
choroid, and belong to the most malignant of neoplasms. They readily 
form metastases in various parts of the body, which, like the parent tumors 
are deeply pigmented,3 moderately so. or even entirely free from pigment. 
A small nodule showing local extension is seen in the subcutaneous tissue beneath. 
Fig. 238.-Melanosarcoma of the Skin, Fungoid in Shape. 
Besides the skin, they originate in the mucous membranes, eye, adrenal, 
meninges, and brain.4 
The melanosarcoma is called by Ribbert6 a chromatophoronia or 
1 For a general discussion of this pigment, see Hada, Virchows Arch., 1914, ccxv, 216 (bibl.). 
2 For bibl. of melanosarcomata of the skin, see Wilson and Kalteyer, Am. Jour. Med. Sc., 1903, 
cxxvi, 751. 
3 On melanuria consult Thacher, J. S., Proc. New York Path. Soc., 1893, p. 105. 
4 Hirschberg, Virchows Arch., 1906, clxxxvi, 229 (bibl.). 
6 Ribbert, Zieglers Beitr., 1897, xxi, 471 (bibl.); and Geschwulstlehre, 2d ed., Bonn, 1914, p. 318; 
Ribbert, H., Bemerkungen zum Chromatophorom, Centralbl. f. allg. Path., 1918, xxix, 273. Pathology-Delafield and Prudden. 
Plate II. 
Fig. 1. Melano-Epithelioma from Pigmented Mole. 
Fig. 2. Primary Melanosarcoma of Nerve Trunk. 
Fig. 3. Melanosarcoma of Choroid of Eye. TUMORS 
433 
melanoma (Plate II and Fig. 239), the former name being preferred as in- 
dicating the origin of this tumor from the chromatophores (see mole, page 
447). It is, in his opinion, a separate variety of tumor, and should not 
be included among the sarcomata. 
While some authorities regard all these neoplasms as sarcomata, 
others believe that some among them may be carcinomata. At any rate, 
certain of the pigmented neoplasms (melanocarcinomata F) have all the 
characteristics of carcinoma, including an alveolar arrangement and the 
absence of connective-tissue fibrils from between the cells; chromato- 
phores, too, are absent, the melanin being carried by the epithelial cells 
(page 467), and the presence of keratin has been recorded.1 
Fig. 239.-Melanoma. 
Differential Diagnosis.-Various forms of neoplasm may contain 
brownish or yellowish pigment, deposited in them by degeneration of the 
hemoglobin from extravasated blood; these should not be mistaken for 
melanotic sarcomata. Blood pigment is not so dark as melanin and is 
generally included in phagocytic cells lying in the stroma; a careful search 
will in many cases reveal crystal or needle forms, and an iron reaction 
can usually be obtained by treating sections with acid and potassium 
ferrocyanide. The granules of black pigment sometimes seen in tissues 
fixed with formalin are so fine that they can hardly be mistaken for mela- 
nin; furthermore, they are soluble in dilute ammonia water. 
Giant-cell Sarcoma.-Growths of this class, which originate most 
often in the marrow (myeloid sarcoma') of the tibia and radius, and less 
'Beckey, Frankfurt. Ztschr. f. Path., 1915, xvii, 365 (bibl.). 434 
TUMORS 
commonly in the periosteum, are composed of fusiform or spheroidal cells 
of various sizes, interspersed more or less thickly with multinucleated 
giant cells (Fig. 240); no bone is formed, as a rule, wherein these differ 
from the true osteosarcomata, tumors of the bone itself. 
While giant cells may be occasionally discovered in almost any kind 
of growth, they are most abundant and characteristic in the lesion now 
under discussion. Here the situation of their nuclei is most commonly 
central rather than peripheral, whereas in the giant cells characteristic 
of tuberculosis {Langhans type) they are apt to occupy a position at one 
Fig. 240.-Giant-cell Sarcoma of Finger. 
Periosteal type. 
end of a somewhat elliptical cell body; in foreign body giant cells their 
distribution is irregular and they may be found at one end, at both ends, 
or gathered about any foreign body with which the cell is in contact. 
Mitotic figures are occasionally seen in the nuclei of giant cells of rapidly 
growing and recurrent tumors (Fig. 241). 
This giant-cell lesion of the bone-marrow is subject to hemorrhage 
and is sometimes so soft and vascular that it may be mistaken for an 
aneurysm;1 its appearance is usually compared with that of currant 
jelly. It is so slightly malignant that simple curettage of the bone often 
suffices to cure it.2 Indeed, so little does it resemble the sarcomata as 
^Gaylord, Ann. Surg., 1903, xxxvii, 834; Nakayama, Beitr. zur klin. Chir. (Bruns), 1909, Ixiv, 524. 
* Bloodgood, Trans. Am. Surg. Assn.. 1912, xxx, 463. TUMORS 
435 
Fig. 241.-Giant-cell Sarcoma of Superior Maxilla. 
Fifth recurrence. Mitosis in giant cell. 
Showing the Langhans' type of giant cell seen in these growths, also the spongy soft connective tissue 
in which the cells lie. Numerous leucocytes and red blood-cells are seen in the section. 
Fig. 242.-Epulis of Gum. 436 
TUMORS 
to virulence, that it is regarded by some observers as a simple inflam- 
matory lesion1 or as a benign growth.2 
An example of the periosteal type of giant-cell sarcoma is one variety 
of epulis, a clinical term including all tumors about the gums (Fig. 242). 
This growth, which arises from the periosteum of the maxillary border, 
is generally quite harmless if carefully removed; thus, in one series only 
two recurrences were noted in seventy cases. If excision be imperfectly 
performed, however, repeated local recurrences may take place, though 
without metastases appearing anywhere in the body. 
A benign giant-cell sarcoma occurs also about the tendons and apo- 
neuroses of the hand and foot.3 
Fig. 243.-Osteoid Sarcoma. 
Metastasis in lung. 
Osteosarcoma.-In contrast to the myeloid sarcoma, which develops 
from the marrow cavity, the osteosarcoma is without any doubt a true 
neoplasm, since it invades the surrounding parts, metastasizes (Fig. 243), 
and usually proves fatal within a comparatively short time. It originates 
1 Barrie, Ann. Surg., 1913, Ivii, 244; Barrie and Hillman, Surg., Gynec., and Obst., 1914, xix, 42. 
1 Adami, Principles of Pathology, 2d ed., Philadelphia, 1910, i, 734; Bland-Sutton, Tumors Inno- 
cent and Malignant, New York, 1917, p. 45. 
For a brief discussion of this question, see Martland, Proc. New York Path. Soo., 1915, xv, 119; 
and Hausslina and Martland, Ann. Surg, 1916, Ixiii, 454. 
3 Spiess, Frankfurt. Ztschr. f. Path., 1913, xiii, 1 (bibl.). TUMORS 
437 
occasionally in the soft parts,1 but more often in the bone itself, usually 
within the shaft {central sarcoma) or from the outer surface {peripheral 
sarcoma); both these are called endosteal to distinguish them from a third 
class which arises in the periosteum {periosteal sarcoma). The structure 
and the clinical course are the same, however, in all true osteosarcomata 
arising in the skeletal system. The bones most commonly affected are 
the long bones, of which the femur is most often involved; next follow 
in order the tibia and the humerus. 
Osteosarcomata are spindle-cell or round-cell tumors containing 
masses of bone; this is usually atypical in structure, the regular lamella- 
tions and Haversian canals being generally absent (Fig. 244). Not in- 
frequently, calcification is imperfect or lacking {osteoid tissue). 
Fig. 244.-Osteosarcoma of Leg. 
Bone sarcomata are said to have been preceded in some instances by 
osteitis deformans (Paget's disease of bone);2 but it has been said also 
that patients with this type of osteitis are apt to develop carcinoma. It 
should be remembered, in any case, that most of the subjects of Paget's 
disease of the bone are in the cancer age, and some doubt may therefore 
be expressed regarding the value of these assertions pending the collection 
of an adequate statistical material. There is also the possibility that 
those cases of supposed Paget's disease in which sarcomata are said to 
have developed, were actually cases of osteitis fibrosa, some forms of 
which are distinguished only with difficulty from sarcomata, and other 
types of which are prone to develop into sarcomata. 
Fibrosarcoma.-In the fibrosarcoma collagen is the intercellular 
material elaborated. Sometimes there is so much that the growth may 
appear at first sight to be merely a rather cellular fibroma, but closer 
examination of such a neoplasm will reveal irregularities in the size of the 
nuclei and in the size and staining properties of the cell bodies, while 
1For bibl., see Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 276. 
2 For bibl., see Heazlit, New York State Jour. Med., 1917, xvii, 330. 438 
TUMORS 
mitotic figures are apt to be more abundant than in the fibroma (see page 
398). In a few cases, the diagnosis will be difficult or impossible. 
Angiosarcoma.-One type of neoplasm to which this term is fre- 
quently applied is a rather vascular sarcoma which has undergone necrosis 
save for several layers of cells bordering the blood-vessels; these remain 
alive because they are nearest to the food supply (Fig. 245, 246, and 247). 
But the preservation of cells favorably situated, in the face of an other- 
wise general necrosis, may be a feature of the carcinomata and of many 
Tumor from the arm. Sometimes called angiosarcoma or perithelial sarcoma. 
Fig. 245.-Vascular Sarcoma. 
Fig. 246.-Vascular or Angiosarcoma of Lymph-node (Endothelioma?) 
other tumors, and no good reason appears why this condition should be 
used as a basis for classifying the sarcomata. 
Another sarcoma frequently referred to as angiosarcoma is that var- 
iety in which the vessels are prominent by reason of their great number 
rather than their isolation in consequence of a wide-spread necrosis. But 
to merit the name angiosarcoma a tumor would have to originate from 
the endothelium of a vessel, and doubt has been expressed1 whether there 
actually is such a growth; nor has the term perithelial sarcoma, sometimes 
applied to those neoplasms in which the vessels are surrounded by a 
mantle of tumor cells, fared any better.2 
1 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 262. 
2». Hansemann, Ztschr. f. Krebsforsch., 1905, iii, 234. TUMORS 
439 
If the need be felt of qualifying the simple designation sarcoma, it 
would therefore be better, on the whole, to replace the name angio- 
sarcoma with some such term as vascular sarcoma. 
Alveolar Sarcoma.-Sometimes the connective-tissue framework of 
a sarcoma, particularly in the round-cell varieties, is abundant and 
assumes the form of a network containing the tumor cells within its 
meshes. The spaces are called alveoli, and this variety of neoplasm has 
acquired importance because it imitates the well-defined alveolar arrange- 
ment characteristic of many of the carcinomata. Growths of this kind 
are not common, but may occur in the skin, lymph-nodes, bone, and pia 
mater. They are usually very malignant. 
Fig. 247.-Vascular or Angiosarcoma of Humerus (Endothelioma?). 
Differential Diagnosis.-An alveolar sarcoma may be confused 
with a carcinoma. In the sarcoma, however, there is a more intimate 
relation between the cells and their stroma-that is to say, the connective 
tissue sends out trabeculae which pass into the alveoli and between the 
individual cells. But a careful study of sections especially prepared to 
show these fine fibrils, by Bielschowsky's silver method, for example, or 
by shaking in water to dislodge loose cells, may be required to distinguish 
one of these growths from the other. In the carcinoma, no connective- 
tissue fibrils are to be found between the cells, and, being unsupported, 
these are readily washed out when the section is shaken in water. 
Mixed Forms of Sarcoma.-In addition to the more or less well- 
defined forms of sarcoma which have now been briefly presented, there 
exist various others, such as the liposarcoma, which contains fat; the 440 
TUMORS 
chondrosarcoma, which contains cartilage; the chondro-osteosarcoma, etc. 
Certain modifications also have received special names; thus, sarcomata 
in which cysts form through degeneration, or the dilatation of alveoli or 
ducts by pressure, have received the name cystosarcoma. Mucous de- 
generation is frequent, and a combination of myxoma and sarcoma 
(myxosarcoma') is common (Fig. 248). A mixture of adenoma and 
sarcoma (adenosarcoma)1 is rare in adult life, the ordinary adenosarcoma 
being a congenital tumor of the kidney in children.2 The terms myosar- 
coma and gliosarcoma many authors3 would replace with malignant 
myoma and malignant glioma, reserving sarcoma as a designation solely 
for tumors of connective tissue. 
Fig. 248.-Myxosarcoma of Parotid. 
Sarcoma is sometimes combined with carcinoma, some twenty-five 
cases having been reported in man.4 In mice, however, the combination 
is not so rare;5 here the sarcoma is supposed to arise secondarily in the 
stroma of a carcinoma, possibly because the cells of the latter exert some 
sort of irritant action upon the connective tissue. This hypothesis is 
strengthened by the study of certain transplantable carcinomata whose 
cells have the power to induce a sarcomatous alteration in the stroma, 
and it has been found that from one to three months' growth in any 
one animal is required for the change to be brought about. It is very 
probable that carcinosarcoma of the human subject, hitherto so puzzling, 
can be explained in the same way. It should be added, however, that 
certain observers, and notably Krompecher, regard the entire growth 
as an epithelial tumor in which the cells in certain areas have assumed a 
spindle shape.6 
1 Wengraf, Virchows Arch., 1913, ccxiv, 161 (bibl.); Trappe, Frankfurt. Ztschr. f. Path., 1907, i, 
130 (bibl.). 
2 The term has been applied by Beneke (cited by Kaufmann, Lehrbuch der spez. path. Anat., Berlin, 
1911, ii, 802) to malignant tumors of the adrenal. 
3e.g., Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 434. 
* Herxheimer, Zieglers Beitr., 1908, xliv, 150; Saltykov, Centralbl. f. allg. Path., 1914, xxv, 419. 
6 Ehrlich, Ztschr. f. Krebsforsch., 1907, v, 62; Apolant, Kolle and Wassermann, Handbuchd. path. 
Mikroorganismen, 2d ed., 1913, iii, 167; Haaland, Third Sci. Report, Imperial Cancer Research Fund, 
London, 1908, p. 175; Russell, Jour. Path, and Bacteriol., 1910, xiv. 344. For a complete review of the 
cases up to |913, see Woglom, The Study of Experimental Cancer, New York, 1913. 
8 For a discussion of this question, see Woglom, Jour. Cancer Research, 1918, iii, 47. 441 
TUMORS 
No class of new growths has given rise to so much controversy and 
yet remained so indefinite as this one. There is, in fact, hardly an ob- 
scure tumor that has not at one time or another, since the appearance of 
Volkmann's monograph,1 been called an endothelioma. 
ENDOTHELIOMA. 
Fig. 249.-Endothelioma (Endothelial Sarcoma) of Dura Mater. 
Fig. 250.-Endothelioma of Dura Mater. 
Psammomatous form. 
If this diagnosis is to be made, however, the origin of the neoplasm 
from endothelium-that is, from blood- or lymph-vessels-must be 
demonstrated, and Ribbert2 demands further that the cells show a tend- 
ency to form such vessels. In short, he regards it as extremely probable 
i Volkmann, Deutsch. Ztschr. f. Chir., 1895, xli, 1. For a full discussion of the endothelioma, see 
Marchand, Verhandl. d. deutsch. path. Gesellsch., 1900, ii, 38. 
2 Ribberl, Geschwulstlehre, 2d ed., Bonn, 1914, p. 243. 442 
TUMORS 
that, apart from the psammoma of the dura mater (Fig. 249, 250, and 
251), which he accepts as an endothelioma,1 there is in the long run no 
endothelioma but the angioma. Yet he does not deny absolutely the 
possibility that endothelium may occasionally grow in solid masses, and 
cites a case2 to show that it may give rise to a tumor resembling a sarcoma 
both clinically and morphologically. It is interesting to find, however, 
that in the younger parts of even this neoplasm Colmers2 described a 
distinct tendency toward the elaboration of vessels. The benign endo- 
thelioma of the pulmonary vein reported by Sailer,3 is perhaps another 
authentic example of endothelioma of the solid type. 
Fig. 251.-Endothelioma of Dura Mater. 
Psammomatous form. 
While all authorities are not so radical4 as Ribbert, a large number of 
new growths have nevertheless been dismissed in recent years from among 
the endotheliomata. For example, that neoplasm which sometimes arises 
in the pleura5 is now often called mesothelioma (Fig. 252), since the lining 
cells of the pleura, peritoneum, and pericardium are no longer universally 
regarded as endothelium,6 but if this tumor could be shown to develop, 
not from the superficial layer (mesothelium) but from the pleural lymph- 
channels, as some observers assert that it does, the name endothelioma 
1 See Prym, Virchows Arch., 1914, ccxv, 212, for a discussion of this question. 
2 Colmers, Zieglers Beitr., 1903, xxxiv, 295 (bibl.). 
3 Sailer, Contributions from the William Pepper Laboratory of Clinical Medicine, 1900, University 
of Pennsylvania (abstr., Centralbl. f. Path., 1901, xii, 263). A somewhat similar case is that of Unruh, 
Deutsch, med. Wchnschr., 1896, xxii, 746. 
4e.g., Adami, Principles of Pathology, 2d ed., Philadelphia, 1910, i, 813. 
6 Rosenbaum, Ztschr. f. Krebsforsch., 1914, xiv, 543 (bibl.). 
6 See Minot, Science, 1901, xiii, 481; Miller and Wynne, Jour. Path, and Bacteriol., 1908, xii, 267; 
Monckeberg, Zieglers Beitr., 1903, xxxiv, 489; Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 240; 
Benda, Deutsch, med. Wchnschr., 1897, xxiii, 324. TUMORS 
443 
would have to be retained. Another type of growth to be excluded from 
the endotheliomata is the mixed tumor of the salivary glands, which is 
regarded by most authorities1 as epithelial. 
The difficulties which stand in the way of a thorough conception of 
the endotheliomata may be illustrated as follows: A recent author2 dis- 
tinguishes lymphangioendothelioma and hemangioendothelioma, the latter 
Fig. 252.-Mesothelioma ob "Endothelial Cancer" of Pleura. 
Showing the formation of mucus within the endothelial-cell masses; the mucus is stained with hema- 
toxylin. 
of which is divided into the endothelioma, originating inside the vessel, 
and the perithelioma, arising from the perithelium at its periphery. A 
second3 doubts the very existence of perithelium; a third4 asserts that 
perithelium is to be found about the blood-vessels of the brain and a few 
other organs; while a fourth writer,5 finally, is loath to acknowledge any 
neoplasm as an endothelioma. 
1 Wood, F. C., Ann. Surg., 1904, xxxix, 57: Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 601; 
Wilson and Willis, Am. Jour. Med. Sc., 1912, cxliii, 656 (bibl.). 
2 Borst, in AschoS's Pathologische Anatomie, Jena, 1913, p. 719. 
3 MacCallum, Textbook of Pathology, Philadelphia, 1916, p. 934. 
*von Hansemann, Ztschr. f. Krebsforsch., 1905, iii, 245. 
^Fick, Monatsh. f. prakt. Dermat., 1909, xlviii, 104. 444 
TUMORS 
Epithelial Tumors-Benign. 
Since even normal epithelium varies greatly in its morphology, that of 
the pulmonary alveoli, for example, looking like endothelium, it may readily 
be imagined that under abnormal conditions epithelium will sometimes 
prove difficult of recognition. Thus the epithelium in mixed tumors of 
the parotid gland is so atypical that there are still those who would derive 
these growths from the connective tissues; again, it has been asserted1 
that the tumor regarded by most pathologists as a carcinosarcoma is 
really a pure carcinoma, its spindle-shaped cells being epithelium in spite 
of their morphological resemblance to the fibroblast; or, to cite a third 
instance, a medullary carcinoma may closely resemble a sarcoma. 
But epithelium has certain characteristics, one or more of which can 
usually be discovered by careful search or by the employment of special 
staining methods, so that in the long run the number of tumors that 
remain persistently in the doubtful class will be small. The presence of 
Fig. 253.-Medullary Carcinoma of Stomach. 
Carcinoma Molle. 
keratinization, for example, or of intercellular bridges, is reliable evidence 
that the neoplasm originated in surface epithelium, while indications of 
a glandular arrangement point to the epithelium of some gland as the 
site of inception. In a certain number of cases, however, all such clues 
will be absent, and recourse must be had to special methods which will 
stain the finer strands of connective tissue. If these fibrils can be found 
between individual cells, the neoplasm under examination may be de- 
clared a connective-tissue growth; if not, it is equally certain that the 
tumor is of epithelial origin. 
Unlike the sarcomata, the epithelial neoplasms have in most cases a 
prominent connective-tissue stroma; this, however, takes no part in the 
activities of the tumor (unless in those few growths regarded by Ribbert 
as fibroepithelial), but forms a mere scaffolding to support the paren- 
1 Krompecher, Zieglers Beitr., 1908, xliv, 88. TUMORS 
445 
chyma and conduct its blood-vessels. It is entirely passive, being formed 
from the surrounding connective tissues at the behest of the epithelial 
portion of the neoplasm. The stroma may be sparse or abundant, may 
contain few cells or many, is sometimes arranged in fascicles or bands, 
and frequently forms the wall of well-defined spaces of various shape 
called alveoli (Fig. 253) within which lie the epithelial cells forming the 
parenchyma. 
As with the connective-tissue new growths, epithelial tumors may be 
divided into mature, or benign, and immature, or malignant. But it 
must be remembered that the distinction cannot always be made in 
practice, for there is no infallible morphological criterion of malignancy. 
All we know is that experience has shown certain histological features to 
be associated with clinical malignancy. Yet these may be absent and 
the tumor nevertheless be malignant; there are new growths of the 
thyroid, for example, which exhibit an absolutely benign structure when 
regarded from the histological standpoint, but which are nevertheless 
quite the equal of many carcinomata in their destructive growth and 
their tendency to metastasize (see page 378). 
Bearing these qualifications in mind we may enter upon a discussion 
of the benign epithelial neoplasms. 
PAPILLOMA. 
This growth is composed of connective-tissue prolongations covered 
by epithelium (Fig. 254). The nasal polyp (Fig. 255) also answers this 
definition, but the following distinction has been drawn between the two 
types.1 The nasal polyp is merely a pure fibroma covered with a layer of 
mucous membrane, while the papilloma is a tumor in which both the 
connective tissue and the epithelial portions proliferate. For this reason 
the latter is sometimes called a fibroepithelial tumor. 
The papilloma of the skin, or common wart (verruca vulgaris), consists 
of a connective-tissue stalk covered by thick epithelium; in vertical 
section it has the outline of a similar section through a cauliflower, on 
account of the irregularities of its surface. Fissures in the epithelium 
may admit a few microorganisms, and the stroma, owing to the resulting 
infection, may be more cellular than is ordinarily the case. 
If the epithelium does not wear away as it is formed, which it usually 
does, a cutaneous horn (cornu humanum), which may be several centi- 
meters in length, is the result. 
For a description of the venereal wart, or condyloma, see page 911. 
Papillomata are common in the bladder and intestine, where they 
appear as the familiar polyp. Here the connective-tissue processes are 
longer than in the skin, and the tumor assumes a tree-like form. As 
polyps sometimes undergo malignant change,2 the pathologist should 
1 Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 473. 
2 Ribbert, Das Karzinom des Menschen, Bonn, 1911, pp. 164, 400 (bibl.); Hauser, Cylinderepithel- 
Carcinom des Magens u. des Dickdarms, Jena, 1890; Verst, Arb. a. d. path. Inst, zu Leipzig, 1908, i. 
No. V; Buerger, Surg., Gynec., and Obst., 1915, xxi, 179; Syring, Beitr. z. klin. Chir. (Bruns), 1911, 
Ixxiii, 66 (bibl.). 446 
TUMORS 
Fig. 254.-Small Papilloma of Skin. 
The section shows the epithelial covering of the fibroma as well as its numerous blood-vessels and a few 
mucous glands. 
Fig. 255.-Mucous Polyp (Soft Fibroma) of Nose. TUMORS 
447 
always examine the stalk at its base, where evidences of invasion of the 
normal tissue will be manifest if the growth has ceased to be benign. 
NjEVUS. 
The naevus (Fig. 256), or mole, might be included with equal justice 
among the connective-tissue new growths, for its true nature is still un- 
known. Classed by many eminent observers1 with the epithelial tumors, 
it is regarded by not a few equally good authorities2 as originating in the 
connective tissues; a minority, finally, believe it to be an endothelioma. 
The naevus is a flat (sessile) or projecting (pedunculated) tumor which 
may or may not be pigmented, covered by epithelium and composed of 
Such small nsevi are sometimes mistaken for epitheliomata and occasionally afford a starting-point 
for the latter. 
Fig. 256.-A Portion of a Congenital, N^vus of the Skin. 
strands of connective tissue interspersed with columns of naevus cells-- 
the elements which have given rise to such earnest dispute. These are 
round or oval structures somewhat larger than a lymphocyte, with a 
comparatively large nucleus, and charged more or less heavily with 
granules of a dark brown, iron-free pigment (melanin). Besides these, 
the naevus contains a variable number of branched cells (the chromato- 
phore, melanoblast, or chromatoblast) containing melanin and similar to 
those found in normal pigmented skin. Ribbert contends that the nsevus 
cell is but an early stage of the chromatophore, becoming pigmented and 
branched as its differentiation proceeds; and that the naevus is a con- 
nective-tissue neoplasm, since the chromatophore is a connective-tissue 
cell. Naevi consisting almost entirely of chromatophores have been 
described.3 
^e.g., Unna, Berl. klin. Wchnschr., 1893, xxx, 14; and Krompecher, Der Basalzellenkrebs, Jena, 
1903, p. 100. 
2e.g., Ribbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 344. 
3 Tieche, Virchows Arch., 1906, clxxxvi, 212. 448 
TUMORS 
ADAMANTINOMA. 
{Cystadenoma adamantinum; epithelioma adamantinum) d 
This is a rather uncommon tumor which develops at the root of a 
tooth in the posterior portion of the inferior maxilla, appearing as either 
a solid or a cystic growth; it is rarely found in the upper jaw. 
It is composed of solid or cystic anastomosing alveoli separated by 
fibrous connective tissue (Fig. 257). The epithelial cells at the periphery 
of the alvepli are cylindrical, while those toward the center exhibit the 
Fig. 257.-Adamantinoma. 
stellar shape characteristic of cells of the enamel organ, from remnants of 
which these growths arise. The stroma may contain bone. 
A remarkable pathological curiosity was reported not long since in 
the shape of a primary adamantinoma of the tibia,2 which was explained 
as having developed from a heterotopic tooth anlage. 
CYLINDROMA. 
Tumors in which homogeneous or striated cylinders of hyaline or 
mucoid material (Fig. 258), often closely surrounded by layers of cuboidal 
or flattened cells (Fig. 259), form a striking feature, are called cylindro- 
mata. Some of these growths are carcinomata. 
1 Chibret, Arch, de m6d. exper., 1894, vi, 278; Borst, Die Lehre von den Geschwiilsten, Wiesbaden, 
1902, p. 605; Malassez, Les debris 6pith61iaux paradentaires, Paris, 1910; Kuru, Centralbl. f. allg.. 
Path., 1911, xxii, 291; L' Esperance, Proc. New York Path. Soc., 1910, x, 136. 
2 Fischer, Frankfurt. Ztschr. f. Path., 1913, xii, 422. TUMORS 
449 
Fig. 258.-Cylindroma of Upper Jaw. 
Showing the formation of mucus in the gland-like epithelial masses. 
There is a tendency to the formation of glands, and hyaline or mucoid material like that shown in Fig. 
25S is not infrequently present. 
Fig. 259.-Basal-cell Epithelioma of Antrum. 450 
TUMORS 
The adenoma (Fig. 260) is a tumor of glandular epithelium, in which 
epithelium and connective tissue grow coordinately. Hence, the relative 
proportion of parenchyma and stroma corresponds approximately to that 
characteristic of the organ from which the neoplasm is derived, and the 
ADENOMA. 
Fig. 260.-Adenoma of Mamma. 
Fig. 261.-Intracanalicvlar Fibroadenoma of Breast. 
adenoma is accordingly included by some writers1 among the fibroepi- 
thelial tumors, in distinction to the carcinoma, where the epithelium 
forms the greater part of the neoplasm. 
In still other respects does the adenoma imitate the organ in which 
it arises. There is considerable morphological resemblance between it 
* e.g., Hibbert, Geschwulstlehre, 2d ed., Bonn, 1914, p. 502. TUMORS 
451 
and the normal architecture of the part, its alveoli and ducts usually 
having a lumen and a membrana propria. The physiological task of the 
organ is also undertaken, and a more or less characteristic secretion is 
produced, which often finds no outlet, since the glands may have no 
connection with the ducts of the organ in which they are situated. 
A form of tumor which is on the border line of carcinoma and might be called adenocarcinoma. 
Fig. 262.-Adenoma of Stomach. 
Fig. 263.-Hyperplasia, of Thyroid Tissue without the Formation of Colloid. 
Often called fetal adenoma of thyroid. 
Cystic dilatation is, therefore, a common event (cystadenoma). When 
papillae grow into the cysts from their walls, a papillary cystadenoma is 
the outcome. An adenoma in which the proliferation of the connective 
tissue is more vigorous than usual is known as a fibroadenoma; this type is 
common in the breast, where it is called either intracanalicular (Fig. 261) 452 
TUMORS 
or pericanalicular fibroadenoma, according to whether the stroma com- 
presses the glands in its growth or merely surrounds them. Myxomatous 
degeneration of the connective tissue of an adenoma sometimes occurs, 
and is particularly common in the intracanalicular fibroadenoma. 
The concept adenoma is not yet so clear as might be wished. Thus, 
there is a condition in the breast (.Schimmelbusch's disease, maladie de 
Reclus) which some authorities regard as a chronic cystic mastitis (Konig), 
others as a senile parenchymatous hyperplasia, and still others as fibro- 
cy stadenoma.1 
Fia. 264.-Sebaceous Adenoma from Skin of Forehead. 
The old term malignant adenoma is falling more and more into disuse,2 
for it is becoming increasingly evident that in tumors which would pre- 
viously have been described by this term the histological signs of malig- 
nancy are almost always to be discovered when they are carefully sought 
(Fig. 262).3 
'For extensive descriptions of this condition, see Berka, Zieglers Beitr., 1912, liii, 2S4 (bibl.); 
Greenough and Hartwell, Jour. Med. Research, 1903, N. S. iv, 416 (bibl.). 
2». Hansemann, Virchows Arch., 1900, clxi, 453; for a discussion of the opposite side of the ques- 
tion see Selherg, ibid., 1900, clx, 552 (bibl.). 
3 See, for example, Eggel, Zieglers Beitr., 1901, xxx, 506. 453 
TUMORS 
Adenomata occur in the mamma, ovary, liver, kidney, adrenal, in 
the thyroid (Fig. 263), salivary, and lachrymal glands, and in the car- 
uncle; in the mucous membrane of the nose, pharynx, stomach, and intes- 
tine,1 and uterus, and occasionally in the sebaceous (Fig. 264) and sweat 
glands.2 
Epithelial Tumors-Malignant. 
CARCINOMA. 
A carcinoma is a malignant neoplasm of epithelial origin. The normal 
arrangement characteristic of the cells from which the growth develops 
is abandoned, and such a tumor often consists chiefly of a chaotic mass 
of vigorously proliferating cells. Frequently, however, there is more or 
less imitation of the architecture of the organ involved, though this is 
hardly ever so complete as in the adenomata. The conditions among the 
epithelial new growths are similar to those obtaining in the connective- 
tissue series, and it is possible to build up a complete scale, beginning 
with the carcinoma which consists of a mere mass of cells; continuing 
with that which shows some approach to the normal structure; passing 
thence to the adenoma, where the architecture of the part is more or less 
faithfully copied; and ending, finally with the normal organ. 
As with the connective-tissue neoplasms, also, the less differentiated 
carcinoma is apt to be the most malignant. 
Carcinoma is a common disease, destroying more than 80,000 people 
annually in the United States alone.3 Though most of these persons are 
in the cancer age (i.e., have passed the age of thirty-five), cancer being 
ten times as frequent at seventy as at thirty,4 the impression is far too 
common that carcinoma never occurs in young people. It does, and not 
so rarely either;5 and having occurred, is much more malignant than in 
older patients. 
But though cancer is most common in those over thirty-five, the rate 
of incidence does not seem to increase indefinitely with advancing years; 
on the contrary, the curve appears to reach its height at about 60 to 70 
and then to decline,6 at least in the case of some of the organs.7 Addi- 
tional evidence on this point is necessary, however, before any dogmatic 
statement can be made, for the large number of deaths among the aged 
certified in some such indefinite way as " senile debility," may cover a 
number of cases of cancer. 
'Verse, Arb. a. d. path. Inst. z. Leipzig, 1908, i, 1. 
2 Landsteiner, Zieglers Beitr., 1906, xxxix, 316 (bibl.). 
3 Hoffman, The Mortality from Cancer throughout the World, Newark, 1915, p. vii. 
Among other studies, with extensive bibliographies, are those of Riechelmann, Berl. klin. 
Wchnschr., 1902, xxxix, 728; and Redlich, Ztschr. f. Krebsforsch., 1907, v, 261. 
'Bashford and Murray, Second Sci. Report, Imperial Cancer Research Fund, London, 1905, part 
1, p. 33. 
6 Roger Williams, The Natural History of Cancer, New York, 1908, p. 327; Bruning and Schwalbe, 
Handb. d. allg. Path. d. Kindesalters, Wiesbaden, 1912, i, erste Abt., p. 420; Lindemann, Ztschr. f. 
Krebsforsch., 1909, vii, 682; Warthin, Arch. Int. Med., 1915, xv, 444. 
6 Roger Williams, The Natural History of Cancer, New York, 1908, p. 319; Wolff, Die Lehre d. 
Krebskrankh., Jena, 1913, Teil iii, erste Abt., p. 89. 
1 Bashford, Deutsch, med. Wchnschr., 1913, xxxix, 4. 454 
TUMORS 
When the curve of the incidence of carcinoma is compared with that 
of sarcoma,1 it is found that both rise for a time as age advances and then 
fall; but whereas the decline in the case of the curve for carcinoma sets 
in at 60 to 70, that for sarcoma begins at about 50. 
More cases of carcinoma occur in women than in men, but only be- 
cause the breast and the genital tract are so commonly attacked in the 
female. When cancer in these localities is subtracted from the total, the 
disease is found to be somewhat more common in men. In both sexes 
the gastro-intestinal canal furnishes a large proportion of cases; thus, in 
the United States in 1914, 37.9 per cent, of deaths from cancer were 
brought about by cancer of the stomach and liver, and 15.6 per cent, by 
cancer of the female genital organs.2 
Colored persons appear to be less susceptible to cancer than white.3 
Such cell masses are liable to be detached and carried along the vessel, forming metastases. 
Fig. 265.-A Growth of Carcinoma Cells in a Lymph-vessel near a Tumor. 
Multiple carcinomata (as well as multiple tumors of other varieties) 
occur in a small percentage of cases.4 
Very rarely a carcinoma undergoes spontaneous cure.5 
The carcinoma is prone to extension, usually by way of the lym- 
phatics, through which the advancing tumor cells at the periphery make 
their way. Masses of these elements (Fig. 265) distend and grow along 
the lymph-channels (lymphatic permeation^ or detached cells or groups 
of cells may be swept along them to lodge in the adjoining lymph-nodes, 
where secondary nodules then develop (Fig. 266). On free surfaces the 
engorged lymphatics appear to the naked eye in form of a whitish 
elevated network; transverse sections of such channels are shown in Fig. 
267 and 442. 
Ulceration of a carcinoma permits the entrance of microorganisms, 
which set up more or less inflammation by which the regional lymph- 
1 Weller, Arch. Int. Med., 1915, xv, 518. See also other references on p. 427. 
2 Mortality from Cancer, etc., 1914, p. 15. Published by the Department of Commerce, Bureau of 
the Census, Sam. L. Rogers, Director of the Census. A similar preponderance is shown also by the 
Annual Reports of the Registrar-General of England. 
3 Mortality from Cancer, etc., 1914, p. 15. Published by the Department of Commerce, Bureau 
of the Census, Sam. L. Rogers, Director of the Census. 
• Warthin, Jour. Am. Med. Assn., 1899, xxxii, 963 (bibi.); i>. Hansemann, Ztschr. f. Krebsforsch., 
1904, i, 483; Redlich, ibid., 1907, v, 285; Goetze, i bid., 1913, xiii, 281; Gade, Jdur. Cancer Research, 
1918, iii, 107; Theilhaber and Edelberg, Deutsch. Ztschr. f. Chir., 1912, cxvii, 457. 
6 Theilhaber and Edelberg, Ztschr. f. Krebsforsch., 1913, xiii, 461; Rohdenburg, Jour. Cancer Research, 
1918, iii, 193 (bibl ). 
6 Handley, Cancer of the Breast, London, 1906, p. 56 ff. TUMORS 
455 
nodes are usually involved. The endothelial hyperplasia (Fig. 301) which 
may thus be brought about may be mistaken for metastases, as the des- 
quamated endothelium may appear to a careless observer to be groups 
of cancer cells. 
Fhe primary tumor was in the vagina. The section shows at the right a small epithelial pearl. 
Fig. 266.-Metastatic Carcinoma (Epithelioma) in a Lymph-node. 
The primary tumor was in the liver. The subpleural lymphatics are widely distended with the tumor- 
cell masses. 
Fig. 267.-Metastatic Carcinoma in Lymph-vessels of the Pleura. 
The parenchymal cells of a carcinoma are all descendants of the cell 
or cells in which the tumor started, and while they may closely resemble 
the type from which they are derived, they frequently differ considerably 
in appearance, owing to the vicissitudes of pressure, nutrition, functional 456 
performance, etc. A great practical difficulty in the description, and, to 
beginners, in the recognition of the carcinomata and their varieties, lies 
in the great diversity of shape which their elements present. It should 
be always borne in mind that while the form of any cell does depend in 
part upon inherited growth tendencies, it is influenced also, and perhaps 
even in a greater degree, by the varying conditions of nutriment and 
pressure to which the cell is subjected during life. In the normal body 
these conditions conform to a certain standard, so that all cells of any one 
variety are approximately similar at a given stage of development. In 
tumors, however, the lawlessness of growth is such that many cells may 
be still immature, while even adult elements may depart widely from 
TUMORS 
Fig. 268.-Epithelioma of the Cervix Uteri, Giant-cell Type. 
their normal morphology. Thus, in a cylindrical-cell carcinoma, for 
example, there will be found many elements not yet fully developed and, 
like any other young cell, quite indifferent in form, as well as more mature 
elements which have never assumed the cylindrical shape. 
Another source of confusion is introduced by inflammatory processes, 
which may give rise to young connective-tissue cells that are not to be 
distinguished individually from atypical epithelium. 
Finally, carcinomata growing in loose tissue like a granulating cervix 
uteri, are particularly apt to contain cells of widely varying size and out- 
line, owing to the absence of pressure. Even giant1 cells may be found 
(Fig. 268). 
Thus there is no morphologically typical cancer cell, as there was 
formerly supposed to be. Some are characteristic of their site of origin 
and some not; and while the more characteristic may resemble normal 
1 Delaware and Lecbne, Arch. d. mfid. expfir., 1906, xviii, 102. TUMORS 
457 
epithelium, the atypical may look like young connective-tissue cells or 
even like lymphocytes. It is from the topography and situation of the 
growth, therefore, together with the general character of its cells, that 
its nature must be determined. 
Mitotic figures (Fig. 269) are usually more abundant in carcinomata 
and other malignant growths than in benign tumors and inflammatory 
processes, and such evidences of rapid proliferation can hardly be thrown 
out of court in determining the nature of a doubtful lesion. On the other 
hand, the rule is to be used with some caution. It would perhaps be 
unwise to attempt to measure the degree of malignancy by the number of 
mitotic figures,1 for only a small portion of any neoplasm is examined by 
the pathologist in most cases, and there is no question that different 
parts of a tumor may at the same time proliferate at different rates. 
Close observation of the growth rate of tumors so situated that their 
dimensions can be accurately determined, shows, finally, that periods 
Fig. 269.-Mitoses in Carcinoma. 
of rapid increase alternate 'with stationary or even recessive phases. 
This fact, by the way, has often led to serious error in estimations of the 
supposed therapeutic effects of so-called cancer cures. 
Carcinomata are liable to fatty, gelatinous, mucous, and amyloid 
degeneration, and are especially prone to ulceration (Fig. 270), hemor- 
rhage, and inflammation (Fig. 271). They may become partially cal- 
cified and are not infrequently combined with other forms of tissue in the 
mixed tumors. 
When carcinomata, or other primary or secondary malignant growths, 
encroach in their proliferation upon adjacent tissues, they bring about 
more or less destruction, either by pressure atrophy or by lysis. It 
frequently occurs that their cells are apposed to, or even infiltrate, struc- 
tures similar to those in which the tumor originates, so that one may see 
malignant and non-malignant tissue growing side by side and presenting 
an almost identical appearance.2 The cells adjacent to the neoplasm 
may also show evidence of proliferation in mitotic figures. These .two 
features, contiguity and mitosis, have led many observers3 to the con- 
1 McConnell, Jour. Am. Med. Assn., 1908, li, 910. 
2Rous, Jour. Exper. Med., 1911, xiii, 239. 
3e.g., Hauser, Zieglers Beitr., 1897, xxii, 587. 458 
TUMORS 
This tumor is of the epitheliomatous type and presents a large, rough, ulcerated surface. 
Fig. 270.-Carcinoma of Hand. 
Fig. 271.-Exudative Inflammation in Carcinoma. 
Showing leucocytes in the stroma and in the epithelium. The epithelium is disintegrating, and in 
the small region shown in the cut the leucocytes are apparently acting as phagocytes in the softening 
and removal of the disintegrating epithelium. TUMORS 
459 
elusion that the tissue adjoining a growing tumor may assume exalted 
powers of proliferation and share in the growth of the neoplasm, of which 
it may frequently become a part. But this view is erroneous, and the 
student of oncology should constantly remember that the characteristic 
cells of a new growth are the direct descendants of these elements in which 
it started, and that a neoplasm grows only by the proliferation of its 
own cells. It does not spread by successive waves of "cancerous 
degeneration." 
Forms of Carcinoma 
The cells of certain carcinomata of the skin and mucous mem- 
branes, imitating the type of epithelium from which they arise, are apt to 
become flattened or squamous as they grow older; these tumors are called 
squamous- or flat-cell carcinomata, or simply epitheliomata. In another 
class of growths, such as frequently attack the gastrointestinal canal 
and the uterus, the cells are more or less cylindrical in shape, forming a 
palisade-like lining to the irregular alveoli; such neoplasms are called 
cylindrical-cell carcinomata. There is a third and very common form 
often derived from cuboidal epithelium, in which the cells have no con- 
stant characteristic shape, but vary as much as do elements of the various 
glands throughout the body. Such tumors are sometimes called carcin- 
oma simplex. A carcinoma which contains an abundant supply of blood- 
vessels is called a carcinoma telangiectaides. 
Fig. 272.-Fibbocabcinoma ok Cabcinoma Dubum (Scibbhous Cabcinoma). 
Perhaps somewhat more useful than this purely morphological classi- 
fication is that which divides carcinomata, according to the site of their 
origin, into epidermal and glandular carcinomata. 
A third method of subdivision is based upon the quantitative relations 
between parenchyma and stroma. A carcinoma consisting almost 
entirely of parenchyma is called a medullary or encephaloid carcinoma, 
or carcinoma molle (Fig. 253); one with approximately equal amounts of 
parenchyma and stroma is a carcinoma simplex; while one in which the 
stroma distinctly preponderates is known as a scirrhous carcinoma or 
simply as a scirrhus (Fig. 272). The first type, as a rule, is perhaps even 
more malignant than the last. While in the scirrhous variety the stroma 
may become so dense as nearly to obliterate the epithelium, it is very 460 
TUMORS 
doubtful if any considerable area ever undergoes spontaneous cure in this 
way. 
In addition to the varieties already mentioned there are several others, 
which depend for their characteristics on various degenerations and 
metamorphoses, such as gelatinous carcinoma (Fig. 273), melanocarcinoma 
(page 467), etc. 
It will be most advantageous to give a brief description of the various 
kinds one after another, with the understanding that they are not specific 
forms, but simply varieties which it is convenient to recognize for clinical 
and anatomical purposes; and that few tumors, in any case, offer an 
entirely pure example of any one type. 
Fig. 273.-Carcinoma Gelatinosum-Colloid Cancer. 
From a tumor of the stomach. 
Epithelioma {Cancroid}.-New growths of this class occur in the skin, 
and in the mucous membranes which are covered with squamous epithe- 
lium, their cells presenting all the various forms which normally exist in 
these parts. 
In order to understand their manifold appearance under the micro- 
scope, the structure and functional characters of the normal skin should 
be borne in mind. The epithelium rests upon connective tissue, the corium 
or true skin, from which its nutriment is derived. The cells of its deeper 
layers, the rete Malpighii, are cuboidal and polyhedral; over these lie 
several layers of more or less flattened elements, while upon the surface 
the cells are scaly and keratinized. The typical epithelial cell is the 
prickle cell or spine cell, joined to its neighbors by intercellular bridges. 
The various forms of cell in squamous epithelium represent regular 
phases of development, as the younger and larger cells underneath are 
pressed outward to flatten and finally desquamate. In epitheliomata, 
the cells have in a measure the same life history, though as they are no 
longer growing on a flat surface, but in inclosed spaces, they become 
packed into masses where the older elements are forced toward the centers. 
So there is formed at length a number of groups of concentrically arranged 
elements {epithelial pearls, Fig. 274). It is important to remember, how- 
ever, that these are not characteristic of the epitheliomata, for any con- TUMORS 
461 
dition which involves the growth of squamous epithelium into limited 
spaces may result in their formation. They are of value only because 
they may clear up the origin of a doubtful tumor, for while they do not 
in any sense prove that the lesion in which they are found is a true neo- 
This metastatic tumor was secondary to a large epithelioma of the back of the hand. The small 
cells with darker nuclei are the cells of the lymph-node. It shows the epithelial pearls in various stages 
of formation. 
Fig. 274.-Epithelioma of Axillary Lymph-node. 
Fig. 275.-Epithelioma of Skin. 
plasm, they do suggest that any tumor in which they are discovered 
has originated in surface epithelium. They suggest this, but do not 
prove it, for in certain rather rare cases other neoplasms (of the mamma, 
the body of the uterus, or the gall-bladder, for example) may contain 
Showing reticular masses of epithelial cells with fibrous stroma. 462 
TUMORS 
squamous epithelium;1 whether this is the outcome of metaplasia, or of 
the presence of embryonal cell rests, is not known. The demonstration 
of prickle cells in a growth is of equal value. 
The alveoli of an epithelioma may be large or small, and separated 
by abundant or scanty stroma; except in incipient tumors they form a 
reticular mass (Fig. 275) which infiltrates the tissues more and more 
deeply; at the same time the tumor may project above the surface in the 
form of a papillary growth. Ulceration (Fig. 270) is common and the 
surrounding skin is apt to become thickened (Fig. 276). It is this thick- 
ening of the skin and its elevation by the burrowing tumor that confers 
Fig. 276.-Epithelioma of Back of Hand. 
The flat tumor occupied nearly the entire back of the hand, and was ulcerating at the surface. The 
figure shows the edge of the tumor and a portion of the ulcer. The papillae of the skin over the edge of 
the growth are hypertrophied, and the tissue about is infiltrated with small spheroidal cells. Fig. 274 
shows a section from a metastatic tumor of the axillary lymph-node in this case. This tumor presented 
the gross appearance shown in the photographic reproduction in Fig. 270. 
upon ulcerating epitheliomata, especially those of the mucous membranes 
the characteristic pearly overhanging edge that distinguishes them from 
tuberculous and syphilitic ulcers. 
Epitheliomata are apt to occur at a mucocutaneous junction (lips, 
nostrils, eyelids, labia, and glans penis), and are frequent also in the 
mouth, esophagus, vagina, and the cervix uteri; they sometimes develop 
in naevi. 
Under the name basal-cell carcinoma a group of tumors (Fig. 277, 
and 278) has been described,2 which differ both clinically and histologic- 
ally from other carcinomata. These do not arise at a mucocutaneous 
junction, but at certain characteristic sites like the temple, forehead, 
cheek, and nose; as a general rule it may be said that a carcinoma of 
the face above the line of the upper lip will prove to be a basal-cell 
carcinoma; below that level, a squamous-cell carcinoma. The basal- 
cell carcinoma occurs in old people in the form of an ulcer {rodent ulcer, 
1 Herxheimer, Zieglers Beitr., 1907, xli, 348 (bibl.); Lubarsch, Verhand], d. deutsch. path. Gesellsch. 
1906, x, 198, 208. 
2 Krom pecker, Der Bazalzellenkrebs, Jena, 1903; Zieglers Beitr., 1905, xliv, 51 and 88. TUMORS 
463 
Jacob's ulcer), which often persists for years and almost never metas- 
tasizes. It is, in fact, the most benign of all the malignant neoplasms 
and one which can readily be cured by excision or by the application of 
carbon dioxide snow, x-ray, or radium. Histologically the growth is 
Fig. 277.-Basal-cell Carcinoma; Metastasis in the Muscle of Abdominal Wall 
The stroma is extremely edematous and contains very few cells. 
composed of cells resembling those of the basal layer of the skin in their 
lack of differentiation; that is, of small oval or spindle-shaped elements 
with deeply staining nuclei and cell bodies, no spinous process, and no 
tendency toward keratinization; a gyrate or glandular arrangement is 
Fig. 278.-Small Superficial Basal-cell Carcinoma of the Face. 
sometimes evident. The rather uncommon tumors of this class in which 
keratin is present (Fig. 279) are regarded as transition forms between 
the basal-cell and the squamous-cell carcinomata. Though the most 464 
TUMORS 
characteristic site of the basal-cell carcinoma is the face, these growths 
may arise from any squamous epithelial surface or from glands opening 
upon such a surface. 
Not all authorities agree with the ideas of Krompecher, briefly re- 
produced in the preceding paragraph. Thus, since its cells resemble 
Fig. 279.-Basal-cell Carcinoma Containing Keratinized Areas. 
Several of these areas can be seen in the lower right-hand corner of the cut. 
those of hair follicles and sebaceous glands, the basal-cell carcinoma has 
been said to arise in these structures and has been called trichocarcinoma 
(Fig. 280) or adenogenous carcinoma;1 and since the growth often has no 
connection with the surface epithelium, it has been asserted that the 
1 Ribbert, Dag Karzinom des Menschen, Bonn, 1911, p. 51, 465 
TUMORS 
basal-cell carcinoma originates from epithelial remnants in the true skin, 
and it has on this account been called corium carcinoma.1 
Differential Diagnosis.-The spindle shape of their cells gives 
these growths a certain superficial resemblance to the sarcoma, from which 
they can usually be distinguished, however, by the possession of such 
characteristics as: the uniform size and shape of the cell bodies and nuclei, 
the affinity of both for basic dyes, a gyrate or glandular arrangement, a 
paucity of mitoses, and, finally, a history of comparative benignancy. 
Fig. 280,-Trichocarcinoma from Cheek. 
The mixed tumors of salivary glands previously referred to (page 443) 
are regarded by some observers as basal-cell carcinomata.2 
Cylindrical-cell Carcinomata.-These tumors, sometimes distinguished 
with difficulty from the adenoma (Fig. 262), occur in the stomach, intes- 
tine, and uterus. The cells are loosely or closely packed in larger or 
smaller alveoli which are separated from one another by a stroma more or 
less dense. These growths merge imperceptibly into the next class. 
Carcinoma Simplex.-Neoplasms of this variety, by far the most 
frequent of the carcinomata of internal parts, are characterized by 
irregular, anastomosing alveoli, sometimes solid, sometimes containing 
spaces which recall the lumina of glands, and inclosed by a more or less 
abundant fibrillar stroma approximating the parenchyma in amount. 
The epithelial cells may or may not resemble the epithelium of the gland 
in which the growth originates; they have no uniform shape, but may be 
1 Borrmann, Ztschr. f. Krebsforsch., 1904, ii, 1; 1906, iv, 91. 
2 Krompecher, Zieglers Beitr., 1908, xliv, 51. 466 
TUMORS 
Fig. 281.-Carcinoma of Mamma. 
Showing fused cells producing appearance resembling syncytium 
Fig. 282.-Gelatinous Carcinoma of Mamma (Carcinoma Myxomatodes.) 
Of ten years' duration without metastasis. TUMORS 
467 
cuboidal, polyhedral, spheroidal, or fusiform, and are often so merged 
that they resemble a nucleated mass of cytoplasm (a syncytium) rather 
than an aggregate of individual cells (Fig. 281). 
Gelatinous Carcinoma.-In the cells of certain carcinomata, especially 
of the gastrointestinal canal, a translucent, gelatinous material (mucin) 
may collect, but whether it appears as the result of secretory activity or 
of degeneration is not known. Such tumors have been called colloid 
cancers, though the material which characterizes them is not true colloid. 
In some cases the amount of mucin is only moderate, the cells containing 
more or less of it in the form of translucent droplets; but in others large 
areas of the parenchyma are partially or entirely destroyed and re- 
placed by mucin (Fig. 273). Sometimes only part of a tumor undergoes 
gelatinous transformation. 
The stroma of a carcinoma may be the seat of myxomatous degenera- 
tion (carcinoma myxomatodes,1 Fig. 282) like that seen in sarcomata or 
in the connective-tissue constituent of fibroadenomata of the breast. 
Melanocarcinoma.-Tumors of this sort, which are distinctly rare, 
are characterized by the presence of variable quantities of black or brown 
pigment granules in the parenchyma (Plate II, Fig. 1). They are 
usually soft and malignant, and occur most frequently in the skin (see 
page 433). One has been recorded which contained keratin, establishing 
its epithelia nature.2 
Bibliography of Tumors. 
An extensive and important work on tumors, containing a vast store 
of information, is Rudolf Virchow's Die krankhaften Geschwiilste, 
Berlin, 1863; it is old and is not complete, but is still invaluable as a work 
of reference. An admirable review of the whole subject has been pre- 
pared by Wolff: Die Lehre von der Krebskrankheit, Jena, 1914. A very 
useful bibliography will be found in Ziegler's Lehrbuch der allgemeinen 
Pathologic, Band I, Jena, 1905. An important resume on the malignant 
tumors in childhood, by Stern, may be found in the Deutsch, med. 
Wchnschr., 1892, p. 494, and another, by Merkel, in Bruning and 
Schwalbe's Handbuch der allgemeinen Pathologic des Kindesalters, 
Wiesbaden, 1912. Current additions to the subject may be found in the 
files of Lubarsch and Ostertag's Ergebnisse der allgemeinen Pathologic; 
see particularly Lubarsch, 1895, i2, 289; and 1899, vi, 952; Aschoff, 1898, 
v, 73; Fisher and others, 1904-05, x, 643; and Herxheimer and Reinke, 
1913, xvi2, 1; Borst's Die Lehre von den Geschwiilsten, Wiesbaden, 1902, 
is a valuable work with many excellent illustrations and a bibliography, as 
is also Ribbert's Geschwiilstlehre, 2d ed., Bonn, 1914. Other oncological 
monographs are Ribbert's Das Karzinom des Menschen, Bonn, 1911; 
Williams' Natural History of Cancer, New York, 1908; Behla's Carcinom- 
litteratur, Berlin, 1901; Contamin's Cancer experimentale, Paris, 1910; 
1 For a discussion of this and the preceding type of carcinoma, see Ribbert, Das Karzinom des 
Menschen, Bonn, 1911. 
2 Beckey, Frankfurt. Ztschr. f. Path., 1915, xvii, 364 (bibl.). 468 
TUMORS 
Menetrier's Cancer, Paris, 1909; Thomas's Cancer, Paris, 1910; Roffo's 
Cancer experimental, Buenos Aires, 1914; Bland-Sutton's Tumors Inno- 
cent and Malignant, New York, 1917; v. Hansemann's Atlas der bosarti- 
gen Geschwiilste, Berlin, 1910; Cullen's Cancer of the Uterus, New York, 
1900; White's Pathology of Growth: Tumours, London, 1913; Kettle's 
Pathology of Tumours, New York, 1916; Borrmann's Wachstum des 
Magencarcinoms, Jena, 1901; Adler's Primary Malignant Growths of 
the Lungs and Bronchi, New York, 1912; Bashford, Murray, and others 
in the Scientific Reports of the Imperial Cancer Research Fund, London, 
1908-12; Studies in Cancer and Allied Subjects, from the Crocker Fund, 
Columbia University, New York, 1912-13; Woglom's Study of Experi- 
mental Cancer, New York, 1913; Cornil's Tumeurs du sein, Paris, 1908; 
Henke's Praktische Anleitung zur Untersuchung von Geschwiilsten, Jena, 
1906; Clunet's Recherches experimentales sur les tumeurs malignes, Paris, 
1910; Folger, A. F., Geschwiilste bei Tieren, Lubarsch-Ostertag, Ergebn. 
d. allg. Path., 1917, xviii2, 372 (bibl.); Lockyer, C., Fibroids and Allied 
Tumors, London, 1918; Kelly, H., and Cullen, T. S., Myomata of the 
Uterus, Philadelphia, 1909; Cullen, T. S., Diseases of the Umbilicus, 
Philadelphia, 1916; Adenomyoma of the Uterus, Philadelphia, 1903. CHAPTER XII. 
THE LESIONS INDUCED BY POISONS. 
Forms of Poisons. 
A poison has been commonly considered to be a substance which 
when introduced into the body from without is capable of inducing, by 
means other than mechanical, pathological alterations of function or 
structure, or both. But this conception of poisons as extraneous pre- 
formed substances has recently been greatly modified. For it has been 
learned that poisons may be formed within the body, either through the 
action of microorganisms upon its organic constituents or through the 
metabolism of the body-cells themselves. 
It is thus convenient in considering the lesions induced in the body 
by poisons-toxic lesions-to place in one group those due to preformed 
extraneous poisons-exogenous poisons-and in another group those due 
to substances formed within the body-endogenous poisons. 
It has furthermore been found convenient to make three classes of 
the endogenous poisons: First, those which are formed under the influ- 
ence of microorganisms in the course of the infectious diseases and whose 
effects are most appropriately studied in that connection; these may be 
called endogenous poisons of infectious origin; second, those which are 
formed under the influence of microorganisms in the gastrointestinal 
canal or elsewhere and absorbed into the body fluids; third, those which 
are formed by the metabolism of the body-cells themselves. 
To endogenous poisoning induced by either of the latter two classes 
of agents the term autointoxication has been most commonly and most 
appropriately applied. 
As we have already studied the toxic lesions of the infectious diseases, 
we have only to consider here: 
First, the lesions induced by preformed or extraneous poisons- 
exogenous poisons; and second, those due to the endogenous poisons which 
are concerned in the so-called autointoxication.1 
Methods of Combating Poisons in the Body. 
The action of certain poisons, such as hydrocyanic acid, phenol 
when swallowed in large quantities, and the corrosive acids, is so rapid 
that death occurs before the body can in any way react. If, however, the 
poison is introduced slowly, the body may protect itself in various ways. 
Among these are the reflexes-holding the breath, closing the eyes, cough- 
1 The limitation of the term autointoxication as it is here used is adopted from Martius, who has 
written most clearly and suggestively upon the subject. See Martius, Pathogenese innerer K rank- 
heiten, Hefte i and ii, 1899-1900. 
469 470 
THE LESIONS INDUCED BY POISONS 
ing, and sneezing-which automatically prevent the entrance of noxious 
gases for a short time, or remove material which has entered the respira- 
tory tract. The increased secretion from the nose, eyes, and bronchi, 
is also a means by which a toxic substance is diluted and rendered rela- 
tively innocuous. When the poison has actually been taken into the 
stomach, vomiting or diarrhea frequently follows, and removes a consider- 
able portion of the substance; an example of this is the vomiting which so 
often occurs after the ingestion of corrosive sublimate. Substances 
taken by mouth are often altered in their passage through the gastro- 
intestinal tract, so that they become relatively harmless, while if they 
are injected subcutaneously or intravenously a much more serious effect 
is produced. Certain poisons when absorbed into the circulation are 
again excreted into the intestinal tract; for example, morphine and the 
heavy metals. It has been shown, for instance, in connection with corro- 
sive sublimate poisoning, that continuous washing of the stomach and 
bowel will remove a large proportion of the toxic substance in the course 
of a few days and often permit recovery, which does not occur if the 
patient is left alone. Certain soluble salts are altered in the body into 
insoluble material; for instance, silver nitrate is altered into silver 
chloride or sulphide and is phagocyted by the action of the tissue cells 
and the leucocytes. 
When dilute mineral acids are taken into the body or when acid pro- 
duction occurs in the course of certain diseases, such as diabetes, neutrali- 
zation of the acid takes place by the surrender of alkaline radicals to 
form neutral salts with the intruding acid. Such a process does not alter 
the reaction of the blood unless large amounts of acid are formed; it is 
the fixed alkalies and the ammonia ordinarily going to the synthesis of 
urea that are combined with the acids and excreted in the urine. 
Certain volatile poisons, like alcohol, ether, and chloroform, are 
removed through the breath; alcohol is oxidized, also, in the tissues. 
Some of the organic poisons, such as phenol, chloral, morphine, and 
similar bodies, are rendered innocuous by combination with either sul- 
phuric acid to form complex sulphates, or glycuronic acid to form gly- 
curonates. More complex examples of neutralization of poisons by 
adaptation of the physiological capacities of the body have been spoken 
of in previous chapters on immunity, in which the processes of immunity 
to or neutralization of proteins and toxins have been set forth in some 
detail. 
While a certain toleration of alkaloids, such as morphine, is noted, 
there is no evidence of the production of antibodies against any sub- 
stance that is not protein in nature. The existence of a tolerance to 
arsenic, said to be exhibited by certain races, has been shown to be ex- 
tremely doubtful. 
The adaptation of trypanosomes to arsenic preparations is not a true 
immunity, but rather an evolutionary process by which all of the organ- 
isms susceptible to the toxic substance die off and only those survive 
which by some means are able to escape injury, a resistant race thus 
being produced. THE LESIONS INDUCED BY POISONS 
471 
The Lesions Induced by Exogenous Poisons.1 
Sulphuric Acid. 
The effects of this poison vary with the amount taken and with its strength. 
Death usually occurs in from two to twenty-four hours after the ingestion of the con- 
centrated acid. A case of death within an hour is recorded. When the poison is less 
concentrated or its effects are less intense, the patient may survive for months. 
The skin of the face about the mouth may be blackened and charred by the acid. 
The mouth and pharynx are of a grayish or blackish color, or are covered with a 
whitish layer, while the deeper tissues are reddened. Sometimes these regions escape 
the action of the poison. 
The larynx, trachea, and lungs are sometimes softened and blackened by the acciden- 
tal passage of the acid into them. This may take place even when the acid does not 
pass into the esophagus. 
The esophagus seldom escapes. It is colored grayish or blackish, softened, and 
the mucous membrane comes off in shreds. If life is prolonged, cicatrices and stric- 
tures are formed. The stomach may contain a blackish, pulpy fluid, due to the action 
of the acid on mucus, blood, etc. It is coated on its internal surface with a black, 
sticky layer, beneath which the mucous membrane is reddened. The mucous mem- 
brane may be blackened in patches or stripes. The organ may be contracted and the 
mucous membrane corrugated. Sometimes perforation takes place and the acid 
blackens and softens the adjoining viscera. In protracted cases cicatrices are formed 
and the organ is contracted. If the poison is dilute there may be only the lesions of 
chronic gastritis. 
The Hood is sometimes thickened and syrupy, and may form thrombi in the 
vessels. 
Fatty degeneration of the renal epithelium is mentioned by some authors. 
The body may be partially preserved from decomposition, owing to the action of 
the acid upon the tissues. 
The solution of indigo in sulphuric acid, commonly known as sulphate of indigo, 
produces the same lesions as sulphuric acid, and also stains the tissues with which it 
comes in contact a dark-blue color. It is stated that an indigo-blue tint is often 
found in the mucous membranes after poisoning by pure sulphuric acid. 
Death may occur very soon after the taking of the poison, but is not usual until 
the lapse of several hours, and may not ensue for several days or weeks. 
The surface of the mucous membrane of the mouth, pharynx, and esophagus is 
covered with yellow eschars wherever the acid has touched it. Beneath and around 
the eschars the tissues are congested and red. The stomach contains a viscous, san- 
guinolent, yellow or greenish fluid. The mucous membrane is congested, red, swollen, 
softened, and ecchymotic. It is rarely perforated. The duodenum may be inflamed, 
and the inflammation extend to its peritoneal coat. The rest of the intestines usually 
escapes the action of the acid. The larynx is very frequently acted on by the acid. 
There are yellow eschars, congestion and swelling of the mucous membrane, sometimes 
edema of the glottis. The trachea may be inflamed and the lungs congested. If the 
patient survive the first effects of the poison, chronic inflammation, cicatrization, and 
contraction may occur. If the fumes resulting from the action of the strong acid on 
organic material are inhaled, a subacute or chronic pneumonia may be caused, which 
is very often fatal (see page 698).2 
Such poisoning is now exceedingly common in munition works in the process of 
producing nitrocellulose for smokeless powder by treating cotton or other vegetable 
material with mixtures of strong nitric and sulphuric acids.3 If the temperature 
rises beyond a certain point large quantities of fumes of nitric oxide are formed. 
Nitric Acid. 
1 For special precautions to be taken in the post-mortem examination in cases of suspected poison- 
ing see p. 1222. 
2 See Wood, Poisoning by Nitric Oxide Fumes, Arch. Int. Med., 1912, x, 478 (bibl.). 
3 Hamilton, A., Jour, Am. Med. Assn., 1917, Ixviii, 1445. 472 
THE LESIONS INDUCED BY POISONS 
The fumes erode the mucous membrane of the bronchi and cause the formation of an 
exudate in the alveoli with desquamation of the alveolar epithelium. Edema of the 
smaller bronchi is so extensive that dyspnea is very intense, and blood frequently 
appears in the sputum. When large quantities are inhaled, death may ensue in a 
few hours; usually, however, the victim survives for four or five days during which 
time interstitial pneumonia with organization of connective tissue and obliteration 
of the smaller bronchi may occur. Death may be due to a terminal pulmonary 
edema. If the intoxication is not extreme, the patient may survive, though the 
lungs usually remain extremely sensitive to light infections, and chronic bronchitis 
and a tendency to hemoptysis may persist for years. 
Similar lesions are caused by the inhalation of chlorine gas, which has been exten- 
sively used in the present war, bromine, ammonia, and other corrosive chemical 
irritants, including the so-called "mustard gas." 
Mustard Gas. 
The toxic effect of dichlorodiethylsulphide, ' ' mustard gas, ' ' which acts as an eschar- 
otic on the skin with the production of deep chronic ulcers, is apparently dependent 
upon its chlorine content. Like other irritating gases, after inhalation mustard gas 
induces a chemical pneumonia. The pneumonia rarely develops in less than thirty- 
six hours after exposure, but an acute conjunctivitis is noticed to occur not infre- 
quently in a few hours. Should the patient recover from the acute effects, the inter- 
stitial pneumonia which remains very often gives rise to hemoptysis and dyspnea 
on very slight exertion.1 
Hydrochloric Acid. 
In fatal cases death occurs on the average in about twenty-four hours. The lesions 
are in general similar to those produced by sulphuric and nitric acids, except that the 
eschars are usually of a whitish color at first, becoming, after a time, discolored and 
disintegrated. It is also more common to find false membranes on the inflamed 
surfaces. 
In fatal cases death may occur within ten minutes (in one case it occurred in three 
minutes) or it may be delayed for two or three weeks. The period of death does not 
depend, as do in general the symptoms, upon the amount and concentration of the 
poison. 
The mucous membrane of the mouth, pharynx, and esophagus is usually white and 
shrivelled, and easily peeled off, and may be covered with brownish vomit from the 
stomach. The esophagus may be much contracted. The stomach is usually contracted 
and contains a dark-brown, acid, mucous fluid. The mucous membrane of the 
stomach may be pale, soft, and easily detached, sometimes looking as if it had been 
boiled in water. Sometimes it is red and congested; sometimes blackened and gan- 
grenous; sometimes peeled off in patches. Perforation is of rare occurrence. If life 
is prolonged the whitened condition of the mucous membrane is succeeded by con- 
gestion and inflammation. The small intestines may be inflamed. Inflammation of 
the pleura and peritoneum, and congestion of the lungs are of occasional occurrence. 
In some cases of death from oxalic acid there are no well-marked lesions. 
Potassium oxalate produces the same lesions as oxalic acid. 
Oxalic Acid. 
Tartaric Acid. 
This acid is seldom used as a poison, but in large doses may prove fatal. The 
lesions in the cases observed were redness and inflammation of the mucous membrane 
of the gastrointestinal canal. The alkaline salts of tartaric acid have been shown2 
to cause a very active nephritic lesion when sufficient quantities are ingested. 
1 For description of skin lesions due to mustard gas, see Warthin, A. S., and Weller, C. V., Jour. Lab. 
and Clin. Med., 1918, iii, 447 (bibl. of reports of lesions other than those of the skin is appended). See, 
also, Nature, 1918, ci, 215. 
2 Underhill, We/Zs, and Goldschmidt, Jour. Exper. Med., 1913, xviii, 322; Karsner, H.T., Jour. 
Pharmacol, and Exper. Therap., 1917, ix, 483 (bibl.). THE LESIONS INDUCED BY POISONS 
473 
Potash, Soda, and their Carbonates. 
These substances are not commonly used as poisons with suicidal or homicidal 
intent, but may be taken by mistake. They may cause death in a few hours, or life 
may be prolonged for several weeks. 
The mucous membrane of the mouth, pharynx, esophagus, and stomach is softened, 
swollen, congested, and inflamed, or may be peeled off. It may be blackened from 
local changes in the blood. The mucous membrane of the larynx and trachea may also 
be swollen and inflamed. 
If life is prolonged for some time, cicatrices and strictures of the esophagus and 
stomach are apt to be produced as a result of the reparative inflammation. 
Ammonia. 
The vapor of strong ammonia may cause death from inflammation of the larynx 
and air passages. The strong solution of ammonia produces lesions similar to those of 
potash and soda. The larynx, trachea, and bronchi are frequently inflamed, and may 
be covered with false membranes. Fatal inflammation of the rectum and colon has 
been produced by an enema of strong solution of ammonia. 
Potassium Nitrate. 
Accidental poisoning sometimes occurs from large doses of this salt. From 8 to 
30 grams have been shown to cause death. In the observed cases there were intense 
congestion and inflammation of the stomach and intestines; in one case a small perfora- 
tion of the stomach existed. 
Potassium chlorate, which is sometimes used as a mouth wash, is quite toxic and 
acts upon the blood to form methemoglobin. In cases of poisoning, jaundice is com- 
mon, and the organs often contain blood pigment. The urine may contain methemo- 
globin or hematin; the kidney tubules, casts of blood pigment. The mucous membrane 
of the stomach is thickened, hemorrhagic, and ulcerated. The spleen is very large 
and dark in color. The changes in the blood cause an extreme cyanosis. 
Bismuth Subnitrate. 
A number of cases have been described of fatal poisoning from the use of bismuth 
subnitrate in roentgenoscopic examinations of the intestinal tract. The most strik- 
ing changes are those in the blood, but there are also lesions in the kidneys.1 The 
poisoning is due not so much to the bismuth, though this affects the kidneys, as to the 
nitrous acid set free. A similar severe poisoning is produced by sodium nitrite. 
Poisoning by phosphorus is much more common in France and Germany than in 
this country. Some of the forms of rat poison, of which this is a frequent ingredient, 
and the ends of matches, are common media for its administration. It is more often 
used with suicidal than with homicidal intent. 
The post-mortem appearances vary according to the length of time which elapses 
before death, which may be from a few hours to several months. 
If death takes place in a few hours the only lesions may be those produced by the 
direct local action of the poison. The mouth, pharynx, and esophagus usually escape. 
The stomach may be only slightly reddened, or there may be patches of inflammation 
and erosion. The contents of the stomach are often mixed with blood and may have 
the characteristic smell of phosphorus. There may be little bits of wood present 
when the poison has been taken from the heads of lucifer matches. It is said that 
the mucous membrane of the stomach may emit a phosphorescent light in the dark. 
If death does not ensue until after several days the lesions are more marked. The 
body is usually jaundiced. There may be ecchymoses beneath the pericardium, 
Phosphorus. 
1 Higgins, W. H., Jour. Am. Med. Assn., 1916, Ixvi, 648 (bibl.). 474 
THE LESIONS INDUCED BY POISONS 
pleura, and peritoneum, in the lungs, the kidneys, the bladder, the uterus, the muscles, 
and the subcutaneous connective tissue, and bloody fluid in the visceral cavities. 
Chromatolysis of the ganglion cells may occur. 
The heart and voluntary muscles, the walls of the blood-vessels, and the epithelium 
of the pulmonary air vesicles may be in the condition of fatty degeneration. The 
blood is usually dark and fluid. 
The stomach sometimes presents no very striking changes. There may be small 
circumscribed spots of inflammation, erosion, or gangrene, and occasionally perfora- 
tion. The most constant change is albuminous and fatty degeneration of the cells 
which line the gastric follicles. In consequence of this the mucous membranes appear 
thickened, opaque, of white, gray, or yellow color. The small intestine appears normal 
or is congested. 
The liver is found in different degrees of albuminous and fatty degeneration, and is 
often stained yellow from the jaundice. It is usually increased in size and of a gray- 
ish-yellow or light-yellow color, unless stained by the bile. Less frequently the centers 
of the acini are congested, or the entire liver is congested, or there are small hemor- 
rhages in the liver tissue. The liver may be soft, flabby, and smaller than normal. 
In the interstitial tissue of the liver and along the branches of the portal vein there 
may be marked infiltration with small spheroidal cells. 
The kidneys often present albuminous and fatty degeneration of the epithelium. 
The mesenteric lymph-nodes may be soft and swollen from hyperplasia. 
Long-continued absorption of phosphorus often leads to an extensive necrosis of 
the inferior maxilla with a secondary productive or suppurative periostitis. Those 
with defective teeth are most apt to be affected. The condition is now rarely seen, as 
the law requires suitable protection for workers with phosphorus.1 
This poison is very frequently employed with suicidal intent. Death may occur 
in a longer or shorter time from the direct irritative effects of the poison upon the 
gastrointestinal canal, with the symptoms which usually accompany the ingestion of 
irritant poisons; or it may occur with symptoms of collapse, or coma, or shock; or the 
symptoms may resemble those of cholera. The average time of death in acute fatal 
cases is about twenty hours, but death has occurred in twenty minutes and has been 
postponed for two or three weeks. 
The mouth, pharynx, and esophagus may be inflamed, but are more frequently 
unaltered. The stomach may be empty or contain mucus mixed with blood. The 
arsenic, in substance, may be found adherent to the mucous membrane or mixed with 
the contents of the organ. It has, in rare cases, been found encysted in the stomach 
in considerable quantity. When invisible to the naked eye a microscopical examina- 
tion of the stomach contents will not infrequently reveal characteristic crystals of 
arsenious acid or some of its compounds. The stomach may be contracted and its 
mucous membrane corrugated. The entire inner surface may be red and inflamed, or 
there may be patches or streaks of inflammation or deep congestion. The inflamed 
and congested patches may be thickened and covered with false membrane mixed 
with larger and smaller particles or masses of the poison. Ulceration, perforation, and 
gangrene are rare. Blood may be extravasated into the mucosa and submucosa, and 
with the congestion give the mucous membrane a very dark-red or brown appearance. 
Frequently the mucous membrane is studded with small petechiae. Sometimes the 
arsenic is converted in the stomach into the yellow sulphide. There may be acute 
gastritis, even when the poison is absorbed by the skin or otherwise and not introduced 
into the stomach. The epithelium of the gastric glands may undergo granular and 
fatty degeneration. 
The entire length of the intestine may be congested and inflamed, but the action of 
the poison does not usually extend beyond the duodenum. In some cases the solitary 
lymph-nodules, Peyer's patches, and mesenteric nodes are swollen. Inflammation of 
the bladder and peritoneum, and congestion and edema of the brain, have been ob- 
Arsenic. 
1 Kober and Hanson, Diseases of Occupation and Vocational Hygiene, Philadelphia, 1916; Oliver, T 
Diseases of Occupation, London, 1908. THE LESIONS INDUCED BY POISONS 
475 
served, but are neither frequent nor in any way characteristic. Fatty degeneration 
of the muscles, liver, kidneys, blood-vessels, and vesicular epithelium of the lungs, and 
chromatolysis of the ganglion cells may follow arsenical poisoning. 
Alterations in the spinal cord indicative of acute myelitis have been described1 
as occurring in dogs poisoned with arsenious acid. 
The walls of the stomach and intestines and other parts of the body may be pre- 
served from decomposition for a long time after death by arsenical poisoning. 
It should always be borne in mind, in examining cases of suspected arsenical 
poisoning, that death may be produced by arsenic and its compounds without any 
appreciable lesions. While in general it may be said that in the cases in which no 
lesions are discovered death has probably occurred soon after the ingestion of the 
poison, it should be remembered that death without lesions may exceptionally take 
place long after the usual time at which inflammatory changes commence. 
Compounds of arsenic, such as the chlorid and sulphide, and the arsenite (Scheele's 
green, Paris green), are sometimes used for suicidal purposes, and produce lesions 
similar to those of arsenious acid. Paris green is a favorite article in New York, par- 
ticularly among Germans, for suicidal purposes. It is usually taken in considerable 
quantities, and is often found in the stomach after death.2 
Corrosive Sublimate. 
The mucous membrane of the mouth and throat may be swollen, inflamed, or have 
a grayish white appearance. The esophagus may be swollen and white, or congested, 
or unaltered. The mucous membrane of the stomach is usually congested or inflamed, 
or there may be patches of softening, ulceration, or gangrene. Perforation is of rare 
occurrence. Small ecchymoses in the mucosa are not uncommon. Sometimes there 
is little or no change in the stomach. Sometimes the mucous membrane of the stom- 
ach is slate-colored from the deposition of metallic mercury from the decomposed 
salt. The small intestine may appear normal or congested; there is usually an intense 
membranous inflammation of the lower portion of the colon. The larynx and trachea 
may be congested. 
The kidneys are congested, there is albuminous and fatty degeneration and necro- 
sis of the epithelium of the convoluted tubules and the first part of Henle's loop. 
The epithelium may desquamate and block the tubules. The glomeruli are not 
obviously involved. Calcification may follow the degeneration and necrosis of epi- 
thelium3 (Fig. 33). The mercuric salt appears to form a firm combination with the 
tissues, as it may be detected in the feces and urine for months after the ingestion 
of half a gram. 
Lead. 
The different preparations of lead may prove fatal either from the immediate 
effect of large doses or from the gradual effects of repeated small doses. Although 
there may be marked symptoms during life, the post-mortem lesions are few and 
variable. 
There may be chromatolysis of the ganglion cells. 
Large doses may produce acute gastritis, and sometimes a whitening of the mucous 
1 Popon, Virchows Arch., 1883, xciii, 351. 
2 It is advisable, in cases of suspected arsenic poisoning, particularly if the body has lain for some 
time, as in exhumations, to preserve not only all of the internal organs entire for the chemist, but also 
portions of the muscles (back, thigh, arm, and abdomen), and also one of the long bones, preferably 
the femur, since arsenious acid and its compounds are quite diffusible, and may be present in proportion- 
ately larger quantity in other parts than in the gastrointestinal canal. It is desirable to save the whole 
of the internal organs, and to weigh the muscle and bones as well as the whole body at the autopsy, 
in order that the calculations of the chemist, in case arsenic be found, may rest upon a definite basis, 
and be as little as possible dependent upon estimates, whose value may be questioned by lawyers should 
the case come into the courts. 
An interesting article on arsenic as a poison, with various collateral data by Pellew, will be found in 
Hamilton's System of Legal Medicine, 1900, vol. i, p. 349. 
3 For studies on the action of sublimate on the kidneys, see Neuberger, J., Zieglers Beitr., 1889, vi, 
429; and Elbe, Virchows Arch., 1905, clxxxii, 445. See also Mouisset and Mouriquand, Jour, de phys. 
et path. g6n., 1906, viii, 292. 476 
THE LESIONS INDUCED BY POISONS 
membrane. The intestines are generally contracted, and there may be fatty degener- 
ation of the renal epithelium; very frequently there are no appreciable lesions with 
the exception of a bluish line on the gums-the so-called lead line. 
In chronic lead poisoning the intestines may be contracted, the voluntary muscles 
flabby and light-colored, or partially replaced by connective tissue, and there may be 
chronic meningitis, though this is possibly not a characteristic find as it has been 
impossible to duplicate it experimentally.1 The most striking change produced 
during life by chronic lead poisoning is the extreme anemia; vascular changes are pro- 
nounced, and the kidneys are arteriosclerotic. Peripheral neuritis often occurs. 
Acute poisoning by salts of copper is not very common, but it is of occasional 
accidental occurrence, and the salts are infrequently used with suicidal intent. The 
sulphate and acetate are the most important salts in this respect. Soluble salts of 
copper may be formed in the use of copper cooking utensils, and accidents most fre- 
quently occur in this way. 
The post-mortem appearances are somewhat variable. The pharynx and esopha- 
gus may be somewhat inflamed or unchanged. The mucous membrane of the stomach 
and intestines may be inflamed, ulcerated, or gangrenous, and perforation and peri- 
tonitis may occur. The mucous membrane may have a diffuse greenish color, or par- 
ticles of the salt may be found adhering to it. 
Copper. 
Tartar Emetic. 
This preparation of antimony may prove fatal when administered in a single large 
dose or in repeated small doses. The post-mortem lesions are not constant. In cases 
of chronic poisoning there are usually no appreciable lesions. 
In cases of acute poisoning there may be evidence of acute inflammation of the 
esophagus, stomach, intestines, and peritoneum. Sometimes the stomach exhibits no 
lesions, while the intestine is involved. The larynx and lungs may be deeply congested. 
Aloes, colocynth, gamboge, jalap, scammony, savin, croton oil, colchicum, veratria, 
hellebore, elaterium, and turpentine. 
All these drugs may produce poisonous effects. The post-mortem lesions are con- 
gestion, inflammation, and sometimes ulceration of the gastrointestinal mucous mem- 
brane; but these lesions are sometimes present and sometimes absent. 
Vegetable Irritants. 
Cantharides. 
This substance may be given in powder or tincture. The entire length or only a 
portion of the alimentary canal may be congested or inflamed. There may be patches 
of gangrene of the mucous membrane of the stomach. When the poison has been 
taken in substance a microscopical examination of the contents of the alimentary 
canal or of the mucous membrane may reveal the glistening green and gold particles 
of the fly. 
The kidneys, ureters, and bladder may be congested and inflamed. There is some- 
times congestion of the brain and its membranes. 
Opium and Morphine. 
The post-mortem appearances in persons who have died from opium or morphine 
poisoning are inconstant and not characteristic. Congestion of the brain and its 
membranes, with serous effusion in the membranes and ventricles, and congestion of 
the lungs, are changes occasionally seen, but they are frequently entirely absent, and 
when present are not characteristic of death from these poisons. 
> Jores, I., Zieglers Beitr., 1902, xxxi, 183 (bibl.). 477 
THE LESIONS INDUCED BY POISONS 
The action of these substances varies greatly, and the post-mortem appearances 
are inconstant and not characteristic. In general, when any lesions are present they 
are those of gastrointestinal irritation or of venous congestion, or both. 
Microscopical examination may reveal characteristic fragments of fungi in the 
contents of the alimentary canal. 
Poisonous Fungi. 
This poison in fatal doses may destroy life in a very short time. The post-mortem 
appearances are inconstant and not characteristic. The skin may be livid and the 
muscles contracted. The stomach may be congested or normal. The most frequent 
internal appearances are those of general venous congestion. Under favorable condi- 
tions the odor of prussic acid may be detected in the stomach or blood or brain, or 
other parts of the body. It may be absent in the stomach and present in other parts 
of the body. If the patient has lived for some time the odor may be absent altogether. 
Cyanide of potassium may produce the same lesions as hydrocyanic acid, and there 
is the same inconstancy in their occurrence. 
Hydrocyanic Acid. 
Organic Poisons of Aromatic Group. 
Phenol. 
When this poison in concentrated form is taken into the stomach the mucous 
membrane of the mouth, esophagus, and stomach may be white, corrugated, and par- 
tially developed in patches, and the edges of the affected parts may be hyperemic or 
there may be patches of extravasation. Brownish, shrunken patches may be present 
about the mouth. The brain and meninges may be congested. There may be conges- 
tion and edema of the lungs, and congestion of the liver and spleen. The blood is 
usually dark and fluid. The urine is commonly of a dark or greenish color. The 
odor of the poison may be evident in the body and in the urine. In cases of long-con- 
tinued poisoning there may be chronic nephritis.1 
In cases which are not at once fatal the affected mucous membrane may slough, 
and healing follow with contraction of the stomach. Death from innutrition may 
follow temporary recovery after a considerable interval. If diluted carbolic acid be 
taken the white appearance of the mucous membrane may be absent but death may 
ensue with marks of necrosis, hyperemia, and inflammation of the esophagus and 
stomach. 
Nitro Compounds. 
The toxicity of nitrobenzol has long been observed; seven or eight drops may 
cause death. No characteristic changes are found in the organs; but the odor may 
often be recognized. The bluish black, hypostatic collections of blood and the gray- 
ish blue color of the skin and mucous membranes may suggest the cause of death. 
The blood is very dark. 
Trinitrophenol, or picric acid, causes severe poisoning in man, the formation of 
methemoglobin in the blood, a yellow color of the skin, exanthematous skin lesions, 
sometimes becoming hemorrhagic, and toxic changes in the kidneys. 
Trinitrotoluene, which is used largely as an explosive, causes an extreme anemia 
with a greenish cyanosis and jaundice.2 The urine usually shows albumin and casts. 
Post-mortem hemorrhages are present in the viscera and serous membranes, and 
degenerative changes are found in the heart muscle and in the kidneys. There are 
also extensive lesions in the liver resembling acute yellow atrophy. An anemia of the 
aplastic type has been described.3 
1 Uyeno, S., Zieglers Beitr., 1910, xlvii, 126. 
2 Martland, H. S., Jour. Am. Med. Assn., 1917, Ixviii, 835; Hamilton, A., Med. and Surg., 1917, i, 
761- 
3 Panton, P. N., Lancet, 1917, ii, 77. 478 
THE LESIONS INDUCED BY POISONS 
Amidobenzol or anilin is an oily substance widely used in the production of aniline 
dyes and causes death chiefly through its action on the blood.1 Methemoglobin is 
produced and extreme anemia results. On post-mortem examination nothing char- 
acteristic is found except that the blood is chocolate colored and there is general con- 
gestion of the organs. 
Other derivatives of anilin, such as acetanilide and the amidophenol group, in- 
cluding phenacetin, phenocoll, etc., are much less toxic than anilin, but when taken 
continuously in doses of 1 to 2 grams in twenty-four hours often produce intense 
cyanosis and a very marked secondary anemia with the appearance of numerous 
nucleated red cells in the blood (see under Blood, page 521). 
Amido Compounds. 
Alcohol. 
The different preparations of alcohol, when taken in concentrated form or in large 
quantities, sometimes produce sudden coma and death in from half an hour to several 
hours. In acute poisoning, if death have followed soon after the ingestion of the 
poison, the body may resist decomposition for an unusual length of time. The stom- 
ach and tissues may even have a more or less well-marked alcoholic odor. The 
stomach, and even the esophagus and duodenum, may be of a deep-red color. There 
may be punctiform ecchymoses in the gastric mucous membrane. In many cases the 
stomach is apparently quite normal. There is apt to be venous congestion in some of 
the internal organs, but this is not constant. There are frequently congestion, and 
sometimes extravasation of blood in the brain and its membranes, and edema of the 
membranes or of the brain substance, or both. There may be a serous effusion in the 
ventricles of the brain, also chromatolysis of the ganglion cells. 
In chronic alcohol poisoning death may ensue from some other disease, or after a 
debauch. In the latter case there may be delirium tremens, or the patient may die ex- 
hausted and comatose. Chronic alcoholism is not infrequently mistaken clinically for 
meningitis. The post-mortem lesions are sometimes marked, sometimes absent. 
There may be chronic pachymeningitis, resulting in thickening of the dura mater and 
its close adherence to the skull. The pia mater may be thickened and edematous. 
The brain may be normal or edematous or atrophied and show chromatolysis of the 
ganglion cells. The lungs are frequently congested. The heart may be thickly 
covered with fat, and its walls may be flabby and fatty. The stomach frequently 
presents the lesions of chronic gastritis. The liver may be cirrhotic, with or without 
fatty infiltration. The kidneys may present the lesions of albuminous or fatty degene- 
ration or of chronic diffuse nephritis. 
It should always be remembered, however, that all or a part of the above lesions 
may be absent in the bodies of drunkards, and, furthermore, that the same lesions 
may be due to other causes. 
Methyl or wood alcohol is much more toxic than ethyl alcohol and very frequently 
produces an atrophy of the optic nerve with permanent blindness.2 
Amyl alcohol, also, is much more toxic than ethyl alcohol; it is occasionally used 
as a solvent in commercial work, but only a few cases of poisoning have been reported. 
Chloroform. 
Chloroform may cause death when it is taken in fluid form into the stomach or 
when inhaled. Death from swallowing liquid chloroform is rare, and its immediate 
cause is usually uncertain. The post-mortem changes are variable; sometimes there 
are no lesions. In some cases there is simple reddening of the gastric mucous mem- 
brane; occasionally there is acute gastritis or ulceration of the mucous membrane. 
The odor of chloroform may or may not be evident. Discoloration and softening of 
the mucous membrane of the pharynx, esophagus, and duodenum have been observed. 
1 Luce, R. V., and Hamilton, A., Jour. Am. Med. Assn., 1916, Ixvi, 1441. 
2 Hunt, Bull. Johns Hopkins Hosp., 1902, xiii, 213: Gettler, A. O., and St. George, A. V., Jour. Am. 
Med. Assn., 1918, Ixx, 145. THE LESIONS INDUCED BY POISONS 
479 
There may be general venous congestion; the heart may be flabby. Bubbles of gas 
have been frequently seen in the blood, but this is not characteristic. Extensive 
degeneration and necrosis of the liver cells may follow chloroform administration 
even for as short a period as a half hour1 (see page 816). 
Death from inhalation of chloroform is a not infrequent accident in surgical 
practice. After death from inhalation the results of the examination are usually 
negative, and in no case are there lesions which in themselves enable the examiner to 
declare death to have been due to chloroform poisoning. 
Tetrachlorethane. 
This substance, which is used as a solvent for cellulose acetate, is extremely 
poisonous to man when the fumes are inhaled.2 The symptoms are those of an acute 
jaundice with gastrointestinal complications. In certain cases the liver has been very 
much shrunken; there have been hemorrhages into the serous surfaces and into the 
heart muscle; and bile and blood have been found in the urine. 
Ether. 
The inhalation of ether occasionally causes death. The post-mortem examina- 
tion is negative. The ingestion of fluid ether may induce inflammation of the stom- 
ach. The odor of ether may be perceptible if the autopsy is made soon after death. 
Death from pneumonia not infrequently follows the prolonged administration of 
ether. The pneumonia may be of lobar or lobular type, usually the latter; it may be 
due to chilling during the course of an operation, the ether dilating the peripheral 
capillaries and facilitating the cooling of the body, or to aspiration of laryngeal or 
oral mucus containing bacteria. 
Chloral Hydrate. 
There are no characteristic post-mortem appearances after death by chloral. 
Hyperemia of the brain, and the odor of the drug, have been noticed. Very large 
doses cause slight fatty changes in the liver.3 Hyperemia of the lungs and brain has 
been noted; and there may occur ecchymoses in the mucous membrane of the stomach. 
The drug can often be found in the stomach contents in cases of recent poisoning. 
Strychnine-Nux Vomica. 
The post-mortem appearances after poisoning by these drugs are not characteristic 
and are inconstant. The body is usually relaxed at the time of death, but rigor 
mortis, as a rule, comes on early and remains long. There may be congestion of the 
brain and spinal cord, and sometimes of the lungs and stomach. Chromatolysis of the 
ganglion cells is recorded. 
Animal Venom, Etc. 
The poisons which may be introduced into the body through the bites of venomous 
snakes and reptiles and the bites of insects cannot be considered in detail here.4 
The action of the venom of snakes, scorpions, etc., upon the animal body, is in 
many respects similar to that of certain bacterial toxins and cytolytic substances. 
By gradual adaptation of the lower animals to these venoms, antitoxins, i.e. antivenins, 
may be secured. 
1 Cragin, E. B., and Hull, E. T., Jour. Am. Med. Assn., 1911, Ivi, 5; Whipple, G. H., and Sperry 
J. A., Bull. Johns Hopkins Hosp., 1909, xx, 278. 
2 Lehmann, K. B„ Arch. f. Hyg., 1911, Ixxiv, 1; Koelsch, F., Munchen, med. Wchnschr., 1915, 
xii, 1567; Wilcox, W. H., Lancet, 1915, i, 544; Hamilton, A., Jour. Am. Med. Assn., 1917, Ixix, 2037. 
3 HopKins, J. G., Am. Jour. Obst., 1912, Ixv, 557. 
4 Consult Langmann, Poisonous Snakes and Snake Poison, Med. Rec., 1900, Iviii, 401; also Brown, 
Twentieth Century Practice, vol. xx, (bibl.). 480 
THE LESIONS INDUCED BY POISONS 
Our knowledge of snake venom and especially of cobra venom is the most extensive. 
Snake venom contains toxins of several kinds, hemolytic, neurolytic, nephrolytic, 
etc.1 Some oi these toxins seem to require the presence of complement to secure their 
hemolytic action upon the red blood-cells. Furthermore this complement may, as 
it would appear, be furnished by the red blood-cells themselves-endocomplement. 
It is conjectured that in this case the lecithin of the red cells may act as complement.2 
The injection of crotalin seems to cause a great reduction in the bactericidal p wer 
of the blood, and severe infections have followed the therapeutic use of this venom.3 
Abrin and ricin are examples of poisonous substances which induce in the body 
lesions similar to those in certain infectious diseases. 
Carbon Monoxide (Carbonic Oxide). 
This gas is generated in coal mines by the explosion of coal dust, and in the 
imperfect combustion of coal or of any other form of carbon, and is present in various 
types of illuminating gas in percentages of from 10 to 50. Producer gas4 and coke-oven 
gas, also, contain large quantities of carbon monoxide; natural gas, as a rule, does not. 
The exhaust from gasoline engines contains enough of the gas to cause fatal poison- 
ing if the motor is run in a closed space, as in a small garage. 
The poisoning is produced by the combination of the carbon monoxide with the 
oxyhemoglobin of the blood.5 This combination is very firm and cannot easily be 
broken up unless an extra supply of air is furnished by artificial respiration or by 
oxygen inhalation; if forced breathing is kept up however, the gas is given off fairly 
rapidly. It is often difficult, even within a few hours, to detect the presence of the 
gas in the blood of a person who has been in a room the atmosphere of which contained 
a moderate amount of carbon monoxide.6 In addition to the asphyxiating action 
which the gas has by replacing oxygen in hemoglobin, it is probable that it has a toxic 
action on the tissues.7 
The quantity of gas required to produce symptoms is very slight; severe symptoms 
may result from as little as 0.02 per cent, of carbon monoxide in the air; and death 
may follow prolonged exposure to an atmosphere containing 0.05 per cent. 
The symptoms of poisoning are indefinite, the most common being severe head- 
ache, vertigo, and muscular weakness, with nausea and vomiting; often, the victims 
are found unconscious. If the poisoning is not severe, the patient may come out of 
coma in a short time, but in many cases unconsciousness persists for a week or more. 
The character of the breathing in the severe poisonings has suggested the possibility 
of a terminal acidosis, but there is no proof that this condition exists.8 
The tissue changes in severe poisoning are very extensive. A great variety of 
skin lesions occur, chiefly of the bullous type; icterus is not infrequent; and glycosuria 
is seen. Polycythemia and leucocytosis are quite regularly present, though mild 
chronic poisoning may induce anemia. While the most important anatomical lesions 
are those of the nervous system, all the organs are congested and usually contain 
numerous small hemorrhages. Parenchymatous degeneration is frequent. The 
gravest lesion is one which appears after four or five days have elapsed, and consists, 
at first, of a yellow area of ischemia, usually in the globus pallidus, with, finally, a 
softening which may extend into the anterior portion of the lenticular nucleus and 
into the neighboring portions of the internal capsule. When the tissues are examined 
in an early stage of the lesion, the vessels are found to be the site of fatty degenera- 
tion and calcification. Later, the beginning of reparative processes may be observed 
1 Flexner and Noguchi, Jour. Exper. Med., 1901-1905, vi, 278. 
2 Keyes, Berl. klin. Wochenschr., 1902, xxxix, 886. 
3 Anderson, J. F., Jour. Am. Med. Assn., 1914, Ixii, 893. 
• Watkins, J. A., Bureau of Mines, Dept, of the Interior, Technical paper 156, Washington, 1917. 
6 For a very complete study of carbon monoxide poisoning, with bibl., see Glaister and Logan, 
Gas Poisoning in Mining and Other Industries, Edinburgh, 1914. 
• The tests for recognition of carbon monoxide in the blood are complicated and difficult. For 
details, see Wood, Chemical and Microscopical Diagnosis, New York, 1917; and Glaister and Logan, 
Gas Poisoning in Mining and Other Industries, Edinburgh, 1914. 
7 Henderson, F., Jour. Am. Med. Assn., 1916, Ixvii, 580, states that the gas is not toxic and that the 
lesions are due solely to oxygen deprivation. 
8 Williams, Jour. Am. Med. Assn., 1918, Ixx, 119. THE LESIONS INDUCED BY POISONS 
481 
with absorption of exudate and overgrowth of tissue. In all probability, the anatom- 
ical peculiarities of the vessels have something to do with the ease with which they are 
damaged, for they are very long and thin, without vasa vasorum, and it is easy to 
see how under the influence of the enormous dilatation of the cerebral vessels, one of 
the first phenomena noted in connection with carbon monoxide poisoning, the cir- 
culation in these delicate branches can be checked so as to permit the formation of a 
thrombus.1 Such thrombi have, indeed, been repeatedly found in many of the smaller 
capillaries, elsewhere, and to them is probably due the minute hemorrhages which 
appear throughout the brain and spinal cord. These, and the consequent softening 
and degeneration, give rise to a great variety of obscure nervous symptoms which 
appear in the course of recovery from carbon monoxide poisoning, or may actually 
cause death long after the exposure. The hyperemia and edema in the brain are more 
marked than in simple asphyxia. In the non-fatal cases, the cherry-red color of the 
blood and its chemical and microscopical peculiarities are the main points for deter- 
mining the nature of the poisoning, if the examination is made a few hours after 
inhalation has occurred. 
Conium, Aconite, Lobelia Inflata, Digitalis, Stramonium. 
These vegetable poisons are administered in their natural form of leaves, berries, 
and roots, or in tinctures, infusions, and extracts, or in the form of their active alka- 
loid principles. 
If the leaves, berries, or seeds are given they may be detected in the contents of 
the alimentary canal by microscopical examination. Otherwise the results of autop- 
sies are not characteristic. 
The brain and its membranes, and the lungs, may be congested. The stomach 
may present patches of congestion, inflammation, and extravasation, or its entire 
mucous coat may be inflamed, or it mhy appear normal. 
Ptomaines. 
Certain organic substances can unquestionably act in a deleterious fashion on the 
body. The general term of ptomaine has been applied to some of these substances, 
but at present their importance is in doubt. The so-called ptomaine poisoning 
which occurs after the consumption of sausage, certain kinds of cheese, ice cream, 
and imperfectly preserved fish and shellfish, is now generally recognized as due to 
bacterial infection rather than to a toxic product of protein or phosphatide decomposi- 
tion, and it would be wise to abandon the word ptomaine entirely. The composition of 
many of the products of putrefaction has been determined, and but few of them have 
been proved to be toxic in quantities likely to be produced in the intestine.2 
Bibliography of Poisons. 
For a more detailed consideration of poisons, their effects, modes of detection, etc., 
consult Kobert, Lehrbuch der Intoxikationen, 2d ed., Stuttgart, 1906; and Compendium 
praktischen Toxikologie, Stuttgart, 1903; or the following: Kunkel, Handbuch der 
Toxikologie, Jena, 1901; Kolisko, Hofmann's Lehrbuch der gerichtlichen Medicin, 9th 
ed., Berlin, 1909; Schmidtmann, Casper-Liman's Handbuch der gerichtlichen Medizin, 
9th ed., Berlin, 1905; Kratter, Lehrbuch der gerichtlichen Medizin, Stuttgart, 1912; 
Lewin, Lehrbuch der Toxikologie, 2d ed., Vienna, 1897; Dragendorff, Ermittelung 
von Gif ten, Gottingen, 1895; Blythe, Poisons, Their Effects and Detection, London, 
1906; Mann, Forensic Medicine and Toxicology, Philadelphia, 1893; Autenrieth, The 
Detection of Poisons and Powerful Drugs, 4th ed., Philadelphia, 1915; Woodman and 
1 KolisKo, Wien. klin. Wchnschr., 1893, vi, 191; Schmidtmann, Handbuch d. gerichtlichen Medizin, 
9th ed., Berlin, 1905, i, 872; Hofmann, Lehrbuch d. gerichtlichen Medicin, 9th ed., 1903, i, 739. 
2 For a review of the chemistry of the subject, see Barger, G., The Simpler Natural Bases, London, 
1914. See, also, Vaughan and Novy, Cellular Toxins, 4th ed., Philadelphia, 1902. 
For an admirable review of the question of poisoning and intoxications, see Roger, in Bouchard 
and Roger, Nouveau traits de pathologic genfirale, Paris, 1914, ii, 1-487. 482 
THE LESIONS INDUCED BY POISONS 
Tidy, Forensic Medicine, Philadelphia, 1877; and Peterson and Haines, Textbook of 
Legal Medicine and Toxicology, Philadelphia, 1904. 
Lesser, Atlas der gerichtlichen Medicin, 2d ed., Breslau, 1892, contains a series of 
colored plates showing the appearance of the stomach after the action of various poi- 
sons; and Worm ley, Micro-chemistry of Poisons, 2d ed., New York, 1885, contains 
pictures of the microscopical appearance of various forms of crystals of poisonous 
substances. 
Lesions Induced by Endogenous Poisons-Autointoxications 
As we turn now from poisons formed outside of the body to those 
formed within it-the endogenous poisons-we encounter two classes: 
I. Those poisons which arise from the metabolism of microorganisms. 
II. Those which arise from the normal or aberrant metabolism of the 
body-cells themselves. 
I. ENDOGENOUS POISONS FORMED LARGELY UNDER THE INFLUENCE OF 
MICROORGANISMS.1 
1, Those which are formed in infectious diseases (see Chapter IX., 
Part I., on Infectious Diseases). 
2. Those formed in the body without infection. 
The most common and important metabolic poisons of this class 
are those which are formed in the gastrointestinal canal through the 
action of microorganisms, mostly bacteria, upon the organic constituents 
of the intestinal contents and secretions. The new chemical substances 
thus formed become deleterious when absorbed into the body fluids, and 
this may occur either when they are produced in unusual quantity or 
when their elimination with the excreta is interfered with. When 
absorbed, some of these poisons may be demonstrable in the urine, and 
they may give rise to a variety of symptoms, such as dizziness, headache, 
some forms of tetany, gastroenteritis, etc. This is the condition to which 
the term autointoxication is applied by clinicians.2 
Endogenous poisons analogous in origin with these may be formed in 
the bladder, in putrid abscesses, or in necrotic tissues in various parts 
of the body. Structural lesions, if such there be, occurring under these 
conditions, are as yet but little known. 
II. ENDOGENOUS POISONS FORMED BY THE BODY-CELLS-HISTOGENIC 
POISONS. 
It is only within the past few years that the studies on cell metabo- 
lism have led to the belief not only that the body-cells may under occa- 
sional abnormal conditions form poisonous chemical compounds, but that 
1 Consult in connection with this and the following section, Herter, Chemical Pathology, Philadel- 
phia, 1902; Taylor, Autointoxication, Osler's Modern Medicine, 2d ed., Philadelphia, 1914, ii, 503; 
Wells, Chemical Pathology, 3d ed., Philadelphia, 1918; Kraus, Lubarsch-Ostertag, Ergebn. d. allg. 
Path,, 1895, i2, 571; Weintraub, ibid., 1897, iv, 1; and Roger, in Bouchard and Roger, Nouveau 
trait6 de pathologie gSnSrale, Paris, 1914, ii, 1-487. 
2 It is the opinion of some pathologists that the term autointoxication should be strictly limited to 
the effects of those substances which are actually derived from the cells of the body; that these alone 
are truly endogenous; that intoxication by bacterial products is not autointoxication; and, especially, 
that it is improper to use this term in connection with the intestinal bacterial composition, since the 
digestive canal is, strictly speaking, exterior to the body tissues and cavities. 483 
THE LESIONS INDUCED BY POISONS 
even in the normal processes some of the intermediary metabolic pro- 
ducts may be inimical to the welfare of the body, if they be not constantly 
rendered inert. This may be affected either by excretion or, as now 
seems probable, in part at least through the influence of what have been 
called the 11 internal secretions" of such glands as the thyroid, pancreas, 
adrenals, hypophysis, etc., or possibly in ways as yet wholly unknown. 
Thus there is a group of autointoxications due, because of defects 
in the excretory apparatus, to the accumulation in the body of the prod- 
ucts of normal metabolism; for example, uremia in renal insufficiency 
or retention of urine; icterus and cholemia in retention of bile; acidosis 
due to beta-oxybutyric acid. Possibly some of the serious symptoms 
following extensive burns of the skin and occurring in sunstroke and 
eclampsia are of similar origin. 
In this connection, also, the rapid and often fatal intoxication follow- 
ing intestinal obstruction, especially of the upper portion of the small 
intestine, is of interest. Many experimental studies have been made 
of this phase of the subject without final conclusions being reached. 
Whether nervous influences, infection, or toxemia are individually re- 
sponsible, or whether a conjunction of these factors is necessary, is still 
undecided.1 This may be called autointoxication through retention. 
On the other hand, there is a group of autointoxications which it is 
assumed may in part at least be due to a failure of the organs concerned 
with the internal secretions to furnish the necessary link in the chain of 
intermediary metabolic products. In this group may be placed cachexia 
strumipriva and myxedema, pancreatic diabetes, Addison's disease, and 
possibly some forms of acute yellow atrophy of the liver. 
While the nature and action of the recently discovered internal 
secretions are still obscure, they do exist and are of extreme importance 
in the subtle adjustments of individual cell metabolism to the welfare of 
the organism as a whole, and there is abundant reason to believe that, 
when this adjustment is disturbed, forms of histogenic autointoxication 
may arise. 
At any rate the hypotheses which have been formed in the new light 
have contributed largely to our understanding of a series of important 
general diseases. These diseases, whether or not involving internal 
secretions in accordance with our present conceptions, may be considered 
as dyscrasic autointoxications.2 
Whether gout, oxaluria, and some forms of simple diabetes should 
be considered as autointoxications may be questioned. Possibly Base- 
dow's disease and some forms of puerperal eclampsia (page 818) should 
be regarded as in part involving the foimation and retention of histogenic 
poisons. 
Of course this grouping of diverse forms of disease should be consid- 
1 See Whipple, G. H., Jour. Am. Med. Assn., 1915, Ixv, 476, who thinks a proteose absorption is 
the main factor; Draper, J. W., ibid., 1916, Ixvii, 1080; Ixix, 1768, who believes in a disturbance of 
enzyme-producing activities of intestinal epithelium; and Dragstedt, L. R., Moorhead, J. J., and Burcky, 
F. W., Jour. Exper. Med., 1917, xxv, 421, who ascribe to bacteria the most important role. 
2 For a discussion of internal secretions, see Starling, Jour. Am. Med. Assn., 1908, 1, 835; Vincent, 
Internal Secretions, 1912; Biedl, The Internal Secretory Organs, New York, 1913; and Falta, The Duct- 
less Glandular Diseases, Philadelphia, 1915. 484 
THE LESIONS INDUCED BY POISONS 
ered as only tentative and suggestive. And it may well be doubted 
whether analogy may not be often overstrained in regarding as the 
effect of poisons what may, after all, be metabolic aberrancies of far more 
subtle character than the word autointoxication would imply. 
It should be borne in mind that in but a very small proportion of 
the abnormal processes which are considered autointoxications have the 
assumed poisons been actually demonstrated. The assumption rests 
largely upon symptoms which are regarded as analogous with those 
incited by known exogenous poisons. It is wise to remember also that 
even in poisoning by well-defined agents whose general effects have long 
been known we are almost totally ignorant, except in the case of the 
so-called destructive or corrosive poisons, of the exact ways in which they 
act. A few induce changes in the blood; many appear to act upon the 
nerve cells; but the nature of this action is still unknown. 
Without insistence upon the advantages of such a grouping as has 
been outlined above, and with the full recognition of its incomplete- 
ness, the more important of the so-called "general diseases," some of 
which may be regarded as autointoxications, will be considered in the 
next chapter. CHAPTER XIII. 
GENERAL DISEASES. 
In the so-called general diseases, various parts of the body are structurally or 
functionally involved, but there is usually a primary lesion in some special organ. 
The grouping of certain diseases under this heading is rather for convenience than 
because these diseases are fundamentally different in their relations to the body as a 
whole from many others, such as infections, intoxications, etc. Fever, which is so 
often one of the manifestations of toxemia, has been grouped with the general dis- 
eases, because in some respects it presents important analogies with them. 
CACHEXIA STRUMIPRIVA-MYXEDEMA. 
The thyroid is one of the ductless glands which furnishes internal 
secretions essential to normal metabolism in the body. 
Removal or destructive lesions of this gland, both in man and the 
lower animals,1 may be followed by serious and fatal disease character- 
ized as cachexia strumipriva. In man the more common manifestation 
of this disease is called myxedema.2 It occurs most frequently in middle- 
aged women. 
The skin of the face is apt to be swollen and waxy, giving a peculiar 
and rather characteristic appearance to the features (Fig. 283). The 
skin of the body is apt to be dry and rough, and the hair may fall out. 
Perspiration is, as a rule, diminished. The general body metabolism 
is diminished while glucose tolerance is increased. Glycosuria however, 
may be found. The mental condition is dull, and loss of memory and 
insanity may occur. Bodily movement and speech are apt to be im- 
paired. The fat tissues may be atrophic, and the subcutaneous tissue 
has been shown in some, though not all, of the cases to contain an un- 
usual amount of mucin. In some cases the fibers of the upper layers of 
the corium are crowded apart by fluid. 
The most marked and constant lesion in this disease is an atrophic 
condition of the thyroid gland. The parenchyma of the gland is more 
or less completely replaced by fibrillar connective tissue, and by new- 
formed reticular tissue resembling the lymphatic tissue of the lymph- 
nodes. The general appearance of the atrophied thyroid gland is shown 
in Fig. 285. 
In addition to the lesion of the thyroid there are apt to be chronic 
endarteritis and chronic diffuse nephritis. In some cases there is an 
accumulation of small spheroidal cells about the smaller blood-vessels in 
various parts of the body, and also petechial hemorrhages. 
1 For an extensive critical and experimental study of this subject, see Cunningham, R. H., Experi- 
mental Thyroidism, Jour. Exper. Med., 1898, iii, 147 (bibl.). For a study of the transplantation of 
the thyroid, see Payr, E., Arch. f. klin. Chir. (Langenbeck), 1906, Ixxx, 730. 
2 For bone lesions in this condition, see page 1044. 
485 486 
GENERAL DISEASES 
If the thyroid is completely removed in young animals there is 
deficient development of the osseous system, while in man the frequent 
association of cretinism with goiter or other thyroid lesions indicates in 
another way the close relationship between the thyroid and cell metab- 
olism.1 
Cretinism is a congenital condition in which development is retarded 
and faulty.2 An adult in years is often infantile or childish in stature 
and mental capacity, ill formed and uncouth (Fig. 284). 
Fig. 283.-Myxedema. 
Showing "puffy" skin of face and falling of the hair-case of Dr. Henry Hun. 
The nature of the substances composing the internal secretions 
of the thyroid is little understood, but the wonderful therapeutic effects 
of the administration in cases of myxedema and in cretins of the extract 
of the gland in which they are deficient, make clear their great impor- 
tance. Whether directly toxic substances are formed in the thyroid or 
1 Consult Osler, Sporadic Cretinism in America, Trans. Cong. Am. Phys, and Surg., 1897, iv, 169. 
2 For bone lesions, see page 1044. 487 
GENERAL DISEASES 
Fig. 284.-A Cretin. 
About twenty years of age. 488 
GENERAL DISEASES 
not, it seems proper to consider the cachexia strumipriva as due directly 
or indirectly to autointoxication. 
EXOPHTHALMIC GOITER. (Basedow's Disease, Graves' Disease.) 
The lesions of this disease are unilateral or bilateral enlargement of 
the thyroid gland and protrusion of the eyeballs-exophthalmos. Asso- 
ciated with these is hyperplasia of the lymphatic system, which is espe- 
cially marked in the thymus, spleen, and lymph-nodes. Correlated with 
this lymphoid overgrowth is a relative or absolute increase in the lymph- 
oid elements of the blood, and, in addition, there are certain character- 
istic disturbances, among them rapid heart action-tachycardia-and 
muscular tremor. The pathological changes found in the thyroid are 
extremely complex. In cases in which the clinical syndrome of exoph- 
thalmic goiter is present there may be found normal thyroid tissue; 
this probably represents an early stage of exophthalmic goiter in which 
the hyperplasia has not yet begun or has been inhibited by the adminis- 
a, Interstitial tissue; b, atrophied lobules with small spheroidal-cell or lymphatic tissue in their 
peripheries. 
Fig. 285.-Section of the Atrophied Thyroid Gland in Myxedema. 
tration of iodine. Secondly, there may be an active hyperplasia of the 
glandular epithelium with atrophy of the colloid material and alteration 
in its staining qualities, the colloid no longer taking a bright red color 
with eosin. The gland may show also the lesions of colloid goiter- 
large alveoli filled with normal staining material and lymphoid tissue in 
the stroma. (See Plate III in which these lesions are photographed at 
the same magnification.) This condition is also induced in hyperplastic 
glands by the administration of iodine for therapeutic purposes. Thirdly, 
adenomata of the thyroid, of either the fetal or the tumor type, may be 
present in exophthalmic goiter, though probably simply coincident with 
the disease and not directly related to it. Finally, the changes in the 
gland may be highly complex, when the condition develops in old colloidal Pathology-Delafield and Prudden. 
Plate 111. 
Exophthalmic Goiter X 75 
Colloid Goiter X 75 
Fetal Adenoma of Thyroid X 57 GENERAL DISEASES 
489 
goiters, the hyperplastic structures being commingled with cysts, hemor- 
rhagic areas, calcification, and adenoma nodules. There is, therefore, 
no specific lesion connected with exophthalmic goiter, but the majority 
of the glands show more or less cellular hyperplasia with diminished 
colloid. This may be considered as the most frequent lesion. In all 
cases lymphoid collections are apt to be found in various portions of the 
gland distributed throughout the connective tissue. The connective 
tissue also undergoes hyperplasia, both the trabeculee and the substance 
of the gland and the capsule. The vascularity of the organ is often 
greatly increased, the arteries and the veins being dilated, and this con- 
gestion may account for a very large portion of the increase in size always 
noted in exophthalmic goiter though it is generally held that there is 
a definite increase in cellular volume also. Some of the symptoms of 
myxedema are frequently shown by patients suffering from exophthalmic 
goiter and the terminal stage of the untreated hyperplastic process is 
often an atrophy of the glandular structures with the ultimate production 
of myxedema. The heart usually shows a considerable hypertrophy of 
the left ventricle which is simply due to the extra labor falling on that 
organ owing to the extreme rapidity of the pulse. The iodine content of 
the gland varies inversely with the amount of hyperplasia, normal 
thyroids and colloidal goiters containing the most iodine, while extremely 
hyperplastic glands contain the least. This is in relationship with the 
amount of colloidal substance microscopically noted as present in the 
structures, the specific protein of the thyroid containing a large amount 
of iodine. 
Four theories are current in explanation of this condition. The first 
is that it is due to a hyperthyreosis or excessive secretion of the thyroid 
gland. This is based upon the fact that overdoses of thyroid extract 
produce some of the symptoms of exophthalmic goiter and that removal 
of a portion of the gland or ligature of some of its vessels is often bene- 
ficial in checking the disease. The second theory is that the condition 
is due to perverted secretion-dysthyreosis-, but experimental researches 
have not adduced definite confirmation of this theory. The third view 
is that the disease is a general disturbance of the chemistry of the body, 
the thyroid undergoing a compensatory hyperplasia in endeavoring to 
overcome the toxic effects of some poison in the system.1 The fourth 
theory is that an abnormal nervous system stimulates the thyroid and is 
in turn excited by the thyroid secretion, thus inciting a vicious cycle.2 
Although the majority of observers believe in the hyperthyroidism theory, 
the whole question is still under discussion.and cannot be regarded as 
finally settled.3 
1 See for study of basal metabolism in exophthalmic goiter, Means, J. H., and Aub, J. C., Jour. 
Am. Med. Assn., 1917, Ixix, 33. 
2 Wilson, L. B., Am. Jour. Med. Sc., 1916, clii, 799. 
3 For studies on the lesions of the thyroid gland and exophthalmic goiter, see Ewing, Trans. Assn. 
Am. Phys., 1906, xxi, 567; and MacCallum, Jour. Am. Med. Assn., 1907, xlix, 1158; and the numerous 
papers by Marine and Lenhart, Arch. Int. Med., 1909, iv, 440; ibid., 1911, vii, 506; ibid., 1911, viii, 265. 
For a study of adenomata of the thyroid gland, some of the cases exhibiting a few of the symptoms of 
exophthalmic goiter, see Bloodgood, J. C., Surg., Gynec., and Obst., 1906, ii, 121. For a presentation 
of the dysthyreosis theory, see Klose, Beitr. klin. Chir. (Bruns), 1912, xxvii, 601. For a study of 
the relation between the nervous system and the thyroid, see Oswald, A., Cor.-Bl. f. schweiz. Aerzte, 
1912, xlii, 1130; Roussy, G., Les lesions du corps thyroide, Paris, 1914; Launoy, L., Thyroide, para- 
thyroides, thymus, Paris, 1914. 490 
GENERAL DISEASES 
ADDISON'S DISEASE. 
This name is applied to a disease especially characterized morpholog- 
ically by a peculiar pigmentation of the skin and by certain changes, 
morphological or functional, in the adrenals. The patients suffer from 
cerebral symptoms, great prostration, syncope, and derangements of 
the functions of the stomach and intestines. 
The pigmentation of the skin is the symptom which has especially 
attracted attention. The change in color usually begins and becomes 
most marked in those parts of the skin which are not covered by the 
clothing or are naturally of darker color. The rest of the skin afterward 
changes color, but not uniformly, white patches being left. The color 
is at first a light yellow or brown; this becomes darker until it is of a 
dark greenish, grayish, or blackish brown. The mucous membrane of 
the tongue, lips, cheeks and gums may be similarly pigmented. 
As examples of Addison's disease different observers have described 
cases in which the symptoms and bronzed skin existed without disease 
of the adrenals; cases in which the bronzed skin was the only lesion; and 
cases in which the adrenals were diseased without symptoms or bronzed 
skin. 
The Skin.-The discoloration of the skin is due to a deposit of yellow- 
ish-brown pigment in the deeper layers of the epidermis, especially in the 
layer covering the papillae, and less constantly in the connective tissue 
of the cutis. 
The Brain.-Pigmentation of the gray matter, acute meningitis, 
chronic meningitis, and distention of the ventricles with serum have been 
observed. 
The sympathetic nerves, especially those which are in contact with 
the adrenals, may show a variety of changes apparently due to chronic 
inflammation. Various changes in the nerve cells of the semilunar gan- 
glia have been described. 
There may be fatty degeneration of the heart muscles and hyperplasia 
of the intestinal lymph-nodules and the spleen. 
The Adrenals.-The most common lesion of these bodies is a tubercu- 
lous inflammation, and this or some other lesion has been found in nearly 
one-half of the cases. On the other hand, it should be remembered that 
similar lesions of the adrenals often occur without other indications of 
Addison's disease. Tuberculous adrenals may be large, hard, and nodu- 
lar; less frequently of normal size or smaller than normal. On section 
they may contain cheesy masses surrounded by zones of gray, semitrans- 
lucent tissue. Later the cheesy masses may become calcified or they may 
soften and break down. The grayish zones are composed of tubercle 
tissue or denser connective tissue.1 
Other cases have been described in which the adrenals were the seat 
of carcinoma or of fatty or waxy degeneration. But these lesions, 
1 For a study of experimental tuberculosis of the adrenals and its relations to Addison's disease, see 
de Vecchi, Centralbl. f. allg. Path. 1901, xii, 577. 491 
GENERAL DISEASES 
especially carcinoma of the adrenals, may occur without the manifesta- 
tions of Addison's disease. The adrenals may be atrophied. They may, 
however, be normal, and in some such cases lesions of the semilunar and 
other sympathetic ganglia have been found. 
On the whole, the clinical, morphological, and experimental data now 
available seem to point to lesions of both the sympathetic system and 
the adrenals as of probable significance in determining this disease. 
The hypothesis which is most in favor at present assumes that the 
adrenals furnish an internal secretion without which normal metabolism 
cannot be effected, and that lesions of the adrenals or of the sympathetic 
ganglia and vessels about them, by altering or diminishing this secretion, 
may lead to the functional and structural changes characterizing the 
disease.1 This active principle, which is present in the medullary and 
chromaffin portion of the adrenal in 1 part in 1000 of the fresh organ, 
has recently been produced synthetically and found to be a base, chem- 
ically designated as methylamino-acetocatechol. The relationship be- 
tween the medulla of the adrenals and the sympathetic is apparently 
intimate but is as yet obscure. Complete removal of the adrenals 
is rapidly fatal. Injection of the extracts after removal of the organs 
fails to maintain life. The action of extracts of the adrenals or the pure 
base upon the muscle fibers of arteries leads to an increase in blood 
pressure. 
DIABETES MELLITUS. 
This disease involves such defects in metabolism as lead to an abnor- 
mal accumulation of sugar in the blood (hyperglycemia) and its appear- 
ance in the urine (glycosuria).2 
A great variety of lesions have been found in the body after death 
from diabetes, but few of them, aside from those of the pancreas, appear 
to be of well-defined significance in this special relationship. The general 
condition of malnutrition and debility, so often marked in this disease, 
renders diabetics especially vulnerable to slight injuries or infections, 
furunculosis, carbuncle, eczema, etc.; gangrene is liable to occur either 
with or without marked injury in cases of diabetes.3 
The nervous system may be normal. Peripheral neuritis with or 
without lesions in the gray matter of the anterior horns is frequent. A ter- 
minal pneumonia is not uncommon. The liver may be cirrhotic or fatty. 
The kidneys may show diffuse nephritis and often a glycogenic infiltra- 
tion of the epithelium of Henle's loop. A moderate amount of fat is 
often present in the blood, and fat emboli in the lungs have been described. 
The lesions in the pancreas are variable; there may be a general atro- 
phy with fat replacement and an increase of interstitial tissue (Fig. 286). 
Hyaline degeneration and fibrosis of the islands of Langerhans are present 
1 For the effects of removal of suprarenal body and the nature of its "active principle," consult Abel, 
Vaughan Anniversary Contributions, 1903, p. 139 (bibl.). Also Barger, Natural Bases, New York, 
1914, and Biedl, The Internal Secretory Organs, New York, 1913; Bayer, G., Lubarsch-Ostertag, Ergebn. 
d. allg. Path., 1910, xiv,2 1. 
2 For a r6sum6 of metabolism in diabetes, see Lusk, Arch. Int. Med., 1909, iii, 1. 
2 For bibliography of diabetic gangrene, consult Davis, Jour. Am. Med. Assn., 1898, xxx, 113. 492 
GENERAL DISEASES 
in a large proportion of the cases (Fig. 287).1 An adenoma-like hyper- 
trophy of the islands is occasionally noted. Tumors, cysts, and calculi 
in the pancreatic duct have also been found. The attempt to correlate 
the pancreatic lesions with syphilis has no warrant from the facts.2 In 
about ten per cent, of the cases no alterations are found in the pancreas, 
though functional lesions may be present without corresponding anatom- 
ical change. Excision of the pancreas in man or animals causes diabetes. 
(See also section on the Pancreas, pages 801 to 807). 
Diabetes mellitus may be associated with hemochromatosis and 
cirrhosis of the liver-so-called "bronzed diabetes" (page 65).3 
Under the influence of the doctrine of internal secretions it is now 
commonly assumed that the pancreas, in addition to its intestinal secre- 
tion, furnishes some other substance to the body which is essential in the 
Fig. 286.-Fibrous Replace- 
ment with Hypertrophy of Re- 
maining Cells in Island of 
Langerhans in Case of Dia- 
betes. 
Fig. 287.-Hyaline Degen- 
eration in Island of Langer- 
hans in Case of Diabetes. 
metabolic changes to which the carbohydrates and proteins must be 
subjected in securing normal nutrition.4 Interference with this internal 
secretion of the pancreas is thus assumed to be accountable for the 
faulty metabolism.6 
Diabetes Insipidus. 
The passage of large quantities of urine of very low specific gravity 
is a condition-for it can hardly be called a disease-which is occasion- 
ally met with in persons otherwise in apparently good health. Functional 
tests of the kidneys show normal excretory power, and histological ex- 
1 For the relationship of diabetes to lesions of the pancreas, and particularly to lesions of the islands 
of Langerhans, see Opie, E. L., Disease of the Pancreas, 2d ed., Philadelphia, 1910; for pathological 
physiology of diabetes, see MacLeod, Diabetes; Its Pathological Physiology, London, 1913; and for 
interesting clinical statistics, see Joslin, Treatment of Diabetes Mellitus, 2d ed., Philadelphia, 1918; 
See also Cecil, R. L., Jour. Exper. Med., 1909, xi, 266, 
2 See Rosenbloom, Jour. Am. Med. Assoc., 1917, Ixviii, 1232. 
* See Opie, Jour. Exper. Med., 1899, iv, 279; Sprunt, T. P., Arch. Int. Med., 1911, viii, 75. 
4 Internal secretions which, formed in one organ, are necessary or useful in correlating the functions 
of the organ of origin with those of other organs of the body are called hormones; see Starling, Harvey 
Lectures, New York, 1907-8, p. 115. 
6 Other forms of glycosuria are known which are to be otherwise accounted for. They may be 
associated with lesions of the nervous system or induced by the action of certain poisons, phloridzin 
diabetes for example, or may occur under other conditions. GENERAL DISEASES 
493 
amination of these organs lends no support to the view that the polyuria 
is due to any structural alteration in them.1 
The theory at present accepted is that the condition is caused by 
some lesion of the hypophysis cerebri, for it has frequently been observed 
that tumors of, or alterations2 in this organ result in polyuria. This 
assumption has been based partly on the observations originally made by 
Schaefer3 that the administration of hypophyseal extract caused diuresis 
and that mechanical or thermal stimulation of the hypophysis in living 
animals causes a polyuria, and partly on the fact that polyuria is a 
somewhat frequent clinical symptom in acromegaly and is occasionally 
seen in hypophyseal adiposity. It has long been known that certain 
diseases of the brain,4 especially intracranial tumors and cerebral syphilis, 
are frequently met with in cases of diabetes insipidus. The occurrence 
of this condition with bitemporal hemianopsia has led to the investigation 
of the causes of this rare eye disease. The lesions found have usually 
been syphilitic meningitis, basal tumors, and injuries of the base of the 
brain. In one observation, where a bullet was found lying in the sella 
turcica, the patient suffered from a very marked polyuria, passing six or 
seven liters of urine per day, and also showed some of the other symptoms 
connected with hypophyseal disease, such as adiposity and lack of 
sexual capacity. Cushing5 also has reported a case of hypophyseal 
tumor with diminished secretion and with hypopituitarism and a normal 
urinary secretion, which after an operative decompression of the sella and 
a partial removal of the tumor showed a polydipsia and polyuria, the 
patient passing ten to eleven liters of urine a day. This lasted for some 
three months. 
Diabetes insipidus has also been noticed to follow a carcinomatous 
metastasis into the pars posterior, the normal structure of which was 
almost entirely destroyed. The pars intermedia and the pars anterior 
remained intact. In many cases of diabetes insipidus in which no autopsy 
has been performed, enlargements, deformation, or erosion of the sella 
have been noticed in x-ray pictures. An extraordinary sugar tolerance 
is found in diabetes insipidus; even as much as 450 grams of glucose may 
be given at one time without the appearance of sugar in the urine. Dunn6 
calls attention to the interesting fact that while the sugar was being taken 
the quantity of urine was markedly diminished. From these facts it 
has been assumed that diabetes insipidus is due to a hyperfunction of 
some portion of the hypophysis, possibly the pars intermedia. 
GOUT. 
The characteristic lesion of gout is the presence of an abnormal 
amount of uric acid in the blood and the deposit of urate of sodium in 
the articular cartilages, the ligaments of the joints, the ears, and the 
1 Christie, C. D., and Stewart, G. N., Arch. Int. Med., 1917, xx, 10. 
2 Weber and Schmidt, Am. Jour. Med. Sc., 1916, clii, 892. 
3 Schaefer, Jour. Physiol., 1899-1900, xxv, 87. 
^NewmarK, L., Arch. Int. Med., 1917, xix, 550. 
6 Cushing, H., Pituitary Body and Its Disorders, Philadelphia, 1912. 
8 Dunn, Am. Jour. Med. Sc., 1914, cxlviii, 214. 494 
GENERAL DISEASES 
eyelids. Inflammatory changes may be associated with the deposits 
in the joints. There appears to be an hereditary predisposition to the 
disease.1 
The most frequent situation of the gouty deposit is the metatarso- 
phalangeal joint of the great toe. The cartilage may be infiltrated or 
encrusted with the deposit. These masses of urates, often called chalk- 
stones or tophi, may appear upon the surface by the ulceration of the 
skin (Fig. 288). 
A very important feature of gout is that patients with the gouty di- 
athesis are especially liable to derangements of digestion and to certain 
chronic inflammations, such as chronic inflammation of the arteries, the 
Fig. 288.-Lesions of Gout in the Hands. 
Some of the smaller tophi at the finger tips are ulcerating. 
bronchi, and the kidneys. Cardiac hypertrophy may be associated with 
the arteriosclerosis. The interstitial tissue, especially in the pyramids 
of the kidney, may be infiltrated with the urates. 
The nature of the disturbances of nitrogenous metabolism underlying 
the manifestations of gout is not yet clear, nor are we able to estimate 
the influences of faulty elimination or local tissue alterations upon accum- 
ulations of uric acid in the body. Nor is the relationship plain of local 
inflammatory processes to the gouty deposits. 
SUNSTROKE. (Insolation; Heat Exhaustion.) 
Persons exposed, while at work or when exhausted, to the sun or to 
high temperatures are liable, especially if of intemperate habits, to sud- 
iFor study of gout, see Minkowski, Die Gicht, Vienna, 1903. GENERAL DISEASES 
495 
den prostration, often associated with cardiac failure, asphyxia, convul- 
sions, and coma. Death in many cases soon ensues. 
After death, decomposition sets in early and progresses rapidly. The 
blood usually remains fluid. 
The brain and its membranes are in some cases congested, in others 
not. There may be an increased amount of serum beneath the pia mater, 
or small and thin extravasations of blood beneath the pia mater and 
between the pia and dura mater. Chromatolysis of the ganglion cells has 
been described by Van Gieson1 and others. The thoracic and abdominal 
viscera may be congested; albuminous degeneration may be evident 
in the liver and kidneys. 
In the cases in which cerebral symptoms are protracted for a number 
of days the lesions of meningitis have been found after death. 
According to Cramer,2 persons surviving for some time the first severe 
effects of the heat may suffer important alterations in certain nerve fibers 
of the brain. 
SCORBUTUS. (Scurvy.) 
This disease appears to result from imperfect nutrition under condi- 
tions which cannot be considered in detail here, but which are usually 
attributed to insufficient or inappropriate diet. The lesions are variable, 
the most common being anemia; extravasation of blood in the skin, 
subcutaneous tissue, and muscles; swelling and ulceration and bleeding 
of the gums. Small and sometimes extensive hemorrhages are apt to 
occur in the mucous membranes and on serous surfaces. Small ulcers 
may form in the mucous membranes. Fatty degeneration of the heart, 
liver, and kidneys is not uncommon. The spleen may be large and soft. 
No constant characteristic changes have been discovered, either in the 
blood-vessels or the blood, which would satisfactorily account for the 
extravasations and other lesions. 
The body is apt to decompose early. The skin may be mottled with 
small and large purple, blue, brown, or blackish spots produced by 
degenerative changes in the extravasated blood in the cutis. Sometimes 
ulcers are produced by the perforation of effused blood on to the surface. 
The joints may be inflamed, may contain serum or blood. Rarely the 
hemorrhages are followed by destruction of the cartilages and ends of 
the bones. Very rarely there is hemorrhage between the periosteum 
and bone, and in the bone itself, producing softening and destruction of 
the bone, and separation of the epiphyses. The sternal ends of the ribs 
are the most frequent seat of this change. Albuminous degeneration of 
the heart, liver, or kidneys, and enlargement of the spleen, are common. 
Infantile Scorbutus.-Infants under two years may develop similar 
anemia and tendency to hemorrhages. The most common location of 
the hemorrhages is beneath the periosteum of the bones of the lower 
extremities, especially of the femora, with separation of the lower epiphy- 
i Van Gieson, Toxic Basis of Neural Diseases, New York State Hosp. Bull., 1896, i, 407; also Lambert, 
A., Med. News, 1897, Ixxi, 97. 
2 Cramer, A., Centralbl. f. allg. Path., 1890, i, 185. 496 
GENERAL DISEASES 
ses.1 There may be hemorrhages in the skin and subcutaneous tissues, 
the eyelids, and orbit, and in the internal organs. Hemorrhagic inflam- 
mation and ulceration of the gums are usually limited to infants having 
teeth and to portions of the jaw in which teeth are apparent or just 
about to come into view.2 
That some forms or phases of scorbutus are of infectious nature is 
not improbable, but definite data in this direction are wanting. 
BERIBERI. 
Beriberi is a disease of warm climates, due to the use of rice from which 
the hulls have been removed. These contain a substance called a vita- 
mine, which is apparently indispensable to the body. If the disease is 
not too far advanced it can be cured by adding fresh meat to the dietary.3 
The lesions are often not well defined. There are in some cases sub- 
cutaneous edema and dropsy. There is often degeneration of the 
peripheral nerves and of the heart and voluntary muscle. 
PELLAGRA. 
Pellagra is a disease especially of the rural districts, long prevalent 
in Europe, and now of serious extent and import in the southeastern 
portions of the United States. It is characterized by protean symptoms 
and lesions of the nervous, digestive, and cutaneous systems, such as 
neurasthenia, ataxia, and paralysis; erythema and dermatitis; and pro- 
found disturbances of nutrition. It is not communicable, nor is evidence 
at hand that it is infectious. Its inciting agents or factors are not 
definitely known. But unbalanced food ration, some toxic substance 
or organism in the spoiled maize or Indian corn which is often an impor- 
tant feature in the dietary of those affected, and many other factors and 
agencies have been considered as of possible etiological importance in 
the disease.4 
ACROMEGALY. 
This disease, which was first recognized by Pierre Marie in 1886, is 
characterized by an enlargement of the bones5 and soft parts of the face 
and extremities, and occasionally also of the internal organs. The symp- 
toms are headache, muscular weakness, a loss of sexual activity, gly- 
cosuria, presumably due to pressure on the posterior lobe of the hypo- 
* For details of bone lesions, see Moller-Barlow disease, page 1055. 
2 For a study of scorbutus in infants, Barlow's Disease, which was first recognized in the United 
States by Northrup, consult Northrup and Crandall, New York Med. Jour., 1894, lix, 641. See also The 
American Pediatric Society's Collective Investigation on Infantile Scurvy in North America, Tr. 
Am. Pediat. Soc., 1898, x, 5. For a study of histological changes, consult Jacobsthal, Zieglers Beitr., 
1900, xxvii, 173. 
8 Vedder, Beriberi, New York, 1913; Funk, Die Vitamine, Wiesbaden, 1914; McCollum, E. V., 
Jour. Am. Med. Assn., 1917, Ixviii, 1379. 
•For summaries and bibl., see Roberts, Pellagra, London, 1912; also r6sum6 by Bartholow, New 
York Med. Jour., 1913, xcviii, 1262; and First Report of the Thompson-McFadden Pellagra Commis- 
sion of the New York Post-Graduate Medical School by Siler and Garrison, Am. Jour. Med. Sc., 1913, 
cxlvi, 42, 238; Goldberger, Jour. Am. Med. Assn., 1916, Ixvi, 471. For study of epidemiology of the 
disease see Jobling, J. IF., and Petersen, TP. F., Jour. Infect. Dis., 1916, xviii, 501. For studies on the 
experimental production of pellagra, see Chittenden and Underhill, Am. Jour. Physiol., 1917, xliv, 14. 
8 For details of bone lesions, see page 1045. GENERAL DISEASES 
497 
physis, and a general failure of mental powers, probably correlated with 
the pressure which the growth exerts on the brain. The glycosuria 
occurs only during the periods of functional hyperplasia; at other times the 
assimilation limit for carbohydrate is extraordinarily high. In all the 
published cases of acromegaly a tumor of the hypophysis has been pres- 
ent, and though many of these neoplasms have been called sarcomata, 
in all probability this is due to a lack of recognition of the peculiar 
anatomy of the gland. According to Fischer,1 all such tumors occurring 
in acromegaly belong to the true adenomata. The cells which form these 
adenomata are usually of the eosinophile type, though tumors largely 
composed of basophile cells have been seen; the granules, however, are 
often less definite than in the cells of the normal gland. Occasionally 
an adenomatous growth may develop at a site apart from the gland. 
Erdheim has described one case in which the tumor was situated in the 
body of the sphenoid bone, and other cases are on record in which the 
enlargement was chiefly in the pharyngeal remnant of the hypophysis. 
Persistence of the thymus gland is not infrequently observed in connection 
with acromegaly and an atrophy of the thyroid is also to be noticed. 
Even more frequent than the changes in the two glands mentioned above 
are atrophy of the testicle with changes in the epithelium of the germinal 
tubules and the interstitial cells of Leydig in men, and a cessation of the 
formation of ova in the ovary with ultimate atrophy of the primordial 
follicles in women. In connection with these changes there is also very 
frequently noticed an obliteration of the secondary sexual characteristics. 
Hyperplasia of the suprarenal gland is not infrequent. The exact con- 
dition which underlies the disease is not as yet completely determined. 
Whether the changes in the sexual organs or in the thymus and thyroid 
have anything to do with the production of hypersecretion from the 
hypophysis or with the growth of the adenomatous masses found therein, 
is not as yet settled; but it is evident from what is now known of the 
disease that it cannot be considered as due wholly to the changes in the 
pituitary gland, but that it is correlated with changes in the other glands 
of internal secretion. Acromegaly may, therefore, be fairly considered 
as belonging to the group of polyglandular diseases. The very favorable 
results which have been noted following the partial extirpation of a tumor 
of the anterior lobe of the hypophysis show, however, that this is the 
most important gland in the production of the symptom complex.2 
Another condition connected with alterations in the hypophysis is 
the so-called hypophyseal adiposity or dystrophia adiposogenitalis. The 
persons afflicted show an increasing adiposity, diminished secretion of 
sweat, atrophic changes in the skin in conjunction with hypoplasia of 
the male or female genitalia, and alteration in the distribution of the 
HYPOPHYSEAL ADIPOSITY. 
1 Fischer, B., Hypophysis, Akromegalie und Fettsucht, Wiesbaden, 1910. 
2 For an excellent resume of acromegaly, with cases and bibl., see Brooks, Arch. Neurol, and Psycho- 
path., 1898, i, 485; also Lewis, Bull. Johns Hopkins Hosp., 1905, xvi, 157. For physiology and pathol- 
ogy of the hypophysis, see Biedl, Innere Sekretion, Berlin, 1913; and Cushing, The Pituitary Body and 
its Disorders, Philadelphia, 1912. 498 
GENERAL DISEASES 
pubic and axillary hair. Connected with these changes are symptoms 
which may be best described as infantilism. The pathological lesion 
found in two-thirds of the cases is a tumor of the hypophysis, which in 
contrast to the condition in acromegaly, originates not in the glandular 
anterior portion, but rather in cells derived from the hypophyseal duct. 
Hence a variety of tumors have been found: squamous-cell carcinomata, 
sarcomata, gliomata, teratomata, and the like. The only vital factor 
seems to be the injury of the posterior lobe and the infundibular region. 
Other processes also, such as injury, hydrocephalus, tumors of the base 
of the brain, can give the same symptoms. Whether the changes are 
due to a1 lack of the neurohypophysis or to an interference with the ab- 
sorption of secretion from the anterior lobe is still doubtful. Pressure 
on the posterior lobe causes symptoms connected with the genital glands; 
still stronger pressure causes adiposity. It is to be remembered in this 
connection that adiposity frequently occurs also in connection with 
acromegaly. Cushing has called attention to the fact that in hypo- 
physeal adiposity the assimilation capacity of the body for glucose is 
extraordinarily increased, so that it is almost impossible to produce a 
glycosuria in these patients by the administration of a large quantity 
of sugar, even up to 500 grams of glucose. In contrast to this is the gly- 
cosuria frequently observed in acromegaly. The occurrence of many of 
these physical characteristics in connection with the removal of the 
testicles before the age of puberty, as in eunuchs and persons of certain 
religious sects in Russia, has led to the suggestion that the condition is 
primarily an atrophy of the genital glands; but this is shown not to be 
true by the fact that out of thirty-two cases examined, in only twelve 
was genital atrophy found. The important part played by the hypophy- 
sis has been demonstrated by the experimental work of Biedl and Cushing, 
who have proved that the removal of the posterior and a portion of the 
anterior lobe of the hypophysis in young animals produces a picture quite 
comparable with that seen in man. The animals grow fat, are of low 
mentality, and show a hypoplasia of the genital organs. A more plau- 
sible explanation of the cause of the disease is, therefore, that it is a 
hypopituitarism produced by interference with the absorption or pro- 
duction of the specific glandular secretion. 
GIGANTISM. 
Another form of disease which is correlated with acromegaly, yet in 
which other factors also dominate the picture, is gigantism. In this 
there is evidently a hypersecretion of the hypophysis, a primary atrophy 
of the genital glands, and, probably in addition in some cases, a hyper- 
activity of the thyroid. The condition is actually an anomaly of the 
growth of bone, which leads to a body length exceeding the average of 
the race. X-ray examinations of the skeleton show that the epiphyseal 
junction may remain uncalcified during the progress of growth and that 
there is also an hypertrophy of the bony substance of the long bones. 
The spinal column is often kyphotic or scohotic. The face and ex- GENERAL DISEASES 
499 
tremities frequently show suggestions of acromegalic alterations, such 
as prominent cheek bones, marked superciliary arches, projections of the 
lower jaw, thickening of the bones of the skull, increase in the size of the 
sella turcica, and changes in the hands and feet, consisting in a thickening 
of the end of the bone with growth in length and breadth.1 Enlargement 
of the thyroid has been mentioned. Other striking changes are those 
of the genital glands; there is diminution in sexual activity, lack of potency 
in man, absence of menstruation and ability to conceive in woman. The 
internal genital organs are commonly atrophic, and the external organs, 
such as the penis, vulva, and vagina, are imperfectly developed. The 
distribution of the hair on the body is abnormal; there is often absence 
of the pubic and axillary hair and a very small development of the beard 
in men. The body is frequently more adipose than is normal for the age 
of the person affected. The disease is more common in men than in 
women and begins primarily at the age of puberty. Some of the cases 
ultimately develop a full picture of acromegaly. Alterations in the 
hypophysis are not infrequent, and may consist in a mere hyperplasia of 
the glandular substance, or in the formation of adenomata or vascular 
tumors, while in some cases sarcomata or epitheliomata have been met 
with. The hypophysis may, however, be both macroscopically and 
microscopically normal. The mental activity of these giants is frequently 
very slight, almost always lower than normal. Not all cases of gigan- 
tism, however, belong in this class, for some of these people are perfectly 
normal mentally and show no evidence of pathological change in any of 
the organs mentioned, that is, the hypophysis, thyroid, and genital 
glands. 
The study of a certain small group of dwarfs in which the body is 
well proportioned and the intelligence fairly well developed has led to the 
conclusion that a diminished function of the anterior portion of the hypo- 
physis may explain the condition. In these individuals the epiphyseal 
junctions remain cartilaginous; just as in the hypophyseal forms of 
gigantism, the distribution of the hair on the body is infantile in type and 
the genital organs also remain undeveloped. In some of the cases there 
has been hemianopsia or optic-nerve atrophy, severe headache, polyuria, 
and other symptoms which, with enlargement of the sella turcica, would 
lead to the conclusion that a tumor was developing in the site of the 
hypophysis, accompanied by a diminution in the activity of the anterior 
lobe.2 
DWARFISM. 
PURPURA. 
This name is applied to a variety of conditions in which extravasa- 
tions of blood are present in the skin or the mucous and serous mem- 
branes. 
Hemorrhages, particularly from the mucous membranes, may be se- 
vere and even fatal. This condition is often called purpura hemorrhagica. 
1 For further details, see page 1045. 
2 For further details, see page 1043. 500 
GENERAL DISEASES 
The ecchymoses characteristic of purpura may occur as a result of 
poisoning with certain drugs, and with snake venom; in various cachectic 
conditions; in diseases of the nervous system; in rheumatism; in gastro- 
intestinal disorders, especially of children. The local ecchymoses in 
pyemia are sometimes classed as a form of purpura; and in these, bac- 
teria, especially the pyogenic forms, may be demonstrable.1 
Either from the direct action of poisons; or through degeneration of 
the endothelium of the smaller vessels; or as the result of capillary 
embolisms, extravasation of blood may take place.2 
LYMPHATIC CONSTITUTION. (Constitutio Lymphatica: Status Lymphaticus.) 
Sudden death after the administration of ether or after slight trauma 
is frequently correlated with a pathological condition in which the chief 
lesion is a hyperplasia of the lymph tissue of the body with hypoplasia of 
the heart and aorta. The thymus is often enormously enlarged and may 
reach such a size as to compress the bronchi and large vessels of the upper 
mediastinum. (See Fig. 291 and 292, and section on the Thymus, page 
581.) The pharyngeal, thoracic, and abdominal lymph-nodes are most 
frequently involved in the hyperplasia, the process infiltrating the sur- 
rounding connective tissue. The spleen shows hyperplasia of the follicles 
but is usually not greatly enlarged. 
Clinically, a diagnosis can be made in male adults if with lymphoid 
enlargement there is connected a feminine type of body outline, with 
scanty hair on the face, axilla, and sternum, and a feminine distribution 
of the pubic hair, a slender thorax, a rounded contour of the upper arms 
and thighs with arching of the latter, and hypoplasia of the external 
genitals. In women the hair on the body may be scanty, though 
usually there is more than normal on the face; there is also hypoplasia 
of the genital apparatus and slender thorax and extremities. In children 
the diagnosis is difficult, but may occasionally be made by x-ray demon- 
stration of an enlarged thymus. Such children are usually pale and 
feeble and show general lymphatic enlargement. Rickets, tuberculosis, 
and syphilis are common accompaniments of the disease.3 
The theory has been advanced4 that sudden death in status lymph- 
aticus is due to one of two causes, of which the first and most frequent is 
an anaphylactic reaction due to sensitization of the body by a specific 
nucleoprotein formed in the lymph-nodes as the result of necrosis of 
numbers of germinal follicles; if, before the incubation period has expired 
the tissues are again subjected to the action of the same protein formed in 
the same type of tissue in response to an apparently trivial injury, the 
■ 1 For a more detailed consideration, in the light of recent studies, of cases often grouped under the 
name "Hemorrhagic Infections," consult Honl, I., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1896, 
i, 793 (bibl.). 
2 Duke, W. IF., Arch. Int. Med., 1912, x, 445; and Osler, Brit. Med. Jour., 1914, i, 517. 
3 For a study of the lymphatic constitution and its relationship to sudden death, see Ewing, New 
York Med. Jour., 1897, Ixvi, 37; Bartel and Bauer, Status Thymico-Lymphaticus u. Status-Hypoplasti- 
cus, Leipzig, 1912; ». Neusser, Zur Diagnose des Status Lymphaticus, Wien, 1911 (contains reference 
to work of Norris, page 228); Paltauf, Wien. klin. Wchnschr., 1889, ii, 147; 1890, iii, 24; and Emerson, H., 
Arch. Int. Med., 1914, xiii, 169. 
4 Symmers, D., Am. Jour. Dis. Child., 1917, xiv, 463. GENERAL DISEASES 
501 
anaphylactic reaction is completed. A second cause is the rupture, either 
spontaneously or following apparently trivial injury, of a hypoplastic 
cerebral vessel, the deficiency in the vessel wall being most noticeable 
in the muscular coat. 
Lymph-N odes and -Nodules.-The pharyngeal, thoracic, and abdom- 
inal lymph-nodes are most frequently involved in hyperplasia, the new 
cells often infiltrating the surrounding tissue. There may be hyper- 
plasia of the tonsils, of the cervical, mediastinal, axillary, and abdominal 
lymph-nodes, as well as of the lymphatic tissue of the gastrointestinal 
canal (Fig. 289). 
Fig. 289.-Hyperplasia of Lymphoid Tissue of the Intestine in Status Lymphaticus 
The thymus may be congested and large and soft from hyperplasia. 
It sometimes exerts such pressure on the adjacent bronchi and large ves- 
sels as seriously to impede the action of the heart and lungs. 
The spleen may be moderately enlarged from hyperplasia, especially 
of the lymphoid tissue of the Malpighian bodies, and it may be congested. 
FEVER. (Pyrexia.) 
The heat of the body is derived from tissue metabolism. The heart, 
the muscles, the liver, and other abdominal organs are the great sources 
of heat production. The temperature of the body under normal con- 
ditions is maintained within narrow limits by the heat-regulating mech- 
anism which preserves the balance between heat production and heat 
loss effected largely through the skin and respiratory surfaces. 
Fever may be defined as a general disturbance of metabolism, usually 
due to infection or various forms of intoxication, which leads to a rise of 
the temperature within the body. 
The rise of temperature in fever depends primarily upon an increase 
in the metabolic combustion. Oxygen is used in larger amount than is 502 
GENERAL DISEASES 
usual, while the combustion products, carbonic acid, and the nitrogenous 
substances, urea, uric acid, etc., are excreted in greater abundance. 
This increased combustion is usually associated with disturbances of 
digestion and assimilation of food, so that the abnormal heat production 
is effected largely at the expense of the body proteins of the various 
tissues and organs concerned in metabolism. 
But with the increased heat production there usually occur, in the 
earlier periods of fever, such disturbances in the vasomotor control of 
the cutaneous blood-vessels as lead to their contraction. Thus, heat 
elimination is retarded. In later periods the vessels of the skin may 
dilate so that, in spite of its persistent dryness and lack of the cooling 
effect of sweat evaporation, there is an excessive loss of heat from this 
source. This is not sufficient, however, to balance the excessive heat 
production. We need not consider here the various subjective and 
objective phenomena characteristic of the febrile condition. The height 
of temperature varies in fever, seldom exceeding 42° C. (107.6° F.), and 
is usually much less than this. Even this temperature, if it lasts for a few 
hours, may induce alterations in the cell protein and thus cause death. 
In the great majority of cases fever is due to the presence in the body 
of deleterious substances, either introduced from without, or, more com- 
monly, produced within the body. These are most often formed in 
infections, and arise either from the growth in the tissues of pathogenic 
microorganisms or from the disintegration of their bodies; that is, they 
are toxins or endotoxins. But there is abundant evidence that fever is 
not infrequently due to perverted metabolism of the tissue cells, leading 
to the formation of toxic substances. Such self-engendered substances 
are called autotoxins. The pyrexia of sunstroke is believed to be an 
example of this phase of autointoxication. 
Similarly it is known that certain drugs-cocaine, caffeine, purin bases, 
phosphorus,-various bacterial toxins, and organic substances-proteins, 
leucocytic proteoses, ferments, etc.-introduced from without may induce 
fever.1 
Exactly how these various substances act in the incitement of fever 
is unknown. But one assumes that the cell metabolism is disturbed 
by the poison, while the heat-regulating mechanism is so modified that 
the normal balance is overthrown. That the nervous system may play 
an important role in these disturbances is indicated by the fact that more 
or less persistent elevations of temperature may follow puncture or 
hemorrhage in the corpus striatum or lesions of the bulb or certain other 
affections of the nervous system.2 
1 See Vaughan, Protein Split Products, Philadelphia, 1913. 
2 For a study of fever and allied conditions, see Chantemesse and Podwyssotsky, Les Processus 
gfinSraux, Paris, 1901; see also Krehl, Clinical Pathology, Trans, by Hewlett, Philadelphia, 1905. 
For metabolism in fever, see MacCallum, IF. G., Arch. Int. Med., 1908, ii, 568; Hort, E. C. and 
Penfold, IF. J., Proc. Roy. Soc., London, 1912 (B), Ixxxv, 174; Jona, J. L., Jour. Hyg., 1916, xv, 169; 
and Gibson, R. B., Philippine Jour. Sc. (B), 1914, viii, 475. CHAPTER XIV. 
THE LESIONS IN CERTAIN FORMS OF DEATH FROM VIOLENCE : 
SUDDEN DEATH. 
The Lesions in Certain Forms of Death from Violence. 
SUFFOCATION-ASPHYXIA. 
By suffocation is meant that condition in which, without direct 
pressure on the larynx or trachea, air is prevented from penetrating into 
the lungs. The interruption of the function of respiration which is thus 
brought about induces the condition known as asphyxia. In this way 
many deaths from drowning and strangulation take place. 
The ways in which the supply of air may be cut off from the lungs 
are various. The mouth and nose may be closed by the hand, by plas- 
ters and cloths, by wrapping up the head in cloths, by covering the face 
with earth, hay, grain, etc. Foreign bodies may be introduced into the 
mouth, pharynx, and larynx. Blood may pass into the trachea from an 
aneurysm or from a wound. The glottis may be closed by inflammatory 
swelling. Vomited material may lodge in the larynx. 
On the other hand, injury or disease of the medulla oblongata, or 
paralysis or spasm of the muscles of respiration from drugs, tumors 
pressing upon the air passages, or diseases of the lungs themselves, or 
irrespirable gases which exclude oxygen from the lungs, may induce 
asphyxia. 
External Inspection.-The body should be examined for marks of violence, 
the cavities of the mouth and nose for foreign substances. 
The face may be livid and swollen or present a natural appearance. The conjunc- 
tiva may be congested and ecchvmotic. There may be small ecchymoses on the face, 
neck, and chest. The mouth may contain frothy blood and mucus. The tongue 
may be protruded. 
Internal Examination.-The brain and its membranes may be congested, or 
anemic and edematous, or unchanged. The blood throughout the body is usually 
dark-colored and fluid. 
The larynx may contain foreign bodies which have induced the suffocation. The 
mucous membrane of the larynx, trachea, and bronchi may be congested and some- 
times ecchymotic: these passages contain frothy blood and mucus. The lungs are 
usually congested and edematous, but sometimes do not differ from their ordinary 
appearance. There may be small patches of emphysema near the surface of the lungs. 
Sometimes, especially in infants, small ecchymoses are found in the costal and pul- 
monary pleura. 
The heart usually presents its right cavities full of blood, its left cavities empty; 
but to this there are frequent exceptions. 
The abdominal viscera are usually congested. 
503 504 
THE LESIONS IN CERTAIN FORMS OF DEATH 
Strangulation is effected by the weight of the body in hanging, by 
pressure on the neck with the hands or by some other object, or by con- 
striction of the neck with a cord or ligature of some kind. Death usually 
occurs by asphyxia, or by asphyxia combined with the effect of the 
cutting-off of the blood supply to the brain by pressure on the large 
vessels of the neck. In some cases of hanging, death ensues as a result 
of fracture or dislocation of the cervical vertebrae. 
External Inspection.-The face may be livid and swollen, the eyes prominent, 
the lips swollen, and the tongue protruded. These appearances are, however, often 
absent. Erection of the penis, ejaculation of semen, and evacuation of feces and 
urine are frequently observed. 
In many cases marks are left upon the neck by the objects which have directly 
produced the strangulation. In cases of hanging, the mark about the neck varies con- 
siderably in position, direction, and general characters, depending upon the kind of 
ligature employed, the time of suspension, period after death at which the observation 
is made, etc. The most common mark left by a cord about the neck is a dry, dense, 
brownish furrow, whose breadth corresponds but in a very general way with the diam- 
eter of the cord. In some cases, according to Tidy and others, there may be no mark 
at all if the hanging be quickly accomplished with a soft ligature and the body cut 
down immediately after death. There may be abrasions and ecchymoses of the skin 
at the seat of ligature. 
In capes of strangulation by the fingers the marks on the neck may correspond in a 
general way to the shape of the fingers. 
The application of the same forces immediately after death may produce the same 
marks as when death is induced by them. 
Internal Examination.-The brain and its membranes may be congested, or 
there may be extravasation of blood, or there may be no abnormal appearances. 
The Neck.-In some cases there is effusion of blood beneath the ligature, rup- 
ture of the cervical muscles, fracture of the os hyoides and the cartilages of the larynx, 
fracture and dislocation of the cervical vertebrae, rupture of the internal vertebral 
ligaments and of the inner and middle coats of the carotid arteries. Similar changes 
may be produced in the dead body by the use of great violence. 
If death occur from asphyxia, the internal lesions are similar to those described 
above. In some cases-for example, where death has occurred from fright or shock- 
the results of post-mortem examination are entirely negative. 
DEATH FROM STRANGULATION-HANGING. 
DEATH FROM DROWNING. 
In examining the bodies of persons who are supposed to have been 
drowned, it is necessary to bear in mind a number of questions which 
may arise: Whether the person came into the water alive or dead? 
How long a time has elapsed since death? Whether the person has com- 
mitted suicide, or was drowned by accident, or was murdered? These 
questions are to be solved sometimes certainly, sometimes with prob- 
ability, sometimes not at all, by the post-mortem examination. Per- 
sons dying in the water, to which condition the term drowning is com- 
monly applied, may die from asphyxia, from exhaustion, from fright 
or syncope, from disease of the heart, apoplexy, injuries, etc. While 
in the majority of cases asphyxia is a predominant or important factor 
in death by drowning, the conditions under which death occurs are so 
apt to be complex that in the minority of cases only are the lesions of 505 
pure asphyxia found after death, while in most cases the bodies present 
the more or less well-marked lesions of asphyxia together with those 
indicative of complicating conditions. There are no post-mortem con- 
ditions which alone are absolutely characteristic of drowning, and it is 
only by considering all the facts elicited by the autopsy together that 
any just conclusion can be arrived at. It should always be borne in 
mind, moreover, that even the most characteristic of the evidences 
of drowning are apt to be modified or to disappear as decomposition 
goes on. 
THE LESIONS IN CERTAIN FORMS OF DEATH 
External Inspection.-Post-mortem rigidity usually sets in early, sometimes 
immediately after death. Decomposition progresses, especially in summer, with 
unusual rapidity in bodies which have been removed from the water. Frequently, 
but by no means constantly, the peculiar roughening of the skin, known as goose-skin 
(cutis anserina), is found, but this may occur after death from other causes. A light, 
lathery froth, either white or blood-stained, is frequently seen about the mouth and 
nostrils within twelve to twenty-four hours after removal of the body from the water, 
but it may be absent, and may be seen after death from other causes. After the body 
has lain for several hours in the water (twelve to twenty-four) the thick skin of the 
palms of the hands and soles of the feet may become macerated and thrown into 
coarse wrinkles., just as it may after prolonged soaking during life, or in a dead body 
thrown into the water. The penis and nipples may be retracted, and the scrotum 
shrunken, but this is not constant nor characteristic. 
If the person has struggled in the water and clutched at objects within his reach, 
there may be evidences of this in excoriation of the fingers or in the presence of sand, 
weeds, etc., under the nails or grasped in the hands. 
External marks of injury, bruises, etc., should be sought for, since persons in falling, 
or on being thrown into the water with homicidal intent, may have died from the 
violence, and not, strictly speaking, from drowning. It should also be borne in mind 
in such complex cases that injuries, not in themselves fatal, may, when the body is in 
the water, prove so on account of the inability of the person to rescue himself or gain 
time for recovery from the injury, and that then the struggle for breath may be but 
slight, and the more prominent signs of drowning but little marked. 
Internal Examination.-The Brain.-Congestion of the brain and its mem- 
branes is found only in a small proportion of cases. 
The blood, when death occurs from asphyxia, is usually fluid throughout the body 
and of a dark color, as in asphyxia from other causes. 
The Air Passages.-In persons who die from asphyxia the mucous membrane of 
the larynx, trachea, and bronchi is usually congested, and the air passages contain a 
variable quantity of bloody or mucous froth. In persons dying in the water from 
other causes than asphyxia, these appearances are absent. Foreign substances from 
the water, such as sand, weeds, etc., or materials regurgitated from the stomach, may 
find their way into the air passages during the act of drowning or as a post-mortem 
occurrence. Thus, in bodies washed about the bottom, sand or mud may get into the 
air passages for a certain distance, from the mechanical action of the water. 
The lungs in typical cases are distended so that they fill the thorax and cover 
the heart. The increased size is due partly to congestion, partly to the presence of the 
fluid in which the person was drowned, which is often inspired during the act of drown- 
ing, and partly to the distention of the air vesicles with air. In cases of drowning in 
which there is a struggle and water is breathed in, the lungs may contain considerable 
fluid; but, as a result of decomposition, this may find its way in greater or less quantity 
into the pleural cavities by transudation, leaving the lungs comparatively empty. 
It should be remembered, however, that a considerable quantity of reddish fluid may 
collect in the pleural cavities under other conditions than drowning, through a post- 
mortem change, by transudation from the blood-vessels and other adjacent tissue. 
The Heart.-In those who die from asphyxia the right cavities are usually filled 506 
THE LESIONS IN CERTAIN FORMS OF DEATH 
with fluid blood, while the left cavities are empty. But when death is due to com- 
plex causes this may not be the case. 
The abdominal viscera may be congested in persons who die from asphyxia. 
The Stomach.-The fluid in which the person was drowned, sometimes mixed 
with sand, weeds, etc., may be swallowed during the act of drowning. On the other 
Fig. 290.-Suffocation from the Lodgment of a Large Piece of Meat in the Larynx. 
This individual died within a few seconds after bolting this mass of meat. 
hand, sand may wash for a short distance into the esophagus in dead bodies washing 
about the bottom. 
In persons dying in the water from syncope, shock, etc., we may find no lesions. 
When the death is partly due to asphyxia and partly to other causes, the lesions may 
vary in numerous ways, which need not be described here. 507 
In important cases of doubtful drowning it is desirable carefully to collect and 
save some of the fluid from the lungs and stomach for microchemical examination, 
since the identification of these fluids with those in which the person was presumably 
drowned will often give certainty to an otherwise doubtful case. 
For the detailed consideration of the anatomical diagnosis of drowning, the changes 
which bodies dead from drowning undergo from decomposition, and the factors 
bearing on the question of suicide, homicide, etc., we refer to works on medical 
jurisprudence. 
THE LESIONS IN CERTAIN FORMS OF DEATH 
Sudden Death. 
Some forms of sudden death from violence have been already consid- 
ered. Aside from these, by sudden death, in the ordinary sense, is usu- 
Fig. 291.-Enlarged Thymus-Sudden Death. Child Twelve Years of Age. 
Showing enlarged lymph-nodules at the base of the tongue and in the walls of the pharynx. 
ally meant "the rapid and unforeseen termination of a latent acute or 
chronic disease." We shall not consider here sudden death either from 
violence or poisoning or in well-defined and evident acute or chronic 
diseases: it will be practicable only to enumerate some of the more com- 
mon conditions under which sudden death may occur-and first in the 
adult. 
Circulatory System.-Heart-fatty degeneration, chronic myocarditis, 
abscess of the myocardium, rupture, lesions of the coronary arteries, 
endocarditis, and pericarditis. Blood-vessels-arteriosclerosis, aneu- 
rysms, especially intracranial, intrapericardial, abdominal, and pulmo- 508 
THE LESIONS IN CERTAIN FORMS OF DEATH 
nary; rupture of the aorta, congenital narrowness of the aorta, thrombosis 
or embolism of the pulmonary or cerebral arteries. 
Brain-hemorrhage, meningitis, abscesses, and tumors. Very slight 
Case of sudden death in child of twelve years. 
Fig. 292.-Enlarged Thymus. 
injuries of various parts of the body have been followed by sudden 
death, probably through vagus inhibition. Syncope or shock may ter- 
minate in death. 
Respiratory System.-Foreign bodies lodging at the entrance to the THE LESIONS IN CERTAIN FORMS OF DEATH 
509 
larynx are not infrequently followed by immediate death without evi- 
dence of asphyxia (Fig. 290). Edema of the glottis, edema of the lungs, 
hypertrophy of the thyroid, mediastinal tumors, pleurisy, pneumothorax, 
and pulmonary embolism may lead to sudden death. 
Abdominal Viscera.-Rupture of visceral abscesses; perforation of 
ulcers of the gastrointestinal canal; rupture of the spleen, especially 
if the latter be enlarged as in malaria or typhoid fever; extrauterine 
gestation, retrouterine hematocele, and rupture of the uterus, are among 
the lesions not infrequently leading to sudden death. 
Sudden death is frequent in diabetes, in various forms of kidney 
lesion and in alcoholism, and in association with the so-called lymphatic 
constitution.1 
In young children sudden death is most often associated with disorders 
of the respiratory system; they thus differ from adults, in whom lesions of 
the circulatory system are of the greatest significance. Brouardel attri- 
butes sudden death in children usually to one of five principal causes- 
syncope, convulsions, asphyxia, pulmonary congestion, and intestinal 
disorders. A large thymus (Fig. 291 and 292) with the lymphatic con- 
stitution is frequent in cases of sudden death in young children2 (see 
page 500). 
1 See Ewing, New York Med. Jour., 1897, Ixvi, 37 (bibl.). 
2 For further details on sudden death, consult Brouardel, Death and Sudden Death, English trans- 
lation, 1897; also Ewing, in Peterson and Haines' Text-book of Legal Medicine, Philadelphia, 1904. PART IL 
SPECIAL PATHOLOGY. SPECIAL PATHOLOGY. 
General Considerations. 
We have now completed the study of those fundamental processes 
and structural alterations which are embraced in general pathology 
These have been considered without reference to special regions or 
organs of the body. We here enter upon the study of these pathological 
processes and their associated lesions as they are modified by the special 
conditions and characteristic structures of one and another of the tissues 
or organs or regions of the body. It is clear that both the disease proc- 
esses and the structural alterations with which these are associated 
may be modified by the functional and structural peculiarities of the 
affected organ. Thus while degeneration, regeneration, inflammation, 
etc., may be fundamentally similar, for example, in liver, kidney, and 
nerve, they may present sufficient variation in one or another of these 
parts to require a separate consideration and even a special nomen- 
clature. We shall have occasion to call attention now and then to those 
functional and structural characteristics of the organs which often throw 
much light upon their mode of response to the various excitants of 
disease. 
It is well, on the other hand, to remember that there are in all the 
organs and in most parts of the body certain elementary structures, such 
as connective tissue, blood- and lymph-vessels, and nerves, whose lesions 
are quite similar wherever they may be. So that many forms of lesion 
involving these structures, while of varying significance to the organism, 
differ in the various parts of the body chiefly in distribution or topography. 
513 CHAPTER I. 
THE BLOOD AND THE BLOOD-FORMING ORGANS. 
The blood may be considered as a fluid intermediary tissue, delimited 
from other tissues by little more than a layer of endothelial cells. This 
tissue contains red corpuscles, platelets, and a variety of leucocytes sus- 
pended in plasma. Its composition is extraordinarily constant in the 
normal individual, the only fluctuations being a tidal rise in solid meta- 
bolic substances, such as glucose, fat, urea, amino acids, etc., during 
digestion, and a slight variation in gaseous content between such times 
when the body is at rest and when it is active. Slight variations in the 
number of red and white corpuscles also follow the ingestion of food or of 
large quantities of fluid. 
When the blood clots, the serum is found to contain a large number of 
ferments and antibodies, either normally present in the plasma or set 
free from the leucocytes and blood plates.1 One of these substances, 
known as complement, plays an important role in many of the protective 
mechanisms of the body. 
Changes in the Composition and Structure of the Blood.2 
The Coagulability of the Blood and the characters of the resulting 
clot vary widely, depending partly upon the composition of the fluid 
and partly upon the conditions under which the coagulation occurs. 
There may be very little coagulation of the blood in death from suffoca- 
tion, or from conditions which interfere with the aeration of the blood 
and permit the accumulation of carbonic acid within it. Thus, in death 
from strangulation, high-voltage electric currents, drowning, many 
chronic diseases, or scurvy, and under many conditions which we do not 
understand, the blood may remain fluid, or nearly so, after death. On 
the other hand, in a variety of infectious diseases, such as rheumatism, 
pneumonia, etc., very voluminous clots may be formed, although this is 
by no means constantly the case. The fact that large clots form after 
death is not conclusive evidence that an undue amount of fibrin-forming 
elements was present in the blood, nor does the absence of marked coagu- 
lation prove a diminution in the blood of fibrin-forming elements. 
The composition of the clot varies with the rapidity of its formation 
and with the specific gravity of the plasma. Clots very rapidly formed 
in plasma of high specific gravity, or in blood still slowly circulating, 
1 See Oppenheimer, C., Die Fermente und ihre Wirkungen, 4th ed., Leipzig, 1913. 
2 A fuller discussion of the subjects in this chapter can be found in DaCosta, Clinical Hematology, 
3d ed., Philadelphia, 1905; Naegeli, Blutkrankheiten und Blutdiagnostik, Leipzig, 1912; and Wood, 
F. C., Chemical and Microscopical Diagnosis, 3d ed., New York, 1917. For an extensive bibl. see 
Paltauf, A., Krehl and Marchand, Handbuch d. allg. Pathologie, Leipzig, 1913, ii, and the files of the 
Folia Hsematologica. 
514 THE BLOOD AND THE BLOOD-FORMING ORGANS 
515 
are apt to be dark red, from admixture of red cells and fibrin. After 
complete failure of circulation, especially in plasma of low specific grav- 
ity, the red cells tend to settle to dependent vessels. Yellowish white 
succulent clots then form in the clear supernatant plasma, while soft 
black clots result from the excess of red cells collected in the dependent 
vessels. 
The theory of coagulation of the blood is that four substances 
are necessary for the production of fibrin: fibrinogen, prothrombin, 
thrombokinase, and calcium salts. By the interaction of the latter three, 
thrombin is produced; and this substance acting on fibrinogen causes 
the formation of fibrin, or clotting. The fibrinogen is in solution in the 
plasma. By the action of thrombin upon it, it is split into a soluble 
serum globulin and fibrin. Prothrombin is present in the circulating 
blood and of itself has no action on fibrinogen, but in the presence of 
thrombokinase and a calcium salt, a new body, thrombin, is formed, 
which acts upon fibrinogen. Thrombokinase is not found in the plasma, 
but is present in the tissues and in the leucocytes and blood-platelets. 
It is probably a lipoid substance, cephalin. In addition, the blood con- 
tains an antithrombin which prevents the combination of thrombin and 
fibrinogen. An antiprothrombin, also, is found in the tissues and may 
be present in the blood, preventing the conversion of thrombin into pro- 
thrombin and thus slowing coagulation.1 
The time of coagulation of the blood in healthy persons is fairly con- 
stant when determined by accurate methods. In disease, consider- 
able variations have been noted in the coagulation time. In cases of 
hereditary hemophilia the blood may require 60 to 70 minutes to coagulate 
instead of the normal 7 to 10 minutes. In jaundice the coagulability of 
the blood may be impaired. Some of the severe anemias and purpuras 
may also show moderate slowing of coagulation. Repeated hemorrhages 
shorten the time of coagulation. It has been stated that the injection 
of gelatine into the vessels and the ingestion of calcium chloride or lactate 
also shorten the coagulation time. The facts concerning calcium chlo- 
ride are fairly well established, but the influence of gelatine is still open 
to question. The difficulty lies largely in our inability to obtain a satis- 
factory quantitative method by which the amount of thrombokinase 
can be accurately determined, and the influence of accidental mechanical 
factors can be eliminated. 
Reaction of the Blood.-Owing to the general use of litmus as an 
indicator the reaction of the blood has long been considered to be alkaline. 
This substance, however, does not afford reliable determinations of the 
actual reaction, and it has lately been shown by physicochemical 
methods that the blood may be considered as approximately a neutral 
fluid; that is, that the proportion between the hydrogen and the hydroxyl 
ions is nearly the same as in distilled water. The reason for the apparent 
alkalinity to litmus and the real neutrality of the blood is that there are 
1 Howell, W. H., Am. Jour. Physiol., 1914, xxxvi, 1; and Harvey lectures, 1916 17, Philadelphia, 
p. 272; Minot, Denny, and Davis, Arch. Int. Med., 1916, xvii, 101; Hurwitz and Drinker, Jour. Exper. 
Med., 1915, xxi, 401. 516 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
present in this fluid substances which when dissociated act both as acids 
and as alkalies. The acids are represented by the carbon dioxide dis- 
solved in the plasma and phosphoric acid present as a monosodium 
salt. The alkalies are represented by sodium carbonate and bicarbonate 
and disodium phosphate, which are alkaline in reaction. The proteins of 
the blood also act both as bases and as acids. Litmus not being sensi- 
tive to carbon dioxide is turned blue by the excess of basic ion present. 
If, however, an indicator is used, such as phenolphthalein, no alteration 
in the color is produced; in other words, the blood is actually acid to 
that substance. 
All the older observations based upon litmus as an indicator have 
been abandoned, and the reaction is determined either by observing 
color changes in indicators made up with standard solutions of known 
reaction, or the actual hydrogen ion concentration as determined by 
electrical methods, or indirectly by estimating the carbon dioxide con- 
tent of the expired air.1 These show that even in diabetes, with a high 
content of beta-oxybutyric and acetoacetic acids in the blood, there is 
but very slight alteration in the reaction toward the acid side. The 
maximum change observed in such cases does not render the blood over 
three times as acid as distilled water, and so great is the binding power of 
the proteins and so large the amount of free alkali available for neutrali- 
zation that the conclusion must be drawn that there is no real acid 
intoxication as indicated by marked changes in the blood reaction. 
Anhydremia-the condition in which the blood contains an excessive 
proportion of albumin, cells, and other solid elements-occurs in 
diseases associated with excessive serous discharges from the intestines. 
It is extreme in some cases of cholera, and has been noted in a lesser 
degree in other infectious diseases, as pneumonia and diphtheria. 
After removal of large quantities of fluid from the peritoneal or 
pleural cavities a passing concentration of the blood even to the doubling 
of the number of red corpuscles present may be observed. This is due to 
the rapid transudation of serum from the blood to take the place of that 
withdrawn from the serous cavity. When the balance is again estab- 
lished the anhydremia quickly gives place to the opposite condition, 
hydremia. 
Hydremia is that condition in which the blood contains a large 
amount of water in proportion to the solid ingredients. It occurs in a 
variety of diseases of the heart, lungs, liver, and kidneys, and character- 
izes all forms of anemia. 
Hemoglobinemia.-Owing to the destruction of red blood-cells in 
some forms of poisoning, burning, etc., the blood plasma may contain 
free hemoglobin, by which it is discolored (hemoglobinemia). Hemo- 
globinemia is produced, also, in healthy persons by the transfusion of 
blood from an unsuitable donor (see page 531). 
1 Further consideration of the methods and results cannot be given here. Those interested should 
consult Henderson, Ergebn. d. Physiol. (Asher-Spiro), 1909, viii, 254; Sellards, A., Principles of Acidosis, 
Cambridge, 1917(bibl.); Michaelis, L., Die Wasserstoffionenkonzentration, Berlin, 1914 (bibl.); Sdrenson, 
S. P. L., Ergebn. d. Physiol. (Asher-Spiro), 1912, xii, 393; Van Slyke, D. D., Jour. Biol. Chem., 1917, 
xxx, 289 ff.; and Macleod, J. J. R., Physiology and Biochemistry in Modern Medicine, 3d ed., St. Louis, 
1920. 517 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
A similar destruction of the red cells with solution of the hemo- 
globin is occasionally observed following direct transfusion in persons 
suffering from severe anemia, especially of the pernicious type. 
Anemia.-In general, anemia means a diminished quantity of blood 
or of red blood-cells in the vessels of the whole or any part of the body. 
With one exception-mild chlorosis-it is invariably characterized by a 
reduction in number and change in form of the red cells (oligocythemia), 
and occasionally by lowered alkalinity and coagulability. It is associated 
with a reduction in specific gravity, in hemoglobin, and in solid elements. 
Hydremia and an increased tendency toward osmosis are equally con- 
stant features of this condition. The albumins remaining in the serum 
after coagulation are very slightly diminished in anemia. 
Generally speaking, anemia is produced by excessive hematolysis, 
or by defective hematogenesis, or by actual loss of blood, in bulk (hem- 
orrhage), or in its fluid ingredients (transudation). 
Anemia may be secondary to hemorrhage, to exudative processes 
to prolonged malnutrition, to chronic organic diseases of many kinds, 
especially of the kidney, to the action of poisons, to congenital hypo- 
plasia of heart and arteries, to functional disturbances of an unknown 
nature in the blood-forming organs, and to wholly unknown causes. 
Simple atrophic changes in many tissues, hypertrophy of the red marrow, 
lymph-nodes, spleen, liver, and thymus, fatty degeneration of the liver, 
kidneys, heart, and blood-vessels, with capillary hemorrhages and 
transudations, are frequent accompaniments of severe anemia. 
Polycythemia.-By polycythemia in its proper usage is meant an 
increase in the number of corpuscles in the blood without necessarily an 
increase in the total volume. This condition is frequently noticed in 
chronic dyspnea from either congenital or acquired heart disease, in 
certain chronic diseases of the lungs accompanied by cyanosis, and after 
poisoning by illuminating gas. What may be termed a physiological 
polycythemia has been observed in persons living at high altitudes. 
This has been attributed to the stimulating effect of the diminished 
oxygen partial pressure on the blood-forming organs, which causes them 
to produce an excessive number of red cells, and to the rapid evaporation 
from the skin which takes place, thus concentrating the blood by the 
transfer of plasma from the blood to the tissues. The question can not, 
however, be regarded as finally settled.1 Another form of physiological 
polycythemia is seen after severe labor and is regularly found in those 
in athletic training. Whether this increase is simply a hyperplasia 
of the blood due to the demand for more working material to carry oxygen 
or to a circulatory readjustment is not yet determined.2 
The other type of polycythemia, seen in diseases in which the circula- 
tion is interfered with, is probably entirely a local phenomenon, the 
increase in the number of corpuscles being due in all probability to the 
concentration of the blood-cells in the peripheral capillaries. This is 
1 For a very full discussion of the work of previous observers and many important personal obser- 
vations, see Zuntz, Lowy, Miiller, and Caspari, Hohenklima u. Bergwanderungen, Berlin, 1906. 
2 See Hawk, P. B., Am. Jour. Physiol., 1904, x, 384; Lamson, P. D., Jour. Pharmacol, and Exper. 
Therap., 1916, ix, 129; Scott, F. H., Am. Jour. Physiol., 1917, xliv, 298, 313. 518 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
induced by the increased viscosity of the blood incident upon the in- 
creased carbon dioxide content following the imperfect aeration in the 
lungs. The polycythemia disappears in such cases very promptly on 
inhalation of oxygen, and at the same time the viscosity falls. As soon, 
however, as the oxygen treatment is terminated the peripheral stasis 
reappears. In cases of chronic cardiac disease with broken compensa- 
tion the disappearance of the polycythemia is noted as soon as the heart 
lesion improves. While the polycythemia is usually a general phenom- 
enon, that is, the blood concentration exists in all the peripheral vessels, 
it may occasionally be local. The most striking example of such local 
concentration of the formed elements of the blood is seen in cases of 
intrathoracic tumor with a compression of the superior vena cava and 
azygos veins. Under these circumstances intense congestion of the upper 
extremity may be induced, and blood taken from the finger may show a 
million more red cells to the cubic millimeter than that taken from 
the toe.1 
Plethora.-The existence of a true plethora, that is, an increase in 
the volume of the blood accompanied by a coordinate increase in cor- 
puscles, has long been debated; but recently cases have been reported, 
occurring chiefly in persons suffering from a disease of unknown etiology, 
generally accompanied by hyperplasia of the spleen or bone-marrow, high 
blood pressure, and cyanosis, and designated clinically as polycythemia 
or erythremia. In a few instances large solitary tubercles of the spleen 
have been found. The number of red and white cells and the amount of 
hemoglobin are greatly increased. The condition of plethora may be 
suggested at autopsy by the very great distention of all the vessels and 
the overfilling of the organs with blood.2 The only accurate method, 
however, is to determine the total amount of blood in the body during 
life by a procedure such as Haldane's,3 by which the patient inspires a 
measured quantity of carbon monoxide. A sample of the blood is then 
taken and analyzed to determine what percentage of hemoglobin has been 
altered into carbon monoxide hemoglobin.4 
THE RED BLOOD-CELLS. 
These may be diminished in number and may undergo various 
changes in shape and size and structure. 
Alteration in Number of the Red Blood-Cells. 
Oligocythemia is that condition of the blood in which the number of 
the red cells is reduced. This reduction in number may be temporary, 
as after hemorrhage, or it may be persistent, as in some forms of anemia. 
The number of red blood-cells may in extreme cases of anemia be reduced 
1 For study of polycythemia, with ,bibl., see Lucas, W. S., Arch. Int. Med., 1912, x, 597; Senator, 
Polyzythamie und Plethora, Berlin, 1911; and Hirschfeld, Polyzythamie und Plethora, Halle, 1912. 
2 Westenhoefer, Ein Beitrag zur pathologischen Anatomie der plethora vera, Deutsch, med. 
Wchnschr., 1907, xxxiii, 1446. 
3 Haldane and Smith, Jour. Physiol., 1897, xxii, 231; 1900, xxv, 331. 
4 For a full review of the subject see monograph by Weber, F. P., Polycythemia, Erythrocytosis and 
Erythremia, London, 1921. THE BLOOD AND THE BLOOD-FORMING ORGANS 
519 
to one-tenth of the normal, or even less; that is, from the normal num- 
ber, which is between four and five millions, there may be a reduction to 
half a million or less. 
A persistent diminution in the number of red cells may be effected 
either by increased destruction (hematolysis) or by defective formation 
of these elements, but the relation of the two factors in the production 
of the chronic anemias is as yet imperfectly determined. 
Excessive hematolysis occurs after burns, is the result of poison- 
ing by arsenic, phosphorus, and chlorates, phenylhydrazin, nitrobenzol, 
acetanilide, etc., and may occur in infectious diseases through the action 
of bacterial toxins. All stages of a peculiar destruction of red blood- 
cells may readily be followed in the blood in malaria. In chronic infec- 
tious diseases and in prolonged suppuration, destruction of red cells is 
probably effected, in part, by toxic agents circulating in the blood. In 
pernicious anemia the condition of the blood may, with considerable 
certainty, be referred largely to a destruction of red cells by some un- 
identified toxic material in the blood. 
In the destruction of the red cells, especially if rapid, hemoglobin 
may separate from the cells, dissolve in the plasma (hemoglobinemia), 
and may then be excreted unchanged in the urine (hemoglobinuria). 
Such destruction occasionally follows chilling of the extremities after 
exposure to cold in persons suffering from a disease known as paroxys- 
mal hemoglobinuria.1 
The gradual and more common form of destruction of red cells is 
attended with an alteration of the hemoglobin, effected chiefly in the 
liver, and with its deposit in the endothelial and glandular cells of vari- 
ous organs, especially in the liver, spleen, kidneys, and bone-marrow, and 
secondarily in any of the tissues. 
A part of the altered hemoglobin is to be found in the form of pig- 
ment granules, or as a diffuse deposit, in the cells of the above-named 
organs, where its content of iron may or may not be demonstrable by 
microchemical tests (hemosiderin). Another product of the hemoglo- 
bin, not containing iron, may be found in the same situations, in the 
forms of granules or crystals (hematoidin). Finally, the derivatives of 
hemoglobin are excreted largely in the form of normal or pathological 
urinary pigment. The remaining fragments and stroma of the red cells 
are soon removed from the circulation largely by leucocytes, and partly 
by endothelial cells and giant cells, in the liver, spleen, and marrow. 
Defective hematogenesis must be regarded as an important factor 
in the production of such anemias as are associated with pathological 
changes in the bone-marrow (pernicious anemia), and in the lymph-nodes, 
spleen, and liver (leukemia). This, too, is probably the chief cause of the 
persistence of an anemia following prolonged malnutrition (secondary 
anemia). The pathological changes in the blood-producing organs may 
sometimes arise as primary diseases of these organs, or similar changes 
may be secondary to excessive demands for the regeneration of the blood. 
1 For an interesting study of the conditions underlying the hemolysis which occurs in paroxysmal 
hemoglobinuria, see Donath and Landsteiner, Ztschr. f. klin. Med., 1906, Iviii, 173. 520 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
In mild grades of anemia the regeneration of the blood is attended with 
an hyperplasia of the red marrow, which replaces the yellow marrow of 
the long bones. The chief defect in the production of red cells may 
then be a deficiency in hemoglobin {chlorosis}. In severe and prolonged 
anemia, under the influence of toxic agents in the blood, the reproduction 
of cells may be insufficient, and these new cells may be more susceptible 
to the action of the toxic agent, which is itself the cause of their structural 
defects. In such cases the normoblasts of the marrow may be produced 
in very large numbers and form red cells of normal or slightly diminished 
size, or they may be replaced by very large nucleated red cells {megalo- 
blasts} ; from these are developed very large red cells which are compara- 
tively incapable of the functions of the normal cell. The megaloblastic 
form of regeneration is confined to the anemia of a pernicious type, with 
the exception of the form due to the Bothriocephalus latus or that 
following the prolonged action of certain organic poisons such as nitro- 
benzol. 
In mild forms of anemia the red cells are deficient in hemoglobin, the 
blood may be pale or watery in appearance, and the cells appear in the 
fresh condition as very pale discs or as slightly refractive rings inclosing 
a nearly colorless central mass. In dry preparations stained with eosin, 
such cells may show only a narrow red ring surrounding a central por- 
tion which is entirely devoid of hemoglobin. In this grade of anemia 
there may be noted moderate differences in size and irregularities in 
shape of the red cells. In severe anemia and under a variety of con- 
ditions, as after certain forms of poisoning, extensive burns, etc., varying 
numbers of very small red cells are seen, called microcytes. They are 
spheroidal or irregular in shape, and may be excessively minute, and their 
hemoglobin is either increased, or normal, or diminished. Under similar 
conditions, red cells are found in a variety of bizarre forms, called poiki- 
locytes. In certain forms of anemia very large red cells occur in consider- 
able numbers. These cells, called megalocytes, are derived from the large 
nucleated red cells of the marrow, and their appearance in the blood 
indicates the early onset or actual establishment of some form of pro- 
gressive pernicious anemia (see Plate IV, Fig. 4). 
Ameboid movement of megalocytes has been observed in specimens 
from the blood of pernicious anemia examined on a warm stage. The 
tendency of the red cells to form rouleaux is much diminished or absent 
in very grave anemia. 
Not infrequently a loss of hemoglobin is associated with a change in 
the stroma of the cell, so that the mass stains slightly with methylene 
blue. To this change the name of anemic or polychromatophilic degen- 
eration has been given, and it is thought to show a more or less com- 
plete coagulation necrosis, by which change the protoplasm of the red cell 
becomes more basophilic1 in its staining reaction, though recent investi- 
Alterations in Morphology of the Red Blood-Cells. 
1 It is convenient to classify the dyes used in staining into the acid, the neutral, and the basic, and 
to designate cells, in accordance with the relative persistency with which they hold these dyes, as acido- 
phile, neutrophile, or basophile. 521 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
gations have shown that similar cells are present in normal bone-marrow 
and in the blood of the fetus. It is therefore probable that our staining 
methods do not differentiate between a degenerative change in the body 
of the cell and a condition expressive of physiological youth. Normally, 
perhaps, such cells are retained in the marrow until fully developed and 
appear in the blood only when excessive demands are made upon the 
blood-forming organs. 
Instead of a uniform absorption of the dye some parts of the cell may 
be condensed in the form of small granules or rings occupying the cell 
body and staining more deeply with methylene blue than do normal 
cells (granular degeneration). 
It should be remembered that during the manipulations required in 
making dried specimens the red cells may suffer a variety of artificial 
changes, many of which are very confusing. 
Nucleated red blood-cells are found in the blood in all forms of anemia, 
and their appearance indicates regenerative activity on the part of the 
blood-producing organs. Their presence in the blood in large numbers, 
though at all periods of extrauterine life abnormal, has been regarded 
as of favorable import in disease. Within a few hours after severe 
hemorrhage nucleated red cells may be noted in considerable numbers.1 
During the regeneration of the blood in anemia, the occurrence of nucle- 
ated red cells is nearly constant, but subject to rather sudden periodical 
variations sometimes called "blood crises." In favorable cases of anemia 
nucleated red cells of normal size only (normoblasts) (Plate IV, Figs. 
2 and 3) are seen, whose compact, darkly staining nuclei may be found 
either in the center of the cell or slightly protruding from the periphery; 
or, nuclei apparently quite extruded from the cell may be found free in 
the plasma. 
In severe anemia attended with an abnormal type of blood formation, 
very large nucleated red cells (megaloblasts) (Plate IV, Fig. 4) appear 
in varying numbers. The protoplasm of these cells often shows an 
excess of hemoglobin, but frequently the purple stain produced by a 
combination of the eosin and methylene blue indicates an altered form 
of hemoglobin, or very fine basophile granules may be demonstrated 
by treatment with methylene blue. The nuclei of the megaloblasts 
may be single and compact, or a single large nucleus may show stages of 
direct division, or in extremely large cells (gigantoblasts) the nuclei may 
present phases of mitosis. 
THE WHITE B'LOOD-CELLS. 
The Leucocytes of Normal Blood. 
The leucocytes of normal blood may be classified according to their 
place of origin, or by the character of their nuclei, or by the reaction 
of the granules in their protoplasm to certain dyes. The most service- 
1 The appearance of nucleated red cells and abnormal forms has been frequently noted in those who 
have recently arrived in mountainous regions, the probable explanation being that the lowered oxy- 
gen tension of the rarefied air demands a larger amount of hemoglobin to supply the wants of the tissues, 
with the result that for a short time immature red cells are set free from the bone-marrow. 522 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
able classification is that based both upon the character of the nucleus 
and upon the reaction of the protoplasm to dyes, according to which we 
may distinguish in normal blood the following forms (see Plate IV, Fig. 1): 
1. Lymphocytes, small leucocytes of about the size of red cells or 
larger, with a single, compact, deeply staining nucleus, surrounded by a 
thin rim of homogeneous protoplasm. The cell body usually possesses 
a stronger basophilic reaction than the nucleus, so that in staining with 
methylene blue the nucleus shows as a pale spot in the center of the dark 
ring of the cell body. This ring is often ragged in its outline and may 
show distinct projections which are sometimes cast off into the circu- 
lating blood. Large and small lymphocytes may be distinguished 
(Plate IV, Fig. 5). 
When deeply stained with a methylene azure-eosin mixture, the 
bodies of a certain number of the lymphocytes show moderate numbers 
of so-called azure granules. These granules are usually not found in the 
lymphocytes from normal blood. They have been variously interpreted 
(a) as granules of the same specific quality as those in other leucocytes, 
(b) as secretory products of the cell protoplasm occurring during degen- 
erative changes, and, finally, (c) as very small nuclear fragments set free 
in the protoplasm of the cell. The last view is strongly suggested by 
morphological appearances in the cells. 
2. Large mononuclear leucocytes, with a single, compact or vesicular, 
rather faintly staining nucleus, and a relatively large amount of proto- 
plasm which stains much less strongly than the nucleus. According to 
Ehrlich, these cells represent a type different from the lymphocytes and at 
present are usually classed with the clasmatocytes or monocytes derived 
in all probability from the lymphatic or vascular endothelium. They 
may contain azure granules or some still regard them as precursors of 
the myelocytes. 
3. Transitional leucocytes, of the same size as many of the large 
mononuclear leucocytes, with a compact or vesicular, irregular or 
incurved nucleus, and a considerable mass of protoplasm, in which fine 
neutrophile granules can occasionally be demonstrated. 
4. Polynuclear neutrophile leucocytes, of the same size as the tran- 
sitional leucocytes, with a partially or completely divided nucleus, of 
which the separate portions are either compact or vesicular, deeply or 
faintly staining, and with considerable protoplasm in which distinct 
granules may be demonstrated by the neutral dyes. 
5. Eosinophile cells, of the same characters as the ordinary poly- 
nuclear leucocytes, but containing in their bodies large refractive gran- 
ules, which stain deeply with so-called acid dyes such as eosin. 
6. Basophile cells, of about the same size as the polynuclear cells, 
but containing coarse granulations stained only by basic dyes such as 
methylene blue. The nucleus is small, stains feebly, and is usually 
lobular. It is often covered very largely by the granulations. 
These various forms of leucocytes occur in normal blood in the fol- 
lowing proportions, which represent averages only and are subject to 
considerable variations: THE BLOOD AND THE BLOOD-FORMING ORGANS 
523 
Polynuclear neutrophile leucocytes 60 to 72 per cent. 
Large mononuclear and transition forms 2 to 4 per cent. 
Lymphocytes 22 to 35 per cent. 
Eosinophiles 2 to 4 per cent. 
Basophile cells less than 0.5 per cent. 
In the normal blood of young children the relative proportion of 
mononuclear cells is considerably greater than in that of adults.1 
The numbers and proportions of the polynuclear leucocytes are in 
disease subject to very wide variations, and abnormal forms of the 
white cells frequently make their appearance in the blood. 
The Leucocytes of Abnormal Blood. 
1. Myelocytes.-In many diseases, especially the leukemias but also in 
acute infections, large mononuclear cells make their appearance in the 
blood. They measure from 15 to 20 n in diameter. (Plate IV, Fig. 6.) 
Three types may be differentiated by the tinctorial relations of their gran- 
ules: neutrophilic, eosinophilic, and basophilic. The nucleus is usually 
pale, and oval or round, and lies to one side of the cell. The protoplasm 
is generally fairly abundant. The neutrophile myelocytes contain large 
numbers of fine neutrophile granules which, however, often show a baso- 
philic habit when compared with the neutrophile granules of normal 
blood. 
Eosinophile myelocytes are of much the same type, but are easily 
differentiated by the large size of the granules. The cells are very easily 
destroyed in the process of making smears, and the granules may be 
scattered to a considerable distance from the nucleus. 
Basophile myelocytes are quite rare, are usually smaller than the 
other two types, and contain large numbers of irregularly shaped baso- 
phile granules. 
All these types of cells arise normally from the bone-marrow and can 
be found in smears from this organ. In advanced leukemias it is probable 
that the liver and spleen assume to a certain extent their embryonic 
function and act as centers for the production of these cells. 
Myelocytes are found in the blood chiefly in leukemias, but the neutro- 
phile form occasionally appears in severe infectious diseases and in 
primary or secondary tumors of the bone-marrow. Eosinophile myelo- 
cytes have been very rarely seen in high eosinophilia due to the presence 
of parasites in the body. 
2. Large Lymphocytes.-While cells of a lymphocytic type appear in 
normal blood in moderate numbers, a very large cell giving the same 
staining reactions also occurs in acute lymphatic leukemia. Until 
recently these cells were considered as unquestionably large types of 
lymphocytes; but the demonstration of proteolytic and lipolytic fer- 
ments by Longcope2 and of oxidases by Schultze3 suggests that the cells 
belong to the bone-marrow group, and not to the true lymphocytes, which 
i See Schloss, O. M., Arch. Int. Med., 1910, vi, 638. 
2 Longcope and Donhauser, Jour. Exper. Med., 1908, x, 618. 
3 Schultze, W. H., Munchen, med. Wchnschr., 1909, Ivi, 167. Description of Plate IV. 
All the Specimens are Stained with Eosin and Methylene-azure. 
Fig. 1. Normal Blood.-The red cells are nearly uniform in size and shape. The hemoglobin 
is fairly evenly distributed, but is slightly more dense near the periphery than at the center, especially 
in those cells which have dried slowly. In rapidly dried red cells the stain is even throughout. To 
the left is a lymphocyte with reddish, deeply stained nucleus and a pale bluish cell body, which is 
narrow in proportion to the size of the nucleus. To the right is a small lymphocyte, smaller than the 
red cells which surround it, with a deeply stained nucleus and a narrow cell body from which projects 
a small mass of protoplasm. At the upper portion of the figure is a large oval cell which corresponds 
to the large mononuclear cell of Ehrlich, but is considered by many equivalent to a large lymphocyte. 
In the center of the drawing is a cell with a lobed nucleus and purplish granules by which this basophile 
cell is distinguished from the neutrophile just below it and from the eosinophile in the right lower 
quadrant. Two neutrophile cells are shown, one with abundant fine granules, the other showing a 
smaller number; both types being abundantly present in normal blood. To the right is a small cluster 
of blood-plates, some of which show darker staining masses near the center which are presumed by 
some observers to be nuclear remains, by others to be fragments of hemoglobin. The eosinophile 
cell in the lower right-hand quadrant is distinguished from the neutrophile by the coarseness of its 
granules, which are shot-like and quite regular in form, though not all the granules are of the same size. 
They often take a much more brilliant red color than the neutrophiles. 
Fig. 2. Chlorosis.-The blood was obtained from a young woman of twenty-two years, who 
had 3,000,000 red cells and 30 per cent, of hemoglobin. The red cells are about of the same size 
as those in normal blood, but show a greatly diminished amount of hemoglobin to the individual 
cell, as evidenced by the much fainter staining of a number of cells in the plate which appear merely 
as remnants. Some of the cells have assumed irregular shapes and are known as poikilocytes. In 
the left upper quadrant are three forms which may be considered as pathological in circulating blood. 
Below, to the left, is a purplish red cell rather deeply stained, showing polychromatophilia. To 
the right of this cell and separated from it by a nucleated red cell of normoblastic type is a cell showing 
granular degeneration. 
Fig. 3. Secondary Anemia.-The blood was obtained from a case of carcinoma of the stomach 
in which the red cells were reduced to 1,500,000; the hemoglobin was 25 per cent.; the leucocytes, 
30,000. The changes in the red cells are much the same as those noted in the chlorotic type. There 
is marked diminution of the hemoglobin of the red cells with poikilocytosis and also granular degenera- 
tion and polychromatophilia. Two nucleated red cells are present, one in the upper right, the other 
in the lower left-hand quadrant. Both show degenerative changes in the nuclei, which should not be 
mistaken for mitotic figures. In secondary anemia of this type the polynuclear neutrophiles are nota- 
bly increased. 
Fig. 4. Pernicious Anemia.-The blood was obtained from a case showing 400,000 red cells, 10 
per cent, of hemoglobin, and 3,000 leucocytes. The striking features of the blood in this disease are 
the marked alterations in size, shape, and staining properties of the red cells. The leucocytes are 
usually diminished in number and show no characteristic changes, with the exception of a relative 
increase in the lymphocytes. The various types of deformation of the red cells are very well noted in 
the various poikilocytes in the sketch, some of which contain large quantities of hemoglobin, others 
a diminished amount. In the red cells approaching more nearly to the normal form it will be imme- 
diately noted that the amount of hemoglobin present as evidenced by the depth of stain is relatively 
large. The cell in the center of the field, for example, stains a great deal more deeply than any normal 
cell. These deeply staining cells are also very large and often of peculiar oval and irregular form. 
The so-called megaloblasts are abundantly present in the blood of pernicious anemia, in contrast 
to the microcytic type of cell usually found in the secondary anemias and in chlorosis. It is this 
macrocytosis with the consequent increase in the hemoglobin content of each cell that gives rise to 
the high relative hemoglobin index of the blood of pernicious anemia. A normal-size cell showing 
marked polychromatophilia is seen above; a macrocyte with granular degeneration is seen below it, 
and a normal-size red cell with nucleus, or normoblast. In the lower left quadrant is a large erythro- 
cyte with a large nucleus with fine chromatin network. The cell body takes on a combination of the 
blue and pink of the stain; in other words is polychromatophilic. Below it is a normal lymphocyte. 
In the lower right quadrant are two other megaloblasts showing a slightly different morphology and 
with an orthochromatic protoplasm; that is, the cell body takes the eosin alone. The upper cell shows 
a dense nucleus with thick strands of chromatin forming a network. In the lower the chromatin shows 
no structure. 
Fig. 5. Chronic Lymphatic Leukemia.-The blood of this case showed 3,500,000 red cells, 
160,000 leucocytes, and 50 per cent, of hemoglobin. Of the leucocytes 95 per cent, were lymphocytes. 
It will be noted from the drawing that the red cells are practically normal in size and shape. The 
abundance and variety of the lymphocytes will be noted immediately. In the upper right quadrant 
is a single normoblast; in the lower right quadrant of the upper part is a washed-out cell with irregu- 
lar outline which is a degenerated lymphocyte. In the acute forms of lymphatic leukemia these cells 
become exceedingly abundant. 
Fig. 6. Myelogenous Leukemia.-The blood of this case showed 1,000,000 red cells, 20 oer 
cent, hemoglobin, and 1,200,000 leucocytes, the exact proportions of which could not be determined 
on account of the large number of irregular and degenerated forms, but myelocytes and basophiles were 
very abundant. In the upper left quadrant can be seen an eosinophile myelocyte with a single oval 
nucleus and large shot-like granules. Below it are a normoblast with granular degeneration of the 
protoplasm and a polymorphonuclear neutrophile with fine granules. In the lower left quadrant can 
be seen a large degenerated neutrophile mvelocyte in which the granules have become scattered over 
the slide in the process of spreading the blood. To the right and below the center are a normoblast 
with clover-leaf nucleus, a pnlvmomhonuclear neutrophile and a lymphocyte, and above an eosinophile 
mvelocvte. Tn the upper right quadrant, beginning at the left, can be seen a small basophile cell with 
faintlv staining nucleus, to the right two myelocytes, one with deeply staining nucleus, the other 
somewhat fainter, both containing neutrophile granules. To the right a normoblast with pyknotic 
nucleus, and still farther to the right a so-called basket-cell or degenerated leucocyte. 
524 Pathology-Delafield and Prudden. 
Plate IV. 
Fig. i. Normal Blood. 
Fig. 2. Chlorosis. 
Fig. 3. Secondary Anemia. 
Fig. 4. Pernicious Anemia. 
Fig. 5. Chronic lymphatic Leucemia. 
Fig. 6. Myelogenous Leucemia. 
Changes in the Morphology of the Blood. 
Drawn by Francis Carter Wood. 
(Magnified 900 Diameters) THE BLOOD AND THE BLOOD-FORMING ORGANS 
525 
do not give these reactions. A further discussion of this question will be 
found under acute lymphatic leukemia (page 538). 
3. Plasma Cells.-In severe anemias and leukemias and in certain 
of the infectious diseases, large cells measuring 6 to 15 p, with a single 
pale nucleus and a cell body staining very deeply with methylene blue, 
appear in the circulation. The cell body shows a definite spongy struc- 
ture. These were named by Turk1 "irritation forms." It has been 
shown that these cells have many tinctorial relations with the cells seen 
in large numbers in chronic inflammations occurring in connective tissue, 
and though there are slight morphological differences between the two 
forms yet these blood cells are usually considered as of the plasma-cell 
group. 
4. Myeloblasts.-In myelogenous leukemia and also in typhoid fever, 
large cells resembling myelocytes appear in the circulation, but they 
contain no characteristic granules stainable either with the Jenner or 
any one of the azure stains. They can be differentiated from the large 
mononuclears by the fact that the nucleus is very rich in chromatin and 
shows large nucleoli. The protoplasm also is more basophilic than that 
of the large lymphocytes. These cells have been named myeloblasts by 
Naegeli. 
Leucocytosis. 
Leucocytosis is that condition of the blood in which the leucocytes 
are temporarily or persistently increased in number. When several 
forms of leucocytes are increased in number and the usual proportions 
are but partially disturbed, we speak of mixed leucocytosis. Such a con- 
dition is seen in some forms of anemia. When the polynuclear neutro- 
phile leucocytes alone are increased, the condition is termed polynuclear 
leucocytosis, or simply leucocytosis. If the mononuclear cells are chiefly 
affected, the condition may be denoted as lymphocytosis. The eosino- 
phile cells alone may be increased. 
Polynuclear leucocytosis may be either physiological or pathological. 
Physiological polynuclear leucocytosis is seen during normal digestion, 
in the later months of pregnancy, and in the first days of infancy, and 
is usually of moderate grade. 
Pathological polynuclear leucocytosis occurs in many inflammatory 
and infectious diseases, and accompanies the various cachexias. Of the 
infectious diseases attended with leucocytosis may be mentioned pneu- 
monia, diphtheria, scarlet fever, erysipelas, rheumatism, suppurative 
cerebrospinal meningitis, and any disease associated with a pronounced 
exudative or suppurative lesion. On the other hand, leucocytosis is 
absent in uncomplicated typhoid fever, typhus, malaria, measles, influ- 
enza, and tuberculosis. 
The origin and significance of the leucocytosis of infectious diseases 
are imperfectly understood, but may be partially explained by the princi- 
ples of chemotaxis and phagocytosis. From experimental evidence and 
1 Turk, Vorlesungen uber klinische Hamatologie, Wien, 1904. 526 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
clinical observation it is known that during the onset of some infectious 
diseases the entrance of bacteria or their products into the blood is fol- 
lowed by a disappearance from the circulation of many polynuclear leu- 
cocytes, which are removed from the larger vessels and lodged in the 
capillaries, principally in the lungs and liver. This condition of the 
blood, called hypoleucocytosis, may be attended with a transient reduc- 
tion in temperature and weakening of the heart's action, and is usually 
succeeded shortly by the reappearance of polynuclear leucocytes in 
large numbers, and by a rise of temperature. These leucocytes are apt 
to gather in regions in which microorganisms are abundant, and are 
believed to take up and destroy microorganisms (phagocytosis'), and to 
prevent their further entrance, and possibly the entrance of their prod- 
ucts also, into the circulation. Of the place and method of origin of 
these new leucocytes very little is definitely known. 
In many very severe cases of infectious disease, such as pneumonia, 
diphtheria, and peritonitis, the initial hypoleucocytosis persists, in which 
event the disease usually runs an asthenic and fatal course, with a ten- 
dency to low temperature and feeble pulse. 
The degree of the leucocytosis varies with the extent of the local 
lesion and the height of the fever associated with the infectious process. 
In general, leucocytosis may be regarded as the effort of the blood- 
producing organs to protect the body against microorganisms and circu- 
lating toxins. When the peripheral leucocytes are reduced by exposure 
to radioactive substances or x-rays, the body becomes susceptible to 
microbic invasions and unable to manufacture antibodies1 (see also page 
201). 
The blood in typhoid fever presents a peculiar variation from that in 
most infectious diseases. In the first weeks of the disease there is usu- 
ally a reduction in the number of leucocytes, especially of the polynu- 
clear forms. In the later weeks the lymphocytes may form 80 per 
cent, of the leucocytes present in the blood. Each relapse is attended 
with an increase of the lymphocytosis, while an increase of polynuclear 
leucocytes usually occurs with complications only. 
In the various forms of tuberculosis there is no leucocytosis unless 
the lesion is markedly exudative in character, as in tuberculous menin- 
gitis, or is complicated by suppuration or chronic anemia. In pulmonary 
tuberculosis with secondary infection by pyogenic cocci, leucocytosis 
is apt to develop. 
Cachectic leucocytosis is a feature of altered conditions of the blood, 
such as are associated with the growth of malignant tumors, and with 
many diseases producing secondary anemia. This increase of poly- 
nuclear leucocytes may serve to distinguish many forms of secondary 
from primary anemia. The inflammation and toxemia accompanying 
many new growths afford a sufficient reason for the appearance of 
cachectic leucocytosis, but under many other circumstances its direct 
cause is less apparent.2 
1 Camp, W. E., and Baumgartner, E. A., Jour. Exper. Med., 1915, xxii, 174. 
2 For further data concerning leucocytosis, consult Rieder, Beitrage zur Kenntniss d. Leukocytoee, 
Leipzig, 1892; TUrk, Klinische Untersuchungen u. d. Verhalten des Blutes, Wien. 1898. THE BLOOD AND THE BLOOD-FORMING ORGANS 
527 
Hypoleucocytosis occurs not only in infectious diseases, when the 
polynuclear cells alone are reduced in numbers, but also from shock, 
reduction of body temperature, and exhaustion, when all forms of leuco- 
cytes may be diminished. It is a fairly constant feature of primary 
pernicious anemia1 and of influenza. 
Polynuclear Eosinophile Leucocytosis is found in a number of unre- 
lated conditions. In bronchial asthma the eosinophile cells are con- 
siderably increased, often forming 10 to 20 per cent, of the total 
white cells. A considerable increase is seen in scarlatina. In acute 
and chronic diseases of the skin, such as pemphigus, prurigo, and psori- 
asis, the eosinophiles are often increased to a marked degree, but the 
condition is not constant. In trichinosis and helminthiasis the increase 
is so constant that it becomes of diagnostic value in these conditions. 
A post-febrile eosinophilia is frequently observed. 
Lymphocytosis, frequently seen in the anemias, in pertussis, and the 
acute intestinal disorders of childhood, has also been noted in some 
forms of secondary anemia (syphilis), and in an extreme degree as the 
chief characteristic of the blood of lymphatic leukemia. It is also fairly 
frequent in exophthalmic goiter. 
Degenerative Changes in the Leucocytes are usually indicated by 
variations in the percentage of normal and abnormal varieties, rather 
than by alterations in the individual cells, for degenerating leucocytes 
are usually quickly removed from the circulation. Occasionally, how- 
ever, there may be seen in normal blood a cell in which the nuclear 
chromatin has entirely lost its power to take the stain; and these degener- 
ating or basket cells are sometimes very abundant in the leukemias. 
Staining reactions of the various granules, by which degenerative changes 
may be recognized, have not yet been devised. In leukemia, pernicious 
anemia, and diphtheria, a diminished reaction to nuclear dyes has been 
observed. In leukemia, and in the severe infectious diseases, the 
leucocytes may be extremely cohesive, and it is believed that a large 
quantity of bacteria or toxins in the circulation may even effect a com- 
plete solution and destruction of leucocytes (leucocytolysis). Fatty and 
glycogenic degeneration of leucocytes has been demonstrated. 
Blood-Plates.-These are small spherical or oval, transparent bodies 
which appear in the blood plasma in large numbers. They measure 
from 2 to 3.5 y in diameter, though occasionally in pneumonia and 
suppurative conditions very large plates may be found measuring up to 
5 or 6 y. Structurally they are composed of a peripheral hyaline trans- 
parent layer with a granular central mass which is not sharply outlined. 
This granular mass takes a faint color with the ordinary chromatin stains; 
the periphery is clear. In stained specimens it is occasionally possible 
to find long curved protoplasmic processes, simulating cilia, given off 
from the periphery of the blood plate. Under suitable conditions the 
blood-plates show ameboid motion. 
1 For hypoleucocytosis, consult Lowit, Studien fiber Physiol, und Pathol, d. Blutes u. d. Lymphe 
Jena, 1892; Ewing, New York Med. Jour., 1895, Ixi, 257. 528 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
Their number in the blood varies; the average number is considered 
as approximately 200,000 to 350,000. The number of blood-plates is 
increased in many anemias, both primary and secondary, and especially 
in carcinoma. In pneumonia, septic processes, and leukemia there is 
also an increased number of blood-plates. A diminution of the plates is 
noted chiefly in cases of purpura and pernicious anemia. 
After prolonged exhibition of benzol to leukemic patients, purpuric 
symptoms may develop, and even fatal hemorrhage. The blood-plate- 
lets may be greatly diminished in number, and a fatal termination is 
certain unless the administration of benzol is stopped. If this is done, 
Fig. 293.-Megakaryocytes from Bone-marrow. Showing Formation of Blood-Platelets. 
From preparation of Dr. J. H. Wright. 
the platelets return to normal unless the leucotoxic action of the benzol 
has gone too far.1 
The blood-plates are closely connected with the formation of thrombi, 
and some of the small, so-called white thrombi are entirely composed of 
these bodies. They are also thought to carry the thromboplastin which 
plays an important role in blood coagulation. 
It is now generally accepted that blood-plates are formed from the 
megakaryocytes of the bone-marrow.2 These cells frequently show 
budding masses of the same structure as the blood-plates (see Fig. 293 
and 294). The hyaline peripheral zone of the giant cell has the power of 
ameboid motion and can be observed on the warm stage to give out pro- 
toplasmic processes. In addition the blood-plates are found only in 
1 See, for a study of benzol anemia, Hurwitz and Drinker, Jour. Exper. Med., 1915, xxi, 401 
2 Wright, Jour. Morphology, 1910, xxi., 2; and Ogata, Zieglers Beitr., 1912, lii, 192. THE BLOOD AND THE BLOOD-FORMING ORGANS 
529 
such mammalia as have megakaryocytes in the bone-marrow, and it has 
been noted that blood-plates appear only in embryonal mammalian 
blood at the time when the giant cells are present in the blood-forming 
organs. 
However, under certain conditions of excessive demand for their 
formation, the transitional leucocytes, representing the persistent form 
of the embryonic premegakaryocyte, and the hyperplastic endothelial 
cells of the marrow may also give rise to the blood-plates.1 
Fig. 294.-Megakaryocytes from Bone-marrow. Showing Formation of Blood Platelets. 
From preparation of Dr. J. H. Wright. 
METHODS OF EXAMINATION OF THE BLOOD. 
The blood may be examined fresh on the warm stage without the addition of any 
fixative, the cover being surrounded with oil or vaselin to prevent evaporation. This 
method is especially useful in the examination of blood for the Plasmodia malariae. 
For most purposes, however, the cells should be treated the instant the blood leaves 
the vessels, in such a way as to retain their normal form. This fixation may be accom- 
plished by the use of chemical agents (wet method) or by quick drying on the cover- 
glass or slide (dry method). 
Wet Method.-Among the chemical fixative agents are osmic acid and a solution 
of corrosive sublimate. Osmic acid: Five c.c. of a 1 per cent, solution of osmic acid 
are mixed with 10 drops of glacial acetic acid in a Petri dish. Short pieces of glass 
tubing are placed in the dish to support the slide which is exposed to the vapor of the 
acids for two minutes. The finger is then punctured and the blood spread in a thin 
film upon the surface of the slide which has been exposed to the vapor. The slide is 
then again exposed to the vapor for one minute. It is allowed to dry, passed three 
times through a flame, washed for one minute in a dilute solution of potassium per- 
manganate (extemporized from a concentrated solution by diluting until the fluid is a 
deep pink), washed in water, dried, and stained by any of the ordinary methods. If 
it is not desirable to dry the slide it may be transferred into a very dilute alcohol and 
carried up by stages of 10 per cent, until thoroughly fixed.2 
1 Brown, W. H., Jour. Exper. Med., 1913, xviii, 278. 
2 Weidenreich, Folia haematologica, 1906, iii, 1. 530 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
Sublimate may be used in the form of Hayem's solution, consisting of 
Chloride of sodium 1.0 gm. 
Sulphate of sodium 5.0 gm. 
Corrosive sublimate 0.5 gm. 
Water, distilled 200.0 gm. 
The blood is received directly into this solution, in which it is studied. The wet 
method of fixation is especially to be recommended for studies on the minute structure 
of blood-cells. 
Another solution which is highly recommended* is made up as follows: 
Muller's fluid 9 parts. 
Formaldehyde, 40 per cent 1 part. 
Distilled water 10 parts. 
The solution should always be made up fresh and warmed to about 40° C. The 
fixed blood is washed in distilled water until all the chrome salts are removed, passed 
through graded alcohols to absolute, transferred to absolute alcohol and carbon 
bisulphide equal parts, and then to pure carbon bisulphide, carbon bisulphide and 
paraffin, and finally embedded in paraffin. Thin sections can be cut, which often 
demonstrate interesting phases of mitosis and other phenomena in the cells. 
None of these methods of fixation in bulk, however, is as satisfactory as the 
Weidenreich or the dry smear methods. 
Dry Method.-It has been found that if the freshly drawn blood from a finger 
prick is immediately dried on a glass in a very thin layer, the cell forms are quite well 
preserved and may be exposed to the action of staining agents. 
The method consists in touching the freshly drawn drop with the smooth edge of 
a glass slide, applying this edge with its adherent blood obliquely to another slide, 
and, when the blood has spread along the edge, drawing it rapidly across the surface 
of the second slide. 
For the permanent fixation of the cells and to prevent their solution by strong dyes, 
one of two methods may be recommended: 
1. Heat Fixation.-The specimens are heated in a hot-air bath or on a copper 
plate, for from five minutes to two hours at a temperature of 110° C. to 120° C. 
2. Chemical Fixation.-The specimens are placed for from one to thirty minutes in 
strong methyl alcohol. 
Various staining agents are to be employed according to the object in view. The 
triacid mixture of Ehrlich2 gives an excellent stain for the neutrophile and eosinophile 
granules, but fails to show basophile granules or parasites, for which reason it is being 
supplanted for general work by combinations of methylene blue and eosin. The 
specimen should be stained in this fluid for three to five minutes, washed in distilled 
water, dried, and mounted in dammar dissolved in xylol. 
The red cells are then found stained orange-yellow, the nuclei dark green or blue, 
the neutrophile and eosinophile granules dark red. 
For general purposes a stain devised by Jenner has supplanted the older methods 
on account of its simplicity, rapidity, and ease of application. It consists of a half 
per cent, solution in methyl alcohol of a compound made by mixing a 1.2 per cent, 
aqueous eosin and a 1 per cent aqueous methylene-blue solution. The precipitate 
which forms is filtered off, washed with distilled water, dried, and dissolved in the 
methyl alcohol. The blood smears are fixed and stained by this solution in from one 
to three minutes. The red cells are of a terra-cotta color, the nuclei blue, the neutro- 
phile and eosinophile granules red, the mast-cell granules purple; bacteria, malarial 
organisms, and blood-plates blue. 
An extremely satisfactory stain which not only demonstrates the important 
morphological details of the red and white cells, but also gives a characteristic chro- 
matin stain to the malarial parasite is the following.3 
1 Schridde and Naegeli, Hamatologische Technik, Jena, 1910. 
2 It is better to purchase the solution already mixed than to attempt to make it. The formula 
will be found in Wood, Chemical and Microscopical Diagnosis, 3d ed., New York, 1917, or in similar 
works on the blood. 
3 Wright, J. H., Jour. Am. Med. Assn., 1910, Iv, 1979. THE BLOOD AND THE BLOOD-FORMING ORGANS 
531 
Five gm. of sodium bicarbonate, 10 gm. of methylene blue (B. X. or "medicinally 
pure") and 1,000 c.c. of water are heated in a steam sterilizer at 100° C. fora full hour. 
The mixture should be contained in a flask of such size as to allow it to form a layer 
not over 6 cm. deep. After cooling it is filtered to remove the precipitate. When 
cold it should be of a deep purple-red color when viewed in a thin layer by transmitted 
yellowish light. 
To each 100 c.c. of the filtered mixture, 500 c.c. of a 0.1 per cent, aqueous solution 
of Grubler's "yellowish, water-soluble" eosin are added and mixed thoroughly. The 
precipitate which appears immediately is collected on a filter and when dry dissolved 
in methylic alcohol (Merck's reagent) in the proportion of 0.1 gm. to 60 c.c. of alcohol, 
rubbing them together in a porcelain dish or mortar to facilitate solution. This forms 
the staining fluid. It should be kept in a well-stoppered bottle, and if it becomes too 
concentrated by evaporation, may be thinned by the addition of the proper amount 
of methylic alcohol. The method of staining is as follows: 
1. Cover the film with a noted quantity of the stain with a medicine dropper. 
2. After one minute add to the staining fluid on the film an equal quantity of 
distilled water by means of the dropper, and allow the mixture to remain for two or 
three minutes according to the intensity of the stain desired. Too long staining may 
produce a precipitate. Eosinophilic granules are best brought out by a short staining 
period. 
3. Wash the preparation in distilled water for thirty seconds, or until the thinner 
portions of the film become yellow or pink. 
4. Dry and mount in xylol-dammar. 
Films more than a few hours old do not stain so well as fresh ones.1 
For the demonstration of fat in blood the finger should be cleansed with alcohol 
and chloroform to remove any fat from the surface skin before the puncture is made, 
and cover-glass preparations dried in the air should be fixed in formaldehyde vapor 
and stained with Sudan III (page 53). To avoid numerous sources of error, a control 
preparation should be previously placed in chloroform for twenty-four hours to dis- 
solve the fat, and the two specimens carried together through the stain. In the one, 
red fat droplets will be seen which are entirely absent in the other. 
Testing for Agglutinins and Hemolysins. 
The occasional fatal accidents which have followed the wide employment of blood 
transfusion, not only after acute hemorrhage but also in diseases such as pernicious 
anemia and. hemophilia, have brought the realization that it is necessary to test for 
the isoagglutinins and isohemolysins present in human blood. It has been found2 
that blood can be arranged in four groups: 
Group I.-Serum agglutinates no corpuscles. Corpuscles are agglutinated by 
the serum of Groups II, III and IV. 
Group II.-Serum agglutinates the corpuscles of Groups I and III. Corpuscles 
are agglutinated by the serums of Groups III and IV. 
Group III.-Serum agglutinates the corpuscles of Groups I and II. Corpuscles 
are agglutinated by the serum of Groups II and IV. 
Group IV.-Serum agglutinates the corpuscles of Groups I, II and III. Cor- 
puscles are agglutinated by no serum. 
It is necessary before transfusion can be done to test the serum of the patient 
against the corpuscles of the prospective donors, and the serum of the donors against 
the corpuscles of the patient. Even a slight amount of agglutinin may make trans- 
fusion dangerous to life.3 
1 For other blood stains see under Malaria, page 349. 
2 Moss, W. L., Bull. Johns Hopkins Hosp., 1910, xxi, 63. 
3 The technique of these methods has been very thoroughly studied. For practical details see St. 
Luke's Hospital Technique, New York, 1917; Brem, W. V., Jour. Am. Med. Assn., 1916, Ixvii, 190; Ottens 
berg, R., and Kaliski, D. J., Jour. Am. Med. Assn., 1913, Ixi, 2138; Moss, W. L., Jour. Am. Med. Assn., 
1917, Ixviii, 1905; Karsner, H. T., Jour. Am. Med. Assn., 1918, Ixx, 769. For a general survey of the 
subject of transfusion, see Bernheim, Blood Transfusion, Philadelphia, 1917. 532 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
FOREIGN BODIES IN THE BLOOD. 
Various bodies which do not belong there, aside from those above 
mentioned, may find access to the vessels and mingle with the blood. 
Pus cells may get into the blood from the opening of an abscess into a 
vessel or from some inflammatory change in its walls. Desquamated 
endothelial cells from the vessel walls, either in a condition of fatty 
degeneration or in various stages of proliferation, may be mingled with 
the normal blood elements; also tumor cells of various kinds, fragments 
of disintegrated thrombi, portions of heart valves, etc. Megakaryo- 
cytes from the bone-marrow have been found after fractures, and syncytial 
cells after eclampsia. Crystals of bilirubin have been found in the blood 
in icterus, and Charcot-Leyden crystals have been seen post-mortem in 
the blood and bone-marrow of cases of leukemia. 
Fat, in a moderate amount, is a normal ingredient of the blood, 
during digestion, and in lactation it is increased. Under pathological 
conditions it may occur in larger and smaller droplets. This lipemia 
occurs in diabetes, in alcoholism, in acute phosphorous poisoning, and in 
some cases of dyspnea from various causes. The droplets are small 
and liable to escape observation, but if the blood is kept a white layer of 
fat collects on the surface of the serum as it separates. 
In many cases of injury, particularly in crushing fractures1 of the 
bone, the fat of the marrow finds its way into the blood, and it may col- 
lect in large drops in the vessels of the lungs, forming the so-called fat 
emboli (Fig. 11, p. 37); or it may pass the lungs and form emboli in other 
parts, as the brain, kidneys, etc. Fat embolism in eclampsia is of 
occasional occurrence. 
The fat may be absorbed from the vessels, having produced little or 
no disturbance; or in some cases it may produce serious results by the 
stoppage of a large series of vessels in the lungs, brain, or other parts of 
the body.2 
Tissues and organs whose blood-vessels are suspected to contain fat droplets should 
be fixed in Muller-formol or 4 per cent, formaldehyde and thoroughly washed in 
water. Frozen sections are then treated with a mixture of equal volumes of Muller's 
fluid and 2 per cent, osmic acid, or stained with Sudan III (page 53). The sections 
should then be stained with hematoxylin and mounted in glycerin. 
Air, as a result of an opening in the veins, is of occasional occurrence. 
If the amount of air'be small, it appears to be readily absorbed, and does 
little or no harm. If, on the other hand, a large quantity is admitted to 
the veins at once, it collects on the right side of the heart, from which 
the contractions of the organ are unable to force it in any considerable 
quantity, and, the supply of blood being thus cut off from the lungs, 
death very quickly ensues. The blocking of the smaller pulmonary ves- 
sels and of the vessels of the heart with air bubbles may also hasten 
death. It is especially from wounds of the veins of the neck and thorax 
that the accident is most apt to occur. But it may be due to the intro- 
1 Bissell, W. W., Jour. Am. Med. Assn., 1916, Ixvii, 1926, has found as much as 3.75 gm. of fat per 
100 c.c. of blood, the norm being not over 0.6 gm. 
2 For resumd of this subject, with bibliography, consult Welch, Embolism, Allbutt, System of 
Medicine, 1909, vi, 258. See, also, page 42. 533 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
duction of air into the uterine veins during intrauterine injections or the 
removal of tumors.1 Considerable quantities of air may be set free in 
the blood in caisson disease (page 18) due to the solution of nitrogen 
in the plasma under the increased pressure. 
Parasites and other Foreign Bodies in the Blood.-The occurrence 
of animal and vegetable parasites is considered more in detail in parts of 
this book devoted to these organisms. It will suffice to mention here 
that the more important of the parasites found in the blood are: The 
Plasmodium malariee, Trypanosomata, Filaria sanguinis hominis, the 
embryo of Trinchinella spiralis, the Spirillum obermeieri, and the Trepo- 
nema pallidum. 
The various forms of bacteria which may be found in the blood will 
be considered in parts of this book in which these organisms are treated 
in detail.2 Parenchyma-cell emboli are considered on page 36. 
Melanemia.-In this condition, which is most frequently the result 
of intermittent and remittent fever, particularly the severer forms, the 
blood contains larger and smaller, irregularly shaped particles or masses 
of brown or black pigment. The pigment may be free, but more often 
is inclosed in leucocytes, and may be deposited in the liver, spleen, 
lymph-nodes, bone-marrow, and blood-vessels, in consequence of which 
these organs may assume a gray or slate color. The condition may be 
transient in character, and may be accompanied by anemia and leuco- 
cytosis. The pigment developed in malaria originates in the decomposi- 
tion of the hemoglobin under the influence of the plasmodium. Pigment 
which has been taken into the lungs from the air, such as coal dust, etc., 
may find its way into the blood either before or after deposition in the 
bronchial or other lymph-nodes, and may be afterward deposited in the 
spleen and liver.3 
General Diseases Involving the Blood and Blood-Forming Organs.4 
There is a group of diseases in which the most striking lesion seems 
to be an alteration in the composition of the blood, although in some 
members of the group other lesions are also present. This group em- 
braces chlorosis, secondary and pernicious anemia, leukemia, and certain 
closely related, but still obscure conditions. 
CHLOROSIS. 
Chlorosis is a disease of the blood seen in women only and attended 
with a diminution in the hemoglobin, and usually in the number of the 
red blood-cells. 
1 Welch, Allbutt, System of Medicine, 1909, vi, 254. 
2 For methods and results of bacterial studies of the blood with bibliography, consult Kiihnau, Ztschr. 
f. Hyg., 1897, xxv, 492; Rosenberger, Am. Jour. Med. Sc., 1903, cxxvi, 234; Canon, Die Bakteriologie des 
Blutes, Jena, 1905; Lenhartz, Die Septischen Erkrankungen, Wien, 1903. For method of demonstrating 
animal parasites see Staubli, Munchen, med. Wchnschr., 1908, Iv, 2601; and Warren and Herrick, 
Am. Jour. Med. Sc., 1916, cli, 556. 
3 For further details concerning changes in the blood, consult Simon, Clinical Diagnosis, 9th ed.; 
Philadelphia, 1918; Cabot, Clinical Examination of the Blood, 5th ed., New York, 1904; or Wood, 
Chemical and Microscopical Diagnosis, 3d ed., New York, 1917. 
4 For a full discussion of the subjects treated in this chapter the reader is referred to von Noorden, 
Bleichsucht, Nothnagel's Spec. Path. u. Therap.; Ehrlich and Lazarus, Die Anaemie, ibid.; Helly, 
Die Hamatopoetischen Organe, ibid., and Naegeli, Blutkrankheiten und Blutdiagnostik, Leipzig, 1912. 534 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
Of the essential element in the incitement of this disease and of the 
exact method of its origin we are ignorant. The condition has been 
attributed to congenital hypoplasia of the heart and blood-vessels, to 
prolonged malnutrition, to intestinal intoxication, and to functional 
disturbance of an unknown nature in the blood-producing organs. 
In the mildest grade of chlorosis the only change to be observed is a 
slight diminution of hemoglobin. In severer forms there may be added 
a diminution in number and moderate variations in size and shape of 
the red cells. In very severe and relapsing cases the hemoglobin may be 
very much decreased, the color index falling even as low as 0.4; the red 
cells may number less than two millions per cubic millimeter, and the 
average size of the cells be less than normal. The leucocytes are not 
increased in number. There may be a slight relative increase of the 
lymphocytes; megalocytes, microcytes, and poikilocytes may appear (see 
Plate IV, Fig. 2). Polychromatophilia is frequent. 
The specific gravity of the blood is diminished in proportion to the 
fall in hemoglobin; the total quantity is greatly increased. The time of 
coagulation is often very short, a change undoubtedly correlated with 
the not infrequent thrombosis seen in chlorosis. Even in cases of 
considerable severity the changes in the viscera characterizing other forms 
of anemia have been found wanting, although degenerative changes in 
the red cells may occur in accordance with the severity of the disease. 
The liver does not contain an excess of iron; the bone-marrow, in the few 
cases which have come to autopsy, has shown little or no hyperplasia; 
and the urine is free from pathological urinary pigments. 
The regeneration of the blood in chlorosis under rest and treatment 
with iron may usually be rather promptly effected by increased activity 
of the red marrow, which is probably hyperplastic. This regenerative 
process may be indicated in the blood by the periodical appearance of 
considerable numbers of normoblasts. The appearance of these nucle- 
ated red cells may be accompanied by a moderate increase of leucocytes, 
both mononuclear and polynuclear. Myelocytes also may rarely be 
seen. 
SECONDARY ANEMIA. 
While chlorosis may be considered usually a disease of adolescence, 
and while its occurrence is confined to the female sex, there is another 
type of blood change which seems best classified under the heading of 
secondary anemia, and which is independent of sex or age. The deter- 
mining agents are either of a general nature, such as poor food and bad 
air, or they are actual diseases, or they may be intestinal parasites, or, 
finally, chronic poisoning. Among those diseases which are likely to 
induce a well-defined anemia we may mention prolonged suppuration, 
mycotic endocarditis, diseases of the stomach and intestines, malaria, 
syphilis, and malignant tumors. The intestinal parasites are chiefly the 
Anchylostoma duodenale and the Bothriocephalus latus. The poisons 
are lead and, more rarely, arsenic. The alterations which are apparent 
on examining the blood are very variable, depending upon the agent. 535 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
The hemoglobin is regularly diminished to a greater extent than the red 
cells; it may fall as low as 15 to 20 per cent.; the red cells rarely fall 
below one million. Nucleated red cells of the normoblastic type are 
frequent in the severe cases; megaloblasts are not found except in 
advanced cases of Bothriocephalus anemia. As a rule the average 
diameter of the red cells is slightly below normal, with a moderate 
poikilocytosis. Granular degeneration is present to a variable extent 
in the red cells except in malaria and lead poisoning, when it is the rule. 
The threads and granules demonstrable by vital stains are present in 
many of the red cells after regeneration begins,1 and their frequency 
above the norm of 2 to 3 per cent, may be taken as an index of the rate 
of repair. Such new-formed red cells, in contrast to mature forms, also 
Fig. 295-.Bone-marrow from Shaft of Femur from Case of Secondary Anemia due to recur- 
rent Carcinoma. 
The normal fat tissue is to a certain extent replaced by an edematous reticular connective tissue 
containing islands of nucleated red cells and myelocytes. The hyperplasia is not so extensive as that 
seen in leukemia or pernicious anemia, in which often all of the fat is replaced by the new growth of 
cells. 
contain mitochondria.2 In the anemias produced by the Bothrio- 
cephalus the blood picture may be that of pernicious anemia, with a great 
increase in the size of the cells and the appearance in the blood of numer- 
ous megaloblasts, thus forming an exception to the general rule that the 
blood of secondary anemia is normoblastic in type. In the anemia due 
to the Anchylostoma or the Uncinaria the blood shows the picture of a 
chlorotic anemia often accompanied by a considerable eosinophilia, 
which is not usually seen in the Bothriocephalus variety. The leuco- 
cytes are increased in anemia due to suppuration and in about 50 per cent, 
of the tumor cases; in other forms there is usually but little change in the 
number, though it is impossible to formulate a general rule (Plate IV, 
1 Vogel, K. M., and McCurdy, U. F., Arch. Int. Med., 1913, xii, 707 (bibl.). 
2 Sappington, C. O., Arch. Int. Med., 1918, xxi, 695. 536 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
Fig. 3). When, however, a tumor invades the bone-marrow an extensive 
hyperplasia of this tissue may occur with consequent flooding of the 
blood current with large numbers of immature leucocytes so that the 
blood simulates that of myelogenous leukemia (Fig. 295). 
PERNICIOUS ANEMIA. 
Pernicious anemia is a disease of the blood and blood-forming organs, 
characterized by excessive destruction associated with defective produc- 
tion ofred cells. 
The exact relation of the factors concerned in the causation of the 
disease has not been determined. It may be said, however, that while 
very rapid cases of pernicious anemia have been observed unaccom- 
panied by the usual lesions in the bone-marrow associated with defec- 
tive hematogenesis, the disease seems not to exist without excessive 
hematolysis. Despite the anemia the general metabolism of the body 
is increased.1 
Pernicious anemia may probably originate as a primary disease of 
the blood or bone-marrow, but many cases apparently primary have 
been shown at autopsy to be secondary to such conditions as cancer, 
nephritis, tuberculosis, atrophy of the gastric mucosa, or the presence of 
parasites in the blood or intestine. The studies of Hunter indicate that 
the destruction of the blood may in some cases result principally in the 
portal circulation and particularly in the spleen from the action of toxic 
substances absorbed from the intestines, and Herter has shown that the 
toxic products arising from anaerobic putrefaction of the proteins by 
certain bacteria may play an important part in the induction of hematoly- 
sis. Whatever its origin, the distinguishing feature of pernicious anemia 
is the fact that the anemia is entirely disproportionate to any apparent 
cause, and when once established tends to progress to a fatal issue. 
The essential lesion is an extreme and progressive diminution in 
number and very great variation in size and form of the red blood-cells 
(as shown in Plate IV. Fig. 4). Nearly constant is a widely distributed 
lesion of the bone-marrow, in which the normal fatty marrow of the long 
bones is replaced by one containing an excessive number of large nucleated 
red corpuscles or megaloblasts. The destruction of hemoglobin is fol- 
lowed by a considerable deposit of iron in the liver, spleen, marrow, and 
other organs, and by the appearance of excessive amounts of urobilin in 
the urine. The prolonged anemia may be accompanied by fatty degenera- 
tion in the viscera, especially of the liver, kidneys, and heart muscle. 
As a combined result of fatty changes in the arterial walls and of the 
diminution in albuminous ingredients and in the coagulability of the 
blood, hemorrhages in various parts of the body, especially the retina, 
are of frequent occurrence. Disseminated areas of sclerosis in the spinal 
cord are not infrequent and are regarded as the result of minute hemor- 
rhages in this region. The spleen is usually small, but may be normal in 
size, and in some instances is slightly enlarged. Microscopically there is 
1 Meyer and DuBois, Jour. Am. Med. Assn., 1916, Ixvii, 440. 537 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
but little change of note. The Malpighian bodies are normal; there is 
no increase in interstitial tissue. As a rule, a large number of nucleated 
red cells may be found, and some phagocytosis of red corpuscular debris 
in large phagocytic cells; but, on the other hand, this phagocytosis may 
be entirely absent morphologically, and the spleen may differ but little 
from the norm. The writer (Wood) has seen an extreme eosinophilia 
without phagocytosis in an early case of pernicious anemia in which the 
spleen was removed at operation. 
The bone-marrow contains nucleated red cells of all types mingled 
with many non-granular myelocytes. Granular myelocytes are apt to be 
more abundant in the centers of the ribs and bodies of the vertebrae, 
where normal hematogenesis still persists. Areas of new formation of 
red cells and myelocytes1 are not infrequent in the spleen and liver, but 
are rare in the prevertebral lymph-nodes. 
In the blood the red cells are usually reduced to less than two millions 
and occasionally to half a million per cubic millimeter. Of the remaining 
cells a considerable percentage may be abnormally large (megalocytes), 
or very small (microcytes). Cells of very irregular shape are often 
present in abundance (poikilocytes) (Plate IV, Fig. 4). The quantity of 
hemoglobin in the majority of the cells is usually increased, but may be 
diminished in a certain proportion of cells, which then resemble those 
found in chlorosis. The hemoglobin or color index-that is, the relation 
of the total percentage of hemoglobin to the total number of cells-may be 
normal when a deficiency of hemoglobin in one cell is counterbalanced 
by a proportionate excess in another, but in general it is greater than 
unity. 
A variety of degenerative changes in the red cells is commonly 
present, including especially those alterations in the staining reactions of 
the protoplasm known as polychromatophilia and granular degeneration. 
In the first the cell stains a more or less uniform blue with methylene 
blue; in the second the cells contain granules which give a strong baso- 
philic staining reaction. 
Nucleated red cells of normal size (normoblasts) are of frequent occur- 
rence in the blood of well-established pernicious anemia. Abnormally 
large nucleated red cells (megaloblasts) are a nearly constant element at 
some stage of the disease and are of great diagnostic importance, as they 
indicate the presence of a grave lesion in the bone-marrow. They are 
more abundant than the normoblasts in well-developed cases. 
Megalocytes and megaloblasts usually show an excess of hemoglobin, 
may exhibit ameboid movement, and have no tendency toward the 
formation of rouleaux. Extremely large nucleated red cells (giganto- 
blasts) are frequently found in advanced cases, and in these cells as well 
as in the megaloblasts the nuclei may be rarely seen in various stages of 
normal or pathological mitosis. Blood crises, by which term is indicated 
the appearance of large numbers of normo- or megaloblasts in the circu- 
lation, may occur in pernicious anemia, but it must be remembered that 
the blood picture in any severe anemia varies much from day to day 
1 Meyer and Heineke, Verhandl. d. deutsch. path. Gesellsch., 1906, ix, 224. 538 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
without any marked alteration in the general condition of the patient. 
In the absence of complications producing leucocytosis in pernicious 
anemia, the leucocytes are usually diminished in number. There is a 
relative increase in the number of lymphocytes, and usually a few myelo- 
cytes may be found. 
Spontaneous remissions in the course of the disease are frequently 
seen and have led to the erroneous conclusion that patients suffering 
from pernicious anemia occasionally recover. Actual recovery is, how- 
ever, only an evidence of an incorrect diagnosis. Excision of the spleen 
has been practised on the theory of a splenic origin of the hemolytic 
toxin, but without avail as to the ultimate result, though temporary 
amelioration unquestionably occurs.1 Transfusion, also, has been of 
temporary benefit when performed fairly often.2 
Aplastic Anemia.-A very rare variety of a rapidly fatal form of 
anemia has been described in which the number of red cells is diminished 
without the blood showing the changes characteristic of pernicious 
anemia. The bone-marrow in these cases has been found to be fatty 
instead of hyperplastic as is the typical marrow of pernicious anemia. 
It has been suggested that the bone-marrow for some unknown reason 
had not responded to the call made upon it by the rapid hematolysis 
taking place in the disease, and therefore did not undergo the megalo- 
blastic changes so characteristic of the bone-marrow in well-marked 
cases of pernicious anemia.3 A very similar picture is produced by. the 
exhibition of benzol, which is a leucotoxin especially but also diminishes 
the production of the red cells and blood-platelets.4 Prothrombin is 
reduced and a purpuric condition may ensue if the drug is pushed.6 
LEUKEMIA (LEUKOCYTHEMIA). 
Leukemia is a disease in which the characteristic changes are an alter- 
ation in the relative proportions of the different leucocytes of the blood, 
with usually an increase in their number, and the appearance of certain 
forms not seen in the circulation under normal conditions. The red cells 
are diminished in number, and abnormal forms appear in the blood. 
Accompanying these alterations in the circulating blood are changes in 
the bone-marrow, less often in the spleen and in the lymph-nodes. Its 
inciting factors are still unknowm. Leukemia may be classed in four 
types, which are fairly well defined clinically and morphologically, but 
between these there exist many transitional forms, especially from the 
point of view of the morphology of the blood. These four types are the 
acute and chronic lymphatic leukemia and the acute and chronic myel- 
ogenous leukemia (splenomyelogenous). 
Acute Lymphatic Leukemia is a disease resembling clinically an 
acute infection, with a rapidly increasing anemia, enlargement of the 
1 For a study of the influence of splenectomy on metabolism in anemia, see Denis, W., Arch. Int. 
Med., 1917, xx, 79. 
2 Percy, N. M., Surg., Gynec., and Obst., 1917, xxiv, 533; Minot and Lee, Boston Med. and Surg. 
Jour., 1917, clxxvii, 761; and Bloomfield, A., Bull. Johns Hopkins Hosp., 1918, xxix, 101. 
3 For a study of a series of such cases, see Lavenson, R. S., Am. Jour. Med. Sc., 1907, cxxxiii, 100. 
4 Selling, L., Zieglers Beitr., 1911, li., 576. 
5 Hurwitz and Drinker, Jour. Exper. Med., 1915, xxi, 401. 539 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
lymph-nodes, as a rule, and a moderate increase in the size of the .spleen 
and liver. Cases are on record, however, in which there was no enlarge- 
ment of the spleen or lymph-nodes.1 The blood changes are very 
characteristic. The red cells diminish rapidly in number, normoblasts 
and occasionally megaloblasts are present, and the leucocytes are 
increased, though usually below 100,000. The forms present are chiefly 
lymphocytes, either large or small, the large, as a rule, predominating. 
While the staining reactions of the large lymphocytes in this disease 
correspond with those of the cells of normal blood, yet it has been shown2 
that in another group of large non-granular-cell leukemias, cells of a 
Fig. 296.-Skin Nodule from Case of Acute Lymphatic Leukemia. 
lymphocytic aspect contain a proteolytic and lipolytic ferment character- 
istic of the granular types of cells from the bone-marrow. This has been 
confirmed3 by the discovery that in the large lymphocytes it is possible 
to demonstrate an oxidase, a ferment heretofore considered to be con- 
fined to the granular types. These findings indicate that the cells in 
question should be considered rather as myeloblasts than as large lympho- 
cytes. The bone-marrow is altered to a tissue showing large numbers 
of lymphocytes, the so-called lymphoid hyperplasia, which often extends 
to the lymphoid tissue in the viscera and may lead to the formation of 
nodules in the skin (Fig. 296). In several cases of acute lymphatic 
leukemia, a bacillus corresponding to that found in Hodgkin's disease 
has been present in the lymph-nodes. It is probably without etiological 
significance.4 
1 Kelly, Univ. Pennsylvania Med. Bull., 1903, xvi, 270. 
2 Long cope and Donhauser, Jour. Exper. Med., 1908, x, 618. 
3 Schultze, W. H., Munchen, med. Wchnschr., 1909, Ivi, 167; and Peters, J., ibid., p. 1478. 
4 Simon and Judd, Jour. Am. Med. Assn., 1915, Ixiv, 1630 (bibl.). 540 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
Chronic Lymphatic Leukemia.-The blood shows a severe anemia 
with great increase in the lymphocytes. The small forms of the lympho- 
cytes are most abundant, in contradistinction to the acute type of the 
disease, in which the large forms are usually in excess. The lymph-nodes 
and spleen are usually enlarged; the bone-marrow is in a condition of 
lymphoid hyperplasia, and there are lymphoid infiltrations in the various 
organs (see Fig. 297 and 298 and Plate IV, Fig. 5). 
Acute Myelogeneous Leukemia.-A few cases of leukemia of the 
myelogenous type have been reported in which the clinical course was 
very acute, with a rapidly increasing anemia and the occasional appear- 
Fig. 297.-Leukemic Infiltration of Kidney in Case of Lymphatic Leukemia. 
ance of nucleated red cells. In some of the cases the blood was not 
characteristic and the diagnosis could be made only after death by a 
study of the changes in the bone-marrow; in others the blood picture 
resembled that of a chronic myelogenous leukemia with the usual large 
percentage of myelocytes. Some of the cases diagnosed as acute myelog- 
enous leukemia were undoubtedly of the type of disease known as 
chloroma, while others were presumably acute infections with a high 
leucocytosis and the appearance of a few myelocytes in the blood with 
a marked hyperplasia of the bone-marrow due to the prolonged septic 
condition.1 The difficulties in the diagnosis of acute myelogenous leu- 
1 Herz, Akute Leukamie, Vienna, 1911 (bibl.); Sternberg, C., Wien. klin. Wchnschr., 1911, xxiv, 1623. 541 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
kemia are complicated by the fact that the lymphocytes in acute lym- 
phatic leukemia may be greatly diminished toward the end of the disease, 
and a few myelocytes may appear under these conditions, thus render- 
ing a differentiation impossible.1 
Chronic Myelogenous Leukemia.-The blood shows a severe anemia, 
rarely of a pernicious type, with marked quantitative and qualitative 
changes in the leucocytes. The increase in number of white cells may 
be to more than one million per cubic millimeter. Myelocytes, both 
neutrophilic and eosinophilic, are quite constantly present in consider- 
able numbers. They may form a large proportion of the leucocytes 
Fig. 298.-Liver from a Case of Lymphatic Leukemia. 
Showing infiltration of the organ with leucocytes. The large collections are in Glisson's capsule, 
but small numbers are seen between the liver cells. 
present. Basophile cells are very abundant in cases of long duration, 
especially the type with polymorphic nuclei, myelocytes with baso- 
philic granulations being rare. In rapidly advancing cases mitoses may 
rarely be seen in the red cells and in the leucocytes (see Plate IV, Fig. 5). 
The pathological forms of leucocytes in myelogenous and lymphatic 
leukemias have little or no ameboid motion. This explains the inter- 
esting fact that the pus from an abscess in a leukemic subject contains 
only the polynuclear neutrophile cells found in such exudates in persons 
with a normal blood condition. In acute infections and after treatment 
with radium or the Roentgen rays, the number of myelocytes present in 
1 Billings and Capps, Am. Jour. Med. Sc., 1903, cxxvi, 375. 542 
TI-E BLOOD AND THE BLOOD-FORMING ORGANS 
the circulation may be greatly reduced and the blood may even lose the 
cell forms characteristic of leukemia, the myelocytes being replaced by 
lymphocytes or the ordinary polynuclear leucocytes of normal type. 
The same condition may be seen in mild cases, which may under treat- 
ment reach a point in which it is difficult to make a diagnosis from the 
blood alone. 
In this connection it must be remembered that the blood picture in 
pernicious anemia and the leukemias is a very variable one. As a rule, 
more than one examination is necessary for a certain diagnosis, and it 
must not be forgotten that occasionally a case, apparently of pernicious 
anemia, may go on to a typical lymphatic or myelogenous leukemia. 
In myelogenous leukemia there is hyperplasia of the bone-marrow, 
which usually fills the shafts of the long bones with a firm, pink mass 
composed largely of myelocytes. This hyperplasia may involve the 
whole bone-marrow of all the long bones, or it may be confined to irreg- 
ular, scattered areas, so that one should be critical in accepting reports 
of cases of leukemia without bone-marrow changes. The other organs 
may rarely show hyperplasia of lymphoid tissue, often especially well 
marked in the gastrointestinal tract, while scattered through the spleen 
are often seen numerous small areas containing myelocytes. In ad- 
vanced cases the spleen is almost wholly transformed into myeloid tissue. 
Infarcts and perisplenitis are frequent. The liver is usually enlarged. 
There is some reason to think that in the spleen, for instance, exten- 
sive multiplication of the cells goes on in the so-called "marrow cell or 
myeloid metastases." While it is generally assumed that these deposits 
correspond very closely to tumor deposits, one school of pathologists 
holds that mesenchymal tissue anywhere in the body may return to its 
fetal function and give rise to myelocytes. Attention is called also to 
the fact that myeloid changes in the sites just mentioned may occur 
when there is but little hyperplasia of the marrow, and it is pointed out 
that in myelogenous leukemia it may be possible temporarily to reduce 
the blood to a normal condition by the application of radium or Roentgen 
rays to the spleen alone. In the blood, spleen, and marrow, after death, 
elongated octahedral crystals (called Charcot-Leyden crystals) are 
occasionally found. Hemorrhages into the serous and mucous mem- 
branes and the retina, especially the latter, are more or less frequent; 
and fatty degeneration of the viscera is a constant expression of the im- 
poverished condition of the blood. For more detail concerning the lesions 
of the organs see chapters on spleen, lymph-nodes, bones, etc. 
CHLOROMA. 
Under this name, which means merely "a green tumor," are grouped 
a number of forms of a disease which shows many points of resemblance to 
both malignant tumors and the leukemias.1 It is now generally con- 
1 Dock, G., Am. Jour. Med. Sc., 1893, cvi, 152; Dock and Warthin, Med. News, 1904, Ixxxv, 971, 
and Sternberg, C., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1903, ix, 360. Lehndorff (Ergebn. d. inn. 
Med., 1910, vi, 221) gives a very complete discussion of all the published cases to date, amounting to 
about ninety, and a copious bibi.; see also Burgess, Jour. Med. Research, 1912, N. S. xxii, 133 (bibl.) THE BLOOD AND THE BLOOD-FORMING ORGANS 
543 
sidered to belong to the group of primary diseases of the hematogenetic 
organs, its closest relationship being with the leukemias. The impor- 
tant lesions are the presence of new growths of a greenish color in the 
osseous system, accompanied in many cases by alterations in the circu- 
lating blood. The tumors are frequently observed in the bones of the 
skull, but may involve any of the organs of the body. Nothing is known 
as to the chemical relationships of the coloring matter. 
Two chief types of tumors can be distinguished histologically, the 
lymphoid and the myeloid. In the lymphoid form the tumor and its 
metastases are composed of cells resembling lymphocytes, generally of 
the large variety. Diffuse infiltration of the other organs may also 
occur, resembling that seen in the leukemias. In the myeloid type 
the tumor is characterized by the presence of large cells resembling the 
myelocytes or myeloblasts of the bone-marrow. In this form widespread 
involvement of the bone-marrow and spleen is apt to occur, and extension 
to other organs generally takes place in the form of small nodules of 
myeloid tissue (see, also, page 1073). 
The blood pictures may be conveniently divided into four types: 
One with small lymphocytes; one with large lymphocytes, which is the 
most frequent type; one with atypical large mononuclear cells resembling 
myeloblasts; and one in which the myelocytes are the cells most abun- 
dantly present. The red corpuscles also show the changes due to an 
anemia. 
Unless definite superficial tumors are present it is often impossible to 
differentiate the blood picture from that of a leukemia, and many of the 
cases have been diagnosticated only after death by the finding of greenish 
tumors scattered throughout the organs. 
PSEUDOLEUKEMIA. (Hodgkin's Disease, Adenie.) 
For a consideration of pseudoleukemia and Hodgkin's disease seo 
pages 555 and 556. 
ANEMIA INFANTUM PSEUDOLEUKEMICA. (Von Jaksch.) 
This is a somewhat peculiar from of anemia occurring in children, 
and characterized by a progressive course, by a considerable increase of 
leucocytes, by enlargement of the spleen and liver, and often by hyper- 
plasia of the lymph-nodes. A large number of nucleated red cells are 
present in well-marked cases. Myelocytes are found, but rarely form 
more than 10 per cent, of the white cells. 
By some authorities it is regarded as an early stage of leukemia or 
as a type of leukanemia, by others as a form of secondary anemia fol- 
lowing rachitis, tuberculosis, or syphilis, the marked blood changes being 
considered as due merely to the greater lability of the infant's hemato- 
poietic system. 
The histological changes in the blood-forming organs are, so far as is 
known, very similar to, but less pronounced than, those of leukemia.1 
1 Evans, F. A., and Happ, W. M., A study of so-called infantile splenic anemia or anemia infantum 
pseudoleukemica. Bull. Johns Hopkins Hosp., 1922, xxxiii, 1 (bibl.). 544 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
A very chronic form of anemia with enlargement of the spleen was 
first described by Banti.1 The course of the disease may be divided 
into three stages; one in which there is marked anemia with increase in 
the size of the spleen and irregular attacks of fever, the white cells re- 
maining normal in number and proportion. This period is usually from 
three to five years, but may be much longer. Then follows an interval 
of a few months in which there are jaundice and gastrointestinal dis- 
turbances, passing into the final stage with fever, jaundice, ascites, 
diminished leucocytes, extreme anemia, and often severe hemorrhages 
from the gastrointestinal tract. The chief lesions are a very much 
enlarged spleen with induration of the splenic pulp, atrophy of the 
Malpighian bodies, and frequently, though not always, an extreme 
sclerosis of the portal and splenic vessels. The sinuses are often dilated 
and may contain large cells filled with phagocyted red corpuscles. A 
moderate interlobular cirrhosis of the liver is usually present, but is not 
of a high grade. In the earlier stages no cirrhosis can be made out. 
Changes have not been observed in either the lymph-nodes or the 
bone-marrow. 
Originally the condition was considered merely an abnormal cirrhosis 
of the liver with enlargement of the spleen, but study of many cases in 
recent years, together with the striking improvement noticed after 
splenectomy, has forced the conclusion that the splenic lesion is the most 
important and that the cirrhosis is largely a secondary phenomenon. 
Umber2 has described an extremely interesting case in which there 
was apparently an extensive toxic destruction of the protein material in 
the body. After excision of the spleen this destruction was checked and 
the protein balance became positive. 
Despite the improvement resulting from splenectomy and the lack of 
correspondence in the clinical course of the disease, there has been much 
opposition directed of late against the consideration of Banti's disease as 
a distinct pathological entity. Some observers hold, apparently without 
sufficient evidence, that syphilis is entirely responsible for the spleno- 
megaly;3 others, having demonstrated the Bacillus hodgkini in the spleen, 
claim a bacterial origin for the condition;4 while a third group believes 
that the splenomegaly is due to a " fibrogenetic toxin probably of intes- 
tinal origin."5 It is evident that more investigation is needed to clear 
up this complex subject. 
In the type of splenomegaly described by Gaucher, there may be severe 
anemia, usually of a chlorotic type. Nucleated red cells are rarely seen; 
normoblasts have been reported in only two instances, and megaloblasts 
in but one. The leucocytes are usually diminished in number, but may 
SPLENIC ANEMIA. 
i Banti, Zieglers Beitr., 1898, xxiv, 21; Lessen, Mitt. a. d. Grenzgeb. d. Med. u. Chir., 1904, xiii, 
753. Fora very careful study of the remarkable improvement in the blood following splenectomy, see 
Bie.rring and Egdahl, Jour. Am. Med. Assn., 1906, xlvii, 1149 (bibl.). 
2 Umber, Ztschr. f. klin. Med., 1904, Iv, 289. 
* Norris, Summers, and Shapiro, Jour. Am. Med. Assn., 1918, Ixx, 191. 
* Yates, Bunting, and Kristjanson, Jour. Am. Med. Assn., 1914, Ixiii, 2225. 
6 Moschcowitz, E., Jour. Am. Med. Assn., 1917, Ixix, 1045 (bibl.). 545 
be normal in amount or even increased. Percentual differences are not 
very marked. (For a description of the lesions of the spleen, see page 
576.) 
Other types of splenomegaly accompanied by anemia are occasionally 
seen in adults, and in some instances the focus of the disease seems to 
be limited to the spleen, but there is no reason to consider the condi- 
tion as worthy of a separate classification. Many of the cases ultimately 
prove to be obscure forms of lymphatic leukemia in which the charac- 
teristic blood pictures appear only a few days or weeks before death. 
Other forms are due to a splenic tuberculosis or syphilis. In children, 
rickets, syphilis, and chronic gastrointestinal lesions are the chief causes 
of splenic enlargement with anemia. 
A separate class of splenic anemias heretofore included in this group 
has been shown to be due to a parasite, the Leishmania donovani (page 
139). The splenic anemia frequently occurring in children in Southern 
Italy and Northern Africa has been shown by Nicolle to be due to a 
similar parasite, the Leishmania infantum (page 140). 
A marked relative lymphocytosis characterizes the blood of both of 
these conditions. The parasites can be found in the blood in about a 
half of the adult cases, but in children they are very scanty. In blood 
obtained by splenic puncture the parasites can, however, be easily found 
in both forms. 
THE BLOOD AND THE BLOOD-FORMING ORGANS CHAPTER 11. 
THE LYMPH-NODES. 
General Characteristics of the Lymph-Nodes 
It is well, in studying the lesions of the lymph-nodes, to remember that they are 
structures so placed in the course of the lymph-vessels that the lymph, in flowing 
toward the larger central trunks, passes through them, undergoing a sort of filtration 
as it percolates through the trabeculae of the lymph-sinuses. If this fact be borne in 
mind the lesions of the lymph-nodes, which are in the majority of cases secondary, are 
much more readily understood. Particles of pigment, cells from malignant tumors, 
fragments of dead or disintegrating cells either free or within phagocytes, red blood - 
cells, bacteria, etc., which in any way get into the lymph-vessels, are carried along 
until a lymph-node is reached, and here they are, in part at least, deposited among the 
trabeculae of the sinuses, or are taken up by phagocytic endothelial cells, while the 
lymph passes on and out of the efferent vessels. Soluble toxic substances also are 
carried into the lymph-nodes, often inciting marked and significant alterations.1 
The lymph-nodes as blood-forming organs stand in close relationship to many 
abnormal processes in the body. In them are produced a large proportion of the 
lymphocytes of the circulating blood. 
What is called lymphatic tissue embraces not only the so-called lymph-glands and 
the less complex but still well-defined structures found in the stomach, intestines, ton- 
sils, and elsewhere, and called lymph-follicles, but also the less well-defined, irregular 
masses of tissue resembling that of lymph-follicles, which, as Arnold2 has shown, 
are widely disseminated in variable amounts in different parts of the body: in the 
lungs, beneath the pleura, in the interlobular septa, and elsewhere; in the liver, 
kidneys, etc. Although the exact nature of these more diffuse masses of lymphatic 
tissue is too little understood, as indeed is that of the lymph-follicles and glands them- 
selves, there is reason to believe that they are analogous structures and prone to be 
affected by similar deleterious agencies. It seems better, in view of the fact that the 
so-called lymph-glands are not glands at all, in the ordinary sense of the word, to call 
them lymph-nodes, and the smaller masses of lymphatic tissue scattered through 
various parts of the body lymph-nodules instead of "lymph-follicles." 3 
There is considerable variation in the situation, number, and size of lymph-nodes 
in special regions of the body, and they vary in size with age. It may be said that 
the lymph-nodes are most fully developed in the adult, and undergo fatty degenera- 
tion and involution in old age.4 
Finally the lymph-nodes are built up of cells many of which have not achieved a 
high degree of differentiation and thus are prone to undergo mitosis and rapid pro- 
liferation, when, from infective or destructive processes in regions to which they 
minister, deleterious agents gather in their recesses. 
HEMOLYMPH-NODES. 
Numerous observers have described the occurrence in man and certain of the 
lower animals, under normal as well as pathological conditions, of structures which 
1 For a study of bacteria in normal lymph-nodes, see Kdlble, Miinchen. med. Wchnschr., 1899, 
xlvi, 622; in abnormal nodes, see Torrey, Jour. Med. Research, 1916, N. S. xxix, 1. 
2 Arnold, J., Virchows Arch., 1880, Ixxx, 315; 1880, Ixxxii, 377; 1881, Ixxxiii, 289; 1882, Ixxxvii, 
114. 
2 For a study of the structure of lymph-nodes, see Weidenreich, Arch. f. mikrosk. Anat., 1905, Ixv, 1. 
4 For a study of regeneration of lymph-nodes and vessels, see Meyer, Bull. Johns Hopkins Hosp., 
1906, xvii, 185 (bibl.); Bayer, Arch. f. klin. Chir. (Langenbeck), 1895, xxxix, 637, and Hammerschlag, 
R., Virchows Arch., 1908, cxciv, 320 (bibl.). 
546 THE LYMPH-NODES 
547 
resemble lymph-nodes, but are usually smaller and are red or mottled red and white. 
In man they are found especially in the prevertebral fat, in the deep cervical region, 
in the retroperitoneal region, near the renal vessels, and about the brim of the pelvis. 
They are normally present, but they maybe more conspicuous under certain pathologi- 
cal conditions-pernicious anemia, acute infections, intoxications, etc. Their color is 
due to the presence of blood in the sinuses of the nodes. There are numerous transi- 
tional forms between nodes containing lymph-sinuses only and those which more 
nearly resemble the spleen in character. They become more prominent and are 
increased in number after splenectomy in animals.1 These structures do not appear 
to be lymph-nodes in which blood has accumulated from hyperemia or hemorrhage, 
and by some are considered to be structures entirely independent of the lymphatic 
system.2 
The perifollicular lymph-sinuses are widely distended with clear fluid. The lymph-nodules and 
lymph-cords are flattened from pressure of the fluid. 
Fig. 299.-Edema of a Lymph-node-Typhoid Fever. 
ATROPHY. 
Atrophy is a very regular occurrence in old age. In this condition 
the nodes are small, hard, and, unless pigmented, light in color. Micro- 
scopical examination shows a marked diminution in the number of par- 
enchyma cells, while the reticulum and the capsule and trabeculae and 
the elastic fibers may be thickened. In the nodes of the peritoneal cavity, 
fatty replacement of the lymphoid structure is frequent in a variety of 
diseases; while in senile atrophy the fat accumulates about the shrunken 
node. 
1 See Warthin, A. S., Jour. Med. Research, 1901, N. S. i, 3; 1902, N. S.ii,435 (bibl.); and Vaughan 
Anniversary Contribution to Medical Research, 1903, p. 216. For a full and excellent summary, with 
bibliography, consult Warthin, A. S., Trans. Chicago Path. Soc., 1902, v, 151. For a study of the 
development of hemolymph-nodes in adipose tissue, see Dayton, H., Am. Jour. Med. Sc., 1904, cxxvii, 
448. 
2 W eidenreich, Anat. Anz., 1902, Erganzungsheft, xxi, 47; Meyer, Jour. Exper. Zool., 1914, xvi, 241. 548 
THE LYMPH-NODES 
EDEMA. 
Edema of the lymph-nodes may be associated with a blocking of the 
associated lymph-vessels. Under these conditions the lymph-sinuses 
may be widely distended (Fig. 299). 
DEGENERATION. 
Amyloid degeneration of the blood-vessels and reticulum of the 
lymph-nodes occurs under the conditions which favor this change in 
general. It may occur in connection with amyloid degeneration of other 
parts of the body, or by itself. It may occur in nodes otherwise normal, 
or in those which are the seat of other lesions-thus in simple chronic or 
tuberculous inflammation. It is frequently found in the mesenteric 
Fig. 300.-Pigmentation of Bronchial. Lymph-node. 
The pigment is largely in the lymph-sinuses and inclosed in cells. A, Capsule of node; B, lymph- 
nodule; C, perifollicular lymph-sinuses. 
lymph-nodes, in connection with waxy degeneration of the intestinal 
mucous membrane. 
Hyaline degeneration of the external layers of the smaller arteries and 
the capillaries and reticulum of the lymph-nodes occurs occasionally in 
old age or in connection with wasting diseases. 
PIGMENTATION. 
The pigment which is very frequently found in lymph-nodes may be 
derived from the hemoglobin of the blood, either in the nodes themselves 
or in remote parts, or it may be formed of various materials introduced 
into the body from without, such as the pigments used in tattooing, 
respired dust particles of various kinds-coal, stone, iron, etc. (Fig. 300). 
The pigment particles, which usually lodge first in the lymph-sinuses,. THE LYMPH-NODES 
549 
may collect here in large quantities, either in the reticulum or in the cells 
lying in its meshes; they may penetrate the follicles and cords and find 
permanent lodgment there. They usually induce a greater or less degree 
of chronic inflammation, so that in extreme cases, such as are frequently 
seen in the bronchial lymph-nodes, nothing is finally left of the node, but 
a more or less deeply pigmented mass of dense connective tissue. The 
function of the node may be, of course, in this way partially or entirely 
destroyed. The pigment in these cases appears to reach the node, in 
part by being carried along free in the lymph current, in part through 
transportation by leucocytes in which the particles have become inclosed. 
Pigmentation of the nodes is most marked in those about the root of the 
lungs, which are frequently of a mottled gray or a black color, but it 
Showing a portion of one of the mesenteric nodes. A, Capsule; B, perifollicular space or lymph- 
sinus, containing in its meshes many large cells; C, portion of one of the nodules, with large and small 
cells in the meshes of its reticulum. 
Fig. 301.-Endothelial Hyperplasia of Lymph-node in Typhoid Fever. 
may occur in the mesenteric and other nodes. Under similar conditions 
the diffuse lymphatic structure in the lungs and liver may be pigmented. 
INFLAMMATION. 
Acute inflammation of the lymph-nodes is commonly due to the pres- 
ence of pathogenic microorganisms or of toxic substances, usually 
bacterial in origin, which may be formed in the node or brought to it in 
the lymph current from the tributary region of the body. Under these 
conditions the nodes are usually swollen, reddened, and softer than 
normal, and are often the seat of small hemorrhages. One or all of the 
nodes of a cluster may be affected. 
Two forms of the acute inflammatory process may conveniently be 
recognized, a hyperplastic and an exudative. 550 
THE LYMPH-NODES 
In. the hyperplastic form a microscopical examination shows the 
lesion to be largely due, in addition to the hyperemia and hemorrhage, 
to a proliferation of the cells of the node, the spheroidal mononuclear 
cells of the nodules and cords, and especially the endothelial cells of the 
lymph-spaces (Fig. 301), which may increase in number and exfoliate 
to such an extent as to fill and largely distend the lymph-sinuses. These 
endothelial cells often contain red blood-cells, leucocytes, and fragments 
of other cells (Fig. 302). In diphtheria, scarlatina, and typhoid fever, 
as well as in many other infectious diseases, necrosis of the hyperplastic 
tissue is common. The necrosis is usually in circumscribed areas-focal 
necrosis-and often involves especially the germinal centers of the nodules. 
After simple hyperplasia of the lymph-nodes, resolution readily 
occurs. But if necrosis have taken place, such areas may be replaced 
by fibrous tissue. 
This form of lesion of the lymph-nodes is common. It may occur in 
the cervical nodes with many forms of angina; in the inguinal nodes in 
connection with acute infectious processes in the external genital organs; 
in the axilla with infectious processes in the hand, arm, or breast; in 
the mesenteric nodes with infection or intoxication of intestinal or other 
origin. Similar lesions occur in the solitary lymph-nodules and Peyer's 
patches of the intestine (Fig. 303). 
In exudative or suppurative forms of inflammation of the lymph- 
nodes, in addition to the simple hyperplastic changes just described, 
there are emigration and collec- 
tion of leucocytes, with the 
formation of more or less fibrin 
in the lymph-sinuses «as well as 
in the interstices of the nodules. 
The capsule of the nodes may 
be infiltrated with exudate. 
With these changes there may 
be necrosis and softening of the 
tissue of the nodes and the de- 
velopment of abscesses. Small 
abscesses may coalesce, and thus 
a considerable part of the node 
be converted into a suppurating 
necrotic mass-bubo. Such a 
bubo may open externally or into the surrounding tissue and heal by 
granulation tissue and cicatricial tissue; its contents may be absorbed 
or become dry and dense and calcified, and surrounded by fibrous tissue. 
Suppurative inflammation of the lymph-nodes often occurs in connection 
with suppurative processes elsewhere, in pyemia, venereal infection, etc. 
The lymph-nodes of children are, as a rule, more readily involved in 
infectious processes of other parts than are those of adults. 
Chronic Inflammation.-This is characterized by the increase of the 
connective-tissue elements of the node, with a gradual and commensu- 
rate disappearance of the lymphoid cells. The reticulum of the folli- 
Fig. 302.-Endothelial Cells in Hyperplasia 
of the Lymph-nodes. 
The exfoliated cells contain red blood-cells, fat 
droplets, and masses of blood pigment. THE LYMPH-NODES 
551 
cles and sinuses becomes thickened and fibrous, and in the trabeculse 
and capsule new connective tissue is formed, until, in advanced cases, 
the entire node may be more or less extensively converted into a mass of 
fibrous tissue. This condition is very frequently seen in the lower tracheal 
Fig. 303.-Hyperplasia of Peyer's Patch in Typhoid Fever. 
Showing new-formed endothelial cells in the meshes of the reticular tissue between the blood-vessels 
and in the bronchial nodes, apparently as a result of the lodgment in them 
of respired pigment particles; but it may occur in any nodes, either as a 
result of repeated moderate degrees of inflammation or from causes 
which we do not know. In some cases the nodes are greatly enlarged 
Fig. 304.-Chronic Inflammation of Bronchial Lymph-node. 
Showing obliteration of the lymph-sinuses and atrophy of the lymph-nodules by the new-formed 
connective tissue. 
and the new tissue contains many large cells, while in other cases the 
connective tissue is dense and contains but few cells (Fig. 304).1 
Tuberculous inflammation may be local, confined to the nodes, or it 
1 Consult Ribbert, Ueber Regeneration und Entziindung der Lymphdriisen, Zieglers Beitr., 1889. 
vi, 187. 552 
THE LYMPH-NODES 
may occur in connection with general acute miliary tuberculosis, or with 
tuberculous inflammation of single organs. It may occur in single nodes, 
or in several nodes of the same group, or in groups situated in different 
parts of the body. In its simple and acute form there may be no evi- 
dent change to the naked eye in the appearance of the nodes, or they may 
be besprinkled with small, grayish white, translucent spots. Under 
these conditions the nodes may be reddened and soft, or swollen and 
denser than normal. In more advanced forms of the lesion the tubercles 
coalesce and undergo a greater or less degree of cheesy degeneration. 
Under these conditions the cheesy areas are evident to the naked eye as 
more or less sharply circumscribed, opaque, whitish or yellowish areas, 
frequently surrounded by an irregular, more translucent, grayish zone 
of tubercle tissue which merges insensibly into the adjacent tissue. 
The entire node may become involved, and more or less completely con- 
verted into a cheesy mass, in the periphery of which a zone of tubercle 
tissue may or may not be evident. 
Microscopically the small nodules or miliary tubercles are seen to 
consist of more or less circumscribed collections of small spheroidal, or 
more frequently larger polyhedral cells, with or without well-defined 
giant cells. They usually commence to form in the follicles and lymph- 
cords of the nodes, and from these may spread and involve the entire 
surrounding tissue. The cheesy degeneration, which here as elsewhere is 
apt first to involve the central portions of the tubercles, presents the 
usual appearances. Tubercle bacilli may be found in the edges of the 
cheesy areas or in the tubercle tissue about them. 
Simple inflammatory changes regularly occur in the periphery of the 
tubercles. There is an increase of cells in the lymph-sinuses and follicles, 
and a more or less marked swelling, and apparently a proliferation of the 
cells of the reticular tissue of the node. In cases in which the process is 
chronic there is often marked increase of the connective tissue of the 
nodes, the reticular tissue becomes dense and fibrous, and the trabeculae 
and capsule are thickened. The tubercles themselves, instead of under- 
going cheesy degeneration, may become fibrous or be converted into a 
hyaline material. 
The cheesy material may dry and shrink, and become inclosed by a 
capsule of dense connective tissue and become calcified; or it may soften, 
and thus cavities be formed in the nodes, filled with grumous material; 
or inflammatory changes may be induced in the vicinity of the nodes, 
leading to abscesses. On the other hand, hyperplastic inflammation in 
the periphery of the affected nodes may result in their becoming bound 
together into a dense nodular mass. 
The formation of bone in lymph-nodes has been described in con- 
nection with tuberculous inflammation, carcinoma, and other lesions.1 
Scrofula.-Tuberculous inflammation of the lymph-nodes, espe- 
cially in those of the cervical,2 bronchial (Plates V and XI), and mesen- 
teric groups, often occurs in children, particularly in those who are ill- 
1 See Merkel, H., Munchen, med. Wchnschr., 1905, lii, 1238. 
2 For bibliography of cervical tuberculous lymph-nodes, see Dowd, Ann. Surg., 1899, xxix, 559. THE LYMPH-NODES 
553 
nourished. Northrup and Bovaird found in an analysis of 200 cases of 
tuberculosis in children that the lungs and bronchial lymph-nodes were 
involved in 148.1 Such persons, in addition to the lesion of the lymph- 
nodes, are very liable to suffer from chronic tuberculous and other in- 
flammations of the mucous membranes, skin, periosteum, joints, and the 
subcutaneous and other connective tissues. This general condition is 
known as scrofula, and the lesion of the nodes is sometimes called scrofu- 
lous inflammation. 
While in many cases the portal of entry of the tubercle bacilli is not 
evident, and the lesions often present the appearance of hyperplasia of 
the lymphoid tissue with cheesy degeneration and the formation of more 
or less dense fibrous tissue rather than the typical characters of tubercu- 
lous tissue, nevertheless miliary and other forms of tuberculous inflam- 
mation are often present in so-called scrofula, and tubercle bacilli, while 
sometimes absent, are often present and virulent.2 
The necrotic portions of such cheesy lymph-nodes in scrofula may 
soften and break down, and by the establishment of purulent and necrotic 
inflammation about them abscesses may form which may open externally. 
These abscesses may heal; but usually the healing is difficult and slow, 
and long-continued suppurations, frequently with the development of 
fistula, are very common. Instead of softening, the cheesy material in 
the nodes may become dry and hard and undergo calcification. 
Generalized Tuberculous Lymphadenitis.-Several cases have 
been recorded of extensive tuberculous hyperplasia of the lymph-nodes 
in various parts of the body, the lesion resembling in its gross characters 
that of Hodgkin's disease. While in some of these cases the morphology 
of the lesions is characteristic of tuberculosis, in others the new tissue is 
diffuse and consists largely of new-formed, small, spheroidal and poly- 
hedral cells with large multinuclear cells, and of fibrous tissue. The 
new-formed cells may undergo necrosis. Thus the tuberculous nature of 
the lesion is not always plain, even on microscopic examination. Animal 
inoculations are often necessary for the establishment of the nature of 
such cases.3 The predilection of tubercle bacilli for lymph-nodes and 
the occurrence in them of the earliest lesions as a result of multiplication 
of the bacteria is apparently not in harmony with Bartel's theory that 
lymph-nodes are protective or with Murphy's belief that the lymph- 
cells act as inhibitory agents.4 
Syphilitic Inflammation.-The lesions of the lymph-nodes which occur 
in connection with syphilis vary greatly, depending upon the stage of the 
disease. In the primary stage the nodes in the region of the seat of 
1 For a study of tuberculous bronchial lymph-nodes in children consult Northrup, New York Med. 
Jour., 1891, liii, 203; and Bovaird, ibid, 1899, Ixx, 1. See further, Marfan, Bouchard, and Brissaud, 
TraitS de MSdecine, 1901, vii, 525. For later study of tuberculosis of lymph-nodes, especially in 
childhood, see Harbitz, Jour. Infect. Dis., 1903, ii, 143, ibid., 1917, xxi, 196. 
2 In the examination of lymph-nodes for tubercles and tubercle bacilli it should be remembered that 
not infrequently, though one fails to find either morphological tubercles or stained bacilli, the inocula- 
tion of portions of the fresh tissue into guinea-pigs wid show that living and virulent bacilli were present. 
3 For a study of this form of tuberculosis, consult Crowder, New York Med. Jour., 1900, Ixxii, 443, 
490, (bibl.L 
Smith, Theobald, Jour. Am. Med. Assn., 1917, Ixviii, 669, 764. 554 
THE LYMPH-NODES 
infection are apt to present the lesions of an ordinary acute inflammation 
occasionally with suppuration. 
In the secondary stage of the disease the nodes of other regions, neck, 
elbow, axilla, etc., are often swollen and hard. On microscopic exam- 
ination, there may be an increase of connective tissue in the capsule and 
trabeculae, but the chief change is the accumulation in the follicles and 
lymph-sinuses of larger and smaller spheroidal and polyhedral cells. 
The reticular tissue may be thickened and the walls of the blood-vessels 
infiltrated with cells. In this condition the nodes may remain for a long 
time, not tending to form abscesses; or they may undergo resolution 
through degeneration and absorption of the cells. 
In the tertiary stage of the disease the nodes may be the seat of 
chronic inflammation characterized by the formation of gummata. 
Under these conditions they may form large, firm nodular masses from 
the growing together by new connective tissue of several altered nodes. 
The gross and microscopical characters of gummata of the lymph-nodes 
are, in the main, similar to those in other parts of the body. 
HYPERPLASIA OF THE LYMPH-NODES. (Lymphoma.) 
In addition to the enlargement of the lymph-nodes due to types of 
inflammation which have been described above, there is still another 
variety, a tumor-like swelling of the nodes whose etiology is still in 
doubt, though the general assumption is that an infectious agent under- 
lies the changes. The disease affects either a single node or a group; 
usually in the cervical region, the axilla, or the groin. The enlarged 
node or nodes remain discrete and, except for the discomfort consequent 
upon the tumor, have little or no influence on the health of the patient, 
and may persist for years. Such nodes on cut section are paler and 
firmer than the normal tissue. They are usually provided with a fairly 
thick capsule. Microscopically, they are composed of lymphoid tissue, 
preserving in general the anatomical divisions of the normal node. The 
germinal centers may be diminished in size, or greatly increased and show 
evidence of hyperplasia. There is no tendency of the lymphoid cells to 
invade the surrounding tissue. The lymphocytes themselves preserve 
morphological and functional qualities the same as the normal, though 
usually they are less compactly distributed between the connective tissue 
trabeculae. The trabeculae also are apt to be somewhat thicker than 
usual. 
Small nodes with chronic hyperplastic inflammatory changes are 
frequent in the drainage areas of benign and malignant tumors of the 
glandular organs. This chronic hyperplasia is unquestionably due to the 
absorption of metabolic products from the gland secretion, or the tissue 
breakdown of the tumor. They disappear if the tumor is removed. 
Such nodes rarely reach a large size. 
In the disease known as status lymphaticus, the lymph-nodes are 
often enlarged to a considerable size in association with a persistent and 
enlarged +hymus. The microscopic changes in these nodes are chiefly 
those of a hyperplasia with increase in size of the germinal centers. THE LYMPH-NODES 
555 
LEUKEMIC LYMPHOMATA. 
In the different types of leukemia, chiefly in the lymphatic form, 
changes in the lymph-nodes are frequent. In acute lymphatic leukemia, 
especially in children, there is often considerable enlargement of the 
lymph-nodes usually in the neck, axilla, or groin, but often also of the 
internal nodes, tonsils, and other lymphatic areas in the body. Such 
nodes are often, though not always, discrete and movable, and do not 
involve the overlying skin. The capsule is as a rule infiltrated with cells, 
the substance of the gland is usually very soft and may be hemorrhagic, 
especially in acute leukemia. In more chronic cases, a considerable 
fibrous hyperplasia may occur so that the nodes are fairly firm. Micro- 
scopically, these nodes show either very great hyperplasia of the normal 
lymphocytes with more or less loss of the nodal architecture, or the re- 
placement of the normal tissue by more or less extensive areas of large 
cells resembling the large lymphocytes found in the circulating blood. 
The nuclei of these cells are larger and the chromatin much less compact 
than in the normal lymphocyte, and the cell body is much4 broader. 
In myelogenous leukemia distinct enlargement of the nodes is 
not very frequently met with, and when the process does occur the 
nodes will be found to have undergone a myeloid metaplasia with replace- 
ment of the lymphoid tissue with that resembling bone-marrow; in 
other words, with cells of a granular type. The change begins with the 
appearance of small areas of myelocytes. These gradually increase in 
size and displace the lymph-follicles, and finally the entire node may be 
replaced by the myeloid structures. Usually such nodes are soft and do 
not undergo fibrous changes. These nodular enlargements must be 
distinguished from the metastatic or tumor-like collections of lympho- 
cytes which form in the skin in certain cases of acute lymphatic leukemia. 
Such nodules do not appear to occur in the myelogenous type, though 
they may be simulated by areas of subcutaneous hemorrhage, which when 
sectioned, owing to the large number of myelocytes in the exuded blood, 
resemble very closely the lymphatic tumors. An examination of the 
blood gives the clue to the nature of both the lymphatic and the myelo- 
genous lymphomata. In specimens in which there is no record of the 
blood count, a careful examination should be made of the contents of the 
larger blood-vessels in the sections, which will often enable a decision 
to be made as to whether a leukemia exists or not. 
PSEUD OLEUKEMIC LYMPHOMATA. 
In another type of diffuse enlargement of the lymph-nodes coexisting 
leukemic changes in the blood do not occur, though a moderate anemia 
may exist. Individual nodes, or a large number, may be simultaneously 
involved, or the process may be progressive, spreading from one region 
to another. The nodes may fluctuate in size from time to time, as in 
leukemic enlargements. There is no tendency for the tumors to break 
down or soften, nor for the neighboring nodes to fuse. They are smoothly 556 
THE LYMPH-NODES 
encapsulated and usually fairly firm and pale on section. The bone- 
marrow is not as a rule altered, though in some cases the same leukemic 
overgrowth may be found as in the nodes. 
Microscopically, the tumors resemble those of lymphatic leukemia, 
though they may contain a large number of eosinophile cells (Fig. 305). 
Whether a myeloid pseudoleukemic enlargement of the lymph-nodes may 
occur is still questionable.1 In rare instances a leukemic blood condition 
Fig. 305.-Lymph-node from Case of Chronic Lymphatic Leukemia. 
Compare with lymph-nodes in Hodgkin's disease. 
develops after the pseudoleukemia has existed for a considerable time.2 
Metastatic myelomata should not be confused with a myeloid leukemic 
or psuedoleukemic lymphoma. 
HODGKIN'S DISEASE. (Adenie.) 
In this relatively frequent disease, the changes in the lymph-nodes 
are entirely different from those previously described. Originally it 
was thought to be a diffuse tuberculosis of the lymphatic system, and 
unquestionably such a lesion may occur with the clinical picture of 
'Hirschfeld, Berl. klin. Wchnschr., 1908, xlv, 2227. 
2 v.Domarus, Folia h®matologica, 1908, vi, 337. 557 
THE LYMPH-NODES 
Hodgkin's disease, though the bacilli can usually be demonstrated only 
by animal inoculation.1 The disease may be simulated also by diffuse 
metastases from an internal unrecognized tumor, but the microscopical 
examination of the nodes will differentiate the conditions. 
The tumor-like swellings of Hodgkin's disease usually involve the 
superficial nodes of the neck, axilla, inguinal, or cubital regions, but the 
lesion may be confined entirely to the bronchial or retroperitoneal nodes. 
In some cases the spleen is very slightly affected; in others extensive 
necroses with a fibrous tissue replacement may occur, and instances have 
Fig. 306.-Bone-marrow in Hodgkin's Disease. 
Showing eosinophile cells in great abundance. 
been reported in which the splenic lesion seems to have been primary.2 
The bone-marrow shows a moderate hyperplasia or, occasionally, areas 
of giant cells and fibrosis with local eosinophilia (Fig. 306). In advanced 
cases the liver may show a few of the characteristic nodules (Fig. 307). 
The uterus3 and, rarely, the skin (Fig. 308),4 may show the characteristic 
1 Sternberg (Ztschr. f. Heilk., 1898, xix, 21) has made a careful study of cases of this type. 
2 Mellon, Am. Jour. Med. Sc., 1916, cli, 625. 
3 Jessup, D. S. D., Proc. New York Path. Soc., 1912, xii, 3. 
4 Arndt, G., Virchows Arch., 1912, ccix, 432 (bibl.); Alderson, H. E., Jour. Cutan. Dis., 1917, xxxv, 
481. 558 
THE LYMPH-NODES 
lesion. The gross appearance of the nodes is considerably altered from 
the normal. They may be lobulated, soft or hard, and white, gray, or 
red, and often show areas of necrosis. They are usually entirely discrete, 
and there is no infiltration of the capsule or perinodular fat with lympho- 
cytes as is the case in the forms of enlargement due to leukemia or 
lymphosarcoma. At first the only lesion, besides a moderate hyperplasia, 
may be the development of areas containing a considerable number of 
The abdominal and bronchial lymph-nodes alone were involved in this case. The hyperplasia in the 
liver is of the same type as that in the nodes; with the formation of connective tissue and large irregu- 
lar multinucleated cells. 
Fig. 307.-Hodgkin's Disease. Nodule in Liver. 
large cells with a faintly staining cell body and a single large nucleus, 
sometimes showing mitosis (Fig. 309 and 310). In this early stage these 
cells correspond closely in morphology with the large cells of the ger- 
minal centers; they are not the same as the multinucleated cells of the 
later development of the disease. Not all the enlarged nodes show these 
changes equally well. Such alterations in the structure can scarcely 
be considered as specific, since they may be found in nodes undergoing 559 
THE LYMPH-NODES 
Fig. 308.-Hodgkin's Disease of Skin. 
Fig. 309.-Hodgkin's Disease. Lymph-node with Lymphoid Tissue still Preponderating, 
but the Large Endothelial Cells Show Hyperplasia. 
There is only a moderate connective tissue replacement. 560 
THE LYMPH-NODES 
Fig. 310.-Hodgkin's Disease. Lymph-node Showing Extensive Hyperplasia of Large Cells 
Fig. 311.-Hodgkin's Disease. Lymph-node in which the Lymphoid Tissue Still Predominates, 
but the Large Endothelial Cells show Hyperplasia. 
There is a beginning connective tissue replacement THE LYMPH-NODES 
561 
chronic hyperplasia in response to the irritation of a neighboring malig- 
nant epithelial growth, or even after long continued chronic inflammation. 
In the second stage, however, the diagnosis is usually possible from 
an individual node, for there are present not only the large cells before 
mentioned, but necrotic areas surrounded by cells of the epithelioid 
type (Fig. 311) and more or less numerous large cells with polymorphic 
nuclei or with two or more small oval nuclei lying in the center of the 
cell body. True giant cells of the Langhans' type (see Fig. 156, p. 285) 
Fig. 312.-Hodgkin's Disease. Lymph-node showing Large Cells. 
with peripherally arranged nuclei are rare in comparison with the other 
form (Fig. 312). This group of cells is probably produced by hyperplasia 
of the reticular endothelial cells. Necrosis in the nodes and spleen in 
these cases may be very extensive. There is usually a beginning re- 
placement hyperplasia of the fibrous tissue of the reticulum. 
In the third stage the nodes may be smaller than the previous stages, 
and are composed very largely of dense anastomosing bands of fibrous 
tissue which occasionally undergo hyaline degeneration (Fig. 313). 
Thrombosis or extensive obliterative endarteritis of the vessels is not 562 
THE LYMPH-NODES 
uncommon, and the lymphoid tissue may project under the endothelium 
so as nearly to close the lumen. The lymphoid tissue is occasionally 
reduced to a few scattered areas surrounded by dense connective tissue 
(Fig. 314). 
Eosinophile cells may be abundant in the nodular substance, and 
sometimes an increase in eosinophiles is seen in the circulating blood: but 
neither condition is constant. Plasma cells also may be found in the 
nodes in large or small numbers. Lymphoid infiltration in the organs, 
such as is seen in leukemia, is not usually found. In fact, an important 
characteristic of Hodgkin's disease is that the lesions have a tendency 
to remain in nodular form and not to destroy the organ involved com- 
pletely, if we except the lymph-nodes. There is always a severe pro- 
Fig. 313.-Lymph-node in Hodgkin s Disease. 
The trabeculae have undergone hyaline degeneration. A considerable number of lymphoid cells 
still remain lying between the connective tissue bands, together with some large cells. 
gressive secondary anemia with occasionally a high leucocyte count, 
though usually the alterations in number and proportions of the white 
cells from the normal are slight.1 The tumors are favorably influenced 
by radium and Roentgen rays, but ultimately the disease is fatal.2 
It is now generally acknowledged that the tubercle bacillus or organ- 
isms resembling it can be demonstrated in only a small percentage of the 
cases of typical Hodgkin's disease, and repeated efforts to isolate the 
specific organism, stimulated by the finding by Fraenkel and Much of 
1 Important papers on the histology of Hodgkin's disease, with bibliography, are those by Longcope, 
Bull. Ayer Clin. Laboratory, 1903, No. 1; Reed, Johns Hopkins Hosp. Rep., 1902, x, 133 (bibl.); 
Simmons, C. C., Jour. Med. Research, 1903, N. S. iv, 378, and Ziegler, K., Die Hodgkinsche Krank- 
heit, Jena, 1911 (bibl.). 
2 Simmons and Benet, Boston Med. and Surg. Jour., 1917, clxxvii, 819. THE LYMPH-NODES 
563 
granular rods resembling bacilli in the antiformin centrifugate obtained 
from nodes, have recently led to the isolation by Negri and Mieremet1 
of a diphtheroid organism which they call Corynebacterium granulomatis 
maligni. These findings have been confirmed by others.2 By the in- 
jection of cultures of this bacillus Bunting and Yates have been able to 
produce in the Macacus rhesus a lymphoid hyperplasia with proliferation 
of the stroma and eosinophilic infiltration, and Billings and Rosenow3 
have noted certain therapeutic improvements following the use of a 
vaccine made from the organism. The fact that similar diphtheroid 
pleomorphic bacteria have been found in carcinomata, in the spleen in 
Fig. 314.-Lymph-node in Hodgkin's Disease, Densely Fibrous. 
The lymphoid structures have been almost entirely replaced by connective tissue. 
Banti's disease, and in diseased lymph-nodes from a variety of conditions, 
and have been isolated from the blood in various diseases render neces- 
sary most critical studies of the relationships between the newly found 
organism and Hodgkin's disease, in order to affirm its etiological 
importance. It is at present not considered by most pathologists to be 
related to the disease.4 
While the infectious nature of Hodgkin's disease is generally accepted, 
a few pathologists, Mallory among them, believe that the process is 
neoplastic.5 
1 Negri and Mieremet, Centralbl. f. Bakteriol., I. Abt. Orig., 1913, Ixviii, 292. 
2 Bunting and Yates, Arch. Int. Med., 1913, xii, 236, and Jour. Am. Med. Assn., 1913, Ixi, 1803; 
1914, Ixii, 516; Verploegh, Kehrer, and v. Hoogenhuyze, Munchen, med. Wchnschr, 1914, Ixi, 1158. 
3 Billings and Rosenow, Jour. Am. Med. Assn., 1913, Ixi, 2122. 
4 Simmons and Benet, Boston Med. and Surg. Jour., 1917, clxxvii, 819. 
6 Mallory, F. B., Principles of Pathologic Histology, Philadelphia, 1914. For a recent review of the 
lesions of the disease, see Beifeld, A. F., Am. Jour. Med. Sc., 1918, civ, 409. 564 
THE LYMPH-NODES 
TUMORS. 
Fibroma, myxoma, and chondroma have been described as occurring 
in the lymph-nodes in a few instances. The presence of cartilage is 
probably due to some congenital displacement rather than to true tumor 
formation. Endotheliomata of the lymph-nodes have been described 
(Fig. 315),1 but probably most if not all of these tumors should be con- 
sidered as sarcomata. Some of the reported cases are unquestionably 
secondary carcinomata. 
The most frequent tumor of the lymph-nodes is the lymphosarcoma. 
This may arise in the lymphatic tissue in any portion of the body, or in 
Fig. 315.-Sarcoma of Lymph-node (Endothelioma) . 
separate lymph-nodes, which rapidly break through the capsule and in- 
volve the surrounding tissue, or may begin diffusely, occupying a series 
of lymph-nodes simultaneously. As has been suggested in the discussion 
of the lymphomata, the chief point of difference between the benign 
and the malignant tumors of the lymph-nodes lies in the invasive growth 
of the latter. Macroscopically, the lymphosarcomata are soft, pale, and 
occasionally hemorrhagic, though in the slower growing forms sufficient 
increase in the connective tissue may produce a fairly firm tumor. Micro- 
scopically, the diagnosis is occasionally exceedingly difficult. Important 
1 Wood, F. C., Proc. New York Path. Soc., 1912, xii, 54. THE LYMPH-NODES 
565 
facts pointing to malignancy are the large size of the cells, which con- 
siderably exceed the normal lymphocyte, the larger nuclei, mitoses, dis- 
appearance of the normal architecture of the node, irregularities in sizes 
and shapes of the individual cells. Cases will be met with in which the 
final decision as to malignancy must be made on the clinical course. 
At the onset the blood is usually normal, but an anemia rapidly develops, 
and in rare instances a considerable number of lymphocytes may appear 
in the blood. Very rarely spindle-cell, melanotic, or large round-cell 
sarcomata arise in the nodes. 
Secondary involvement of the lymph-nodes is very frequent. Sar- 
comata, especially of the melanotic type, may form metastases in the 
nodes, but in the vast majority of instances secondary tumors are of 
epithelial origin. When the cells of malignant tumors perforate into the 
lymph-channels, they may be carried away in the lymph-current aided 
by the massage given by muscular movements, while possibly the ame- 
boid capacity of the cells of the tumors may aid further in transport. 
The lymph-channels enter the perifollicular sinuses and the first invasion 
of the tumor cells is to be noted at this portion of the node. A very 
slight reaction may be set up by the epithelial cells, or they may remain 
quiescent in a node for a long period of years, finally to begin again their 
malignant proliferation; but the usual course is a progressive multiplica- 
tion of the cells with enlargement of the node into a firm, white, opaque 
mass which permits easy recognition, even in a fresh specimen. In the 
later stages, the tumor cells involve the tissue around the capsule of the 
node, grow into the neighboring vessels, and are distributed throughout 
the body, producing a generalized carcinosis. 
Care should be taken not to confuse the chronic inflammatory hyper- 
plasia of the lymph-sinuses with invasion by carcinoma, and to remember 
that occasionally lymph-nodes in the abdominal cavity may contain 
small gland-like alveoli as a congenital displacement, or due to hyper- 
plasia of the endothelial lining of the lymph-channel. 
PARASITES. 
Aside from the various forms of bacteria which are not infrequently 
found in the lymph-nodes in infectious diseases, the animal parasites 
nlaria, trichinella, and pentastoma have been described. CHAPTER III. 
THE SPLEEN AND THYMUS. 
The Spleen. 
General Characteristics of the Spleen. 
In studying the lesions of the spleen it is important to bear in mind the peculiar 
relations in which this organ stands to the blood-vessels and to the circulation. After 
passing through the various branches of the splenic artery and the limited systems of 
capillaries which are associated with it, the blood is not received at once into venous 
trunks, as in other parts of the body, but is poured directly into the pulp tissue. In 
this it circulates, under conditions which render it liable to stagnation and undue accu- 
mulation, before it is taken again into well-defined vessels through the open walls of 
the cavernous veins. Moreover, these conditions, naturally unfavorable to undisturbed 
and vigorous circulation, are reinforced by the association of the splenic with the 
sluggish and often interrupted portal circulation. Bearing these considerations in 
mind, it is in a measure plain why, as is in fact the case, the spleen should be more 
liable to alterations in size than any other organ in the body, and why, serving as it 
does as a sort of blood filter, it should be especially susceptible to the influence of 
deleterious materials of various kinds which in one way or another gain access to the 
blood. The relationship between the lymph-vessels and the spleen is also intimate. 
Plexiform lymph-sinuses, which partly form actual cavities and partly consist of a 
spongy meshwork of capillaries in the connective tissue reticulum, connect with the 
larger cavities and drain into the arteries and veins. The efferent lymph-vessels of 
the spleen pour out their contents into the sinuses, but there are no afferent or efferent 
trunks leading to the organ or carrying lymph from it.1 Finally, the spleen, as an 
organ which destroys the red corpuscles and may under certain circumstances act as 
a depot for myeloid tissue, bears an important relationship to many abnormal condi- 
tions in the body. It may also contribute lymphocytes to the blood stream.2 
Malformations and Displacements. 
The spleen may be absent in acephalous monsters, and with defective development 
of other abdominal viscera. Absence of the spleen in otherwise normally developed 
individuals has been recorded. There may in this condition be a compensatory hyper- 
plasia of the lymphatic tissues of the body.3 The removal of the spleen in adults 
has only a transitory effect on the number of red and white cells in the blood.4 Small 
accessory spleens, from the size of a hazlenut to that of a walnut, are not infrequent. 
They usually lie close to the spleen, but may be at a considerable distance from it; 
thus they have been found embedded in the head of the pancreas.6 Two spleens of 
about equal size have been observed. The spleen may be made up of several distinct 
lobes. It may be displaced congenitally or as the result of disease. It may be on the 
1 Weidenreich, Arch. f. mikros. Anat., 1901, Iviii, 247. 
2 For extensive experimental studies on the spleen and its functions, see Pearce, Krumbhaar, and 
Frazier, The Spleen and Anaemia, Philadelphia, 1918. 
3 See Hodenpyl, Med. Rec., 1898, liv, 695 (bibl.). For a study of the effect of splenectomy in 
animals on the hemolymph-nodes, see Warthin, Vaughan Anniversary Contributions, 1903, p. 216. For 
certain pathological relations of the spleen, see Eppinger, H., Berl, klin Wchnschr., 1913, lii, 1509. 
4 Paton, Gulland, and Fowler, Jour. Physiol., 1902, xxviii, 83. 
6 Hemolymph-nodes may be mistaken for accessory spleens. 
566 THE SPLEEN AND THYMUS 
567 
right side in transposition of the viscera. As the result of congenital defects in the 
diaphragm the spleen may be found in the thorax; or in deficient closure of the ab- 
dominal wall it may, together with other abdominal viscera, be found outside of the 
body. 
The spleen may be pressed downward by any increase in the contents of the thorax. 
It may be bound by adhesions to the concave surface of the diaphragm, so that its 
long axis is nearly horizontal instead of vertical. It may be displaced by changes in 
the contents of the abdominal cavity. If the organ be increased in size it frequently 
becomes tilted, so that its lower border reaches the right iliac region. If the ligaments 
be too long congenitally, or if they are lengthened by traction, and if the organ is at 
the same time increased in weight, it may become very movable. It may sink down- 
ward, with its hilus turned upward; or it may be rotated on its axis, and, owing to 
torsion of the vessels thus produced, the organ may atrophy; or the pressure of the 
ligaments and vessels across the duodenum may cause occlusion of the gut. 
WOUNDS, RUPTURE, AND HEMORRHAGE. 
Wounds of the spleen are usually accompanied by extensive hemor- 
rhage and are commonly fatal. Death usually occurs as the result of 
this hemorrhage, but it may be due to secondary inflammatory changes. 
Healing and recovery may, however, occur. 
Rupture of the spleen may be traumatic or spontaneous. In the 
former case it may be due to direct violence in the region of the organ 
or to injury to the thorax, falls, etc. In certain diseased conditions the 
spleen is more liable to rupture than when it is normal. The rupture 
usually involves not only the capsule, but a more or less considerable 
portion of the parenchyma, and of course leads to hemorrhage. Spon- 
taneous rupture is rare, but may occur in excessive enlargement of the 
organ, as in typhoid fever, malaria, etc.-see below-or as the result of 
abscess. 
Hemorrhage.-Aside from the extensive hemorrhages from injury 
and rupture, the spleen may be the seat of small circumscribed hemor- 
rhages in various infectious diseases, although, owing to the peculiar 
distribution of the blood, it is often very difficult to distinguish between 
a moderate interstitial hemorrhage and hyperemia. Sacculated aneu- 
rysm of the splenic artery has been reported. 
Atrophy of the spleen may occur in old age; as a result of prolonged 
cachexiae, and in connection with profound and persistent anemia; or, 
more rarely, from unknown causes. The capsule may be wrinkled and 
thickened, the color pale, the trabeculae prominent, the consistence in- 
creased. The change is largely in the pulp, whose parenchyma cells 
are decreased in number. 
ATROPHY. 
DEGENERATION. 
Amyloid Degeneration.-This may affect the Malpighian follicles or 
the pulp tissue, or both together. When it is confined to the follicles the 
spleen may or may not be enlarged, and the cut surface more or less 568 
THE SPLEEN AND THYMUS 
abundantly sprinkled with round or elongated, translucent bodies re- 
sembling considerably in general appearance the grains of boiled sago. 
These are the waxy glomeruli. Such a spleen is often called "sago 
spleen " (Fig. 316). Microscopical examination shows that the degenera- 
tion is confined to the walls of the arteries, capillaries, and reticulum of 
the glomeruli, with atrophy and often finally total disappearance of the 
lymphoid cells. 
In other cases, either with or without involvement of the follicles, 
there is waxy degeneration of the blood-vessels and reticulum of the 
pulp, which may occur in patches or be general and more or less exces- 
sive. If the alteration is general and considerable, the spleen is enlarged, 
its edges are rounded, its consistence is increased. On section it appears 
Fig. 316.-Amyloid Degeneration of the Glomeruli of the Spleen-"Sago Spleen." 
The waxy portions are stained. 
translucent, and the distribution of the degenerated areas may be readily 
seen when a thin slice is held up to the light. The spleen alone may be 
affected, or there may be similar degenerations in other organs. 
PIGMENTATION. 
This may occur as the result of the decomposition of hemoglobin in 
the organ or elsewhere, under a great variety of conditions: thus after 
hemorrhagic infarctions, small multiple hemorrhages, acute hyper- 
plastic splenitis, and in hemochromatosis, etc. Or the pigment may be 
anthracotic and be brought to the organs from the lungs or bronchial 
nodes; bile pigment also may be deposited in the spleen in jaundice. 
The pigment may lie in the walls of the smaller arteries, in the cells and THE SPLEEN AND THYMUS 
569 
reticulum of the pulp, or free in the latter tissue, or in the follicles. It is 
usually quite unevenly distributed. The pigment may be red, brown, 
or black. Anthracotic pigment is deposited especially along the adven- 
titial sheaths of the arteries. It may be sometimes seen with the naked 
eye in the periphery of the glomeruli as dark crescents. This pigment, 
derived from the lungs, has gained access to the blood-vessels, through 
which it is brought to the spleen. 
DISTURBANCES OF THE CIRCULATION. 
Anemia.-This may be associated with general anemia, but it is not 
always present in this condition. When it is marked and unassociated 
with other lesions the spleen may be diminished in size, the capsule more 
or less wrinkled, the cut surface dry and lighter in color than normal, 
the trabeculae unduly prominent. 
Fig. 317.-Hyperemia-Congestion-of the Spleen. 
at Malpighian follicle; 6, dilated cavernous veins; c, trabeculae of pulp tissue compressed between dilated 
cavernous veins. 
In this, as in other alterations simply of the blood content of the 
spleen, neither the gross nor microscopical appearances are constant, 
because of the redistribution of blood which is apt to occur in the viscera 
after death. 
Hyperemia.-Passive hyperemia may occur in obstruction to the 
portal circulation, most frequently in cirrhosis of the liver, but also 
with certain valvular lesions of the heart, emphysema, etc. The spleen 
is enlarged, but usually only to a moderate degree. The capsule is apt 
to be tense, and on section the pulp is dark red and may be soft or firm. 
The cavernous veins are dilated (Fig. 317). Usually, when the lesion 
has existed for some time, there is a thickening of the trabeculae and 
reticular framework of the spleen, so that these are prominent on section. 
In other words, there is a chronic interstitial splenitis following the 
chronic congestion. 570 
THE SPLEEN AND THYMUS 
Active hyperemia of the spleen, which in most cases is scarcely 
to be differentiated from some forms of acute inflammation, and proba- 
bly in many cases is associated with it, very frequently occurs in a great 
variety of acute and infectious diseases, such as typhoid fever, pneu- 
monia, diphtheria, pyemia, the exanthemata, etc. The spleen is en- 
larged, the capsule tense; on section the pulp is soft, dark red in color, 
often swelling out from the cut surface and concealing the follicles and 
trabeculae. Under these conditions the cavernous veins are distended 
with blood and the interstices of the pulp infiltrated with a variable, 
sometimes large quantity of red and white blood-cells. Or, in addition 
to this, there may be hyperplasia (see below). 
Embolism and Infarction of the Spleen.-Embolic infarcts of the spleen 
are of frequent occurrence. They may be single or multiple, small or 
very large, sometimes occupying half of the organ. They usually arise 
from the detachment of thrombi from the aorta or the heart valves. 
Fig. 318.-Infarction of the Spleen. 
Embolus from heart valve in chronic endocarditis. 
They are in general approximately wedge-shaped, corresponding to the 
area of tissue supplied by the occluded artery (Fig. 12, p. 37). They 
may be hemorrhagic, i.e., red, or they may be white. Infarctions, 
originally red, may become white after a time from changes in the blood 
pigment (Fig. 318). They may usually be seen as dark red, reddish 
white, or white, hard, sometimes slightly projecting areas on the sur- 
face of the organ. Not infrequently the center of the infarction is light 
in color, while the peripheral zone is dark red. A layer of fresh fibrin 
is sometimes seen over the surface of the infarction. The general as 
well as the microscopical appearances which they present depend largely 
upon the age of the infarctions. In the earlier stages the hemorrhagic 
infarctions present under the microscope little more than a compact 
mass of red blood-cells, among which may be seen the compressed paren- 
chyma. The white infarction may show at first an outline of the splenic 
structure, but the entire tissue may be in a condition of coagulation THE SPLEEN AND THYMUS 
571 
necrosis. The tissue may disintegrate and soften, and be more or less 
completely absorbed, with or without fatty degeneration. A zone of in- 
flammatory tissue may appear around the infarction and upon the cap- 
sule, and this tissue, becoming denser, may assume the characters of a 
cicatrix and contract around the unabsorbed remnant of the infarction, 
so that finally nothing may be left but a dense mass of fibrous tissue, 
which frequently draws in the surface, causing more or less distortion of 
the organ. This cicatrix may be pigmented or white. 
If the embolus be infective, in addition to its mechanical effects there 
may be suppuration, gangrene, and the formation of an abscess. There 
may be perforation of the capsule and fatal peritonitis. Infarctions of 
the spleen may follow thrombosis of the splenic vein. 
Thrombosis of the splenic vein is rare as a primary lesion, but it 
may be of secondary occurrence in connection with portal or mesenteric 
thrombosis, with other lesions of the spleen, or with acute inflammation 
of the pancreas. Thrombosis of the splenic vein has been reported 
following typhoid fever. 
INFLAMMATION. 
Inflammatory Hyperplasia {Acute Hyperplastic Splenitis, Acute Splenic 
Tumor).-The conditions under which hyperplasia and acute inflamma- 
tion of the spleen occur have already been mentioned under active 
hyperemia, with which it is usually associated. It is a frequent though 
not a constant accompaniment of the acute infectious diseases. The 
spleen is enlarged, sometimes to two or three times its normal size. On 
section the pulp is soft, often almost diffluent, and projects upon the cut 
surface. The color is sometimes dark red, sometimes grayish red, or 
mottled red and gray. The trabeculae and Malpighian follicles are 
usually concealed by the swollen and softened pulp, but the Malpighian 
follicles are sometimes very prominent. 
Microscopical examination shows the marked increase in size to be 
due in part to the hyperemia; in part to a swelling and increase in the 
number of cells, sometimes of the pulp, sometimes of the glomeruli, or 
of both. There are multinuclear cells; cells resembling the ovoid and 
polyhedral cells of the pulp, but larger and with evident division of the 
nuclei. Cells resembling leucocytes may be present in large numbers, 
and larger and smaller cells in a condition of fatty degeneration, or con- 
taining pigment, are often seen. The elongated cells lining the cavernous 
veins may be swollen or increased in number. Not infrequently the 
larger and smaller cells contain red blood-cells or their fragments. In 
some cases, particularly in scarlatina, hyperplasia of the follicles is a 
prominent feature; in other cases, particularly in typhus and recurrent 
fevers, the cells of the follicles undergo marked degenerative changes, 
so that they may form small softened areas looking like little abscesses. 
Focal necroses and areas of small-cell accumulation or cell prolifera- 
tion are common in typhoid fever and other infectious diseases (see 
page 232). As the primary disease runs its course the swelling of the 572 
THE SPLEEN AND THYMUS 
spleen subsides, the capsule appears wrinkled, the color becomes lighter, 
and sometimes the organ remains for a long time, or permanently, small 
and soft. 
The lesions of the spleen are in many cases due to the presence of 
microorganisms which are usually present in the spleen in septicemia, 
or they may be due to soluble toxic substances in the blood.1 
Suppurative Splenitis {Splenic Abscess').-Small abscesses may be 
found in the spleen as the result of minute infectious emboli, and these 
may coalesce to form larger abscesses. Sometimes the entire paren- 
chyma is converted into a soft, necrotic, purulent mass surrounded by 
the capsule. It is rare for simple infarctions to result in abscess. Ab- 
scess of the spleen may occur from the propagation of a suppurative 
inflammation to the organ from adjacent parts; from perinephritic 
abscesses, ulcer and carcinoma of the stomach, etc. They may open 
into the peritoneal cavity, inducing fatal peritonitis, or, owing to an 
adhesive inflammation, the opening may occur into the post-peritoneal 
tissue, into the pleural cavity, lung, stomach, intestines; or they may 
open on the surface. On the other hand, the contents of the abscess may 
dry, shrink, and become encapsulated and calcified. Abscesses may 
occur in ulcerative endocarditis, pyemia, typhoid fever, and, more rarely, 
in intermittent fever, and under a variety of other conditions. 
Chronic Indurative Splenitis {Chronic Splenic Tumor).-There may be, 
as we have already seen, a new formation of connective tissue in the 
spleen as a result of chronic congestion or infarctions, or about abscesses. 
But there is a more diffuse formation of connective tissue, usually in the 
nature of a hyperplasia, which occurs under a variety of conditions, 
and is now marked and extensive, and again comparatively ill-defined. 
It is always associated with more or less extensive changes in the paren- 
chyma. In its most marked form it is found in chronic malarial poison- 
ing; and under these conditions it may be found not only in persons who 
have suffered from repeated attacks of intermittent fever, but also in 
those who have not thus suffered but have resided in malarial regions, 
and presumably had malaria in masked form. The enlarged spleen is 
often called "ague cake." Similar conditions, though usually less 
marked, may occur in congenital and acquired syphilis, from prolonged 
typhoid fever, and as a result of acute hyperplastic splenitis from various 
causes, and also in leukemia and pseudoleukemia. 
The gross appearance of the spleen in chronic indurative splenitis 
varies greatly, both in the size of the organ and in the appearance of the 
section. The spleen may be enormously enlarged or it may be of about 
normal size. It is usually enlarged, however. The capsule is commonly 
more or less, sometimes unevenly, thickened. The consistence is as a 
rule, considerably increased, but this is not always tne case. The color 
and appearance of the cut surface present much variation. It may be 
nearly normal or it may be grayish, or dark brown, or nearly black. 
The color may be uniform or the surface may be mottled. The folli- 
1 For a study of the r61e of the spleen in infections, see Courmont and Duffau, Arch, de m6d exp., 
1898, x, 431 (bibl.); and Smith, Th., Jour. Am. Med. Assn., 1917, Ixviii, 669, 764. THE SPLEEN AND THYMUS 
573 
cles may be scarcely visible or very prominent; the trabeculae are in some 
cases nearly concealed by the pulp; in others they are large, prominent, 
and abundant, so that the surface is crossed in all directions by an in- 
terlacing network of broader and narrower 
irregular bands, between which the red or 
brown or blackish pulp lies. 
Not less varied are the microscopical 
appearances of the spleen under these con- 
ditions. In one class of cases there is 
more or less uniform hyperplasia of both 
pulp and interstitial tissue. The paren- 
chyma cells are increased in size and 
number; there may be swelling and pro- 
liferation of the lining cells of the caver- 
nous veins (Fig. 319). The reticulum of 
the pulp, as well as that of the follicles, 
and also of the trabeculae, is thickened. In 
another class of cases the thickening of the 
reticular and trabecular tissue, either uni- 
formly or in patches, is the prominent feature (Fig. 320), while the 
changes in the pulp are rather secondary and atrophic. In both forms 
irregular pigmentation is frequent, the pigment particles being deposited 
either in the cells of the pulp or glomeruli, or in the new-formed inter- 
Fig. 319.-Chronic Indurative 
Splenitis. 
Showing swelling and proliferation 
of the lining cells of the cavernous 
veins. 
Fig. 323.-Chronic Interstitial Splenitis. 
a, Thickened capsule; b, thickened trabecula?; c, dilated cavernous veins; d, dense pulp tissue 
with obliterated cavernous veins. 
stitial tissue (Fig. 321). Finally, there are all intermediate forms of in- 
duration between those described, and the changes are by no means 
uniform in the same organ. When these spleens are large they are liable 
to displacement. 574 
THE SPLEEN AND THYMUS 
Syphilitic Splenitis.- Ims lesion may present itself as an indurative 
process due to the formation of new connective tissue, and present no 
distinct morphological characteristics. In rare cases, however, gum- 
mata may be present in connection with the new fibrous tissue; then 
the nature of the lesion is evident. 
Tuberculous Splenitis.-This lesion is usu- 
ally secondary to tuberculous inflammation in 
some other part of the body, or is the result 
of the general infection in acute general mili- 
ary tuberculosis. The tubercles may be very 
numerous and still invisible to the naked 
eye, or they may be just visible, or as large 
as a pin's head, and very thickly strewn 
through the organ or sparsely scattered. In 
other cases the tubercles are larger, some- 
times as large as a pea (Fig. 322), and they 
are then ordinarily not numerous. Micro- 
scopically, they present the usual variety of 
structure, sometimes as simple tubercle gran- 
ula, sometimes as conglomerate tubercles; they may consist simply of 
a collection of small spheroidal cells, or there may be larger polyhedral 
cells and giant cells with a well-defined reticulum. Cheesy degeneration 
occurs under the usual conditions. Tubercle bacilli are commonly pre- 
Fig. 321.-Malarial Spleen. 
Showing thickening of the 
trabecular network of the pulp, 
with pigmentation of the pulp 
cells. 
Fig. 322.-Tuberculosis of the Spleen. 
The tubercles are large and irregular in shape and distribution, and are in places confluent. 
sent, particularly in the more acute forms, sometimes in small, some- 
times in enormous numbers. They seem to be especially abundant in 
acute general miliary tuberculosis of children. These tubercles may be 
formed in the glomeruli, in the walls of the smaller arteries, in the 
pulp tissue, and in the trabeculae and capsule. Owing to the peculiar THE SPLEEN AND THYMUS 
575 
character of the spleen tissue the earlier stages are not readily recog- 
nized, since simple collections of small spheroidal cells are not distinctly 
outlined against the normal tissue. There is frequently a moderate 
swelling of the spleen, owing to hyperemia and hyperplasia of the 
parenchyma.1 
Perisplenitis.-Acute inflammation of the capsule of the spleen 
may occur as a part of a general or localized peritonitis, or as a result 
of lesions of the spleen itself, such as infarctions, abscesses, and acute 
hyperplastic inflammation. Under these conditions a fibrinous pellicle, 
with more or less pus, may be formed on the surface of the organ. 
Chronic inflammation, resulting in the production of new connective 
tissue, either in patches or as a more or less general thickening of the 
capsule, is of frequent occurrence. It may follow acute inflammation of 
the capsule, or be a part of general or localized chronic peritonitis. It 
is common in connection with chronic indurative splenitis, and it may 
occur from unknown causes. Sometimes the capsule is three or four 
millimeters in thickness over a considerable area; sometimes very small 
nodular thickenings or papillary projections occur. As a result of this 
process, adhesions, sometimes very extensive, may form between the 
spleen and adjacent parts. The thickened capsule is sometimes more 
or less extensively calcified. 
HEMOLYTIC ICTERUS. 
There is a type of jaundice accompanied by enlargement of the 
spleen which is apparently hereditary, as it occurs in families through a 
number of generations. The disease is found in persons who are other- 
wise in good health and who often live to old age. The symptoms occur 
in attacks, the patient suffering from chills or fever, with headache, 
general muscular pain, and jaundice. Bile is usually present in the blood, 
may or may not be present in the stools, and is rarely found in the urine. 
During the crisis the spleen enlarges. The attacks last for a few weeks, 
though often the patients are continuously slightly jaundiced. When 
bile is absent during the attacks, urobilinogen and urobilin are abundant 
(58 per cent., Giffin) in the urine. Gall-stones are not infrequently 
found in the gall-bladder and in the ducts. Their formation probably 
depends upon the excretion of large quantities of thick bile from which 
cholesterin separates in the gall-bladder. Removal of the stones does 
not cure the jaundice, but remarkably good therapeutic results have been 
obtained by splenectomy.2 
The blood shows a moderate anemia and during the attack the red 
cells are polychromatophilic; normoblasts are often present; and large 
numbers of cells with reticulations appear. Autoagglutination of the red 
cells may be demonstrated in some instances. These blood changes 
1 For study of tuberculosis of spleen, with bibl., see Winternitz, M. C., Arch. Int. Med., 1912, ix, 680. 
For a case of splenic tuberculosis with polycythemia, see Douglas, J., and Eisenbrey, A. B., Am. Jour. 
Med. Sc., 1914, cxlvii, 479. 
2 Elliott, C. A., and Kanavel, A. B., Surg., Gynec., and Obst., 1915, xxi, 37 (good bibl.); Giffin, H. Z., 
ibid., 1917, xxv, 152; Peck, C. H., Jour. Am. Med. Assn., 1916, Ixvii, 788; Friedman, G. A., and Katz, 
E., Jour. Am. Med. Assn., 1916, Ixvii, 1295. 576 
THE SPLEEN AND THYMUS 
disappear when the jaundice ceases. A striking phenomenon in the blood 
is the great increase in the fragility of the red corpuscles when tested by 
suspension in sodium chloride solutions. Normal blood begins to hemo- 
lyze in a solution containing 0.44 per cent, of sodium chloride, and hemo- 
lysis is complete in a 0.28 per cent, solution. In these jaundiced patients, 
the blood begins to hemolyze as a rule in 0.5 to 0.55 per cent, solutions, 
and complete hemolysis is frequently observed in a 0.35 per cent., but 
may be produced even in a 0.4 per cent, solution. Exceptionally hemo- 
lysis may occur in a 0.7 per cent, solution. After operation this fragility 
may diminish somewhat and even disappear, but usually it remains for 
a long time. 
The cause of the disease is unknown; but it is presumably due to some 
hemolytic agent set free during the crisis or possibly to a congenital 
feebleness of the red cells; and the enlargement of the spleen may be 
caused entirely by the increased blood destruction. 
Another type of the disease is not hereditary, but appears spontane- 
ously, though in its clinical symptoms it does not differ from the familiar 
type. 
The findings at autopsy are very slight. The spleen is large; the 
follicles are poorly marked; large numbers of red cells lie in the pulp and 
there is often dilatation of the sinuses and swelling of the endothelium. 
Usually there is a considerable deposit of iron-containing pigment in the 
liver, kidneys, and bone-marrow. Considerable hyperplasia of the latter 
may be found if the patient dies while the disease is active. 
A third form of hemolytic icterus is probably due to infections in 
persons with substandard blood resistance. The patients may be at- 
tacked with an endocarditis or a pneumonia of the lobar, bronchial, or 
lobular type, suddenly become jaundiced, and show, if the blood be 
examined, an enormous destruction of the red cells. In these cases the 
jaundice may be due to the large amount of hemoglobin set free. The 
spleen is usually not so much enlarged as in the chronic types.1 
CHRONIC ENDOTHELIAL HYPERPLASIA OF THE SPLEEN. ("Primary 
Splenomegaly. ' ') 
Gaucher described as a primary endothelioma of the spleen a slowly 
progressive lesion in which the organ is greatly enlarged and firm, present- 
ing numerous irregular white or yellowish areas. The splenic and 
mesenteric lymph-nodes and the liver are enlarged. Microscopically, the 
splenic lesion is found to be due chiefly to the presence of large numbers of 
cells of peculiar type (Fig. 323), with small, deeply staining nuclei and 
large reticulated cell bodies, highly attractive to eosin. Pigment may or 
may not be present. The cells line or fill the sinuses of the spleen, and 
occur in the lymph-nodes (Fig. 324), in the sinusoids of the liver, and in 
the bone-marrow. They do not contain stainable fat or lipoid. They are 
probably derived from the cells of the reticulum, possibly also from the 
1 See for general survey of icterus in infectious diseases, Posselt, Lubarsch-Ostertag, Ergebn. d. 
allg. Path., 1915, xvih, 719; and Chauffard, A., and Troisier, J., Gilbert and Weinberg, Traite du sang, 
Paris, 1913, i, 227. THE SPLEEN AND THYMUS 
577 
Fig. 323.-Chronic Endothelial Hyperplasia of the Spleen. 
Showing increase in number and exfoliation of the endothelium of the cavernous veins. 
Fig. 324.-Lymph-node from Case of Hyperplasia of Spleen-Gaucher Type 578 
THE SPLEEN AND THYMUS 
endothelium of the sinuses. The cause of the disease is unknown; it 
begins in childhood and frequently affects several members of the family. 
The patients show anemia, tendency to hemorrhage, and emaciation; 
but death is usually due to complicating diseases.1 
Other types of splenomegaly resembling slightly the Gaucher form 
have been described,2 but in them the lesion is confined to the endothe- 
lium of the capillary walls and does not affect the reticulum cells of the 
pulp as in the true primary splenomegaly. 
ALTERATIONS OF THE SPLEEN IN LEUKEMIA, ANEMIA, AND 
HODGKIN'S DISEASE. 
The lesions of the spleen in leukemia consist in general of a hyper- 
plasia, sometimes most marked in one of the structural elements of the 
Fig. 325.-Hodgkin's Disease. Showing Large Cell Hyperplasia in Spleen. 
organ, sometimes in another, though usually all participate in the alter- 
ation. The changes which occur in the earlier stages are but little 
1 For details of this lesion, see Bovaird, D., Am. Jour. Med. Sc., 1900, cxx, 377; Brill, Mandlebaum, 
and Libman, ibid., 1905, cxxix, 491; Brill and Mandlebaum, ibid., 1913, cxlvi, 863; Mandlebaum, F. 8., 
Jour. Exper. Med., 1912, xvi, 979; Mandlebaum, F. S., Am. Jour. Med. Sc., 1919, clvii, 366. 
a See Pentmanri', IFrankfurt. Ztschr. f. Path., 1915, xviii, 121. 579 
known (Fig. 325). The gross appearances of the spleen vary. It is, 
as a rule, enlarged and sometimes is ten or fifteen times the normal size. 
It is commonly hard, but is sometimes of the ordinary consistence, or 
softer, and the capsule is generally thickened and rough (Fig. 326). The 
section of the spleen may be of a uniform dark red color, but it is more 
frequently mottled red and gray. Sometimes the Malpighian follicles 
are inconspicuous, but they are very often enlarged and prominent* 
They may be two to four millimeters in diameter, and, owing to an in- 
filtration of the arterial sheaths with lymphocytes, may appear to the 
THE SPLEEN AND THYMUS 
Fig. 326.-Subendothelial Infiltration of Splenic Sinuses by Lymphoid Cells in a Case of 
Lymphatic Leukemia. 
A similar lesion occurs in Hodgkin's disease. 
naked eye as grayish, round or elongated bodies, arranged along branch- 
ing, interrupted, grayish streaks. The trabecula? may be greatly thick- 
ened, as also the reticulum of the pulp, so as to be evident to the naked 
eye. Brown or black pigment may be collected around the glomeruli 
or in the pulp. Hemorrhagic infarctions or circumscribed extravasa- 
tions of blood may further complicate the picture. 
Microscopically, the appearances are essentially the same as those 
above described in acute hyperplasia and in chronic interstitial splenitis, 
depending upon the stage and variety of the disease. 
In lymphatic leukemia the pulp is largely lymphatic; in the myelo- 
genous form vast numbers of myelocytes are present. In severe anemias, 580 
THE SPLEEN AND THYMUS 
especially in children, myeloid hyperplasia is frequent but not extensive, 
and marrow giant cells may be found. 
In pernicious anemia phagocytosis of red cells is often, though not 
always, present. In Hodgkin's disease the characteristic changes may 
be discrete or very extensive. The morphology is the same as in the 
nodes. In splenic anemia and in Banti's disease a chronic interstitial 
process with sinus dilatation is often, though not constantly, present. 
Owing to the great size which some such spleens attain they are liable 
to displacement, and they may interfere by pressure with the functions 
of neighboring organs. 
TUMORS. 
The spleen is but rarely affected by primary tumors. Fibromata, 
chondromata, and osteomata have been seen; lymphangiomata are 
rather more frequent; and hemangiomata are not very rare.1 Cavernous 
angioma has been reported.2 
Sarcomata3 of various types have been reported, usually of the spindle- 
cell or the very vascular form; and the latter have sometimes been incor- 
rectly termed endotheliomata.4 
Secondary tumors also are rare. Lymphosarcoma and melanosar- 
coma are the most frequent; while carcinomatous nodules are but very 
rarely seen, the spleen being involved in not over 1 per cent, of the fatal 
cases. There are two reasons for this: 1, carcinoma is usually spread 
by the lymphatics, which have no direct connection with the spleen, so 
that metastatic nodules to reach this organ must pass through the blood- 
vessels; and 2, the pulsations of the organ make it exceedingly difficult 
for embolic particles of carcinoma to grow through the endothelium of 
the sinuses and attach themselves to the tissues. 
It has been shown experimentally that the spleen when directly in- 
oculated with carcinoma is just as suitable a soil for the growth of the 
tumor as is any other portion of the body (see page 379).5 
Dermoid cysts are described, but are rare. Other larger and smaller 
cysts, whose mode of origin is in most cases obscure, not infrequently 
occur; some of these may be lymphangiomata; others are probably 
hemorrhagic cysts following trauma.6 
PARASITES 
Pentastoma denticulatum, the larval stage of Linguatula rhinaria, 
is very rarely found in the spleen. Cysticercus is rare. Echinococcus 
is occasionally found, and, if the cysts are large or numerous, may cause 
more or less extensive atrophy of the organ. Spirochaete obermeieri may 
' Thiele, Virchows Arch., 1904, clxxviii, 296. 
2 Dowd, C. N., Ann. Surg., 1915, Ixii, 177. 
3 Bunting, Univ. Pennsylvania Med. Bull., 1913, xxv, 318 (bibl.); and Simon, Beitr. z. klin. Chir. 
(Bruns), 1902, xxxv, 318 (bibl.). 
4 Risel, Zeiglers Beitr., 1909, xlvi, 241 (bibl.). 
3 Goldmann, E. E., Beitr. f. klin. Chir. (Bruns), 1911, Ixxii, 1. 
6 For studies of cysts of the spleen, see Wohlwill, F., Virchows Arch., 1908, cxciv, 306 (bibl.); and 
Schmidt, M. B., ibid., 1901, clxiv, 50 (bibl.). 581 
THE SPLEEN AND THYMUS 
Leishmania donovani and infantum have been found in the spleen (see 
page 139). Plasmodium malarhe is often present in enormous 
numbers. Various forms of bacteria have been found in the spleen, the 
pyogenic cocci in pyemia, smallpox, ulcerative endocarditis, diphtheria, 
and under other conditions; the Bacillus anthracis occurs here in anthrax; 
the Bacillus tuberculosis in tuberculous inflammation; and the Bacillus 
typhosus in typhoid fever. 
Thymus. 
ANATOMY AND FUNCTION. 
The thymus develops in man as a flattened sac from the third and fourth branchial 
pouches on each side of the neck, the main portion of the gland being derived from the 
third. The lumen of the sac becomes obliterated with the growth of the organ, but 
traces of the original canal may be found. In the fully developed gland the two lobes 
can be easily made out. Aberrant fragments of thymus have been found in the 
thyroid and parathyroid and thyroid tissue in the thymus. Microscopically two 
types of cells are distinguishable, one lymphocytes, the other epithelial cells which 
form the reticulum of the cortex, the greater part of the medulla and also exist in 
masses known as Hassal's corpuscles. The thymus reaches its largest size in the 
early period of life, then undergoes involution or atrophy, losing a considerable pro- 
portion of its characteristic cells. In old age it is represented by a mass of fat tissue 
in which a few lymphocytes and Hassal's bodies may be found. In the newborn1 
the average weight of the gland is about 13 grams. Between first and fifthy ears it is 23 
grams; from the sixth to tenth years, 37 grams; and from the tenth to the twentieth 
years, 25 grams. From this period on it atrophies rapidly, though small portions 
always remain. The thymus may persist under exceptional conditions until middle 
age (Fig. 292). Furthermore, it may become enlarged, the so-called hypertrophy of 
the thymus, which is, however, rather a hyperplasia than a hypertrophy. The new 
formed tissue may present a more or less marked lobulated or glandular appearance. 
Such tissue is largely composed of lymphoid cells, or in some instances of larger polyhe- 
dral cells, the so-called epitheloid cell.2 
The function of the thymus is still unknown. The theory that its extirpation 
induces rickets has been shown to have no foundation.3 Its excision in young animals 
has been stated to exert a deleterious effect on the development of the skeleton, the 
genital apparatus and psychic maturity, but others have found no such influence.4 
INVOLUTION AND HYPERPLASIA. 
A very rapid shrinkage of the thymus gland is seen in acute and chronic wasting 
diseases, severe infection, after exposure to X-ray, and in starvation. Histologically, 
the lymphocytes diminish and the Hassal's corpuscles become apparently more abun- 
dant. This is probably due to the reduction in the total volume of the gland and not 
to new formation.5 
In the condition known as status lymphaticus or status thymicolymphaticus the 
thymus is often very greatly enlarged. The question whether the symptoms of diffi- 
cult respiration are produced by pressure of the thymus on the trachea is still under 
dispute. Also the exact relationship between sudden death and the existence of a 
large thymus in status lymphaticus is unsettled. The relief of symptoms seen after 
1 For the significance of a persistent thymus in certain cases of sudden death, see Norton, Phila- 
delphia, Med. Jour., 1898, i, 249 (bibl.). On the relationship of hyperplasia in a persistent thymus to 
Hodgkin's disease, consult Brigidi and Piccoli, Zieglers Beitr., 1894, xvi, 388. 
For a study of the weight of the thymus in infancy, see Bovaird and Nicoll, Arch. Pediat., 1906, 
xxiii, 641. For a thorough and admirable study of the normal and pathological histology of the thymus, 
see Pappenheimer, A. M., Jour. Med. Research, 1910, N. S., xvii, 1; Jour. Exper. Med., 1914, xix, 319; 
1914, xx, 477. 
3 Lochte, Centralbl. f. allg. Path. 1899, x, 1 (bibl.). 
3 Renton and Robertson, Jour. Path, and Bacteriol., 1916, xxi, 1. See also Matti, Ergebn. d. inn. 
Med. u. Kinderheilk., 1913, x, 1; and TFfeseZ, J., Lubarsch-Ostertag, Ergebn. d. Allg. Path. 1911, xv, 
417; Klose and Vogt, Beitr. z. klin. Chir. (Bruns), 1910, Ixix, 1. 
4 Park and McClure, Jour. Exper. Med., 1917, xxv, 129; Am. Jour. Dis. Chil., 1919, xviii, 317. 
6Hammar, J., Ergebnisse d. Anat. u. Entwcklngs., 1909, xix, 1. 582 
THE SPLEEN AND THYMUS 
the excision of such enlarged thymus glands, however, points to the possibility of 
mechanical pressure being of importance in the production of symptoms. In about 
three-quarters of the cases of exophthalmic goiter a more or less considerable enlarge- 
ment of the thymus exists.1 
Histologically the lesion in the enlarged thymus gland connected with exophthal- 
mic goiter, is a great increase in the lymphoid cells. Such patients are apt to show 
also a blood lymphocytosis. Hyperplasia of the thymus also occurs in a great propor- 
tion of cases of Addison's disease, acromegaly, genital hypoplasia, or eunuchoidism, and 
also in myasthenia gravis. The exact nature of the correlation between these diseases 
and thymic enlargement is still undetermined. In animals castration at an early age 
inhibits the involution of the thymus. 
HEMORRHAGE. 
Small and sometimes large hemorrhages are occasionally seen in the 
thymus of young children as the result of venous congestion in asphyxia, 
poisoning and severe infections. They may also occur in purpura and 
other hemorrhagic diseases.2 
Suppurative inflammation of the thymus is of occasional occurrence, 
and is usually secondary to a similar inflammatory process in some other 
part of the body. Tuberculosis is seen in connection with general 
miliary tuberculosis, and occasionally is found as an extension of tuber- 
culosis of the mediastinal lymph-nodes. Hodgkin's disease may also 
involve the tissue of the thymus gland. Syphilis of the thymus is 
very rare,3 but in a certain proportion of cases of congenital syphilis a 
peculiar lesion called a Dubois abscess is found. These abscesses consist 
of sharply bounded areas containing a rather inspissated and firm puru- 
lent material. Treponema pallidum has been demonstrated in the 
material of the abscess.4 
INFLAMMATION. 
TUMORS. 
Tumors of the thymus are rare. A few examples of angioma, lipoma, 
myxoma, dermoid and other cysts have been noted. Some of these 
cysts have been found to be lined with ciliated epithelium, which might 
be expected from the branchial cleft origin of the thymus gland.5 Spindle- 
celled sarcomata have also been described as a great rarity. 
The frequent tumor is a neoplasm resembling in some ways a lympho- 
sarcoma, but showing slight differences which sometimes permit a 
differential diagnosis being made. Occasionally the Hassal's corpuscles 
also take part in the tumor formation, though not contributing any 
large bulk of the tumor mass. Usually the cells of the tumor are some- 
what larger than the normal lymphocyte and such growths are also apt 
to contain large, pale cells resembling those seen in Hodgkin's disease. 
In some instances giant cells of the bone marrow type have been met with. 
Some hold that many of these tumors represent a peculiar malignant type 
of Hodgkin's disease, and that the large cells arise from the reticulum of 
the gland. 
1 Matti., Mitt. a. d. Grenzgeb. d. Med. u. Chir., 1912, xxiv, 665; also Capelie, Munchen, med. Wchn- 
schr., 1908, Iv, 1826. 
2 For a study of apoplexy of the thymus, see Mendelsohn, Arch. f. Kinderheilk, 1906, xliv, 1; and 
Wahl, R. N., and Walthall, D., Am. Jour. Dis. Chil., 1922, xxiv, 27 (bibl.). 
3 Hammar, J. A., Zieglers Beitr., 1920, Ixvi, 37 and 195. 
4 Oliver, J., Am. Jour. Dis. Chil., 1917, xiii, 158. 
6 Hueter, C., Zieglers Beitr., 1913, Iv, 117. CHAPTER IV. 
THE THYROID AND ADRENALS. 
The Thyroid. 
Malformations. 
The thyroid gland is sometimes very small, either as the result of atrophy or 
as a congenital deficiency.1 
The thyroid may be irregularly lobulated. There may be small accessory glands 
situated at some distance from the normal position, as in the tongue, trachea, medias- 
tinum or pleura.2 
DEGENERATION. 
Colloid degeneration of the epithelial cells of the gland, and the filling 
of the alveoli with colloid material, are of common occurrence, and when 
in moderate degree may be regarded as normal, since a certain amount of 
this change is found in many otherwise apparently normal glands. It 
may occur, however, to such an extent as to constitute an important 
lesion (see below). 
Amyloid degeneration, particularly of the blood-vessels, is of infre- 
quent occurrence. 
Hyaline degeneration of the stroma of the thyroid may occur. 
DISTURBANCES OF CIRCULATION. 
Hyperemia of the thyroid gland, often accompanied by considerable 
enlargement of the organ, may be the result of valvular disease of the 
heart; it occurs also in exophthalmic goiter. It may be temporary or 
permanent, and in the latter case may be associated with the formation 
of new connective tissue. Hemorrhages may occur, leading to cysts and 
to pigmentation of the organ. 
INFLAMMATION. (Strumitis.) 
Inflammation of the thyroid gland is not very common and may occur 
under a variety of conditions, especially in infectious diseases, septi- 
cemia, typhoid fever, diphtheria, etc. It may result in the formation of 
larger and smaller abscesses or in the production of new connective 
tissue which may be associated with atrophy of the parenchyma. A 
pseudotuberculous lesion is occasionally seen, in which the colloid con- 
tents of the alveoli set up an active connective tissue reaction with the 
1 For the relationship of this condition to cretinism and myxedema, see page 485. 
2 Payr. E., Arch. f. klin. Chir. (Langenbeck), 1906, Ixx, 730. 
583 584 
THE THYROID AND ADRENALS 
production of giant cells.1 This chronic inflammatory lesion has often 
been mistaken for true tuberculosis (Fig. 327). Tuberculous inflamma- 
tion, with the formation of miliary tubercles, is of infrequent occurrence.2 
Syphilitic inflammation, with the formation of gummata, has been de- 
scribed, but is rare. 
STRUMA. (Hyperplasia of the Thyroid; Goiter.) 
Among the most important of the lesions of the thyroid is the enlarge- 
ment of the organ commonly known as goiter or struma. The enlarge- 
Fig. 327.-Pseudotubercle in Chronic Thyroiditis. 
This lesion is frequently mistaken for tuberculosis, but is due to the setting free of the colloid material 
of the thyroid during the inflammatory process in chronic thyroiditis. 
ment of the gland may occur in several ways. Thus, a simple hyper- 
emia may, as above stated, lead to considerable enlargement of the organ, 
and this is sometimes called struma hyperazmica. The true goiter, how- 
ever, consists in the enlargement of the old and the formation of newr 
gland alveoli, while with these changes there is very frequently associ^ 
ated a greater or less amount of colloid degeneration.3 When there is 
1 Wilke, Virchows Arch., 1913, ccxi, 165. 
2 Roger and Garnier, Arch. gen. de m6d., 1900, iii, 385 (bibl.). 
8 For a study of the normal and pathologic histology of the thyroid, with bibl., see Erdheim, Zieglers 
Beitr., 1903, xxxiii, 159. For myxedema and Basedow's disease see pp. 485 and 488. For relations 
of thyroid to pregnancy, see Ward, G. G., Surg., Gynec., and Obst., 1909, ix, 617. For relations of 
thyroid hyperplasia to various diseases and infections, see Farrant, R., Brit. Med. Jour., 1914, i, 470; 
also Bircher, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1911, xv, 82. THE THYROID AND ADRENALS 
585 
new formation of gland tissue the growth has the character of an ade- 
noma. The hyperplasia may occur diffusely, so that the whole gland is 
more or less enlarged; or it may occur in the form of circumscribed nod- 
ules. When the colloid degeneration is prominent, so that the tumor 
has a gelatinous appearance, it is called colloid struma (Fig. 328).1 Accu- 
mulations of fluid, blood, colloid, etc., in the old or new-formed alveoli, 
may lead to dilatation and atrophy of the walls of the alveoli, so that 
cysts, sometimes of large size, are formed. Thus occurs the cystic struma. 
Again, the blood-vessels may undergo marked dilatation, so that we may 
have a telangiectatic struma; or cavernous angiomata may form within 
Fig. 328.-Colloid Struma-Goiter. 
The colloid material filling the alveoli is stained red. 
goiters. Very frequently all these varieties of lesions are present in the 
same goiter. The appearances may be rendered still more complex by 
the occuirence of hemorrhage and pigmentation, calcification, purulent 
or indurative inflammation (strumitis), and by the not very infrequent 
association with carcinoma and sarcoma. The excitants of goiter are not 
well understood. The growth is, as a rule, slow, but occasionally a very 
rapid enlargement occurs as the result of a sudden increase of the col- 
loid degeneration. In many cases even very large goiters give rise to 
but moderate inconvenience, but they may assume great significance by 
encroaching upon neighboring parts. Thus death may be caused by 
pressure on the trachea, esophagus, or on the large vessels. (For lesions 
frequently observed in exophthalmic goiter see page 488.) 
1 For a study of the pathological anatomy of the thyroid, see Marine and Lenhart, Arch. Int. Med., 
1911, vii, 506. For a general study of the diseases of the thyroid, see McCarrison, The Thyroid Gland 
in Health and Disease, New York, 1917. 586 
THE THYROID AND ADRENALS 
TUMORS. 
Adenomata,1 which are not rare and may be congenital, are either 
encapsulated or diffuse; in the latter instance, it is often difficult to dis- 
tinguish between an adenoma and a hyperplasia. Hemorrhagic cysts 
are not uncommon,2 while cysts of another type sometimes originate in 
adenomata.3 Papillary adenomata are occasionally found (Fig. 329). 
The fetal adenoma,4 a very frequent type, consists of solid plugs or 
alveoli of small epithelial cells much like those in the gland of the fetus; 
Fig. 329.-Papillary Adenoma of Thyroid. 
no colloid is produced (Plate III, facing page 488). It is frequently in- 
volved in edematous or hyaline changes. 
Carcinoma may be either solid, glandular, or papillary, or may re- 
semble a goiter or even the normal gland,5 showing its malignant nature 
in the instance last mentioned only by its clinical behavior. Another 
peculiarity of carcinoma in the thyroid is that tumors with a morphology 
which, in other organs, would lead to the diagnosis of carcinoma may 
exhibit little or no malignancy, and, indeed, may often disappear spon- 
taneously. The so-called benign metastasizing goiters* (general thyroid 
malignancy) are perhaps more properly to be regarded as carcinomata. 
1 Bloodgood, Surg., Gynec., and Obst., 1906, ii, 121; Hibbert, Frankfurt. Ztschr. f. Path., 1915, 
xviii, 55. 
2 Bradley, Jour. Exper. Med., 1896, i, 401. 
3 Bloodgood, Surg., Gynec., and Obst., 1905, i, 113. 
4 Wblfler, Arch. f. klin. Chir. (Langenbeck), 1883, xxix, 1, 754. 
6 Gierke, Third Sci. Report, Imperial Cancer Research Fund, London, 1907, p. 115; Virchows Arch., 
1902, clxx, 464; Oderfeld and Steinhaus, Centralbl. f. allg. Path., 1903, xiv, 84. 
6 Honsell, Beitr. z. klin. Chir. (Bruns), 1899, xxiv, 112 (bibl.). But see Kanoky, Surg., Gynec., 
and Obst., 1916, xxii, 679. THE THYROID AND ADRENALS 
587 
A very rare form of tumor is the squamous-cell carcinoma, supposed to 
develop from remnants of the thyroglossal duct or the branchial clefts. 
Carcinomata of the thyroid are extremely malignant since they com- 
promise the surrounding tissues at any early period of their growth and, 
therefore, soon become inoperable. They are very apt to metastasize 
in the bones,1 particularly of the head and face, the daughter tumors being 
sometimes so vascular as to pulsate like an aneurysm. 
Sarcomata2 of all varieties occur, but offer no peculiarities character- 
istic of this site,3 except that the very 
vascular types, usually designated 
hemangiomata or endotheliomata, oc- 
cur in this organ more frequently 
than elsewhere (Fig. 330).4 
The less common new growths 
of the thyroid include the fibroma, 
osteoma, carcinosarcoma,5 melano- 
sarcoma,6 and teratoid tumors con- 
taining muscle, bone, cartilage, 
brain,7 etc. 
It has already been said (page 
373) that the cells of a malignant 
tumor might be temporarily of use 
to the body by continuing to furnish 
the material characteristic of the 
gland which they involve, and an 
excellent illustration of this is to be 
found in the thyroid.8 Indeed, even 
hyperthyroidism has been reported 
in connection with tumors of this gland.9 
Fig. 330.-Sarcoma ok Thyroid Gland 
(Endothelioma) . 
Showing an early phase of cell proliferation in 
the venous sinuses. 
Echinococcus cysts have been found in the thyroid. 
PARASITES. 
Closely connected with the thyroid, occasionally within, sometimes without its 
capsule, are four small gland-like bodies, usually two on each side. These are the 
PARATHYROID GLANDS. 
i von Eiselsberg, Arch. f. klin. Chir. (Langenbeck), 1893, xlvi, 430; Middledorpf, ibid., 1894 
xlviii, 502. 
2 Marf, Jour. Am. Med. Assn., 1899, xxxii, 911 (bibl.); Binnie, Surg., Gynec., and Obst., 1918, xxvi, 
288; vii, 357 (bibl.); Saltykow, Centralbl. f. allg. Path., 1905, xvi, 547 (bibl.); Simmonds, Ztschr. f. 
Krebsforsch., 1913, xiii, 307. 
3 For a review of malignant tumors of the thyroid in general, see Muller and Speese, Univ. Pennsyl- 
vania Med. Bull., 1906-07, xix, 74 (bibl.). For the clinical aspect of thyroid tumors, see Crotti, Thy- 
roid and Thymus, Philadelphia and New York, 1918. 
4 Hedinger, Frankfurt. Ztschr. f. Path., 1909, iii, 487. 
s Loeb, Leo, Am. Jour. Med. Sc., 1903, cxxv, 243 (bibl.); Wells, Jour. Path, and Bacteriol., 1901, 
vii, 357 (bibl.); Saltykow, Centralbl. f. allg. Path., 1905, xvi, 547 (bibl.); Simmonds, Ztschr. f. 
Krebsforsch., 1913, xiii, 307. 
6 Franckel, Prag. med. Wchnschr., 1897, xxii, 321; abstr. in Centralbl. f. allg. Path., 1900, xi, 246. 
7 See, for example, Flesch and Winternitz, Jahrb. f. Kinderheilk., 1905, Ixii, 410; abstr. in Centralbl. 
f. allg. Path., 1906, xvii, 346. 
s vOn Eiselsberg, Arch. f. klin. Chir. (Langenbeck), 1894, Ixviii, 489; abstr. in Centralbl. f. allg. 
Path., 1895, vi, 1671. 
3 Lbwy, Wien. klin. Wchnschr., 1909, xii, 1671. 588 
THE THYROID AND ADRENALS 
parathyroids ("epithelial bodies") and are both embryologically and functionally 
distinct from the thyroid. Accessory glands are occasionally found.1 
The parathyroids appear to be of great importance in the metabolism of the body, 
since their complete removal apparently usually leads to fatal tetany. It has been 
shown by MacCallum and Voegtlin2 that the calcium salts of the body are rapidly 
excreted on the removal of the parathyroids in dogs, and that the symptoms of tetany 
following the removal cease on the administration of calcium salts. It is inferred 
from these observations that the parathyroids control the calcium metabolism of the 
body. Berkeley and Beebe3 conclude from their experiments that the symptoms 
following removal of the thyroid are due to deranged metabolism giving rise to some 
active poison and not to the abnormal excretion of calcium. 
Other lesions have been described, but the nature and pathology of these organs 
are too little understood to permit of further consideration cf them here.4 
TUMORS. 
Neoplasms of the parathyroid are so rare that only some thirty cases5 
are to be found in the literature. The great majority are benign; and 
such growths are often discovered accidentally at autopsy,6 though it is 
frequently impossible to decide whether a given enlargement is an ade- 
noma or merely a hyperplasia.7 
Malignant growths arc extremely rare, only about 10 per cent, of 
the few recorded cases having been malignant metastasizing neoplasms.8 
Metastatic growths of the parathyroid are distinctly uncommon.9 
The Adrenals. (Suprarenal Bodies, Suprarenal Capsules.) 
Malformations. 
In acephalic and other monsters the adrenals may be atrophied or entirely absent. 
Sometimes in well-formed adults these organs cannot be discovered. There may be 
little rounded nodules loosely attached to the surface of the adrenals and having the 
same structure. Accessory and misplaced adrenals are not uncommon. A few cases 
have been reported of accessory adrenals in the broad ligament.10 They may be 
present in the liver.11 
If one kidney be absent or in an abnormal position its adrenal usually retains its 
normal position.12 
The exact mechanism of the adrenal function is still undetermined, for it has not 
yet been finally shown whether there is a constant outflow into the blood of a specific 
secretion to keep up the vasomotor tonus. It is quite probable that an active secre- 
tion does take place under an emotional or a nervous stimulus, as evidenced both 
1 For a study of the parathyroids, with bibl., see Thompson, R. L., Jour. Med. Research, 1906, N. S. 
x, 399; MacCallum, Ergebn. d. inn. Med., 1913, xi, 569 (bibl.). 
2 MacCallum and Voegtlin, Bull. Johns Hopkins Hosp., 1908, xix, 91, and Jour. Exper. Med., 1909, 
xi, 118. 
3 Berkeley and Beebe, Jour. Med. Research, 1909, N. S. xv, 149. 
4 For transplantation of parathyroids, see Thompson and Leighton, Jour. Med. Research, 1909, N. S. 
xvi, 135. 
5 Berard and Alamartine, Lyon chir., 1908-09, i, 721 (bibl.). 
6 Harbitz, Jour. Med. Research, 1915, N. S. xxvii, 361 (bibl.). For a discussion of the sympto- 
matology of parathyroid tumors, see Gussio, Policlinico, Rome, 1910, xvii, Sezione Chir., 494. 
7 Da Costa, Surg., Gynec., and Obst., 1909, viii, 32. 
8 Birard and Alamartine, Lyon chir., 1908-09, i, 721; see also de Quervain, Deutsch. Ztschr., f. 
Chir., 1909, c, 334. 
9 Thompson, Jour. Med. Research, 1911, N. S. xix, 291. 
10 See Warthin, Am. Jour. Obst., 1900, xlii, 797 (bibl.). 
11 See Noyes, W. B., Trans. New York Path. Soc., 1899-1900, p. 4; also Beer, Ztschr. f. Heilkunde, 
Abth. f. path. Anat., 1904, xxv, 381. 
12 For consideration of relationship of the adrenals to the nervous system, see Alexander, Zieglers 
Beitr., 1892, xi, 145 (bibl.). THE THYROID AND ADRENALS 
589 
through the raising of the blood pressure by contraction of the vessels (with the 
exception of the coronary artery) and through mobilization of the glucose supply in 
the organs.1 Nevertheless, the question cannot be settled as yet, as the experimental 
results are still contradictory.2 
Another function, probably that of the adrenal cortex which does not produce 
adrenaline, is shown in the precocious sexual maturity observed in children with 
tumors of the adrenal cortical tissue; female children may assume some male character- 
istics.3 These tumors in adults are sometimes associated with unusual hairiness 
(hirsuties). 
ATROPHY AND DEGENERATION. 
Atrophy of the adrenals may be extreme. 
Fat Infiltration.-An accumulation of fat or of lipoid droplets4 in 
the cortical portion is the rule in the adult. It sometimes occurs in 
Fig. 331.-Fatty Infiltration of the Adrenal. 
nodular areas (Fig. 331). In children under five years of age it is patho- 
logical. 
Amyloid degeneration may involve both the cortical and medullary 
portions. In the cortex it usually involves only the walls of the blood- 
vessels; in the medulla both the blood-vessels and the cells of the paren- 
chyma may undergo this degeneration. The organs are usually firm 
and have a grayish, semitranslucent appearance. 
Pigmentation of the inner cortical zone is frequent in old persons. 
Focal necroses may occur in infections. 
1 Cannon, Bodily Changes in Pain, Hunger, Fear and Rage, New York, 1915. 
2 For views opposed to those of Cannon, see Stewart, G. N., and Rogoff, J. M., Am. Jour. Physiol.. 
1917, xliv, 543. 
3 Glynn, E. E., Quart. Jour. Med., 1912, v, 157; Jump, H. D., Beates, H., and Babcock, W. W., 
Am. Jour. Med. Sc., 1914, cxlvii, 568; Bland-Sutton, Tumors Innocent and Malignant, New York, 
1917, p. 106. 
4 For a study of lipoid substances in the adrenal, see Herrmann, Arb. a. d. path. Inst., Tubingen, 
1906, v, 417. 590 
THE THYROID AND ADRENALS 
THROMBOSIS AND HEMORRHAGE. 
Venous and capillary thrombosis may occur. 
In children, soon after birth, it is not very infrequent to find large 
hemorrhages in one of the adrenals, converting it into a cyst filled with 
blood (Fig. 332). This lesion has been observed in a few cases in adults.1 
INFLAMMATION. 
Suppurative inflammation, with the formation of abscesses, has been 
seen in a few cases. 
The most frequent lesion of the adrenals is tuberculous inflammation. 
They are usually increased in size; their surfaces are smooth or nodular. 
Fig. 332.-Hemorrhage into and about the Adrenal. (Infant.) 
The normal structure of the gland is more or less replaced by tubercle 
tissue, which usually undergoes cheesy degeneration and may soften 
or, in rare instances, calcify and as a final result lead to bone and marrow 
formation.2 Fibrous tissue may form in considerable amount. (For a 
consideration of the relationship of lesions of the adrenals to Addison's 
disease see page 490.)3 
Syphilitic inflammation, with and without the development of gum- 
mata, is of occasional occurrence. 
1 For bibl., see Arnaud, Arch. g6n. de m6d., 1900, iv, 5. 
2 Woolley, P. G., Jour. Lab. and Clin. Med., 1916, i, 502. 
' For reference to nature of adrenal secretion, etc., see Abel, Vaughan Anniversary Contributions, 
1903, 139 (bibl.). For a study of pathology of adrenals, see Karakascheff, Zieglers Beitr., 1906, xxxix, 
373 (bibl.); see also Davis, New York Med. Jour., 1906, Ixxxiv, 263 (bibl.). THE THYROID AND ADRENALS 
591 
TUMORS.1 
Misplaced remnants of the suprarenal body occur in the kidney, 
testis, ovary, uterus, broad ligament, pancreas, and liver, and about the 
internal spermatic vein, so that neoplasms composed of adrenal tissue 
may develop at any of these sites as well as in the gland itself. The 
most common situation, however, is the kidney (page 892). 
Fig. 333.-Congenital Neuroblastoma of Kidney Region. 
Adenoma (hyperplasia, hypernephroma, struma suprarenalis).- 
This is a rather small growth composed of cortical elements and generally 
encapsulated or at least well delimited. Diffuse lesions occur, however, 
and in such an event the question which term to employ-adenoma or 
hyperplasia-must be a perplexing one. In all these the architectural 
1 For a general discussion of adrenal tumors, see Woolley, P. G., Am. Jour. Med. Sc., 1903, cxxv, 
33 (bibl.); Winkler, Die Gewachse der Nebennieren, Jena, 1909 (bibl.); of medullary growths, see 
Herxheimer, Zieglers Beitr., 1914, vii, 112 (bibl.). For a review of tumors of the adrenal in lower ani- 
mals, see Steinke, Frankfurt. Ztschr. f. Path., 1910, v, 167. For hypernephroma of the adrenalin a 
frog, see Carl, Centralbl. f. allg. Path., i913, xxiv, 436. 592 
THE THYROID AND ADRENALS 
plan of the normal cortex is followed more or less closely, and the so-called 
fat droplets in the cells of these growths are largely lipoid as in the nor- 
mal suprarenal gland. These tumors are occasionally bilateral1 and may 
be pigmented.2 
All grades are found between these small benign growths, which are 
often discovered accidentally at autopsy, and large necrotic infiltrating 
and metastasizing neoplasms. The arrangement and morphology of the 
cells in these malignant tumors approaches much less closely the normal 
type and whether they should be called adenomata, as they frequently 
are, is a question. They have been termed malignant hypernephromata, 
but in the interests of consistency the name hypernephroma might well 
be abandoned, since in modern terminology appellations are chosen, not 
according to the organ in which the neoplasm arises, but to the variety 
of tissue from which it develops. Carcinoma and epithelioma have also 
been employed,3 though as the cortex is derived, not from epithelium, 
but from mesothelium, it would seem more appropriate to call these 
growths mesotheliomata* The problem, however, is a difficult one and 
even the best authorities so far have been unable to solve it. 
Metastatic carcinomata sometimes involve the adrenal,6 and even 
when both glands are destroyed symptoms of adrenal insufficiency may 
not develop, further proof that a tumor is not always useless to the organ- 
ism (pages 373 and 587). 
Sarcoma.-Many of the growths that have been described as sar- 
comata are now known to have been neuroblastomata (Fig. 333) or allied 
tumors (page 408). Some of the others are asserted6 to belong rather 
to the "malignant hypernephromata," neoplasms which completely re- 
semble neither the sarcoma nor the carcinoma, but have some of the 
characteristics of both. The remainder' includes spindle-cell sarcoma, 
myxosarcoma, and melanosarcoma (melanoma).3 
For glioma of the adrenal see page 408. 
The Carotid Gland. 
This is a small, ductless, encapsulated structure, 5 to 7 millimeters 
long, lying at the bifurcation of the carotid artery and composed of a 
connective-tissue framework inclosing masses of polyhedral cells grouped 
about blood capillaries. Some of its cells may stain brown with chromic 
acid and yield a substance exerting the physiological action of adrenaline.9 
The gland contains many nerves and is believed to represent a paragang- 
lion and to be analogous with the adrenals, the hypophysis cerebri, and 
1 Prym, Frankfurt. Ztschr. f. Path., 1913, xiv, 409. 
2 Lucksch, Zieglers Beitr., 1912, liii, 324. 
3 Winckler, Die Gewachse der Nebennieren, Jena, 1909. 
4 Woolley and Adami, Tr. Assn. Am. Phys., 1902, xvii, 627 (bibl.). For a discussion of the contro- 
vexsy, see Davis, Arch. Int. Med., 1911, viii, 60 (bibl.). 
5 Reiche, Centralbl. f. Allg. Path., 1893, iv, 1; Beitzke, Deutsch, med. Wchnschr., 1904, xxx, 897. 
6 Kaufmann, Lehrbuch d. spezielle pathologische Anatomie, Berlin, 1911, ii, 802. 
7 For a description of sarcoma and other malignant growths of the adrenal, see Ramsey, Bull. Johns 
Hopkins Hosp., 1899, x, 20. 
8 Schmidt. Frankfurt. Ztschr. f. Path., 1912, ix, 400. 
9 Monckeberg, I. G., Zieglers Beitr., 1905, xxxviii, 1. THE THYROID AND ADRENALS 
593 
Fig. 334.-Paraganglioma of Carotid-Alveolar Form. 
Fig. 335.-Paraganglioma of Carotid-Diffuse Form. 594 
the coccygeal gland. Total extirpation of the carotid gland causes gly- 
cosuria in animals.1 
THE THYROID AND ADRENALS 
Tumors. 
Tumors of the carotid gland are very infrequent. In their structure 
they more or less closely imitate the morphology of the normal organ; 
usually they possess an alveolar structure, the alveoli being bordered by 
delicate capillaries (Fig. 334). Occasionally, there is no definite arrange- 
ment, and the tumors appear more like a carcinoma (Fig. 335). Chro- 
maffin cells have been demonstrated in some of the tumors of this gland.2 
1 Massaglia, Frankfurt. Ztschr. f. Path., 1916, xviiii, 333. 
2 For further details and bibl. of tumors of the carotid, see Paraganglioma, p. 413. CHAPTER V. 
THE CIRCULATORY SYSTEM. 
The Pericardium. 
INJURIES. 
The pericardium may be injured by penetrating weapons, by gunshot 
wounds, and by the cutting action of sharp fragments of bone. It may 
be ruptured by severe contusions of the thorax, and by rapid extravasa- 
tion of blood into the pericardial sac. Perforations may occur with 
empyema, mediastinal abscesses, and abscesses of the chest wall and of 
the liver, or in connection with aneurysms of the aorta and suppurative 
inflammation of the pericardium. 
HEMORRHAGE. (Hemopericardium.) 
Extravasations of blood into the cavity of the pericardium may follow 
wounds and rupture of the heart, rupture of the aorta and of aneurysms, 
and may occur with pericarditis from the rupture of new-formed blood- 
vessels. Small extravasations in the substance of the pericardium are 
found with scurvy, purpura, leukemia, anemia, and poisoning with phos- 
phorus or benzol, after very severe dyspnea, and in infectious diseases. 
HYDROPERICARDIUM. (Dropsy.) 
At autopsies performed a few hours after death, a few cubic centi- 
meters of clear, light-yellow serum are usually found in the pericardial 
sac. If decomposition have commenced, this may be reddish, or it may 
be slightly turbid from the falling-off of the pericardial endothelium. 
The presence of considerable amounts of fibrin indicates an inflammatory 
origin of the fluid. 
Large accumulations of clear yellowish serum are often present as 
part of general dropsy from heart disease, kidney disease, etc. The 
amount is sometimes so great as to interfere with the movement and 
nutrition of the heart. 
PNEUMOPERICARDIUM. 
Air or gas in the pericardium may be the result of post-mortem 
decomposition and there may then be drying of portions of the pericar- 
dium. Wounds or paracentesis of the pericardium; the perforation of 
carcinomata or ulcers of the stomach, cavities of the lungs, and ulcers of 
the esophagus, or subdiaphragmatic abscess, may admit air into the 
595 596 
THE CIRCULATORY SYSTEM 
pericardial cavity.1 In purulent pericarditis with foul, decomposing 
exudate, gases may be evolved. 
INFLAMMATION. (Pericarditis.) 
Pericarditis is rarely primary, but is usually secondary to infectious 
diseases, such as pneumonia, pleurisy, tuberculosis, typhoid fever, endo- 
carditis, and pyemia. It may follow injuries and is frequently associated 
with rheumatism or inflammation of the kidneys. It may be exudative 
or productive in character. 
Exudative Pericarditis.-It is convenient to distinguish in exudative 
pericarditis a fibrinous, a serofibrinous, and a purulent form. 
Fig. 336.-Fibrinous Pericarditis. 
The pericardial sac is laid open and the heart is seen covered with an irregular villous layer of fibrin. 
Fibrinous and Serofibrinous Pericarditis.-In the earlier 
stages or lighter forms of fibrinous pericarditis, the whole surface or 
portions of the pericardium may be dull or slightly roughened from a 
delicate fibrinous pellicle, more or less hyperemic, and often studded with 
minute petechise. Later, if the exudate accumulate, the entire surface 
of the pericardium may be covered with a net-like layer of thick masses 
of fibrin. This may cover both the visceral and parietal surfaces and 
1 See James, Am. Med., 1904, viii, 23. THE CIRCULATORY SYSTEM 
597 
is often beset with irregular villosities (Fig. 336). Fibrinous adhesions 
may form between the two layers. There is usually some serous fluid 
as well as leucocytes mingled with the fibrin. 
Serum may accumulate in considerable quantity-serofibrinous peri- 
carditis. The pericardial sac may be greatly distended with this form of 
exudate so as to displace the heart and compress the larger air passages, 
the esophagus, or the aorta. 
Purulent Pericarditis.-In this form of exudative pericarditis 
there are usually more or less serum and fibrin mingled with pus cells and 
often red blood-cells. The process may start as a serofibrinous inflam- 
mation. It is apt to occur as an extension of an infectious process in the 
neighborhood or as a part of a general pyemic process. Streptococcus 
pyogenes, Diplococcus pneumoniae, Staphylococcus pyogenes aureus, 
and the tubercle bacillus are the bacteria most commonly found in 
exudative pericarditis. 
Fig. 337.-Adhesions of the Pericardium. 
The pericardial sac is opened so that the heart is viewed from the direction of the apex. There are 
two clusters of delicate fibrous bands joining the parietal and the visceral pericardium. 
Chronic Pericarditis.-In exudative pericarditis the mesothelium1 
(endothelium) in the early stages, and later this with the underlying 
connective tissue cells contributes to the cellular elements in the exudate. 
In recovery the exudates degenerate and are gradually absorbed, while 
from the blood-vessels and the connective-tissue cells of the pericardium 
more or less new fibrous tissue is formed, at first very cellular and vascular, 
later dense in character. There may, finally, be local or general thicken- 
ings of the pericardium. If a moderate amount of new fibrous tissue 
is formed this may appear as thin, white patches on the surface of the 
pericardium, the so-called maculce tendinece. The new fibrous tissue may 
1 Minot, C. S., Science, 1901, xiii, 481. 598 
THE CIRCULATORY SYSTEM 
extend between the subpericardial muscle fibers of the heart; and calcifi- 
cation of this new-formed fibrous tissue may occur. More or less per- 
manent adhesions may form between the visceral and parietal pericar- 
dium; and these may be in the form of delicate fibrous strings (Fig. 337) 
or of larger areas of firm adhesion.1 
Obliteration of the Pericardial Sac.-As the result of the for- 
mation of vascular new connective tissue between the pericardial walls, 
the sac may be partially or wholly obliterated (Fig. 338). 
This may be the conclusion of an acute inflammatory process or it 
may result from the organization of a blood-clot following hemorrhage 
into the sac. It may occur as the result of the latter process early in life. 
Supra-arterial Epicardial Fibroid Nodules.-Small fibrous nod- 
ules are occasionally formed along the branches of the coronary arter- 
ies, especially on the surface of the ventricles. They are frequently 
Fig. 338.-Obliteration of the Pericardial Sac in a Child, Following Pericarditis. 
Showing blood-vessels growing from the visceral pericardium into the blood-clot filling the sac. 
Transverse section. A, Heart; B, pericardium; C, new-formed vascular tissue extending above to 
the unorganized clot. A similar layer of new vascular tissue was present over the parietal pericardium, 
and in places the two layers had coalesced, obliterating the sac. 
associated with lesions of the arteries,2 leading to the weakening of their 
walls at these situations, but are not to be confused with the lesion 
called periarteritis nodosa (page 646), though they closely resemble it 
grossly. 
Tuberculous Pericarditis.-This lesion may occur by itself, but is apt 
to be associated with other tuberculous inflammation in the vicinity of 
the* heart. There may be miliary tubercles scattered diffusely, or limited 
to certain regions in the pericardium, which is otherwise little changed. 
Not infrequently, however, there is a considerable thickening of the peri- 
cardium, either visceral or parietal, or both. 
In such cases the new-formed tissue consists of fibrous tissue and of 
1 For a study of such cases, see Smith, W. H., Jour. Am. Med. Assn., 1913, Ixi, 739. 
2 Knox, M., Jour. Exper. Med., 1899, iv, 245. THE CIRCULATORY SYSTEM 
599 
tubercle tissue which has undergone extensive cheesy degeneration (Fig. 
339). The thickened visceral and parietal layers of the pericardium are 
often more or less grown together, so that the pericardial sac may be 
partially or almost completely obliterated. An inflammatory exudate 
often accompanies the tuberculous process.1 
TUMORS. 
Tumors of the pericardium are rare, though fibroma,2 lipoma,3hem- 
angioma,4 and sarcoma5 have been described. Free masses of fat have 
been found in the pericardial sac. 
Fig. 339.-Tuberculous Pericarditis. 
The greatly thickened pericardium shows diffuse tissue with giant cells and irregular areas of 
cheesy degeneration. The free-upper-surface is covered with a layer of fresh fibrin. 
Cysts of the visceral pericardium have been described. Prudden has 
seen a pedunculated cyst, containing about 6 c.c. of clear fluid, hanging 
into the pericardial sac from its attachment near the pulmonary artery. 
Similar edematous polyps are described by Kaufmann.6 The origin of 
such cystic masses is obscure, but they may be derived from the growth 
of the pericardial mesothelium over deposited masses of fibrin, which then 
soften and thus form a pedunculated cyst. Small blebs of fluid along 
such mesothelial overgrowths are not uncommon in chronic pericarditis. 
1For bibl. of tuberculous pericarditis, see Norris, Univ. Pennsylvania Med. Bull., 1904, xvii, 155. 
2 Forni, Tumori, 1914-15, iv, 522 (bibl.). 
3 Struppler, Munchen, med. Wchnschr., 1907, liv, 472. 
4 Timme, Cleveland Med. Jour., 1915, xiv, 453. 
b Tobiesen, Ztschr. f. klin. Med., 1912, Ixxv, 53 (bibl.). 
6 Kaufmann, Lehrbuch d. spez. path. Anatomie, 3d ed., Berlin, 1911, i, 12. 600 
THE CIRCULATORY SYSTEM 
The Heart. 
Malformations of the Heart.-The malformations of the heart are usually 
closely associated with malformations of the aorta and pulmonary artery. They 
depend on arrest of, or abnormal, development; on endocarditis, myocarditis, throm- 
bosis, or mechanical causes. 
I. The common arterial trunk is only partially, or not at all, separated into aorta 
and pulmonary artery. The divisions between the heart cavities are at the same time 
defective, so that there may be one ventricle and no auricles; one ventricle and one 
auricle-reptilian heart (Fig. 340); or one ventricle and two auricles. 
II. The trunk of the pulmonary artery or of the aorta is stenosed or obliterated, 
and from the obstruction to the current of blood there is interference with the develop- 
ment of the septa between the heart cavities. 
Malformations and Malpositions.1 
Shows one auricle and one ventricle.2 
Fig. 340.-Reptilian Heart. 
1. The aorta, at its origin, or in^the ascending portion of the arch, is stenosed or 
closed. The pulmonary artery gives off the descending aorta, and supplies the carotids 
and subclavians. The foramen ovale remains open, or there is no septum between 
the auricles. The ventricular septum is also usually defective. The right ventricle is 
hypertrophied. 
2. The pulmonary artery is stenosed or closed (Fig. 341). Its branches are sup- 
1 A just understanding of the malformations of the heart can be obtained only by a study of the 
normal embryonic development. Good texts are Bryce, T. H., Quain's Anatomy, London, 1908, i, 
206; Keith, Human Embryology, 3d ed., London, 1913, p. 294; Broman, Normale und abnorme 
Entwicklung des Menschen, Wiesbaden, 1911, p. 519; and Herxheimer, Schwalbe, Die Morphologie der 
Missbildungen des Menschen, Jena, 1910, iii, 339; see, also Mall, F. F., Am. Jour. Anat., 1912, xir, 249. 
2 For a description of this case, see Northrup, W. P., Trans. N. Y. Path. Soc., 1888, p. 40. THE CIRCULATORY SYSTEM 
601 
plied by the aorta, through the ductus arteriosus. The ventricular septum is defec- 
tive, the foramen ovale is open, or the auricular septum defective. 
III. The malformation affects the aorta and pulmonary artery after they are more 
fully developed. 
1. There is stenosis of the aorta between the left subclavian and ductus arteriosus, 
or just at the opening of the ductus arteriosus. The descending aorta is then a con- 
tinuation of the pulmonary artery. 
2. The aorta gives off all its branches from the arch, but the descending aorta is a 
continuation of the pulmonary artery; or the carotids may spring from the aorta, the 
subclavians from the pulmonary artery. 
Fig. 341.-Stenosis of the Pulmonary Artery. 
The ductus arteriosus is open. 
3. The vessels are transposed; the pulmonary artery arises from the left, the aorta 
from the right ventricle; the pulmonary veins empty into the left, the ven® cav® into 
the right auricle; or the veins also may be transposed. The septa are defective. 
IV. The aorta and pulmonary artery are normal, but the cardiac septa are 
defective. 
1. The foramen ovale remains partly open. This condition may continue through 
life without ill effects. It has been found by some observers in about one-fifth of 
their autopsies. 
2. The ductus arteriosus remains open for many years; this also may cause no 
disturbance. 
3. There is a small or large opening in the ventricular septum, usually in its upper 
part (Fig. 342). This may give rise to no symptoms, unless disease of the heart or 
lungs be superadded. 602 
THE CIRCULATORY SYSTEM 
V. Either of the auriculoventricular orifices is entirely closed. The foramen 
ovale remains open, and the ventricular septum is defective.1 
VI. The valves of the different orifices of the heart are absent or defective. The 
arteries or the ventricles are usually defective at the same time. 
The aortic and pulmonary valves consist of two large or four small leaves, instead 
of the usual three. 
The edges of the semilunar valves are fenestrated. This alteration is usually 
of no significance. It is frequent in the aortic and pulmonary valves. The valves 
may be thinner than normal, and near their free edges are small slits or openings (see 
Fig. 343). 
Fig. 342.-Opening in the Ventricular Septum of the Heart-Interventricular Foramen 
The opening is about 5 mm. in diameter, and its edges are formed by fibrous tissue. 
Generally speaking, the existence of openings between the two auricles or the two 
ventricles, admitting some admixture of venous and arterial blood, produces no 
marked change in the circulation. If, however, the passage of the current of venous 
blood into the right heart is in any way interfered with, the consequences are very 
serious. Cyanosis is produced, the skin is of a bluish color, the small veins and capil- 
laries are dilated, exudation of serum and hypertrophy of connective tissue take place, 
especially in the fingers and toes. 
There may be absence of the heart; abnormal septa and chordae tendineae2 (Fig. 
1 Consult for a study of rare forms of cardiac anomalies, Hektoen, Am. Jour. Med. Sc., 1901, cxxi, 
163 (bibl.). 
2 For a study of the origin of abnormal chord® tendine® in the heart, see Tawara, Zieglers Beitr., 
1906, xxxix, 563. 603 
344) in the heart cavities; abnormal shapes of the heart. Very rarely two more or 
less perfect hearts are found in the same thorax. 
Malpositions of the Heart.-1. There is a smaller or larger defect in the 
walls of the thorax, so that the heart projects on the outside of the chest; the pericar- 
dium is usually absent. 
2. The diaphragm is absent, and the heart is in the abdominal cavity. 
3. The heart is in some part of the neck or head; this occurs only in fetuses very 
much malformed. 
4. The heart is transposed, being on the right side, and may be a mirror picture 
of the normal. This should be distinguished from simple dextrocardia, in which 
complete reversal of vessels and ventricles does not necessarily occur. The other 
organs of the thorax and abdomen, also, may be transposed (situs inversus) or may 
not. The former condition is the more frequent. 
Abnormal Size of the Heart.-1. The heart may be abnormally large in con- 
nection with obstructive anomalies of the great vessels. 
2. The heart may be abnormally small (hypoplasia). This abnormality is apt to 
be associated with status lymphaticus (page 500). 
Displacements of the Heart.-Changes in the position of the heart are con- 
genital or acquired. The congenital malpositions have already been mentioned. 
The acquired malpositions may be associated with: 
THE CIRCULATORY SYSTEM 
Fig. 343.-Fenestration of the Semilunar Valves. 
1. Hypertrophy of the heart; its long axis approaching the horizontal position. 
2. Changes in the thoracic visceia. Emphysema of both lungs may push the heart 
downward. Emphysema, pleurisy with effusion, or pneumothorax of one side pushes 
the heart to the other side. Pleurisy or chronic pneumonia, producing retraction of 
one side of the thorax, draws the heart to that side. New growths, aneurysms, and 
curvatures of the spine displace the heart in various directions. 
3. Changes in the abdomen. Accumulations of fluid and new growths in the 
abdomen, and tympanites, may push the heart upward. 
WOUNDS AND RUPTURES. 
Wounds of the heart are most frequently made by penetrating instru- 
ments, by bullets, and by fragments of bone. The right ventricle is the 
most frequently wounded (Fig. 345); next the left; rarely the auricles. 
The wound may penetrate into the cavities of the heart or pass only partly 604 
THE CIRCULATORY SYSTEM 
through its wall, or a bullet or the broken end of a weapon may be 
embedded in the wall. If the wound penetrates a cavity and is gaping, 
death may follow instantly and the pericardium be found filled with 
blood. If the wound is small and oblique, the blood may escape grad- 
ually and death may not ensue for several days. In rare cases adhesions 
are formed with the pericardium and the wound cicatrizes. Wounds 
which do not penetrate may cause death by the inflammation which they 
excite, or they may cicatrize. Bullets and foreign bodies may become 
encapsulated in the heart wall and remain so for years.1 
Fig. 344.-Abnormal Chord.® Tending.®. 
These unite to form a slender band stretching across the cavity of the ventricle 
Rupture of the heart wall occurs in various ways: 
1. Severe contusions of the thorax may produce rupture, usually of 
one of the auricles.2 
2. Spontaneous rupture occurs most often in advanced life. Rupture 
is most frequent in the left ventricle, and, in a considerable proportion of 
cases, near the apex. There is usually one rupture, but sometimes there 
1 For a study of foreign bodies in the heart, see Bailey, C. H., Arch. Int. Med., 1913, xi, 440. 
2 For bibliography, see Newton, Med. Record, 1899, Iv, 864. Also Hamilton, A. 8., Philadelphia 
Med. Jour., 1903, xl, 173. THE CIRCULATORY SYSTEM 
605 
are more. The rupture is usually oblique and larger internally than 
externally. The heart wall, near the seat of rupture, may be infiltrated 
with blood, or blood may infiltrate the subpericardial fat. The heart 
wall may be of normal thickness, or thin; it is usually soft and in a con- 
dition of fatty infiltration or degeneration. The rupture very frequently 
takes place when the patient is quiet. Death may be almost instan- 
taneous or may not ensue for several hours. 
Fatty degeneration leading to rupture of the heart may be general, but 
it is frequently circumscribed and due to obliterating endarteritis, ather- 
oma, thrombosis, or embolus of one of the coronary arteries, whereby a 
portion of the heart wall is deprived of nourishment and degenerates. Or 
Fig. 345.-Rupture of the Heart. 
From contusion. 
rupture of a branch of one of the coronary arteries may induce rupture 
of the heart wall. Acute and chronic myocarditis, with or without the 
formation of abscess or cardiac aneurysm, or the presence of tumors in 
the heart wall, or hydatids, may lead to rupture.1 
3. In rare cases rupture is associated with stenosis of the aorta and 
dilatation of the heart cavities. 
4. Rupture of the papillary muscles and tendons may be due to fatty 
degeneration or inflammatory or ulcerative processes. 
1 For a study of sudden deaths due to the heart, consult Councilman, W. T., Boston Med. and Surg. 
Jour., 1893, cxxix, 457. 606 
THE CIRCULATORY SYSTEM 
Atrophy of the walls of the heart may be accompanied with no change 
in the size of its cavities; or with dilatation (passive dilatation); or, 
more frequently, with diminution in the size of the cavities. 
The atrophy involves most frequently all the cavities of the heart, 
but may be confined to one or more of them. 
The muscular tissue appears normal, or may be brown from the pres- 
ence of little granules of iron-free, lipoid pigment in the muscle fibers- 
brown atrophy; or the muscle fibers may undergo fatty degeneration; or 
there may be an abnormal accumulation of fat beneath the pericardium; 
or there may be a peculiar gela- 
tinous material beneath the peri- 
cardium-this consists of fat 
which has undergone mucous de- 
generation. The heart may be so 
much atrophied as to weigh only 
four ounces. 
Atrophy of the heart may be 
congenital; it may be associated 
with repeated hemorrhages, with 
wasting diseases or senility, with 
chronic pericarditis, with effusion, 
with obstructive lesions of the coro- 
nary arteries, with chronic myo- 
carditis, or with mitral stenosis. 
Atrophy of the pericardial fat 
tissue not infrequently occurs in 
persons emaciated by chronic dis- 
ease, and then the usual situa- 
tions of the fat are occupied by a 
tissue resembling mucous tissue in its gross characters. Microscopical 
examination shows that in this atrophic fat the fat cells have largely 
lost their contents, and the whole tissue has undergone a partial reversion 
to its embryonic form (Fig. 346). 
ATROPHY. 
Fig. 346.-Atrophic Pericardial Fat Tissue. 
From a young person dead of carcinoma of the 
stomach and peritoneum. Stained with osmic acid 
and teased. 
Aneurysm of the Heart.-Sacs filled with blood, situated in the walls 
of the heart and communicating with its cavities, are formed in several 
different ways: 
1. In interstitial myocarditis a small or large portion of the wall may 
be replaced by fibrous tissue, and this, yielding to the pressure of the 
blood from within, may be pressed outward. Such a pouch may be a 
circumscribed sac communicating with the heart cavity by a small open- 
ing, or may be a simple dilatation of part of the ventricle. The wall of 
such an aneurysm becomes thinner as the sac increases in size. It is com- 
posed of the endocardium, new fibrous tissue, visceral pericardium, and 
ANEURYSM OF THE HEART AND VALVES. 607 
sometimes the adherent parietal pericardium. The walls may calcify, or 
rarely may become so thin as to rupture externally or into the right ven- 
tricle. The sacs may contain fluid blood or be filled with fibrin. 
Such aneurysms are usually situated in the wall of the left ventricle; 
rarely in that of the left auricle. If they are in the septum they may 
project into the right ventricle or auricle (Fig. 347). They are usually 
single, but sometimes two or three are found in the same heart. 
2. Fatty degeneration of the heart wall may reach such a degree that 
the wall yields and is pouched out into an aneurysmal sac. 
THE CIRCULATORY SYSTEM 
Fig. 347.-Aneurysm of the Heart Opening from the Left Ventricle into the Right Auricle 
Seen from behind. 
3. Endocarditis and myocarditis, or fatty degeneration, may so soften 
a portion of the heart wall that the endocardium and part of the muscular 
tissue are ruptured and a ragged cavity is formed. This form of aneu- 
rysm usually does not attain a large size, but soon ruptures externally 
and causes the death of the patient. 
Small aneurysms of the sinus of Valsalva are of occasional occurrence. 
Aneurysms of the Valves.-These are formed in two ways: 
1. They are the result of endocarditis. One of the lamellae of the 
leaf of a valve is destroyed, and the other lamella is converted into a sac 608 
THE CIRCULATORY SYSTEM 
filled with blood. These aneurysms are found in the aortic valve, pro- 
jecting into the ventricle, and in the mitral valve, projecting into the 
auricle. Not infrequently the wall of the aneurysm gives way, so that 
there is a rupture entirely through the valve. 
2. The entire thickness of a leaf of a valve is pouched, forming a sac 
filled with blood. This occurs in the aortic, mitral, and tricuspid valves. 
THROMBOSIS OF THE HEART. 
It is common to find in the heart cavities, after death, yellow, succu- 
lent, semitranslucent masses. They are most common and of firmest 
texture in persons who die of acute inflammatory diseases. They may 
Fig. 348.-Polypoid Thrombus in the Left Auricle of the Heart. 
The thrombus was dark red in color, with smooth surface. 
adhere quite firmly to the walls of the heart and may extend in long, 
branching cords into the vessels. They are formed in the last hours 
of life and just after death, and are not of clinical or pathological im- 
portance. It is, however, often difficult to determine to what extent 
such masses have been formed during life, for the so-called "agonal" 
clots may be continuous with those formed some time before death as 
well as with those formed after life has become extinct. 
Coagula of the fibrin of the blood in the heart form during life, and 
may exist for years. If the fibrin adheres to the valves in small masses 
these are called vegetations; if it coagulates in the heart cavities in larger 
bodies they are called thrombi or heart polypi. 
Such thrombi are found in any of the heart cavities. They form THE CIRCULATORY SYSTEM 
609 
flattened masses firmly adherent to the endocardium; or rounded bodies in 
the spaces between the trabecul®; or have a polypoid shape and are 
attached by a narrow pedicle (Fig. 348 and 349); or very rarely are glob- 
ular and free in the cavity of the auricle (Fig. 350). Cardiac thrombi are. 
most frequent in the auricular appendages and between the column® 
carne® near the apices of the ventricles (Fig. 351). 
They are usually found in connection with some valvular lesion (Fig. 
352), which involves a roughening of the surface, or prevents the free 
circulation of blood through the heart.1 
Fig. 349.-Globular Thrombus in the Left Ventricle. 
This thrombus was softened at its center. 
Old cardiac thrombi are firm, dry, and of a whitish color; they may 
soften and break down at their centers, so as to look like cysts filled 
with pus; or they may calcify. They are usually entirely unorganized, 
consisting simply of fibrin, but may become organized. 
Cases are reported of organized thrombi in the auricles, the seat of 
tuberculous inflammation.2 
Malignant tumors especially hypernephromata may be accompanied 
1 For a study of cardiac thrombosis, see Martin and Rennie, Lancet, 1899, ii, 782. See also Welch, 
Allbutt, System of Medicine, 1906, vi, 182. 
a Kollar, Centralbl. f. Bakteriol., Orig. I, 1894, xv., 498; also Moser, Boston City Hosp. Rep., 1900, 
11th set., p. 194. 610 
THE CIRCULATORY SYSTEM 
by the formation of thrombi in the heart cavities, which are composed 
partly of coagulated blood, partly of tumor tissue.1 
DEGENERATION. 
Albuminous Degeneration. (Parenchymatous Degeneration.)-This 
lesion frequently occurs in diphtheria,2 typhoid and typhus fever, pyemia, 
Fig. 350.-Large Globular Thrombus in the Right Auricle of the Heart. 
erysipelas, and other infectious diseases, as a result of burns, and under 
a variety of other conditions. It is characterized by the presence in the 
muscle fibers of the heart of greater or less numbers of albuminous gran- 
ules of various sizes, most of them very small. They are not as refractile 
as fat droplets, and are insoluble in ether, while swelling up and becom- 
ing almost invisible under the influence of acetic acid. Sometimes 
they are so abundant as to conceal the striations of the fibers. The 
degeneration is usually quite uniformly diffused through the heart, whose 
1 Kirschner, M., Berl. klin. Wchnschr., 1911, ii, 1746, (bibl.). 
2 Scaffliosi, G., Virchows Arch., 1896, cxlvi, 115. THE CIRCULATORY SYSTEM 
611 
walls are softer than normal and of a grayish color. This lesion may be 
associated with or followed by fatty degeneration. 
Fatty Degeneration of the Heart Muscle.-This consists in the ap- 
pearance in the muscle fibers of the heart of fat or closely allied sub- 
stances,1 which collect in larger and smaller droplets, sometimes few in 
number, sometimes so abundant as almost entirely to replace or conceal 
the normal striations (Fig. 353). These droplets are soluble in ether, 
Fig. 351.-Thrombi among the TrabeculzE of the Heart. 
and remain unchanged on treatment with acetic acid. This change is 
sometimes quite universal, but is more apt to occur in patches, giving 
the heart muscle a tigroid striation or mottled appearance, which can 
usually be best seen on the papillary muscles. The degenerated areas 
have a pale yellowish color, and the muscle tissue is soft and flabby; 
but when moderate or slight in degree the gross appearance may be little 
changed, and microscopical examination be necessary for determination 
of the lesion. This degeneration may lead to thinning of the walls, or 
1 See, in this connection, p. 49. 612 
THE CIRCULATORY SYSTEM 
to rupture of the heart, or to inability to fulfil its functions. It is not 
infrequently the cause of sudden death. 
Fatty degeneration may be secondary to hypertrophy of the heart, to 
inflammation of the heart muscle, to pericarditis; or to disturbances of 
the circulation of the coronary arteries by inflammation, atheroma, etc. 
It may be due to deteriorated condi- 
tions of the blood in wasting dis- 
eases, excessive hemorrhages, ex- 
hausting fevers, leukemia, etc., to 
poisoning with phosphorus and ar- 
senic, and to the toxins of microbic 
origin developed in infectious dis- 
eases, such as diphtheria, scarlatina, 
typhoid fever, etc.1 It may occur 
in otherwise apparently healthy 
persons. 
Fatty Degeneration of the Endo- 
cardium.-It is not uncommon to 
find, especially in elderly persons, 
fatty degeneration occurring in 
patches, especially on the valves, but 
also on the general endocardium. It 
may also occur in ill-nourished and anemic individuals. Small, or even 
considerable, areas of fatty degeneration appear, as a rule, to be of little 
or no clinical significance; they are at least not inconsistent with perfect 
health. In these areas of fatty degeneration the connective tissue cells 
are more or less completely filled with larger and smaller fat droplets. 
Glycogen is especially abundant in the muscle fibers of the auricles and 
in those of the conducting system. 
Amyloid degeneration of the endocardium or the walls of the blood- 
vessels and intermuscular con- 
nective-tissue septa is a not very 
infrequent, but usually not very 
important, lesion. The muscle 
fibers do not show amyloid 
changes.2 
Hyaline degeneration some- 
times occurs in the blood-vessels 
and in the muscle fibers. 
There may be calcification of 
the products of inflammation in 
pericarditis, or of connective- 
tissue membranes in chronic' 
pericarditis; in the latter case 
the heart may be more or less inclosed by a calcareous shell. The muscle 
Fig. 352.-Thrombus Formed over the 
Roughened Edge of the Mitral Valve. 
Fig. 353.-Fatty Degeneration of Heart Muscle. 
i Consult Flexner, Bull. Johns Hopkins, 1894, v, 26. For focal fatty degeneration of heart associ- 
ated with Treponema pallidum, see Warthin, Jour. Am. Med. Assn., 1912, Iviii, 409. 
a Huebschmann, P., Virchows Arch., 1907, clxxxvii, 35; Beneke, R., and Bbnning, F., Zieglers Beitr., 
1908, xliv, 362. THE CIRCULATORY SYSTEM 
613 
fibers of the heart wall may, though rarely, become densely infiltrated 
with calcium phosphate. The deposition of the lime salts is generally 
preceded by degeneration of the muscle. The phenomenon is observed 
in osteomalacia, in interstitial nephritis, and in areas of degeneration 
following infections or embolic necrosis.1 
Fatty Infiltration.-This lesion, which should be clearly distinguished 
from fatty degeneration, consists of an unusual accumulation of fat 
about the heart and between its muscle fibers. 
The subpericardial fat, which may be present in considerable quantity 
under normal conditions, may be so greatly increased in amount as to 
form a thick envelope inclosing nearly the entire organ. Sometimes the 
accumulation of fat extends into the walls of the heart, between the 
muscles, causing atrophy of the latter, frequently to a very great extent 
Fig. 354.-Fatty Infiltration of the Heart-Lipomatosis. 
The lesion is excessive, the heart muscle being to a large extent atrophied. (The fat cells are repre- 
sented in the drawing, for the sake of clearness, of relatively too large size.) 
(Fig. 354), so that the function of the heart is seriously interfered with. 
This occurs sometimes in general obesity, or as a result of chronic peri- 
carditis, or in drunkards, or in debilitated or old persons. 
SEGMENTATION AND FRAGMENTATION OF THE MYOCARDIUM. 
Attention has been called by a number of observers to a condition of 
the heart muscle sometimes observed, it is said, in acute infectious dis- 
eases, in acute and chronic diseases of the central nervous system, and 
in sudden death from a variety of causes. The muscle tissue is soft, 
friable, opaque, and often yellowish. Examination shows a loosening of 
the muscle cells from one another, as if by some change in the cement 
substance-segmentation-or the fibers may be broken across-fragmen- 
tation. The significance of this alteration is not yet fully established, for 
1 Cullen, T. 8., Bull. John Hopkins Hosp., 1906, xvii, 267. 614 
THE CIRCULATORY SYSTEM 
though in some cases it is associated with degeneration and other changes 
in the heart muscle, in others these are not present and the alteration 
may be agonal, or it may in some instances be due to post-mortem 
changes.1 
Lesions of the Coronary Arteries in Acute Infections.-It has recently 
been shown that in acute infectious diseases, typhoid fever, diphtheria, 
influenza, scarlatina, pyemia, and others, the media and the intima of 
the coronary arteries may be involved in necrotic and hyperplastic 
processes which are apparently of great significance in leading to certain 
forms of sclerosis of these vessels. 
The coronary arteries may show, on gross examination, in both larger 
and smaller trunks, circumscribed, yellowish white, elevated spots, from 
2 to 6 mm. in diameter, or small dull white depressions of the intima. 
These lesions seem to begin as a localized serous infiltration in the media 
which undergoes necrosis. At a later period, after recovery from the 
acute disease, fibrous tissue may form in the media and intima, some- 
times associated with calcification. Thus a patchy form of arterio- 
sclerosis may be developed.2 
LESIONS OF THE CORONARY ARTERIES. 
SCLEROSIS AND THROMBOSIS 
Obliterating Endarteritis-Sclerosis-of the coronaries, which occurs 
frequently, is of great significance, since diminished nutrition of the heart 
wall may lead to local anemia, degeneration of the muscle, fibrous hyper- 
plasia, or aneurysm, etc.; but the formation of thrombi increases the 
gravity of the lesion. Thrombosis most commonly occurs in connection 
with degenerative or inflammatory processes in the coronary arteries. It 
may, however, be associated with occlusion of the coronary arteries at 
their orifices either through inflammation of the aorta in this region or by 
vegetations or clots on the aortic valves. 
The blocking of one main trunk of the coronary arteries by a throm- 
bus may cause death, but this is not always the case. 
When through obliterating endarteritis, thrombosis, or embolus of 
a branch of the coronary arteries,3 the blood supply is cut off from a 
circumscribed portion of the heart wall, the tissue in the affected area 
may undergo fatty degeneration, leading to rupture.4 Or, instead of 
'Consult Hektoen, Am. Jour. Med. Sc., 1897, cxiv, 555 (bibl.); MacCallum, Jour. Exper. Med. 
1899, iv, 409 (bibl.); Stamer, Zieglers Beitr., 1907, xlii, 310; Cohn, Verhandl. d. deutsch. path. Gesellsch., 
1909, xiii, 182 (bibl.). 
2 For a study of this lesion of the coronary arteries see Wiesel, J., Wien. klin. Wchnschr., 1906, xix, 
723; and Ztschr. f. Heilk., Abt. f. path. Anat., 1906, xxvii, 262; also Wiesner, R., Wien. klin. Wchnschr., 
1906, xix, 725. 
3 According to Sternberg, the right coronary artery supplies the following regions of the heart: 
most of the right auricle; the posterior part and most of the anterior part of the right ventricle; most 
of the interauricular and interventricular septa; the posterior part of the left ventricle and the posterior 
papillary muscles. The remainder of the heart is supplied by the left coronary artery. 
While there are superficial anastomoses between the larger trunks of the coronary arteries, their 
branches do not communicate after they enter the heart muscle. For a study of coronary arteries 
see the monograph of Jamin and Merkel, Die Koronararterien des menschl. Herzens, Jena, 1907. 
4 Through the Thebesian vessels sufficient nutriment may reach the myocardium t > maintain 
the muscle for a time, even with considerable lesion of the coronary arteries. See Pratt, Am. Jour. 
Physiol., 1898, i, 86; also Baumgarten, ibid., 1899, ii, 243. For the results of occlusion of one or 
more of the coronary arteries, see Porter, W. T., Jour, of Physiol., 1898, xv, 121; also Jour. Exper. 
Med., 1896, i, 46; Herrick, J. B., Jour. Am. Med. Assoc., 1919, Ixxii, 387. 615 
extensive fatty degeneration, the cutting off of the blood supply from 
a limited region may result in necrosis-white infarction. These areas, 
grayish in color, often slightly projecting from the surface, are fre- 
quently surrounded by a red zone of hyperemia. The nuclei of muscle 
and fibrous tissue fail to stain, the muscle cells become necrotic, lose 
their striation and degenerate, and may be absorbed or gradually 
replaced by fibrous tissue. When larger areas are involved, the muscle 
fibres may break down into a granular detritus and the connective tissue 
about them suffer degeneration or necrosis, so that the whole affected 
area may be soft and yellowish white or grayish in color. If, as not 
infrequently occurs, there is considerable extravasation of blood, the 
degenerated area may be of a dark red color.1 Under these conditions 
the heart wall may rupture, or acute inflammatory processes may occur, 
or the degenerated muscle tissue may be gradually absorbed and replaced 
by granulation tissue formed from the surrounding fibrous tissue and 
blood-vessels. This gradually grows dense, shrinks, and assumes the 
characters of cicatricial tissue. 
Thrombosis may occur in any part of the heart wall or in the papillary 
muscles, but is most common in the region supplied by the left coro- 
nary artery; that is, in the interventricular septum and the anterior wall 
of the left ventricle near the apex. Thrombosis of the coronary arteries 
is more frequent than embolism and more commonly leads to infarction. 
When the heart wall is involved the new-formed connective tissue may 
yield to the blood pressure from within and aneurysm of the heart be 
formed. 
Impaired nutrition of a portion of the heart wall as the result of 
narrowing or obliteration of the coronary arteries or their branches, 
whether it leads to such extreme lesions as those just described, or to 
fatty degeneration, or to atrophy of the muscle cells with a production of 
new connective tissue, is of great significance, and may be the domi- 
nant factor in many cases of sudden death. 
Embolism of the coronary arteries is much less common than thrombo- 
sis and may be followed by similar lesions of the myocardium. Infective 
emboli are freuqent excitants of suppurative lesions of the myocardium. 
Aneurysm of the coronary arteries is a rare phenomenon.2 The 
enlargement is most frequent near the origin of the vessels from the 
aorta. 
THE CIRCULATORY SYSTEM 
INFLAMMATION. 
Myocarditis. 
The inflammatory changes in the walls of the heart involve primarily 
the interstitial tissue and blood-vessels, the muscle fibers being second- 
arily affected by atrophic and degenerative changes. 
Interstitial myocarditis may be acute and suppurative, or chronic 
with the formation of new connective tissue. 
Acute suppurative myocarditis may be diffuse, infiltrating the wall of 
the heart with pus. This may occur as a complication of infectious 
1 This condition of the heart is often called "myomalacia." 
2 Capps, Am. Jour. Med Sc.. 1899. cxviii, 312. 616 
THE CIRCULATORY SYSTEM 
diseases, such as influenza, scarlatina, diphtheria, typhoid fever, and 
gonorrhea,1 or may be associated with ulcerative endocarditis.2 
More frequently the suppurative inflammation is circumscribed, 
resulting in abscesses. These occur with pyemia, mycotic ulcerative 
endocarditis, and other infectious diseases. They are of different sizes 
and either single or multiple. They are produced by the lodgment of 
infectious emboli in small vessels. There is at first necrosis of the muscle 
fibers near the bacterial mass (Fig. 355), followed by local suppuration 
and the formation of abscess. The contents of the abscesses consist 
of pus, broken-down muscle tissue, and bacteria. These abscesses may 
open into the pericardial sac and set up a purulent pericarditis; or into 
a heart cavity, giving rise to thrombi in the heart and infective emboli 
in different parts of the body; or the wall of the heart may be weakened 
by the abscess so that it ruptures, or an aneurysmal sac is formed; or an 
abscess in the interventricular septum may establish an opening between 
the ventricles; or the suppurative process may extend upward and form 
Fig. 355.-Bacterial. Embolus in Heart Muscle. 
The bacteria have multiplied since lodgment in the small vessel, so that the latter is widely dis- 
tended. The surrounding muscle is necrotic. 
an abscess in the connective tissue at the base of the heart. In diph- 
theria, necrosis, and hyaline or waxy degeneration of the muscle fibers are 
not infrequent.3 Interstitial inflammatory collections are seen, also. 
Streptococcus and Staphylococcus pyogenes are the most common 
excitants. 
In rare cases the patients recover, the contents of the abscesses 
become dry and hard and inclosed by a wall of fibrous tissue, or the con- 
tents may be absorbed and the whole replaced by fibrous tissue.4 
Chronic interstitial myocarditis may be associated with chronic peri- 
carditis or endocarditis; with chronic nephritis or it may be secondary to 
1 For a consideration of gonorrheal myocarditis, consult Councilman, W. T., Am. Jour. Med. Sc., 
1893, cvi, 277. 
2 For a study of experimental focalized myocarditis in relation to Aschoff nodules, see Thalhimer and 
Rothschild, Jour. Exper. Med.,'1914, xix, 429. 
3 Anitschkow, Virchows Arch., 1913, ccxi, 193. 
• For study of experimental myocarditis, see Fleischer and Loeb, Arch. Int. Med., 1909, iii, 78. For 
a summary of conditions under which myocarditis occurs, see Brooks, H., Am. Jour. Med. Sc., 1911, 
cxlii, 781. THE CIRCULATORY SYSTEM 
617 
damage to the muscle by bacterial or other toxins, but in a large propor- 
tion of cases it occurs in connection with lesions of the coronary arteries. 
Lesions of the coronary arteries which interfere with the blood supply 
of the heart muscle, such as obliterating endarteritis with or without 
thrombosis or embolism, may lead to degeneration or necrosis of the 
muscle and to a new formation of fibrous tissue which is in reality a 
replacement hyperplasia. Thus either in small foci or over more diffuse 
areas, patches of fibrous tissue may be formed as the muscle disappears 
(Fig. 356). 
If the occlusion of the coronaries has led to infarctions of the heart, 
then also, as we have seen above, new fibrous tissue may form, replacing 
the muscle. 
Local degenerative processes and necrosis in the muscle tissue of the 
heart may be associated with acute infectious diseases, especially with 
diphtheria, typhoid fever, and scarlatina. In such areas of damaged 
muscle new connective tissue may form. This is at first cellular, later 
dense and cicatricial in character. As the result of this replacement 
hyperplasia, patches of fibrous tissue may be scattered through the 
myocardium. Similar lesions may be induced experimentally in animals 
by the injection of bacterial toxins.1 Calcification of the muscle fibers 
has been observed in connection with the degenerative processes due to 
the action of toxins.2 
Fig. 356.-Chronic Interstitial. Myocarditis (Fibrous Replacement Hyperplasia). 
1 Flexner, S., Johns Hopkins Hosp. Rep., 1897, vi, 259. 
Degeneration of muscle fibers and the formation of new connective tissue has been induced in the 
hearts of rabbits by the injection of adrenaline into the ear vein. See Pearce, R. M., Jour. Exper. Med., 
1906, viii, 400. 
2 Cullen, E. K., Bull. Johns Hopkins Hosp., 1906, xvii, 267. 618 
THE CIRCULATORY SYSTEM 
Chronic interstitial myocarditis, whether diffuse or focal, leads to a 
weakening of the heart wall. This may be slight or excessive. Hyper- 
trophy of the muscle may follow or be associated with it; degeneration 
of the remaining muscle may occur; or the heart wall may yield to the 
internal pressure and pouch, forming aneurysm of the heart. Thrombi 
may under these conditions form in the dilated cavities. Lack of 
rhythm in the heart-beats or cardiac pain-angina pectoris-may result 
from myocarditis. On the other hand, in many chronic conditions in 
which the heart clinically shows symptoms referable to enfeeblement of 
the cardiac muscle, no microscopic lesions can be made out. 
Showing cross section of a papillary muscle. The muscle tissue is least involved about the vessels 
and near the surface. 
Fig. 357.-Chronic Interstitial Myocarditis. 
It is believed by most modern observers that the new connective 
tissue which develops in the heart in connection with atrophy of the 
muscle fibers, as a result of impaired nutrition due to a narrowing of the 
lumen of the coronary arteries or to other causes, is not, in the stricter 
sense, inflammatory in its nature, but is rather a fibrous hyperplasia, 
the new-formed connective tissue forming secondarily, to replace the 
muscle fibers which have atrophied. Nevertheless we still for con- 
venience call the lesion myocarditis, thus implying inflammation. It 
is interesting in this connection to note that under these conditions 
the muscle fibers immediately beneath the endocardium and close 
around the blood-vessels, where the nutritive supply is most abundant, 
are often not atrophied, nor is the growth of connective tissue marked 
(Fig. 357). THE CIRCULATORY SYSTEM 
619 
In almost all cases of valvular heart disease, changes in the heart 
muscle can be found if sufficiently extensive microscopical examinations 
are made. Usually these changes are in the nature of a fibrosis; but in 
a certain number of cases of rheumatic endocarditis, though not in all, 
perivascular collections of cells of an epithelioid type with large pale 
nuclei have been found. Some of these elements resemble plasma cells, 
but are probably not strictly of this type; others are of very large size, 
and resemble the giant cells seen in the lymph-nodes in Hodgkin's dis- 
ease. Occasionally, eosinophilic and neutrophilic leucocytes may be 
found in small numbers. These nodules, the so-called Aschoff bodies, are 
especially abundant in the wall of the left ventricle, near the base, and 
in the interventricular septum.1 
The valve and adjacent portion of the heart wall are ulcerated, and a ragged clot has formed upon 
the roughened surfaces. 
Fig. 358.-Ulcerative Endocarditis. 
Tuberculous myocarditis is of occasional occurrence and may be asso- 
ciated with tuberculosis of the pericardium or endocardium.2 
Syphilitic Myocarditis is accompanied by the growth of connective 
tissue or granulation tissue in the wall of the heart between the muscle 
fibers or in the walls of the blood-vessels. The pericardium and endo- 
cardium may also be thickened, and pericardial adhesions may be 
formed. Gummata of the heart are of rare occurrence,3 although in 
1 See Aschoff, Verhandl. d. deutsch. path. Gesellsch., 1904, viii, 46; and Fraenkel, E., Zieglers Beitr., 
1912, lii, 597. 
2 Consult Moser, Tuberculosis of the Heart, Boston City Hosp. Rep., 1900, 11th ser., p. 194. Also 
Andres, Jour. Am. Med. Assn., 1902, xxxix, 1081. Also Raviart, Arch, de m6d. expSr., 1906, xviii, 
141 (bibl.). 
3 See Loomis, H., Am. Jour. Med. Sc., 1895, ex, 389 (bibl.); Adler, Tr. Assn. Am. Phys., 1898, xiii, 
73 (bibl.); and Berblinger, Centralbl. f. allg. Path., 1910, xxi, 1045 (bibl.). 620 
THE CIRCULATORY SYSTEM 
recent years many more cases have been recognized because of the fre- 
quency with which the gumma produces heart block by interference with 
the conducting system. 
ENDOCARDITIS. 
The endocardium is a connective-tissue membrane, containing but 
few blood-vessels, which lines the cavities of the heart and forms its 
valves. Its inner surface is covered with a layer of endothelial cells. 
It is frequently subject to inflammatory changes, in which the connective- 
tissue cells and the basement substance are principally concerned. The 
new tissue thus produced is prone to degeneration and calcification. The 
roughening of the endocardium due to the inflammation often leads to 
the formation of fibrin on the affected surface. 
The endocardium which forms the valves is that which is most fre- 
quently involved, but the other portions of it are by no means exempt. 
Fig. 359.-Masses of Bacteria in Vegetation on the Heart Valve in Infective (Malignant) 
Endocarditis. 
In adult life it is the endocardium of the left ventricle, and especially of 
the aortic and mitral valves, which is most commonly affected. In fetal 
life it is the endocardium of the right heart which is usually affected. 
i. Simple Acute Endocarditis.-This is frequent with rheumatism, but 
may occur under other conditions. It may occur in a heart previously 
healthy, or in one already the seat of chronic endocarditis. 
In some cases the only lesion is a simple swelling of the valves. These 
are thick and succident, but their surfaces remain smooth. The base- 
ment substance is swollen, and there is a moderate production of new 
connective-tissue cells. In other cases the growth of connective-tissue 
cells is more marked, the basement substance is split up, and little cellu- 
lar fungous masses of connective tissue, called "vegetations," project THE CIRCULATORY SYSTEM 
621 
from the free surface of the endocardium. This is sometimes called 
verrucous endocarditis. On these roughened surfaces the fibrin of the 
blood may be deposited, and thus vegetations of considerable size may 
be formed (see Fig. 358). In still other cases the cell growth, while in 
some places forming vegetations, in other places degenerates, and thus 
portions of the valves are destroyed. Less frequently, the ventricular 
wall may be affected by the formation of small soft granular masses of 
fibrin, blood-plates, and leucocytes. This is simple acute ulcerative 
endocarditis. In some cases of this disease the patients recover and the 
valves seem to return to a normal condition; in other cases the valves 
are left permanently damaged; and in still others chronic endocarditis 
follows the acute form. 
Fig. 360.-Chronic Endocarditis. 
Section showing thickening of the cusp of the aortic valve. 
2. Mycotic or Malignant Endocarditis (Malignant Ulcerative Endo- 
carditis).-The direct excitants of simple acute endocarditis of the forms 
described above are unknown, but in a considerable number of cases of 
acute endocarditis bacteria have been found in and about the vegeta- 
tions, and proved, by careful experiments, to stand in a causative relation 
to the lesion. 
Those cases of acute endocarditis in which the lesions are induced by 
the direct action of bacteria are called mycotic or malignant endocarditis; 622 
THE CIRCULATORY SYSTEM 
or, since the new-formed as well as the old tissue about the bacteria is 
apt to become necrotic and thus lead to larger or smaller losses of sub- 
stance, the lesion is often called malignant ulcerative endocarditis. Cases 
of multiple aneurysm in connection with mycotic endocarditis have been 
reported. Various species of bacteria may be excitants of malignant 
endocarditis (Fig. 359). 
It is most commonly induced by Staphylococcus pyogenes aureus and 
Streptococcus pyogenes and viridans. Diplococcus pneumoniae,1 B. 
Showing thickening and coalescence of two of the aortic cusps. 
Fig. 361.-Chronic Endocarditis. 
typhosus, B. tuberculosis, B. anthracis, Micrococcus gonorrhoeae,2 and 
other organisms have been occasionally found.3 The specific organisms 
1 For a resume of pneumococcus endocarditis, see Preble, H. B., Am. Jour. Med. Sc., 1904, cxxviii, 
782. 
2 For bibl. of gonorrheal endocarditis, see Kalbs, Wien. klin. Wchnschr., 1907, xx, 11. 
s For a general consideration of infective endocarditis, see Washbourn, and others, Brit. Med. Jour., 
1899, ii, 1269, Billings, F., Arch. Int. Med., 1909, iv, 409; and Simons, I., Quart. Jour. Med., 1914, 
xxii, 291. For a study of the meningococcus in endocarditis, see Warfield, Univ. Pennsylvania Med. 
Bull., 1903, xvi, 180; and Cecil and Soper, Arch. Int. Med., 1911, viii, 1. For studies on bacteria in 
blood in "subacute" endocarditis, see Libman and Celler, Am. Jour. Med. Sc., 1910, lex, 516; and 
Libman, E., ibid., 1912, cxliv, 313, THE CIRCULATORY SYSTEM 
623 
can usually be demonstrated in the blood stream during life, if repeated 
cultures are made; but individual examinations are often negative. 
Fig. 362.-Vegetation on Aortic Valve in Endocarditis. 
Showing granular thrombus over the surface. 
Showing fibrous "vegetation" on the mitral valve, with a large blood clot formed upon it. 
Fig. 363.-Chronic Endocarditis. 
It has, furthermore, been found that a lesion or injury of the endo- 
cardium, either on the heart valves or elsewhere, predisposes to the lodg- 
ment and growth upon it of pathogenic bacteria when once they have 
gained access to the circulating blood. 624 
THE CIRCULATORY SYSTEM 
Mycotic endocarditis is frequently a secondary complicating lesion, 
but may occur as a primary disease. It is most apt to be associated 
with the acute infectious diseases, and may be one of the local mani- 
festations of pyemia.1 
In some cases there is a formation of new tissue in the form of organ- 
ized vegetations on the valves or general endocardium; in other cases 
necrosis either of the new-formed or the old tissue is the most marked 
feature. Thrombi are apt to form on the affected surfaces and often 
largely make up the so-called vegetations. The mitral and aortic valves 
Fig. 364.-Chronic Endocarditis (Verrucous Endocarditis). 
The new papillary growths of connective tissue involve the mitral valve and obstruct the mitral orifice. 
are frequently the seat of the lesion, but it may occur elsewhere, not 
infrequently on the septal wall of the left ventricle. 
Detachment of bacteria-containing fragments of the vegetations or 
clots may give rise to single or multiple infectious emboli and abscesses 
in various parts of the body, such as the spleen, kidneys, brain, skin, 
heart wall, etc. Bacteria similar to those in the heart lesion may be 
found in these secondary abscesses. 
It is probable that abscesses in ulcerative endocarditis do not always 
arise from cardiac emboli, but may precede the heart lesion. 
i For a study of local predisposing factors in malignant endocarditis, see Prudden, T. M., Am. Jour. 
Med. Sc., 1887, xciii, 55. For experimental endocarditis, see Rosenow, E. C., Jour. Infect. Dis., 1912, 
xi, 210. THE CIRCULATORY SYSTEM 
625 
3. Chronic endocarditis may succeed acute endocarditis, or the inflam- 
mation may be chronic from the outset. It affects most frequently the 
aortic and mitral valves, and the endocardium of the left auricle and 
ventricle, similar changes in the right side of the heart being much less 
frequent. 
There are two main anatomical varieties of chronic endocarditis, which 
may occur separately or together: 
1. The endocardium is thick and dense, its surfaces are smooth or 
covered with small, hard vegetations or ridges (Fig. 360 and 361); it is 
often infiltrated with the salts of lime. 
Fig. 365.-Chronic Endocarditis with Calcification of the Thickened Valves. 
2. There is a growth of connective-tissue cells in the endocardium, 
with a splitting-up of the basement substance. Some of the new cells 
continue to live, others degenerate. By the combination of such a cell 
growth and destruction the endocardium is in some places destroyed, in 
others changed into projecting vegetations (see Fig. 362). Fibrin is 
deposited on the roughened surfaces (Fig. 363 and 364). After a time 
the condition may be further complicated by shrinkage and the deposition 
of the salts of lime in the new tissue and in the endocardium (Fig. 365). 
All these changes may extend to the wall of the heart beneath the endo- 626 
THE CIRCULATORY SYSTEM 
cardium. As the result of the new formation of connective tissue the 
cusps of the valves may be shortened or grown together or adherent to 
the heart wall. The chordae tendineae may be shortened and the papillary 
muscle fibers shortened and distorted. 
The most important result of chronic endocarditis is its effect on 
the heart valves, producing insufficiency and stenosis (Fig. 366). The 
changes in the valves are followed by changes in the walls and cavities 
of the heart, and disturbances of the circulation throughout the body 
(page 630). 
4. Chronic Ulcerative Endocarditis.-Large ulcers or perforations of 
the valves may be formed in chronic endocarditis, upon which clots 
may form, so that in gross appearance a great similarity exists between 
this and malignant ulcerative endocarditis, particularly if the latter 
Fig. 366.-Stenosis of the Aortic Valves. 
In chronic endocarditis. 
has been engrafted upon an already chronically diseased endocardium. 
Microscopical and biological examinations must usually be resorted to 
in order to determine the exact significance of the lesion. 
5. Tuberculous Endocarditis may occur in connection with tubercu- 
lous pericarditis or general miliary tuberculosis. The tubercles may be 
small and single, or grouped in masses, and show the usual degenerative 
changes.1 
HEART BLOCK. 
The cardiac muscle beats independently of nerve control, as is shown 
by the rhythmic contractions of isolated strips of the muscle and by the 
beating of individual muscle fibers growing in plasma. The rate is influ- 
enced by impulses from the extrinsic nerves of the heart, stimulation of 
the vagi slowing, that of the sympathetic hastening the rate. The gen- 
1 See Moser, Boston City Hosp. Rep., 1900, 11th ser., p. 194; also Etienne, Arch, de m6d. exper., 
1898, x, 146. THE CIRCULATORY SYSTEM 
627 
eral control of the rate of cardiac contractions, however, lies in a small 
area of specialized muscle tissue surrounded by branches of the vagus 
and sympathetic nerves and containing a few ganglion cells. This area 
is known as the sinoauricular node (Fig. 367). It is situated beneath the 
epicardium in the groove between the right auricle and the superior vena 
cava. The muscle cells are smaller, the cross striations are less definite 
than in the heart muscle from other areas, and the cells contain more 
glycogen. Finally, a connection seems to exist between this node and 
another neuromuscular organ, known as the auriculoventricular conduct- 
ing system, which begins as a small clump of cells, Tawara's or the auric- 
uloventricular node, and continues as the bundle of His. These mor- 
phological elements lie beneath the endocardium in the lower part of 
the right auricle. The His bundle splits ultimately, as it ramifies down- 
Fig. 368.-Dissection of Heart. 
Showing A, sinoauricular node; and B, 
auriculoventricular node. 
Fig. 367.-Diagram of Heart. 
Showing conducting bundles in the 
wall of the ventricle. {Tawara.) 
ward, into two main branches, one going to the right ventricle, the other 
to the left. The cells resemble those of the sinoauricular node (Fig. 368). 
The normal impulse of contraction arising in the sinoauricular node 
spreads through the auricle, reaches the junctional tissue, and from 
there, through the two branches of the terminal arborizations, spreads 
to the papillary muscles and throughout the ventricle.1 
The condition known as heart block is found in hearts in which there 
is a dissociation between the action of the auricle and that of the ventricle 
induced by lesions which more or less completely sever the conduction 
system. Functional interference with this conduction system may be 
produced, also, by drugs, such as digitalis, and probably by tobacco; 
and partial heart block is not infrequently seen in various nervous and 
infectious diseases. A lesion often found is a syphilitic process, fre- 
quently of a gummatous nature, somewhere along the course of the con- 
1 For an admirable review of the excitatory and connecting muscular system of the heart and its 
relation to disease, see Josue, O., Lewis, T., and Mackenzie, J., XVIIth Internat. Cong. Med., 1913, 
Sect. Ill, part 1, p. 1. 628 
THE CIRCULATORY SYSTEM 
ducting bundle. Tumors, calcareous deposits, inflammatory infiltration, 
fibrosis, and hemorrhage into the nodal tissue, also, may produce partial 
or complete heart block. In a certain number of cases, no microscopic 
lesion has been demonstrated. In removing material from suspected 
heart-block patients, the heart should be opened as shown on page 1208, 
not by the usual method. 
Clinically, the disease is evidenced by great slowing in the ventricular 
rate. The auricle continues to beat at its ordinary speed, the ventricular 
contractions occur at every other, every third, or even every fourth 
auricular contraction. In some instances, however, the auricular speed 
is very high; contractions at the rate of 300 per minute have been ob- 
served, while the ventricular contractions were only 75, the so-called 1 to 
4 ratio. If block is complete the ventricular contractions bear no time 
relation to those of the auricle. 
The usual signs of heart block are slow irregular pulse, and dyspnea 
on exertion and weakness; when these are accompanied by attacks of 
syncope, epileptiform convulsions, and muscular twitchings, the condi- 
tion is known as Stokes-Adams disease.1 
HYPERTROPHY AND DILATATION OF THE HEART. 
We have seen in an earlier chapter that the circulation of the blood 
may be impaired by deficient cardiac power, such as may result from 
innutrition of the muscle from general causes, or from obstruction of the 
coronary arteries, from degenerative changes in the muscle, faulty 
innervation, the action of poisons, etc. 
But with unimpaired vigor of the heart muscle the circulation may 
be interfered with by many abnormal conditions. If the orifices of the 
heart are narrowed the blood is forced through them with difficulty; 
if the valves are defective the blood regurgitates. If there be obstruction 
in the vascular system the flow of blood is retarded. 
Under these and many other conditions an unusual amount of work 
is thrown upon the heart muscle, which may adapt itself to its unusual 
tasks by a hypertrophy which more or less fully compensates for the 
difficulties of the circulation.2 This is compensatory hypertrophy of the 
heart. The portion of the heart muscle especially involved in hyper- 
trophy is determined by the location of the obstruction to the circulation. 
The hypertrophy is usually associated with dilatation of one or more of 
the heart cavities. 
Hypertrophy may involve the walls of one or more or all the cavities 
1 For details of other cardiac arrhythmias and further information regarding heart block, see stand- 
ard textbooks on diseases of the heart, such as Mackenzie, J., Disease of the Heart, 3d ed., New York, 
1914; Neuhoff, S., Clinical Cardiology, New York, 1917; and Lewis, T., Mechanism of the Heart Beat, 
London, 1911; and Clinical Disorders of the Heart Beat, London, 1912. For a summary of the cause 
of the heart beat, see Howell, W. H., Harvey Lecture, Jour. Am. Med. Assn., 1906, xlvi, 1165, 1749. 
For detailed anatomy of the conducting system, see Tawara, S., Das Reizleitungssystem des Sauge- 
thierherzens, Jena, 1906. For methods of recording, see Wiggers, C. J., Modern Aspects of the Circu- 
lation in Health and Disease, Philadelphia, 1915. 
2 For a suggestive study of cardiac hypertrophy as an adaptive process, see Welch, Adaptation in 
Pathological Processes, Trans. Congr. of Am. Phys and Surg., 1897, iv, 284. 
For a comprehensive r6sum6 of the normal and pathological physiology of the heart and its mor- 
phological and functional lesions, see Heinz, Handbuch d. exp. Path, und Pharmakoi., Jena, 1905, Bd. i. THE CIRCULATORY SYSTEM 
629 
of the heart. While the wall of a ventricle is thickened, its cavity may 
retain its normal size-simple hypertrophy; or be dilated-excentric hyper- 
trophy; or be contracted-concentric hypertrophy. Simple hypertrophy is 
not common, but may occur in connection with the atrophied kidneys 
of chronic diffuse nephritis. 
Care should always be exercised in judging of cardiac hypertrophy, for 
a firmly contracted heart seems to have a small cavity and thick walls 
(Fig. 369). It should also be borne in mind that an increase in the 
amount of fat in and about the heart may make the organ appear larger, 
when there may be actually a considerable decrease in the amount of 
muscle tissue. The existence of such a condition as concentric hyper- 
Fig. 369.-Cross-sections of Heart Showing Hypertrophy. 
The heart at the left is normal. The heart at the right shows hypertrophy (concentric) with contrac- 
tion of the left ventricle. 
trophy is denied by some authors. Excentric hypertrophy is the most 
common form. The muscle tissue in hypertrophied hearts is firmer and 
denser than normal, and is apt to have a darker color. Fatty degenera- 
tion may, however, be associated with it, giving the walls a lighter appear- 
ance. It is probable that the increase of tissue in the hypertrophied 
heart wall is the result of increase in the size but not in the number of 
the muscle fibers. In extreme hypertrophy, there is, also, in some 
instances a moderate increase in the intermuscular connective tissue. 
Hypertrophy of both ventricles increases both the length and breadth 
of the heart. Hypertrophy of the left ventricle (alone) increases its 
length. The apex is then lower and farther to the left than usual. 630 
THE CIRCULATORY SYSTEM 
Hypertrophy of the right ventricle (alone) increases the breadth of the 
heart toward the right side; but sometimes the right edge of the heart 
retains its normal situation and the apex is displaced to the left. With 
large hypertrophy of both ventricles, the base of the heart may sink, so 
that its long axis approaches a horizontal direction. 
Hypertrophied hearts may weigh from forty to fifty ounces, or even 
more. 
Hypertrophy of the heart may depend upon a variety of conditions 
which increase its work; of these, chronic arteriosclerotic changes in the 
kidneys are the most frequent. 
LESIONS OF THE HEART VALVES IN RELATION TO HYPERTROPHY AND 
DILATATION. 
As the result of acute infective processes in the endocardium the heart 
valves may undergo numerous changes. These are most frequent in 
connection with acute articular rheumatism, various forms of sep- 
ticemia, typhoid fever, scarlatina, gonorrhea, etc. We have already 
seen in detail the alterations induced in infections of the endocardium. 
As the result of these and other processes the heart valves suffer ulcera- 
tion, thrombosis, adhesions, distortions; the chordae tendineae may be 
shortened or the papillary muscles deformed; while the orifices may be 
less exactly controlled than normally as the result of myocardial lesions. 
Thus it frequently occurs that the orifices of the heart are too narrow 
or the valves close imperfectly, or both conditions are present together. 
The narrowing of the orifices is called stenosis; the failure of the valves 
to close properly is called insufficiency. 
AORTIC INSUFFICIENCY AND STENOSIS. 
In insufficiency of the aortic valves the blood which has been sent 
forward into the aorta by the contraction of the left ventricle in part 
returns to the ventricle in the following diastole through the incompletely 
closed aortic orifice. This, unless the ventricle wall adapts itself to the 
changed conditions, may lead to an interference with the entrance of 
blood from the left auricle and so to pulmonary congestion. Under these 
conditions, then, of aortic insufficiency more work is thrown upon the 
muscle of the left ventricle, which may undergo compensatory hyper- 
trophy. With this there is usually associated a dilatation of the ventricle 
cavity on account of the larger amount of blood which it is forced to 
accommodate. 
Syphilis is a frequent inciting agent in this valvular lesion, especially 
in young men. The disease may show itself within a year or two after 
infection, and anginal symptoms are frequent, being due, in many in- 
stances, to an aortitis. Dilatation of the aorta is an additional factor 
and is present in many syphilitics without any vascular or cardiac symp- 
toms. In old persons, the lesion is more frequently due to a non-specific 
arteriosclerotic retraction of the valves. THE CIRCULATORY SYSTEM 
631 
In stenosis of the aortic valves there is obstruction to the passage of the 
blood into the aorta, and the muscle of the left ventricle is forced to do 
so much extra work that the wall of the ventricle becomes hypertrophied. 
This hypertrophy may be followed by dilatation of the ventricle through 
a subsequent weakening of the wall. 
MITRAL INSUFFICIENCY AND STENOSIS. 
In mitral insufficiency a part of the blood during systole of the left 
ventricle is forced back into the auricle. As the result of this the auricle 
is forced to do more work; its wall undergoes more or less hypertrophy 
and dilatation. Under these conditions the blood cannot properly flow 
from the pulmonary veins, which become congested. This in turn brings 
more work upon the right ventricle, which undergoes hypertrophy. But 
when the diastole of the left ventricle occurs, blood flows into it from 
the auricle and the pulmonary system under increased pressure, while 
it is forced to do more work in systole to compensate for the backward 
current through the faulty mitral valve. Thus the wall of the left 
ventricle becomes hypertrophied and at the same time becomes dilated 
from the increased amount of blood which it is forced to accommodate. 
In mitral stenosis the flow of blood from the left auricle into the left 
ventricle is obstructed so that more work must be done by the muscle of 
the wall of the auricle. This undergoes a certain amount of hypertrophy 
and also of dilatation on account of the increased pressure in the pul- 
monary veins. For the pulmonary vessels become overfilled owing to 
the resistance which the blood encounters in the obstructed mitral 
orifice. The heightened pressure of the pulmonary vessels is felt in the 
right ventricle, which must do more work, and undergoes hypertrophy. 
As to the left ventricle, the wall may remain unaffected in uncom- 
plicated mitral stenosis or may suffer degenerative changes or atro- 
phy if the right heart fails to compensate properly for the obstructive 
lesion. 
INSUFFICIENCY AND STENOSIS IN THE RIGHT HEART. 
We need not trace these lesions of the right side of the heart in detail, 
for the changes are quite similar in principle to those which we have just 
considered. But they are by no means as frequent or as pronounced, 
nor is the compensatory mechanism as perfect as in the left heart. 
Lesions of the valves of the right heart are less frequent than those of the 
left. Tricuspid lesions infrequently develop in adult life. Lesions of the 
pulmonary valves developing in the adult are rare. During fetal life, 
however, lesions of both of these valves are not infrequent. Congenital 
heart lesions, such as stenosis of the pulmonary artery, may lead to hyper- 
trophy of the right ventricle. 
While we have thus briefly touched upon some of the more common 
and obvious of the conditions associated with the lesions of one or the 
other of the heart valves, there are many intricacies and variations for 632 
THE CIRCULATORY SYSTEM 
the details of which we must refer to special works on the subject.1 
But we should remember that there are frequent combinations of valvu- 
lar lesions on both sides of the heart. Thus simple mitral insufficiency 
is common, while uncomplicated mitral stenosis or aortic insufficiency 
or stenosis is less frequent than are combinations of insufficiency with 
stenosis in either the mitral or aortic valves. 
SUMMARY OF CONDITIONS LEADING TO HYPERTROPHY OF THE 
VENTRICLES. 
Hypertrophy of the Right Ventricle. 
This occurs especially under conditions which lead to increased 
resistance to the flow of blood in the pulmonary vessels, for exam- 
ple, in interstitial pneumonia, pulmonary tuberculosis, emphysema 
with chronic bronchitis and pleuritis, rarely with sclerosis of the pul- 
monary artery or incompetence or stenosis of the pulmonary or tricuspid 
valves. But lesions of the mitral valve or lesions of the wall of the left 
ventricle interfering with the pulmonary circulation may indirectly lead 
to hypertrophy of the right ventricle. 
Hypertrophy of the Left Ventricle. 
Aside from the valvular lesions already considered, hypertrophy of 
the left ventricle may arise from stenosis or aneurysm of the aorta, from 
an increased resistance of the flow of blood through the peripheral arteries 
as in various forms of obliterating endarteritis or arteriosclerosis, and 
from certain forms of diffuse nephritis.2 
Arteries whose walls are stiffened from new-formed tissue or from 
degeneration or calcareous infiltration, or whose lumina are obstructed 
through obliterating endarteritis, do not so readily dilate as those in nor- 
mal condition, nor do they promptly and readily recover when the heart 
pressure is reduced in diastole. Thus it is that, since the elasticity of 
the arteries is an important factor in the maintenance of the circulation, 
more work in the conditions above indicated is thrown upon the heart, 
which may lead to its hypertrophy. 
The relationship of arteriosclerosis to hypertrophy of the heart is most 
complex and the results of recorded observations are conflicting. One 
of the chief reasons for this uncertainty is doubtless the crude method 
of determination of both the degree and seat of the hypertrophy and the 
character and grade of the arterial lesion. The common method of 
determining hypertrophy of the heart by simple inspection or by measure- 
ment of the thickness of the heart wall is essentially faulty because no 
account is taken of the degree of contraction of the muscle wall of the 
heart which makes the greatest difference in its thickness. Only by the 
1 See Krehl, Clinical Pathology, English trans, by Hewlett, 2d ed., Philadelphia, 1907; Stadler, 
Ergebn. d. Med. u. Kinderheilk., 1910, v, 1; Mackenzie, J., Diseases of the Heart, 3d ed., New York, 
1914; and Norris, G. W., Studies in Cardiac Pathology, Philadelphia, 1911 (beautiful photographs of 
various heart lesions). 
2 For an experimental study of hypertrophy of the left ventricle with diminished kidney substance 
see Passler and HetneAe,Verhandl. d. deutsch. path. Gesellsch, 1905, ix, 99. THE CIRCULATORY SYSTEM 
633 
method of W. Muller, in which, after the removal of the fat about the 
heart, the muscle wall of each cavity is separated and weighed and the 
weight of each part compared with the weight of the whole heart, and 
its proportional weight to that of the whole body, or by some similar 
method, can exact data be obtained.1 
Furthermore, the full significance of arteriosclerosis can be deter- 
mined only by the more exact methods suggested by Thoma.2 
The arterial lesions which appear to be of most significance in relation 
to hypertrophy of the heart are those of the upper aorta and those of 
the splanchnic system.3 To what extent the association of kidney lesions 
and hypertrophy of the heart are dependent upon arterial lesions can be 
determined only by the accumulation of data by the more exact methods 
above indicated. 
Hypertrophy of Both Ventricles from General Conditions. 
Hypertrophy of the heart may accompany any condition which 
leads to a prolonged increase in the rapidity of its contractions. It 
may accompany exophthalmic goiter. It may be associated with severe 
or persistent muscular exertion, or excesses in beer-drinking or other 
indulgences. It may be associated with chronic pericarditis with 
adhesions. With the hypertrophy arising under these general conditions 
there may be also varying degrees of dilatation.4 
The Limitations of Compensatory Hypertrophy. 
While the hypertrophy of the heart may for a longer or shorter time 
measurably compensate for the various disturbances of the circulation 
which have been considered, it is by no means always a perfect or 
permanent adaptive measure. 
Excessive functional demands upon the heart, interstitial myocar- 
ditis, which may have preceded the hypertrophy or followed it, degener- 
ation of the muscle, dilatation of the cavities, obliterating inflammation 
and degeneration of the coronary arteries, singly or in various combina- 
tions, may in hypertrophied as in other hearts lead to irreparable damage 
to the organ. 
DILATATION OF THE HEART. 
In certain valvular lesions of the heart, as stated above (page 630), 
there occurs a dilatation of the heart cavities associated with hyper- 
trophy of the muscle. This provides for the larger amount of blood which 
the cavities are obliged to receive and propel, and is thus compensatory 
and conservative. This is called active dilatation. On the other hand 
1 See Muller, Die Massenverhaltnisse des menschl. Herzens, 1883; also summary by Hasenjeld, 
Deutsch'. Arch. f. klin. Med., 1897, lix, 205; and Hirsch, Deutsch. Arch. f. klin. Med., 1900, Ixviii, 55 
and 321. 
2 Thoma, Virchows Arch., 1886, civ, 209, and following volumes. 
3 See Hasenfeld, Deutsch. Arch. f. klin. Med., 1897, lix, 205. 
4 Howard's table of 105 cases of cardiac hypertrophy shows its association with arteriosclerosis in 
59 per cent.; with nephritis in 13.4 per cent.; with valvular lesion in 12.4 per cent. Johns Hopkins 
Hospital Rep., 1894, iii, 265. For possible errors in such statistics see p. 632. 634 
THE CIRCULATORY SYSTEM 
there may be no increase of muscle tissue, but a thinning of the walls 
proportionate to the dilatation of the cavity-passive dilatation. 
Either one or all of the heart cavities may be dilated, the auricles 
most frequently; next the right ventricle; least often the left ventricle. 
Active dilatation has been already considered with hypertrophy. 
Passive dilatation may be associated with: 
1. Changes in the valves. Mitral or aortic stenosis or insufficiency 
may lead to dilatation of the auricles and right ventricle. Pulmonary 
stenosis or insufficiency may lead to dilatation of the right auricle and 
right ventricle. Aortic insufficiency, with or without stenosis or mitral 
insufficiency, may lead to dilatation of the left ventricle. Dilatations 
under these conditions are often succeeded and compensated for by 
hypertrophy of the heart walls. 
2. Changes in the muscle tissue of the heart walls. Serous infiltra- 
tion from pericarditis, myocarditis, fatty degeneration and infiltration, 
atrophy of the muscle fibers, may all lead to dilatation. 
3. A heart which is already hypertrophied may, as we have seen, from 
degeneration of the muscle, become dilated. 
4. Acute exudative inflammation of the lungs and acute pleuritic 
exudations by rendering a large number of vessels suddenly imperme- 
able to the blood current, may produce sudden stasis in the pulmonary 
artery and dilatation of the right heart. 
5. There are curious and often serious cases of acute and chronic 
dilatation of the ventricles for which no mechanical explanation is 
found. 
TUMORS.1 
One of the most common among the rare primary growths of the 
heart is the myxoma.2 There is considerable doubt, however, regarding 
the true nature of this lesion,3 for while it is regarded by some as a true 
neoplasm,4 others describe it as an organized thrombus or inflammatory 
proliferation, and still others5 refer it to congenital syphilis and describe 
it as a myxogumma. 
Other benign growths of the heart or its valves6 are fibroma, lipoma,7 
hemangioma,7a and cavernous angioma.8 Many of the so-called tumors 
of the valves, however, are to be viewed with suspicion:9 some are un- 
doubtedly examples of LambUs excrescences10-non-vascular papillary 
1 For a r6sum6 of cardiac tumors in man, see Hagedorn, Centralbl. f. Path., 1908, xix, 825 (bibl.); 
in animals, see Magnusson, Ztschr. f. Krebsforsch., 1915, xv, 212. For a discussion of the clinical 
aspect, see Meroz, Internal. Clin., 1917, iv, 231; Napp, Ztschr. f. Krebsforsch., 1905, iii, 282; Link, 
Ztschrift. f. klin. Med., 1909, Ixvii, 272 (bibl.). 
2Brenner, Frankfurt. Ztschr. f. Path., 1908, i, 492 (bibl.); Louria, Proc. New York Path. Soc., 1917, 
xvii, 85. 
3 See Thorel, Lubarsch-Ostertag, Ergebn, d. allg. Path., 1907, xi2, 442; ibid., 1903, ix1, 901 (bibl.); 
and Wegelin, Frankfurt. Ztschr. f. Path., 1912, ix, 97. 
4 Hanser, Frankfurt. Ztschr. f. Path., 1911-12, ix, 362 (bibl.); Ribbert, ibid., 1910, iv, 30 (bibl.). 
6 Warthin, Jour. Infec. Dis., 1916, xix, 138. 
6 See Hagedorn, Centralbl. f. allg. Path., 1908, xix, 825 (bibl.). 
7 Brewis, Lancet, 1905, ii, 829. 
For bibliography see Timme, Cleveland Med. Jour., 1915, xiv, 453. 
8 Manifold, Lancet, 1915, ii, 1027; Schuster, Virchows Arch., 1914, ccxv, 335 (bibl.). 
9 Wegelin, Frankfurt. Ztschr. f. Path., 1912, ix, 97; Thorel, Lubarsch-Ostertag Ergebn. d. allg. Path., 
1907, xi2, 442. 
10 Koechlin, Frankfurt. Ztschr. f. Path., 1908, ii, 295 (bibl.). THE CIRCULATORY SYSTEM 
635 
projections of hyaline material interspersed with connective tissue and 
degenerated elastic fibers, and covered with endothelium. 
A few cases of sarcoma have been recorded, most of them spindle- 
cell,1 though giant-2 and round-cell3 growths have been described. 
For rhabdomyoma of the heart see pages 421 and 1114. 
Metastatic tumors, both sarcoma and carcinoma, are about as rare 
as primary neoplasms. 
PARASITES. 
Echinococcus sometimes occurs in the heart wall and may perforate 
into the cavities. Cysticercus cellulosae has been observed. 
The Blood-Vessels. 
HYPOPLASIA, ATROPHY, AND HYPERTROPHY. 
Hypoplasia.-The aorta and larger vessels are sometimes dispro- 
portionately small as a congenital condition-hypoplasia-in which 
the heart may also share.4 This condition may be associated with 
status lymphaticus (page 500), and may accompany chlorosis. 
Atrophy of the blood-vessels may involve the entire trunk or some of 
its elements. It may occur as a part of general malnutrition of the body, 
or in connection with atrophy of particular organs, or as an accompani- 
ment of various diseases of the vessels themselves. 
Hypertrophy, which is especially seen in the arteries, may occur in the 
establishment of a collateral circulation upon the closure of arterial 
trunks; or it may occur as the result of increased blood pressure, as in 
some forms of hypertrophy of the heart, or from overwork. While all 
the coats of the vessel may be involved in hypertrophy the media is apt 
to be especially affected. This is seen in chronic diffuse nephritis. The 
hypertrophied media is liable to degeneration and weakening leading 
to arteriosclerosis (page 644). 
The Arteries. 
The arteries are predisposed to rupture by fatty degeneration, in 
arteriosclerosis with atheroma, and in various forms of acute inflamma- 
tion.5 Stenosis of the aorta may be followed by rupture between the 
occlusion and the heart. The rupture may be complete or a dissecting 
aneurysm may form (page 651). Rupture of the aorta may lead to sud- 
den death (Fig. 370). There may be partial or complete rupture of an 
artery from contusions, wrenchings, falls, etc. The injury to an artery 
RUPTURE AND WOUNDS. 
1 Sternberg, Verhandl. d. deutsch. path. Gesellsch., 1910, xiv, 356. 
2 Fraenkel, Munchen, med. Wchnschr., 1901, xlviii, 648. 
3 Binder, Frankfurt. Ztschr. f. Path., 1914, xv, 194 (bibl.); Drysdale, Tr. Path. Soc., London, 1903, 
liv, 311. 
4 For a study of hypoplasia of the arterial system, see von Rito6k, S., Ztschr. f. klin. Med., 1907, 
Ixi, 32. 
5 For a study of perforations of aorta in pyemia, see Witte, J., Zieglers Beitr., 1905, xxxvii, 151. 636 
THE CIRCULATORY SYSTEM 
from a penetrating wound may be fatal if the vessel is large. The wound 
of a small artery may close or a false aneurysm may develop at its seat. 
In the healing of a wounded artery the vessel retracts and contracts, 
and a thrombus is formed within it. The contraction alone may be 
sufficient to close the vessel; its coats thicken, and the inner surfaces 
finally are fused together; or the blood coagulates and forms a thrombus 
in the vessel near the wound. This thrombus later becomes organized 
and the vessel is converted into a fibrous cord. 
Pio. 370.-Transverse Rupture of the Aorta. (Traumatic.) 
DEGENERATION. 
Fatty Degeneration.-This may occur in the walls of otherwise unal- 
tered vessels, or in those which have undergone a variety of inflamma- 
tory or degenerative changes. It may occur either in the intima or 
media, or both, and may be so extensive as to form a very prominent THE CIRCULATORY SYSTEM 
637 
gross lesion, or so little developed as to require the microscope for its 
recognition. When it is marked, especially if in the intima of large ves- 
sels, smaller and larger spots or stripes or patches may be seen, of a 
yellowish white color, usually sharply circumscribed, and sometimes 
smooth, sometimes roughened on the surface. It is most apt to occur in 
the aorta, but may be found in any of the vessels. In moderate degrees 
of the lesion we find on section that the cells of the intima contain fat 
droplets in greater or less number. Many of these fat droplets are double 
refracting, which shows that they are cholesterin esters and not true fat. 
When further advanced, not only are the cells crowded with fat droplets, 
but the intercellular tissue also may be more or less densely infiltrated 
with them. Sometimes the infiltration is so dense that the tissue breaks 
down, and there may be an erosion of the surface, forming a so-called 
fatty ulcer. When the media is involved the muscle cells contain fat 
droplets. Fatty degeneration may lead to the formation of aneurysm 
or to rupture of the vessels. 
Amyloid degeneration, which may affect all the coats of the arteries, 
but especially the intima and media, has already been described in gen- 
eral (page 57). It will be further considered under the lesions of the 
organs in which it most commonly occurs. 
Hyaline degeneration may cause thickening of the intima of the blood- 
vessels by its conversion into or infiltration with a homogeneous matter 
somewhat similar to amyloid (page 57); or it may involve the entire 
wall of smaller vessels, converting them into irregular lumpy cords. 
The lumen of vessels thus changed may be obliterated or occluded by 
thrombi. 
Calcification usually occurs in vessels otherwise diseased, and may 
involve either the intima or media. It consists in the deposition of salts 
of lime either in the cells or intercellular substance. The lime may be 
in the form of larger or smaller granules or in dense translucent plates. 
INFLAMMATION. 
Acute Arteritis.-Acute inflammation of the walls of the arteries is, in 
the majority of cases, the result of injury, or of an inflammation in the 
vicinity of the vessels, or of the lodgment within them of some foreign 
body of an irritating or infectious nature. The inflammatory process 
may be largely confined to the inner coat of the vessels-endarteritis; or 
it may commence in the outer coats-periarteritis; or it may involve the 
entire wall. 
The blood-vessels in the outer coats may be congested, the tissue 
edematous and infiltrated with pus cells and the entire wall may become 
necrotic. The intima, if this layer be involved, loses its natural gloss, 
looks dull yellowish, and is swollen, and may then ulcerate. Under 
these conditions thrombi usually form, and in these may occur the various 
changes which have been already described (page 31). But the process 
may originate in an infective thrombus or embolus, most commonly asso- 
ciated with Streptococcus or Staphylococcus pyogenes-thromboarteritis 
-embolic arteritis. 638 
THE CIRCULATORY SYSTEM 
In cerebrospinal meningitis, whether this be incited by the meningo- 
coccus, streptococcus, pneumococcus, or tubercle bacillus, there may be 
an acute endarteritis characterized by the accumulation of leucocytes 
and polyhedral cells beneath the endothelium, often raising this layer 
from the underlying tissue (Fig. 136 and 137, page 255). This lesion may 
occur with or without the involvement of the outer layers of the vessel.1 
Rupture of the artery with more or less extensive hemorrhage may 
follow acute suppurative and necrotic inflammation of these vessels. 
Late stage with canalization of the organized thrombus. 
Fig. 371.-Thromboangiitis Obliterans. 
Thus false aneurysms (page 651) may be formed. Or true aneurysms 
may be developed at the weakened point. In healing, fibrous tissue may 
form, leading to various phases of arteriosclerosis. Finally, as the result 
of organization of thrombi (page 34), which may be present, new tissue 
may form within the lumen of the involved vessel-thromboarteritis 
proliferans. 
A special form of acute or subacute arteritis is seen almost exclusively 
1 For a study of this lesion of the subendothelial layers of the arteries in tuberculosis, see Hektoen, L., 
Jour. Exper. Med., 1896, i, 112; in cerebrospinal meningitis, see Flexner, S., ibid., 1907, ix, 142; in 
typhoid fever, see Thayer, W. S., Bull. Johns Hopkins Hosp., 1904, xv, 323. For a study of arterial 
lesions and infectious disease, see Frothingham, C., Arch. Int. Med., 1911, viii, 153. THE CIRCULATORY SYSTEM 
639 
in Polish, Galician, and Russian Hebrews, affecting the lower extremities.1 
This thromboangiitis obliterans, as it has been termed, begins as an acute 
inflammatory process with the formation of red thrombi, most frequently 
in the arteries, but occasionally in the veins. In some of the thrombi, 
purulent foci may develop, suggesting that the disease is of a microbial 
nature. In the later stages, the thrombi become organized, and in the 
new connective tissue giant cells may occur about the areas of necrosis. 
In the last stages, all vestiges of the acute process disappear and the 
thrombi become converted into vascularized connective tissue (Fig. 371). 
The wandering cells disappear from the media, adventitia, and perivas- 
cular connective tissue; and an obliterated, canalized, and adherent ves- 
sel is left as the final product. Most of the process is confined within 
the elastic lamina, though this may be very much broken up and frag- 
mented, and an acute inflammatory infiltrate may collect in the mus- 
cularis and adventitia. The elastic tissue is, however, less affected than 
in the ordinary obliterating endarteritis. 
The nerves of the affected extremities show considerable connective 
tissue proliferation about the bundles, thickening of the perineurium, 
and occasionally atrophy of the fibers when the lesion is extensive. 
While the arteries are most frequently attacked, the deep veins are in- 
volved in about 40 per cent., and the superficial veins of the upper and 
lower extremities in about 20 per cent, of the cases. The venous throm- 
bosis is in some instances recurrent, involving the different groups of 
vessels and simulating thrombophlebitis migrans. 
Clinically, thromboangiitis obliterans is accompanied by intermittent 
limping,2 pains in the muscles, with or without vasomotor symptoms, and, 
ultimately, gangrene. Glycosuria is occasionally present, or the sugar 
tolerance is very much reduced. While the Wassermann reaction is not 
infrequently positive in these cases, there is no evidence that the lesion 
is syphilitic in origin. Some observers have thought that the excessive 
use of tobacco might have a relationship to the disease, but there is no 
definite proof of this. 
Arteriosclerosis (Chronic Arteritis).-Since the publication of the 
studies of Gull and Sutton3 on arteriocapiliary fibrosis, attention has been 
every year more and more directed to chronic pathological changes in 
the arteries as of great frequency and importance. These changes 
are productive and degenerative in character and have an important 
bearing upon the circulation and upon the integrity of the vessel walls. 
They are in part primary, in part secondary, and may involve single 
vessels or vascular territories or may affect the entire vascular system. 
The lesions differ somewhat in the small and large vessels. In very 
small arteries there is a more or less general though not uniform thicken- 
ing of the intima (Fig. 372 and 373). This is due in part to a prolifer- 
1 Buerger, L., Am. Jour. Med. Sc., 1908, cxxxvi, 567; 1917, cliv, 319; Surg., Gynec., and Obst., 
1914, xix, 582; and Erb, Munchen, med. Wchnschr., 1910, Ivii, 1105, 1181, 2450. 
2 This syndrome may be due to a chronic arteriosclerotic disease of the vessels, as well as to thrombo- 
angiitis obliterans. For a full discussion of intermittent limping, see Cassirer, R., Levandowsky, 
Handb. d. Neurologie, Berlin, 1914, v, 291 (bibl.).. 
3 Gull and Sutton, Arteriocapiliary Fibrosis, Med.-Chir. Tr., London, 1872, Iv 273; Brit. Med. 
Jour., 1872, i, 256. 640 
THE CIRCULATORY SYSTEM 
ation of the endothelium, in part to increase in the connective tissue of the 
intermediary layer. In this way a considerable amount of moderately 
cellular fibrous tissue (Fig. 374) may form within the membrana elastica, 
and the lumen may be largely or wholly obliterated-obliterating endarter- 
itis. The middle coat as well as the inner may be thickened (Fig. 375). 
Fig. 372.-Chronic Arteritis- 
Arteriosclerosis-Obliterating En- 
darteritis. 
Fig. 373.-Chronic Arteritis-Arterio- 
sclerosis-Obliterating Endarteritis. 
Showing a thickening of the intima in 
a small artery of the brain. 
The new-formed tissue is most abundant at 
one side of the vessel, where the external coats 
are pouched. There is degeneration of the 
new-formed tissue. 
In larger arteries the new tissue may form beneath the endothelium 
diffusely or in circumscribed masses, or may encircle the vessel. The 
endothelium over the involved areas may remain intact or it may pro- 
liferate or become fatty or necrotic. The new-formed fibrous tissue of 
the intima, which may contain also new elastic fibers,1 is usually dense, 
having few cells, and is prone to undergo 
fatty degeneration, to become necrotic, 
and to disintegrate, and thus larger and 
smaller cavities, filled with disintegrated 
tissue, fat, lipoids, and cholesterin crys- 
tals, may develop in the new-formed 
tissue (Fig. 373 and 376). These are 
called atheromatous cysts.2 They may 
extend toward the lumen of the vessels, 
into which they may open, giving rise to emboli and forming rough-edged 
ulcers, often with undermined edges. Upon these thrombi may form. 
In the new-formed tissue of the intima, as well as in the necrotic foci 
and in the detritus of the cysts, calcification may occur. 
Fatty degeneration, atrophy, and calcification may occur in the mus- 
cularis and adventitia of the involved vessels. There may be degener- 
ation, fragmentation, and atrophy of the elastic laminae. A frequent 
Fig. 374.-Connective Tissue Formed in 
the Intima in Arteriosclerosis. 
1 See Jores, L., Zieglers Beitr., 1898, xxiv, 458 (bibl.). 
2 The word atheroma is sometimes applied to the whole process of arteriosclerosis, designating it as 
atherosclerosis, but it would be well to limit it to the degenerative phases which result in softening of 
the tissues. THE CIRCULATORY SYSTEM 
641 
form of sclerosis in the vessels of the lower extremities is that in which the 
main process is calcification of the media.1 The recognition of this type 
of arteriosclerosis has become more frequent with the general use of the 
Fig. 375.-Obliterating Endarteritis. 
Complete occlusion of the lumen followed by gangrene of the toe. There is also fibrous thickening of 
the muscular coat. 
Fig. 376.-Chronic Arteritis-Arteriosclerosis-Cerebral Artery. 
Inner coat thickened; degeneration and softening (atheroma) of a part of the thickened area. 
x-ray, the calcified arteries absorbing nearly as much light as the bone 
and appearing as clear shadows. The lime salts are deposited in ring- 
1 Monckeberg, J. G., Virchows Arch., 1903, clxxi, 141; 1914, ccxvi, 408. 642 
THE CIRCULATORY SYSTEM 
like collections so that the opened artery somewhat resembles a miniature 
trachea. The nodules lie outside the internal elastic lamellae in the medial 
layers; they may undergo transformation into true bone. The lumen of 
the vessel is, as a rule, not greatly compromised except in the late stages. 
If the intima is diseased, it is difficult to distinguish the changes from 
those of an advanced stage of arteriosclerosis. The lesion is often coin- 
cident with diabetes, and is probably responsible for much of the gan- 
grene of the lower extremities which occurs in that disease, and also for 
some of the forms of gangrene seen in senility. 
Similar processes may occur in the aorta, the new tissue growth and 
the degeneration being less definitely limited to the inner layer of the wall. 
The elastic laminae may be degenerated, partially atrophied, fragmented, or 
Fig. 377.-Atrophy of Elastic Tissue in Wall of the Aorta in Atheroma. 
The elastic tissue is replaced by dense fibrous tissue. 
absent, in patches in the wall of the vessel (Fig. 377). The aorta may 
thus be beset with larger and smaller, irregular, white, hard, elevated 
thickenings (Fig. 378), often yellowish from fatty degeneration. Beneath 
these there may be atheromatous softening, or these sclerotic areas may 
be calcified and project as hard, often brownish plates with smooth or 
rough edges. True bone with marrow has occasionally been seen. The 
surface of the aorta may be rough from erosion over the degenerated 
areas, and upon these or elsewhere parietal thrombi may form (Fig. 379). 
Such sclerotic areas are often well marked at the junction of smaller 
vessels with the aorta. 
We have seen that in the smaller vessels arteriosclerosis may lead to 
extreme narrowing or occlusion of the lumen. When this does not occur, 
and especially in the medium-sized arteries, since the new tissue is less 
elastic than normal and liable to yield to the pressure of the blood, the 
lumen may in places be dilated (Fig. 380) or the wall may rupture. In 
this way aneurysms may form. This is especially apt to occur when 
atheromatous degeneration has taken place and the muscularis is either 
atrophied or degenerated. In the aorta also dilatation and rupture may 
occur. THE CIRCULATORY SYSTEM 
643 
Arteriosclerosis may be largely limited to the aorta or to other single 
vessels, or it may occur in special vascular tracts, such as those of the 
brain or heart. 
There are fatty degeneration, thickening of the intima, calcification, and erosion. Thrombi have 
formed over the roughened surface of the erosions. 
Fig. 378.-Atheroma of the Aorta. 
As the result of arteriosclerosis a great variety of circulatory dis- 
turbances may arise, both local and general. The effect upon the heart 
Section showing involvement of all the layers. The thickening of the intima is irregular, and 
areas of degeneration are seen in its deeper portion. Patches of fibrous tissue are present in the muscu- 
laris. A small thrombus has formed upon the surface. 
Fig. 379.-Chronic Inflammation of the Aorta-Atheroma of the Aorta. 
of the narrowing of the lumen of the arteries, as well as the loss of their 
elasticity, has been discussed above (page 632).1 • 
1 For a comprehensive resum6 of the normal and pathological physiology of the blood-vessels, see 
Heinz, Handbuch d. exp. Path, und Pharmakoi, Jena, 1905, Bd. ii. 644 
THE CIRCULATORY SYSTEM 
The Conditions Leading to Arteriosclerosis.-The lesions of 
arteriosclerosis often occur with gout, syphilis, diabetes, chronic lead and 
alcohol poisoning, overwork, and overfeeding. They are usual in senil- 
ity,1 and predisposition to them may be inherited. They may be asso- 
ciated with cardiac hypertrophy from valvular lesions or with chronic 
diffuse nephritis or other conditions involving increased arterial tension. 
They may occur locally in connection with tumors, especially in the 
uterine fibromyomata. In various acute infections-diphtheria, scarla- 
tina, typhoid fever, influenza, pneumonia, and pyemia-localized lesions 
of the medium-sized arteries may occur, leading to sclerosis. There is 
degeneration of the smooth muscle cells and the elastic tissue of the media, 
occurring in patches and followed by necrosis. These local lesions may 
heal by connective-tissue formation, or they may involve the intima, 
leading to sclerosis and more or less obstruction of the lumen. The 
aorta, the arteries of the brain, and the coronaries are frequently involved.2 
Showing pouching of the wall of the artery at the side on which is the largest formation of new fibrous 
tissue. 
Tig. 380.-Chronic Arteritis-Arteriosclerosis. 
While the mechanical conditions under which arteriosclerosis devel- 
ops are not very fully understood, the primary lesions have been con- 
sidered by Thoma as a compensatory hyperplasia of the intima. If for 
any reason-congenital defects, for example-the wall of the artery in a 
given region, as is the case in the circumscribed or nodular forms of 
arteriosclerosis, be weakened and yield to the blood pressure, it is at this 
point that the new tissue forms in the intima and restores the lumen to 
its natural caliber (see Fig. 373 and 380) with restitution of the rate of 
blood flow. That this compensation is often incomplete or temporary, 
or that it brings with it other and often serious complications, does not 
militate against this view of the significance of these blood-vessel lesions, 
which are only one of many examples of imperfect adaptation in patho- 
logical processes.3 
1 For changes in elastic tissue in aorta in advancing age, see Foster, L. S., Jour. Med. Research, 1909, 
N.S. xv, 297. 
2 See Wiesel, Ztschr. f. Heilk., Abt. f. path. Anat., 1906, xxvii, 262. 
3 See Welch, Trans. Cong. Am. Phys, and Surg., 1897, iv, 284; and Faber, Die Arteriosklerose, Jena, 
1912 (bibl.). THE CIRCULATORY SYSTEM 
645 
Many conditions other than congenital defects in the vessel walls 
may result in arteriosclerosis. In fact, any long continued disturbance 
of the normal balance between the blood pressure and the resistance of 
the vessel wall apparently may lead in a variety of ways to arterial 
changes. Thus syphilitic inflammation of the arterial wall with necrosis 
may result in the formation of scar tissue, replacing the muscular and 
elastic supports of the walls by less resistant structures. The effects of 
alien substances or of natural substances in undue amount in the blood, 
which induce a continuing contraction of the muscularis of the arteries, 
or of overwork may lead through a primary hypertrophy followed by 
degeneration of the muscle cells to a general weakness of the walls with 
coincident general or local thickening of the intima. The aortic scleroses 
produced in rabbits by injections of adrenaline are probably of this class. 
Senile or other general degeneration of the media with widespread cal- 
careous deposits may determine sclerotic changes in the intima. In all 
these cases the intimal thickening is not, according to the widely enter- 
tained view, inflammatory, but has the nature of a replacement hyper- 
plasia in walls damaged and weakened in various ways. 
But this view, largely inspired by the work of Thoma,1 that the 
intimal lesions in arteriosclerosis are compensatory, has not found 
universal acceptance. Indeed there are many conditions under which 
it seems clear that the sclerotic lesions of the intima, while often asso- 
ciated with damaging or destructive changes in the other layers, especially 
the media, are not secondary to them but are due to common agents 
acting on both. Furthermore, there appear to be intimal inflammatory 
thickenings induced by infective or toxic agents acting primarily on the 
intima.3 
The primary fatty changes in the cement substance of the elastic 
lamina of the vessels have led a number of pathologists to the view that 
this alteration, with imbibition of plasma leading to further deposits of 
lipoid substances, may be of fundamental importance in explaining the 
non-inflammatory types of arteriosclerosis. The breaking-down of the 
lipoids sets free fatty acid which, by combining with calcium salts, leads 
to calcification of the tissue. The cholesterin also set free crystallizes 
and incites connective tissue reactions.3 
Finally, there may be lesions of the intima secondary to those of the 
media, without the former being in any sense compensatory. 
Classification of the Forms of Arteriosclerosis.-Various 
classifications of the lesions of arteriosclerosis have been made. These 
must all be considered somewhat arbitrary and superficial until our 
knowledge of the mechanics of the circulation and the evolution of the 
lesions are more clearly defined. Much of the uncertainty in the inter- 
1 See Thoma, R., Virchows Arch., 1883, xciii, 443; 1889, cxvi, 1; Arch. f. Entwickl. Meeh., 1901, 
xii, 352; and Textbook of General Pathology, Eng. trans., vol. i. 
2 For summaries of more recent conceptions of arteriosclerosis, see Adami, J. G., Am. Jour. Med. Sc., 
1909, cxxxviii, 485; Klotz, O., Jour. Exper. Med., 1910, xii, 707; and Frothingham, C., Bull. Johns Hop- 
kins Hosp., 1913, xxiv, 323. For production of arteriosclerosis by injection of diphtheria toxin, see 
Bailey, C. H., Jour. Exper. Med., 1917, xxv, 109; and Saltykow, Zieglers Beitr., 1908, xliii, 147. A 
general bibl. up to 1903 is given by Thorel, Lubarsch-Ostertag, Ergebn. d. allg. Pth., 1903, ix1, 559. 
3 See Aschoff, Arteriosklerose, Med. Klin., 1914, x., Beiheft.1 For experimental production of 
atheroma by feeding with cholesterol, see Bailey, C. H., Jour. Exper. Med., 1916, xxiii, 69. 646 
THE CIRCULATORY SYSTEM 
pretation of arterial lesions is due to the fact that observations in the past 
have been made largely on vessels in the contracted condition in which 
the cessation of blood pressure at death left them, so that the exact con- 
dition of the lumen during life in various sclerotic lesions is not really 
known. Thoma places in one class the primary and more limited nodular 
forms of fibrous-tissue growth, especially in the larger vessels, which he 
regards as compensatory in the way just indicated; in another the diffuse 
or secondary form, which is attributable to an increased resistance to the 
flow of blood in peripheral vessels, such as those of the kidney, a weak- 
ening of the muscularis through degeneration, the consequent dilata- 
tion, and then the compensating fibrous-tissue growth in the vessels 
at large. 
Other observers1 group the lesions into three forms: 1st, the nodular, 
corresponding with the primary form of Thoma; 2d, a senile form, in 
which there are often great distortion of the vessels, calcification, and 
frequent thinning of the walls; atrophic changes in the viscera are apt to 
be associated with this form of senile arteritis; 3d, a diffuse form of 
marked obliterating endarteritis with fibrous involvement of the muscu- 
lar layer. This is apt to be associated with hypertrophy and often with 
dilatation of the heart, as well as with chronic diffuse nephritis with 
atrophy. The arterial changes may be marked in the liver as well as in 
the kidneys. 
Periarteritis Nodosa. 
A few cases have been described of an acute febrile disease in which 
many of the small arteries in the muscles and in the viscera were beset 
with small white knobs projecting from the side or surrounding the ves- 
sels. These circumscribed thickenings of the vessel walls are apt to in- 
volve all the layers of the vessel, and may encroach upon the lumen. 
The thickened portions are infiltrated with leucocytes. Multiple aneu- 
rysms may develop at the seat of the local thickening.2 The course of 
the disease is rarely longer than three months, and it is usually fatal. It 
is supposed to be of an infectious nature, but this is as yet unproved. 
In some cases a Wassermann reaction has been obtained, but the Trepon- 
ema pallidum has not been demonstrated in the lesions. 
Tuberculous Arteritis.-Tuberculosis of the arteries is usually second- 
ary, the process extending to their walls from an already established 
focus (Fig. 381).3 Tubercle tissue with necrosis may involve the ex- 
ternal layers, while an obliterating inflammation often closes the lumen. 
Thus it is that in tuberculous cavities of the lungs large arterial trunks 
may be laid bare (see Plate XII) without a distribution of the bacilli 
through the body and without hemorrhage. Tuberculosis of the aorta is 
of occasional occurrence.4 
1 For a r6sum6 of views based upon Thoma's studies, see Councilman, W. T., Tr. Assn. Am. Phys., 
1891, vi, 79. For a general study of pathogenesis of arteriosclerosis, see Pic and Bonnamour, Jour, de 
phys. et de path. g6n., 1906, viii, 495 (bibl.). 
2 Consult v. Kahlden, C., Zieglers Beitr., 1894, xv, 581; Graf, E., ibid., 1896, xix, 181; Klotz, O., 
Jour Med. Research, 1917, N. S., xxxii, 1; Dickson, W. E. C., Jour. Path, and Bacteriol., 1907, xii, 31 
(bibl.); and Guldner, E., Virchows Arch., 1915, ccxix, 366 (bibl.). 
3 For a study of tuberculosis of arteries, see Geissler, Virchows Arch., 1906, clxxxvi, 135 (bibl.). 
4 Haythorn, S., Jour. Am. Med. Assn., 1913, lx, 1413; Woolley, Bull. Johns Hopkins Hosp., 1911, 
xxii, 82, and Blumer, G.. Am. Jour. Med. Sc., 1899, cxvii, 19 (bibl.). THE CIRCULATORY SYSTEM 
647 
Syphilitic Arteritis.-A characteristic form of arteritis is due to 
syphilis, the vessel most frequently affected being the aorta.1 The lesion 
in this viscus is confined, as a rule, to a definite portion, especially the 
ascending and transverse parts, with a fairly sharp line of demarcation 
between the diseased area and the remainder of the aorta, which may 
be fairly normal; indeed, the abdominal aorta is almost entirely immune. 
That portion of the vessel which is diseased is usually dilated and may 
show aneurysmal pouching. The smooth, glistening, pale yellow appear- 
ance of the intima disappears early in the disease and instead there are 
seen irregular white areas intermingled with dull yellowish patches of 
fatty degeneration. The mouths of the coronary and intercostal arteries 
Showing the encroachment of an area of tuberculous inflammation upon the wall of the artery, 
and the formation of a mass partly occluding the lumen of the vessel. This section shows how the 
generalization of the tuberculous inflammation through the body may occur by the sweeping away 
of the tubercle bacilli by the blood and the establishment of new foci in various parts of the body. 
Fig. 381.-Tuberculous Arteritis in the Lung. 
are frequently surrounded by a raised ring of new-formed tissue and the 
openings reduced to pinpoint size. 
Microscopically, the most constant feature of syphilitic aortitis is a 
round-cell infiltration of the outer coats of the vasa vasorum, the infil- 
trating cells being of the lymphocytic or plasma-cell type. Giant cells 
are, as a rule, very few but occasionally are abundant in small gummatous 
areas. They should be distinguished from the foreign body type often 
1 Chiari, Verhandl. d. deutsch. path. Gesellsch., 1904, vi, 137; Benda, ibid., 164; Marchand, ibid-» 
197; Gruber, Uber die Doehle-Heller'sche Aortitis (Aortitis luetica), Jena, 1914; Thorel, Lubarsch-Oster" 
tag, Ergebn. d. allg. Path., 1911, xiv2, 681; Larkin, J. H., and Levy, I. J., Jour. Exper. Med., 1916, 
xxiii, 1; Symmers, D., and Wallace, G. H., Jour. Am. Med. Assn., 1916, lxvi, 397; Moore, W. C., Am. 
Jour. Med. Sc., 1918, civ, 660. 648 
THE CIRCULATORY SYSTEM 
found inclosing elastic fibers or cholesterin crystals. In addition to the 
small-cell infiltration there is a fibrous thickening chiefly in the adventitia 
and only occasionally is there much degeneration in the media or intima. 
The elastic fibers are fragmented and granular and often much reduced 
in number. Ultimately the lumen of the smaller vessels is greatly re- 
duced or entirely obliterated by the new-formed tissue. In the late 
stages small areas of cellular fibrous tissue sometimes inclosing necrotic 
zones may be found in the media. About these areas there is often, in 
addition, a lymphocytic infiltration. 
While a positive Wassermann reaction is present in all but about 5 
per cent, of persons suffering from aortitis, the demonstration of the 
Treponema pallidum is rarely possible.1 
The aortic valves are involved in about half the cases. Cardiac 
hypertrophy is not often found in connection with syphilitic aortitis, 
even though regurgitation exists. The coexistence of aneurysm is not 
very frequent, certainly in not more than 30 per cent of the cases and 
in some series not more than 20 per cent. It is more frequent in males 
than in females. Some degree of aortitis is usually present in all un- 
treated syphilitic patients, even in children, and is occasionally seen also 
in tabetic and paretic persons.2 
In addition to the aorta, other vessels of the body may suffer syphilitic 
changes, which are especially noteworthy in the brain and spinal cord. 
The alterations in these regions may be very early, even congenital, and 
may precede the occurrence of symptoms, as shown by the characteristic 
changes in the spinal fluid, the presence of globulin, a high lymphocyte 
cell count, and changes in the colloidal relationships of the salts and 
proteins demonstrated by the colloidal gold test.3 
While, as has been stated, vascular disease is occasionally found in 
tabes and paresis, there may be very extensive cerebral vascular syphilis 
without degenerative changes. In other words, a certain number of 
cases of cerebral hemorrhage and softening are due to specific mesarterit is.4 
ANEURYSM. 
An aneurysm is a dilatation of an artery and may be either cylindrical, 
fusiform, or sacculated. Initially, when the protuberance is small, the 
walls consist of all coats; later, rupture of the elastic and other layers 
takes place; and the wall of an aneurysm of any considerable size is 
formed by connective tissue of a cicatricial type, probably originating 
in the adventitia and the structures immediately external to that coat. 
Often there is a thick laminated layer of fibrin lining the sac in addition 
1 For demonstration of Treponema pallidum in five cases of syphilitic aortitis, see Wright, J. H 
and Richardson, O., Boston Med. and Surg. Jour., 1909, clx, 539. 
2 For a clinical study of the disease, see Longcope, W. T., Arch. Int. Med., 1913, xi, 15, Schrumpf, 
P., Arch. f. Dermat. u. Syph., 1918-19, cxxvi, 793. 
3 See Black, Rosenberg, and McBride, Jour. Am. Med. Assn., 1917, Ixix, 1855. For a simple pro- 
cedure for the preparation of colloidal gold for diagnostic purposes, see Lee, O. I., Am. Jour. Med. Sc., 
1918, civ, 404. 
4 For discussion of some problems in the pathology of syphilis, see Fordyce, J. A., Am. Jour. Med. Sc., 
1915, cxlix, 781. THE CIRCULATORY SYSTEM 
649 
to the external so-called vascular callus1 composed of dense connective 
and new-formed elastic tissue. 
The aneurysmal sac is usually lined with endothelium; this is not the 
result of a mere stretching of the normal covering of the inner surface 
of the vessel, but is due to an ingrowth of cells from the borders of the 
rupture. Thus the older view, that the sac of an arterial aneurysm is 
solely the result of the dilatation of a vascular wall, must be abandoned. 
The conditions which commonly lead to aneurysms are arterio- 
sclerosis, either with or without associated degeneration; such local 
Fig. 382.'-Fusifobm Aneubysm of the Abch of the Aosta. 
weakening of the walls of the vessels, from various causes, as often leads 
to compensatory arteriosclerosis, but in which protective compensation 
does not take place; or the blocking of a vessel by embolus or trauma. 
Syphilis is probably the most important single factor, being demonstrable 
in 20 to 30 per cent, of the cases. Aneurysms may develop at the point 
of partial rupture of the walls of an artery. They may follow the local 
necrotic and ulcerative process in the walls of the vessels or on the heart 
valves incited by infectious agents, which as emboli or otherwise have 
reached these parts. Such mycotic aneurysms are frequently multiple.2 
1 Manz, Zieglers Beitr., 1898, xxiv, 531. 
2 For a study of mycotic aneurysms, with bibl., see McCrae, J., Jour. Path, and BacterioL, 1905, 
x, 373. 650 
THE CIRCULATORY SYSTEM 
In cylindrical or fusiform aneurysm there is apt to be at first a disten- 
tion of all the walls of the vessel; but this is often irregular, so that the 
sac may bulge more in one place than in another (Fig. 382). The walls 
may become thin or through new-formed tissue may become thickened; 
they may undergo degeneration or calcification. Such aneurysms are 
most frequent in the aorta, but may occur in other vessels. 
In the sacculated aneurysm there is either a dilatation of the entire 
circumference of an artery over a short portion of its length, or a dilatation 
of only a small portion of one side of the wall, so that the aneurysm looks 
like a swelling attached to one side of the artery. The aneurysm may 
commence as a dilatation of all the coats of the vessel; but the middle 
coat may soon atrophy, so that the wall is composed of the inner and 
outer coats; or the inner coat may be destroyed by endarteritis, so that 
Fig. 383.-Aneurism of the Popliteal Artery. 
Showing lamellated clot. 
the outer coat alone forms the wall of the aneurysm, all coats finally dis- 
appearing; or the dilatation may commence at the seat of rupture of one 
or more coats of the vessels. As the aneurysm increases in size it may 
press upon and lead to partial destruction of neighboring tissues and 
viscera, so that portions of these tissues and viscera may take the place 
of the wall of the aneurysm. The cavity of the aneurysm is filled with 
fluid or clotted blood, or with layers of fibrin (Fig. 383) which adhere 
closely to its wall. The communication between the aneurysm and the 
artery may be small or large. If arterial branches are given off from the 
aneurysm they may remain open or become plugged with fibrin; or their 
walls may be thickened and their cavities narrowed by endarteritis. THE CIRCULATORY SYSTEM 
651 
Death may occur from the pressure of the aneurysm and interference 
with the adjoining viscera or by rupture. 
Dissecting aneurysms are those in which, owing to a solution of con- 
tinuity of the inner layers of the artery, the blood gets between the media 
and adventitia, and forces its way for a greater or less distance between 
them, or separates the media into two layers.1 
Spurious or false aneurysms are most frequently connected with ves- 
sels of the extremities. When an artery is wounded the blood escapes 
into the surrounding soft parts, and a cavity is formed filled with blood 
and broken-down tissue. 
The wound in the artery may heal and the effused blood be absorbed; 
or it may become the seat of secondary inflammatory processes. 
Finally, a wall of fibrous tissue may be formed, while the wound of 
the artery remains open, so that there is an aneurysmal sac through 
which the blood is constantly pouring. This is called a false aneurysm. 
It does not, however, differ from a true aneurysm after the latter has 
reached a certain size. 
Aneurysmal Varix: Varicose Aneurysm.-If an artery be wounded, 
and at the same time the vein which accompanies it, we have as the result 
the conditions called aneurysmal varix and varicose aneurysm. In aneu- 
rysmal varix the artery and vein become adherent at the seat of injury, so 
that the arterial blood passes directly into the vein. There is a smooth, 
rounded opening between the two vessels, the vein is dilated into a sac, 
and the veins emptying into it are dilated and tortuous. In varicose 
aneurysm the artery and vein do not communicate directly, but a false 
aneurysmal sac is formed between the vessels, into which the blood is 
poured before passing into the vein. Varicose aneurysm may also be 
formed by the spontaneous rupture of an aneurysm into a vein. The 
aneurysm presses against the vein, becomes adherent, and finally ruptures 
into it. This condition has been observed between the aorta and 
pulmonary artery; the aorta and inferior and superior vena cava; the 
popliteal artery and vein; the femoral artery and vein; the splenic 
artery and vena azygos; the internal carotid and sinus cavernosus. 
Cirsoid aneurysm is one formed by the dilatation and lengthening of 
large or small arteries or arterial tracts. The walls of the arteries are 
thinned, the vessels are tortuous and in places sacculated. These 
changes are most frequent in small arteries, especially the temporal and 
occipital. They involve the trunk of the vessel and its branches, or 
may extend to the capillaries and small veins. They form larger or 
smaller tumors beneath the skin. 
The aorta may be dilated over its entire length, or there may be diffuse 
or circumscribed dilatations at any portion of its course; or there may 
be several aneurysms, situated at different points. The ascending por- 
tion of the arch of the aorta may be uniformly dilated in a fusiform shape 
ANEURYSMS OF THE DIFFERENT ARTERIES. 
1 For a study of dissecting aneurysm, see Adami, Montreal Med. Jour., 1896, xxiv, 87, 410. 652 
THE CIRCULATORY SYSTEM 
(Fig. 382), or there may be circumscribed dilatations on its anterior 
wall, or, more rarely, on its posterior wall. The sacculated aneurysms 
vary in size and may rupture within the pericardium; or they may 
form a cavity in the upper part of the ventricular septum and commu- 
nicate by openings into the pulmonary artery and left ventricle; or they 
may dilate downward between the visceral and parietal pericardium, in 
front of the heart, pushing that organ backward. They may perforate 
into the right or left auricle or right ventricle, the superior vena cava, 
or the pulmonary artery; or they may reach a large size, press on and 
erode the right side of the sternum and adjoining ribs, project under the 
skin, and even rupture externally.1 
The transverse portion of the arch may be dilated in a fusiform shape, 
or there may be sacculated aneurysms at any point in its wall. The sac- 
culated aneurysms usually reach a considerable size. They press on the 
sternum and ribs in front, or on the esophagus, trachea, and bronchi 
behind. The large arteries given off from the arch may be occluded. 
They cause death by pressure on the air passages, the esophagus, and 
the vena cava; or may rupture externally or into the esophagus, trachea, 
bronchi, pulmonary artery, or pleural cavities. 
On the abdominal aorta aneurysms are usually sacculated. If they 
are situated high up they may project into the pleural cavities; if lower 
down, into the abdomen. They may compress and displace the vis- 
cera, vessels, and nerves, and erode the vertebrae. They may rupture 
behind the peritoneum, into the peritoneal cavity, the pleural cavities, 
the inferior vena cava, the bronchi, the lungs, the duodenum, the colon, 
the pelvis of the kidney, or the posterior mediastinum. Rupture of the 
aorta with the development of a long dissecting aneurysm parallel to the 
vessel may give rise to a condition simulating a double aorta.2 
The coronary arteries may be dilated throughout, or may be the seat of 
small sacculated aneurysms.3 These may rupture into the pericardium, 
or may lead to rupture of the heart wall. 
The pulmonary arteries are rarely the seat of aneurysms. Diffuse and 
circumscribed dilatations, however, sometimes occur on the main trunk 
and on the two principal branches of the artery. They do not usually 
reach a large size, but may cause death by rupture. General dilatation 
of all the branches of the pulmonary artery is more common. It is 
found in connection with stenosis of the mitral valves and with compres- 
sion or induration of the lung tissue. Small multiple aneurysms-miliary 
aneurysms-may occur in the cerebral arteries; less frequently in the 
pulmonary and mesenteric. These are probably due to some congenital 
weakness of the walls at the point of formation of the aneurysm. 
Of the other arteries of the body there is hardly any one which may 
not become the seat of an aneurysm.4 
1 For extension of aortic aneurysm into the heart, and dissecting aneurysms of the heart, see Hektoen, 
L., Trans. Assn. Am. Phys., 1901, xvi, 127. 
2 See case reported by G. P. Biggs, Proc. New York Path. Soc., 1897-98, p. 109. 
3 Consult Capps, J., Am. Jour. Med. Sci., 1899, cxviii, 312 (bibl.); also Griffith, Brit. Med. Jour., 
1901, i, 266 (bibl.). 
4 For details concerning form, distribution, and frequency of aneurysms see the larger works on the 
practice of medicine or surgery. 653 
THE CIRCULATORY SYSTEM 
This lesion near the entrance of the ductus arteriosus has been 
observed in a considerable number of cases. The degree of stenosis varies. 
The aorta may be entirely closed and converted into a solid cord for a 
half-inch; or there may be a constriction through which there is a 
larger or smaller opening. The walls of the aorta at this point may be 
thickened and sclerosed. The ductus arteriosus may be closed or open. 
Above the constriction the aorta is usually dilated; below it, it is normal, 
dilated, or stenosed. 
Stenosis of the aorta is followed by hypertrophy of the left ventricle, 
and, later, of the right ventricle, with venous congestion throughout the 
body; or there may be a collateral circulation developed between the 
arteries given off above and below the constriction; or there may be 
rupture of the aorta, or of the right ventricle or auricle. 
This condition is found at all ages, but is induced during fetal life 
or in the first year of extrauterine life. It is probable that it may be 
caused after birth by an abnormal closure of the ductus arteriosus. This 
vessel normally becomes closed without the formation of a thrombus. 
If a thrombus is formed it may extend into the aorta and obstruct it; or 
the ductus arteriosus may be filled with a thrombus, but for a time in- 
crease in size; afterward, as the thrombus is absorbed, the vessel may 
contract and draw the walls of the aorta together. 
STENOSIS AND OBLITERATION OF THE AORTA. 
TUMORS. 
For a description of angioma,1 see page 422. 
Primary malignant new growths of the arteries are so rare as to be 
almost unknown; a few sarcomata of the aorta, however, are said to have 
been reported.2 
Secondary growths, chiefly carcinoma and sarcoma, may occur in 
the walls of the arteries by continuous growth from without, involving 
first the external layers. To these they are usually confined, for the 
density of the inner coats offers such distinct resistance to infiltration 
by the tumor cells that arteries may, and often do, pass intact through 
tumors encircling them. 
Arteries become secondarily involved by malignant neoplasms more 
often through the deposition of tumor-cell emboli. These are usually 
of small size and are apt to get into the circulation by growing through 
the walls of the veins into their lumina; large ones most frequently lodge in 
the branches of the pulmonary artery. Composed as they are for the most 
part of cells capable of proliferation, tumor emboli are apt soon to form 
connection with the wall of the vessel, and by the growth into them of 
blood-vessels from the vasa vasorum to find the conditions necessary for 
their development, so that they may soon involve the entire wall and even 
grow out into adjacent parts. 
But not all emboli which attain the circulation are able to obtain a 
1 Bibi, by Thorel, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1907, xi2, 194. 
2 Benda, Aschoff, Pathologische Anatomie, Jena, 1913, ii, 87. 654 
THE CIRCULATORY SYSTEM 
foothold,1 those from tumors of slow growth perishing before they have 
time to effect a union with the endothelium and become vascularized.2 
The Veins. 
DILATATION. (Phlebectasia, Venous Varicosity.) 
Dilatation of the veins, or phlebectasia, occurs under a variety of 
forms: 
1. Simple Dilatation.-The vein is uniformly dilated in a cylindri- 
cal or fusiform shape; its length is not increased; its walls may be thicker 
than normal or thinned; the valves are thickened, or are insufficient, or 
atrophic, or are torn. 
2. Cirsoid Dilatation.-The vein is cylindrically dilated, but is 
also increased in length, so that it assumes a very tortuous course. The 
walls may be thickened or thinned. 
3. Varicose Dilatation.-Portions of the wall of the vein undergo 
saccular dilatation. The wall of the sac is formed of the coats of the 
vein, but these may be thickened or thinned; the middle coat may dis- 
appear entirely. There may be only one such dilatation, or there may 
be a number on the same vein, or a number of veins may be affected at 
the same time. The vein may be otherwise normal, or, more frequently, 
may be more or less uniformly dilated. 
4. Anastomosing Dilatation.-A number of contiguous and 
anastomosing veins are dilated, both in the cirsoid and varicose forms. 
The vein then looks like a series of cavities separated by thin partitions. 
The dilatations of the same vein become adherent to each other and to 
those of the adjoining veins; portions of the walls of the dilated parts 
may atrophy so that there may be a number of cavities containing venous 
blood and separated from each other by thin partitions. 
Distribution, Causes, and Effects of Phlebectasia.-There is 
hardly one of all the veins of the body which may not be dilated. The 
hemorrhoidal veins, forming " hemorrhoids;" the veins of the leg and 
thigh; those of the pelvis and pelvic viscera; those of the spermatic cord, 
scrotum, and labia; those of the abdominal wall; those of the neck and 
arms-are most frequently involved. The immediate cause of dilatation 
is usually some obstruction to the passage of the blood through the veins 
toward the heart as in the esophageal varicosities, the caput medusae of 
hepatic cirrhosis, or the varices of the lower extremity which occur with 
great frequency in women following repeated pregnancies. Alterations 
in the walls of the vessels from degeneration, inflammation, or injury 
must often be important predisposing factors, however, for purely 
mechanical conditions cannot account for all of the phenomena observed. 
For example, the older idea that varices are due to leakage from the valves 
of the veins in the legs is negatived by the fact that the greatest dilatation 
is on the peripheral side of the valve, not central, as it would be if pressure 
played a large part. The lesions found are very variable. Sclerotic and 
1 Schmidt, Der Verbreitungswege der Karzinome, Jena, 1903. 
2 Takahashi, Jour. Path, and Bacteriol., 1915, xx, 1. THE CIRCULATORY SYSTEM 
655 
fibrous changes in the walls with atrophy of the muscle, rupture of the 
elastic laminae, and small-cell infiltration of the perivascular connective 
tissue are seen. In all probability, the inflammation occurs chiefly in 
those veins in which the pressure is high, and the progress of the disease 
amplifies the initial lesion set up by mechanical factors. Spontaneous 
restitution of dilatations of the veins is not common, and usually occurs 
only in the lesser degrees of the lesion. The tendency of the dilatation 
is to increase. Thrombi frequently form in the dilated veins, and either 
partially or completely fill them. These thrombi may become organized, 
or they may dry and become calcified, forming phleboliths. These have 
received much attention of late, for they have frequently been taken for 
calculi in the ureter and, on the basis of an uncontrolled z-ray plate, 
have led to a considerable amount of meddlesome surgery. By the 
formation of new connective tissue in the walls, the thrombi may become 
inclosed in a fibrous capsule and permeated by capillaries, with the ulti- 
mate obliteration of the vessel by connective tissue. The wall of the 
dilated sac may become so thin that it finally ruptures. Inflammation of 
the dilated vein may occur, and be followed by fibrous thickening. 
When occurring in mucous membranes, dilated veins are usually associ- 
ated with persistent catarrh. 
WOUNDS-RUPTURE. 
Wounds of the veins usually heal by a simple contraction and an 
adhesive inflammation of their walls; sometimes by the formation of a 
thrombus. Rupture of the veins may be produced by severe contusions 
and crushings of the body and by violent falls. Perforation of a vein 
may be produced by suppuration of the soft parts and the invasion of 
the walls of the vessel; by the pressure of an aneurysm or of a new growth; 
or by the thinning of the wall of the vein in phlebectasia. 
THROMBOSIS. 
Thrombosis of the inferior vena cava has been many times recorded. 
It is usually due to pressure on the vessel or may occur as an extension 
of thrombi from the contributory veins.1 
Thrombosis of the superior vena cava usually follows pressure from 
without by tumors, aneurysms, or enlarged lymph-nodes. 
Thrombosis of other large venous trunks may occur under various local 
and general conditions (see below, Phlebitis, and page 31).2 ' 
DEGENERATION. 
Fatty degeneration and calcification may occur in the walls of the veins 
under conditions similar to those in which these changes take place in 
the arteries. 
1 For a case of complete fibrous obstruction of superior and inferior venee cavae, see Meyer, Mt. Sinai 
Hosp. Rep., 1903, iii, 35. 
2 For a consideration of peripheral venous thrombosis in heart disease, consult Welch, W. H., Trans. 
Assn. Am. Phys., 1900, xv, 4^1 (biol.). 656 
THE CIRCULATORY SYSTEM 
INFLAMMATION. (Phlebitis.) 
Inflammation of the veins, phlebitis, may involve chiefly the external 
layers-periphlebitis; or the internal-endophlebitis; or, as is very fre- 
quently the case, the entire wall may be affected. Phlebitis may be due 
to an infectious thrombus, to injuries, or to an infectious inflammation 
of the surrounding tissues. Thrombosis of the vein, either primary or 
secondary, is a very constant accompaniment of phlebitis. Thrombosis 
and phlebitis are not infrequent in association with or following infec- 
tious diseases, especially endocarditis, in cachectic conditions, and in 
rheumatism and gout. 
Acute infective phlebitis may follow a suppurative periphlebitis. The 
outer layers of the vein wall are congested, swollen, infiltrated with serum 
and pus. The inner coats may become infiltrated with pus; they may 
become necrotic and disintegrate. A thrombus is constantly formed 
under these conditions, which may for a time stop the circulation and 
keep the products of inflammation and degeneration and infectious 
Fig. 384.-Tuberculous Phlebitis. 
The section is from one of the pulmonary veins in a child dead of acute general miliary tuberculosis. 
material from mixing with the blood; but the thrombus itself is prone to 
disintegration, and thus the exudates and fragments of disintegrated 
thrombi or tissue or bacteria may enter the circulation. 
On the other hand, owing to the presence of irritating or infectious 
material within the vein, and the formation of a thrombus, the inflamma- 
tory process may be at the commencement an endophlebitis, but usually, 
if the inflammation be at all severe, the entire wall of the vessel is even- 
tually involved. 
Acute phlebitis may terminate in the absorption of the thrombus and 
the return of the vein to its normal condition, or in the obliteration of 
the vein. The pyogenic cocci, the typhoid bacillus, the pneumococcus, 
and several other microorganisms have been found in phlebitis. In the 
phlebitis with thrombosis which frequently complicates infectious dis- 
eases such as typhoid fever, pneumonia, etc., the bacteria present are 
often not those which are the excitants of the primary disease. 
The most important results of phlebitis are usually those which depend 657 
THE CIRCULATORY SYSTEM 
upon the introduction into the blood of infectious or other emboli (page 
35). The relationship between non-infectious thrombi and phlebitis is 
in many cases not clear.1 
Chronic periphlebitis results in thickening, principally of the outer 
coats of the veins, but the inner coats also may be involved. The sur- 
rounding tissue may also be thickened and coalesce with the walls of the 
vein. There may or may not be thrombosis. 
Chronic endophlebitis is a not very common lesion, of the same general 
character as chronic endarteritis, with which it is often associated. 
More or less circumscribed patches of new connective tissue are formed 
in the inner coats, which may undergo fatty or calcareous degeneration. 
Tuberculous inflammation of the walls of the veins may occur as an 
extension of the process from without or from a lodgment of the tubercle 
bacilli in the blood current on the intima (Fig. 384). This is most fre- 
quent in the pulmonary veins, and Weigert has called attention to the 
fact that in acute miliary tuberculosis the growth of tubercle tissue into 
the lumina of these veins from tuberculous lymph-nodes is of frequent 
occurrence and readily explains the topography and mode of occurrence 
of the general disease. The tubercle bacilli which are present in the 
tuberculous tissue growing into the lumen of the veins find thus an easy 
distribution.2 
Syphilitic inflammation may involve the walls of the veins either as 
gummata or as more diffuse thickenings; even complete obliteration may 
occur. 
TUMORS.3 
For a description of angioma, see page 422. 
Other benign tumors of the veins include leiomyoma and fibroleio- 
myoma.4 Myoma of the uterus is regarded by some observers as perhaps 
derived from the walls of the uterine blood-vessels,5 rather than from 
the uterus itself. 
Sarcoma of the veins has been recorded.6 
PARASITES. 
Echinococcus is sometimes found in the veins, having either devel- 
oped there or perforated from without. 
Several species of trematodes are found in the circulation in man. 
Fasciola hepatica (liver fluke) occurs rarely and, while usually found in 
the bile-ducts, may be present in the vena cava. Schistosoma hcematobium 
is very common in man in Egypt and in other parts of Africa, and usually 
occurs in the portal vein or its branches, and frequently in other veins. 
1 Consult in this connection Welch on Thrombosis, Allbutt, System of Medicine, 1909, vi, 170. 
2 See Ribbert, Deutsch. Med. Wchnschr., 1906, xxxii, 5. 
3 Bibi, by Schnyder, Centralbl. f. allg. Path., 1914, xxv, 529; Thorel, Tjubarsch-Ostertag, Ergebn. d. 
allg. Path., 1903, ix1, 559; 1907, xi2, 194. 
4 Ecoffey, Arch, de med. exp6r., 1917, xxvii, 454. 
5 e.g., Knauer, Festschr. f. Chrobak, Vienna, 1903, i, 695 (bibl.); Borst, Die Lehre von den Ge- 
schwiilsten, Wiesbaden, 1902, i, 212. 
6 Pollack, Berl. klin. Wchnschr., 1904, xli, 1055. 658 
THE CIRCULATORY SYSTEM 
The Capillaries. 
The walls of the capillaries are so thin and so intimately connected 
with the surrounding tissues that their lesions are studied most appro- 
priately among the diseases of the several organs. Dilatation of the 
new-formed capillaries in tumors, granulation tissue, etc., fatty, amyloid, 
and hyaline degeneration of their walls, and capillary aneurysms, may 
be mentioned here as readily observed lesions occurring under a variety 
of conditions. Angiomas and telangiectases, usually congenital, are 
occasionally seen. 
The changes which we assume to occur in the walls of the smaller 
veins and capillaries in exudative inflammation, by reason of which 
fluids and blood cells pass through them, are not yet sufficiently under- 
stood to be described with definiteness. 
The Lymph-Vessels. 
General Characters of the Lymph-Vessels. 
The larger lymph-vessels are often the seat of various more or less abundant 
lesions. They form, with their many ramifications into the tissues, a closed system, 
though a large number of the smaller vessels can hardly be demonstrated except by 
ink injections, because their walls are so closely bound with the tissue through which 
they pass. It is now held that there is no direct communication between the tissue 
spaces, which lie between the individual cells, and the lymph-capillaries, and that all 
interchange of fluid takes place through a distinct wall of endothelial cells.1 As has 
been stated elsewhere, the ultimate drainage of the lymph-vessels is through the 
lymph-nodes, which act as filters for inert particles and bacteria and probably to 
a certain extent as absorbing tissues which receive the brunt of the toxic afetion of 
certain bacterial and other poisons derived from foci in the tissues. 
LYMPHANGIECTASIS. 
Dilatation of the lymph-vessels occurs under a variety of conditions. 
It may be congenital, or it may be due to some hindrance to the flow of 
lymph onward-as by pressure from any cause, or from the occlusion of 
the vessels by inflammation. If the dilated vessels form a circumscribed 
mass, this is often called a lymphangioma (Fig. 229). In certain forms 
of elephantiasis and in macroglossia the dilatation of the lymph-vessels is 
an important factor. Its occurrence is not infrequent in the labia, pre- 
puce, and scrotum. Dilatation of the chyle vessels may occur in the 
mucous membrane of the intestine and in the mesentery. Filarial lym- 
phatic varix is of occasional occurrence.2 
Obstruction of the thoracic duct may be due to tumors,3 or enlarged 
lymph-nodes, or inflammatory processes in the mediastinum; to aneu- 
rysm, to thrombosis of the left innominate vein, to insufficiency of the 
tricuspid valve; or to inflammatory processes in the wall of the duct. It 
may occur under various other conditions. It may be compensated by 
1 Adler and Meltzer, Jour. Exper. Med., 1896, i, 482. 
2 See Opie, Filarial Lymphatic Varix, Trans. Assn. Am. Phys., 1901, xvi, 331. 
8 For bibliography of carcinoma involving the thoracic duct, see A. H. Smith, Med. Record, 1899, 
Ivi, 813. THE CIRCULATORY SYSTEM 
659 
collateral lymphatic anastomoses, or it may lead to various lymph- 
angiectasiae and to transudation of lymph. Thus chylous ascites may 
occur. 
Congenital doubling or division and other abnormalities of the tho- 
racic duct are recorded.1 
LYMPHORRHAGIA. 
If through injury, necrosis, or other pathological process, the walls 
of the lymph-channels suffer solution of continuity the lymph may escape 
into surrounding tissues or spaces. Thus, upon the surface of the skin 
or into loose connective-tissue spaces or into the great body cavities, 
lymph may be poured out. A chylous hydrothorax or chylous ascites 
may occur from a rupture of the thoracic duct or its radicles. Chyluria 
may result from a similar injury to the lymphatics in the bladder or 
ureter. 
THROMBOSIS. 
Thrombi may form in the lymph-vessels by the coagulation of the 
lymph or by the deposition of fibrin on the walls of the vessels at the seat 
of degeneration or inflammation. These lymph thrombi are formed 
largely of fibrin and leucocytes. Such thrombi may cause disturbances 
of the lymph circulation or portions of them may become detached, form- 
ing emboli.2 
INFLAMMATION. (Lymphangitis.) 
Acute Infective Lymphangitis.-Inflammation of the larger lymph- 
vessels is usually secondary and often connected with an infected wound 
or injury. Owing to the entrance into the lymph-trunk of bacteria or 
other infectious agents, poison of venomous reptiles, insects, etc., the 
vessels, sometimes for a considerable distance away from the wound, 
become red, tender, and painful. Under these conditions the appear- 
ances which the vessels present vary. In some cases, the redness dis- 
appears after death and we find no appreciable alteration. In other 
cases, the walls of the lymph-vessels are more or less densely infiltrated 
with pus cells, there is proliferation of the endothelium, and the lumen 
may contain variable quantities of pus and fibrin and desquamated 
degenerated endothelium. The vessel may be occluded by a thrombus. 
The tissue about the vessels may also be infiltrated with serum and pus. 
These lesions may undergo resolution and the vessel be restored to its 
normal condition; or the vessel wall and surrounding tissue may die or 
become involved in abscess; or new connective tissue may form in and 
about the vessel, sometimes with obliteration of its lumen. The asso- 
ciated lymph-nodes may participate in the inflammatory process. 
Tuberculous Lymphangitis.-Tuberculous inflammation occurs in both 
large and small lymph-vessels. Miliary tubercles and diffuse tubercle 
tissue may form in the walls and project into the lumen of the larger 
trunks; or in the smaller vessels the new growth may entirely fill the 
1 Butler, Jour. Med. Research, 1903, N. S. v, 153 (bibl.). 
2 Opie, Jour. Med. Research, 1913, N. S. xxiv, 131. 660 
THE CIRCULATORY SYSTEM 
lumen, and grow within it, with more or less involvement of the walls. 
This may occur independently, but it is most frequently seen in connec- 
tion with tuberculous inflammation of adjacent tissues. Thus from 
tuberculous lymph-nodes in the vicinity of the thoracic duct there may 
be a direct extension of the tuberculous inflammation, an involvement 
of the walls of the duct, and a growth of tubercle tissue into its lumen. 
Such growths in the thoracic duct have been shown by Weigert to occur 
in acute general miliary tuberculosis (page 283). In the vicinity of 
tuberculous ulcers in the intestines, furthermore, we often see the sub- 
serous lymph-vessels, which pass from the vicinity of the ulcers, distended 
with the products of tuberculous inflammation and looking like dense 
white knobbed cords (Fig. 474, page 766). 
Syphilitic lymphangitis not infrequently occurs in the vicinity of 
syphilitic ulcers in the primary stage. In later stages there may be 
thickening of the walls of the vessels and the development of gummata 
in and about them. 
TUMORS. 
The primary tumors of the lymph-vessels, the lymphangiomata, are 
described in the Chapter on Tumors. 
The dissemination of malignant tumors through the lymph-channels 
is of frequent occurrence, and is particularly marked in the case of 
carcinoma. In the vicinity of carcinomata, the lymph-vessels are not 
infrequently crowded with the tumor cells, forming white, irregular 
cords; or small masses of the tumor cells are found in the lymph-vessels, 
either near to or remote from the tumor. White, irregular networks are 
often formed in this way beneath the pleura in carcinoma of the lung, or 
beneath the capsule of the liver. Transverse sections of lymph-vessels 
thus distended sometimes show swelling and detachment of the endothe- 
lium and a crowding of the lumen with tumor cells.1 
1 Unger, Virchows Arch., 1896, cxlv, 581. CHAPTER VI. 
THE RESPIRATORY SYSTEM. 
The Nose and its Associated Cavities. 
The nasal cavity is lined for a short distance from its opening with skin covered 
with flat epithelium, thickly sown with sebaceous glands and containing the hair 
follicles of the short bristles which project into the lumen. The remainder of the 
cavity is lined with a mucous membrane which is covered with a layer of ciliated 
epithelium. The submucosa is composed of a loose connective tissue with some elastic 
fibers and variable amounts of lymphoid tissue. Mucous glands and a very rich 
venous complex are also present. The accessory cavities of the nose are lined with 
a similar but somewhat thinner membrane. 
The direction of vibration of the cilia is such that the dust from the air which 
impinges upon the mucous membrane is swept toward the nares. Owing to its ex- 
posed position the membrane is subjected to the action of deleterious agents, and 
sudden changes of temperature may lead to great and abrupt alterations in the condi- 
tion of the blood-vessels, and hence, also, to variations in the turgidity of the mem- 
brane. Because of its great vascularity and extensive nerve supply, the mucous 
membrane is very responsive to bacterial infections, to chemical irritation, and to 
anaphylactic poisoning, the best instances of the last being sensitiveness to the 
effluvia from horses, which is seen in some individuals, and to plant pollen, which is 
observable in those suffering from hay fever. 
MALFORMATIONS. 
Absence or deformity of the nose or some of its parts, deviations of 
the septum, clefts, usually associated with cleft palate and harelip (Fig. 
185 and 186), are among the more frequent of the congenital anomalies 
of the nose. 
HEMORRHAGE. (Epistaxis.) 
This may result from injury; it may be an expression of local or 
general hyperemia from cardiac or vascular lesions, obstruction of 
vessels, etc. It not infrequently occurs in an early stage of acute in- 
fections, such as typhoid fever. It may accompany general conditions 
such as hemophilia, pernicious anemia, etc. Epistaxis may result from 
lesions of the nasal mucous membranes, ulcers, telangiectasis, etc. 
INFLAMMATION. (Rhinitis.) 
Acute catarrhal inflammation is common and often associated with a 
similar process in the pharynx and larynx. There is at first a hyperemic 
swelling followed by an increased production of mucus and transudation 
of serum from the blood-vessels; emigration of leucocytes and desquama- 
tion of epithelium may follow. This and other inflammatory processes 
661 662 
THE RESPIRATORY SYSTEM 
may extend to the frontal or ethmoidal sinuses and the antrum, where 
the exudates may collect (Fig. 385). As the process resolves, the exuda- 
tion ceases, the epithelium regenerates, and the mucosa is restored to its 
normal condition.1 
Pseudomembranous inflammation, either simple or diphtheritic, may 
involve the nasal cavities. Phlegmonous inflammation involving adja- 
cent parts is of occasional occurrence. Bacteria apparently play an im- 
portant part as excitants of acute catarrhal and pseudomembranous 
inflammation.2 
Chronic catarrhal inflammation may follow the acute form, and is 
marked by hyperplasia of the fibrous tissue in the submucosa, often 
followed by atrophy of the mucosa. Ulceration of the mucosa may 
occur; the exudate may assume a fetid 
character. A hyperplasia of the mucosa 
may lead to the formation of the so- 
called mucous polyps3 (Fig. 386 and 
387). These are usually pedunculated, 
soft prolapses of the mucous membrane 
covering a gelatinous and edematous or 
spongy connective tissue. The palisade 
cells covering the surface are often cili- 
ated. The vessels are abundant, but 
have very thin capillary walls. In the 
interstices of the connective tissue are 
often collected many eosinophile leuco- 
cytes and numerous plasma cells. 
Hyperplastic mucous glands are occa- 
sionally found in the polyps. 
Tuberculous and syphilitic inflamma- 
tion with the usual morphological char- 
acters of these processes are common in 
the nasal cavities. 
Fig. 385.-Catarrhal Inflamma- 
tion of the Mucous Membrane of 
the Antrum. 
Showing migration of leucocytes 
through the epithelium. 
TUMORS. 
Aside from the nasal polyp (page 445) which may be adenomatous 
in character, the most common tumors are sarcoma4 and carcinoma;5 
both are unusual, but the former is perhaps a little less rare. Carcinoma 
may be either of the cylindrical-cell, the squamous-cell, or the adenoma- 
tous type.6 
Melanosarcoma' and dermoid cysts have been described. 
i For a study of the pollen of plants as excitants of hay fever, see Liefmann, Ztschr. f. Hyg., 1904, 
xlvii, 153, and for r6sum6 of treatment with Dunbar serum, see Glegg, Jour. Hyg., 1904, iv, 369. 
2 For a study of the bacteriology of nasal inflammation, see Howard and Ingersoll, Am. Jour. Med. Sc., 
1898, cxv, 520. See also for bacteria of the nose, Neumann, R. O., Ztschr. f. Hyg., 1902, xl, 33; also 
Hasslauer, Centralbl. f. Bakteriol., Ref. I, 1906, xxxvii, 1 (bibl.). For a study of the lymph-vessels 
of the nose and pharynx, see Most, A., Arch. f. Anat. u. Physiol., Anat. Abth., 1901, i, 75, 94. 
3 For a summary of facts concerning the nature of the ordinary nasal polyps, see Wright, Med. 
Record, 1901, lix, 132 (bibl.). 
4 Sonnenschein, Arch. f. Laryngol. u. Rhinol., 1909, xxii, 528 (bibl.). 
6 Trautmann, Arch. f. Laryngol. u. Rhinol., 1905, xvii, 386 (bibl.). 
6 Cordes, Berl. klin. Wchnschr., 1903, xi, 164 (bibl.). 
7 Cozzolino, Arch. f. Laryngol. u. Rhinol., 1903-04, xv, 77. THE RESPIRATORY SYSTEM 
663 
Fig. 386.-Mucous Polyp of the Nose. 
Showing branching cells with loose delicate stroma containing much fluid. 
Fig. 387.-Mucous Polyp of the Nose. 664 
THE RESPIRATORY SYSTEM 
Benign tumors of the nasal septum have been recorded.1 
Adenoids.-In many children there occurs hyperplasia of the lymph 
tissue of the posterior pharyngeal region, which is often associated with 
nasal or pharyngeal catarrh, with frequent "colds," and with mouth- 
breathing. The redundant tissue forms a lobular mass which often 
blocks the nasopharyngeal passage. These adenoids may contain tuber- 
culous lesions. 
The Pharynx. 
The lesions of the pharynx similar to those just described as involving 
the nasal cavities are reviewed on page 736. 
The Larynx and Trachea. 
Malformations. 
The larynx and trachea may be absent. The larynx may be abnormally large or 
small; the epiglottis also may be too large or too small, or may be cleft. Small 
larynges are observed in castrates or persons with genital hypoplasia. There may 
be communications between the trachea and the esophagus, and then the pharynx 
generally ends in a cul-de-sac, and the esophagus opens into the trachea. A dia- 
phragm may be formed across the anterior or posterior portion of the larynx.2 There 
may be imperfect closure of the original branchial arches, so that there are fissures in 
the skin leading into fistula; which open into the pharynx or trachea. The fissure in 
the skin is small and is situated about an inch above the sternoclavicular articulation, 
usually on one or both sides, more rarely in the middle line. Individual cartilages, as 
the epiglottis, or one or more rings of the trachea, may be absent, or there may be 
supernumerary rings. The trachea may divide into three main bronchi instead of 
two, and in that case two bronchi are given off to the right lung and one to the left. 
The trachea may be on the left side of the esophagus or behind it. 
In trauma and acute inflammatory processes, in syphilis and tubercu- 
losis, and when tumors are present, especially carcinoma and some forms 
of vascular papilloma, there may be hemorrhage from the larynx. It 
may occur also under the general favoring conditions, such as hemo- 
philia, scurvy, and various abnormal conditions of the circulation leading 
to local or general hyperemia.3 
HEMORRHAGE. 
EDEMA OF THE GLOTTIS. 
This is a condition in which there is an accumulation of serous fluid 
in the submucosa of the upper part of the larynx. This may be due to 
simple circulatory disturbances, local or general, or it may be inflamma- 
tory in character. The greatest accumulation of fluid is in places in 
which the submucous tissue is abundant and loose in texture, as in the 
posterior wall of the epiglottis, in the arytenoepiglottidean folds, and in 
1 Hasslauer, Arch. f. Laryngol. u. Rhinol., 1900, x, 60 (bibl.). For a discussion of polypoid tumors 
of the nasal septum, see Onodi, ibid., 1914-15, xxix, 30. 
2 Glas, Wien. klin. Wchnschr., 1908, xxi, 603. 
3 For a study of hemorrhage of the larynx, see Rhodes, Jour. Am. Med. Assn., 1904, xliii, 1284. THE RESPIRATORY SYSTEM 
665 
the false vocal cords. The swelling of these parts may be so great as to 
occlude the air passage. After death the edematous swelling may largely 
disappear, owing to the evaporation of the exudate; but the mucous 
membrane may be left unusually wrinkled and flabby. 
Edema of the glottis is comparatively infrequent in association with 
such heart, kidney, and lung lesions as lead to general edema. It is, on 
the contrary, frequent in connection with various forms of laryngeal 
inflammation, either following extensions of local infection or in the in- 
fectious diseases, such as diphtheria, scarlet fever, smallpox, and typhoid 
fever. An acute edema may follow the administration of the iodides in 
susceptible persons. It may occur in drunkards or others who are poi- 
soned and fall asleep in a sitting posture so that the head drops sharply 
forward with constriction of the neck. Under these conditions the indi- 
vidual may die from asphyxia with no obvious lesion accounting for it 
other than the edema of the glottis. 
INFLAMMATION. (Laryngitis.) 
Acute Catarrhal Laryngitis.-This occurs as an independent process 
in common "colds." It may be a complication of the infectious dis- 
Fig. 388.-Localized Hyperplasia of the Epithelium and Submucous Connective Tissue of 
the False Vocal Cords. 
The section shows a portion of a small rough wart-like or papillary growth. 
eases, especially whooping-cough and measles, or may be induced by the 
inhalation of irritating vapors and of hot steam and smoke. The inflam- 
mation varies in its intensity in different cases. The mucous membrane 
is at first congested, swollen, and dry; then the mucous glands become 
more active and an increased quantity of mucus is formed. There is 
desquamation of the superficial epithelial cells, while through emigration 
leucocytes may infiltrate the submucosa, and together with mucus and 
desquamated epithelium form the exudate. There may be edema of the 
glottis. All of these lesions may disappear with complete restoration of 
the mucous membrane. 
After death the congestion of the mucous membrane marking an 
acute form of the disease frequently disappears altogether. 666 
THE RESPIRATORY SYSTEM 
Chronic Catarrhal Laryngitis.-This may follow repeated attacks of 
acute inflammation or be the result of the persistent inhalation of harm- 
ful substances. It may accompany chronic hyperemia from cardiac or 
vascular lesions. It may be associated with syphilis and tuberculosis. 
The surface of the mucous mem- 
brane is dry or coated with mucopus. 
The epithelium is thickened in some 
places, thinned in others, or in 
places entirely destroyed. The sub- 
mucosa may be infiltrated with cells, 
diffusely thickened, or form little 
papillary outgrowths; it may be 
thinned, or necrotic and ulcerated. 
The mucous glands may be 
swollen and prominent. The in- 
flammation may extend to the peri- 
chondrium of the cartilages, which 
may become necrotic. In chronic 
laryngitis there may be a more or 
less diffuse thickening of the epithe- 
lium often associated with a hyper- 
plasia of the submucous tissue. This 
is called pachydermia diffusa. A 
similar process, if localized, may lead 
to larger and smaller wart-like ex- 
crescences-pachydermia verrucosa 
(Fig. 388). Carcinoma has been ob- 
served to develop on such a lesion.1 
Pseudomembranous Laryngitis 
(Croupous Laryngitis).-This occurs 
most frequently as the characteristic 
local lesion in diphtheria, of which 
the Bacillus diphtheriae is the exci- 
tant (see page 313). It may, how- 
ever, be incited by the Streptococcus 
pyogenes and other bacteria, and 
not infrequently accompanies other 
infectious diseases, scarlatina, ty- 
phoid fever, and the exanthemata 
(see page 339). The false mem- 
brane may be continuous with a 
similar structure in the pharynx, and 
it may extend down into the bronchi (Fig. 389). 
Phlegmonous Laryngitis.-Suppurative inflammation involving the 
mucosa and submucosa is usually secondary to catarrhal, croupous, 
tuberculous, or syphilitic laryngitis; or it may be associated with pyemia, 
erysipelas, smallpox, or typhoid fever. It may follow mechanical 
Fig. 389.-Diphtheria of the Larynx and 
Trachea. 
The membrane extends from the epiglottis 
down to the bifurcation of the trachea. 
1 Fr&nkel, B., Arch. f. Laryngol. u. Rhinol., 1903, xiii, 1. THE RESPIRATORY SYSTEM 
667 
injury from a foreign body. It is not uncommon on the posterior sur- 
face of the epiglottis or in the arytenoepiglottidean folds, and may be 
associated with edema of the glottis. Abscesses may form which rupture 
into the larynx, or extend into the neck, the pharynx, or the esophagus. 
Tuberculous Laryngitis.-This lesion is most frequently associated 
with pulmonary tuberculosis. Early in the process there is a formation 
in the submucosa of miliary tubercles together with more or less new 
connective tissue and lymphocytes; with this is a catarrhal inflammation 
with an exudate of mucus, pus cells, and desquamated epithelium (Fig. 
390). 
As coagulation necrosis of the subepithelial tubercles occurs, ulcers 
are formed, often with an increase of the catarrhal exudate. These 
The epithelium on the surface has ulcerated over a small area. The tubercle is situated in the sub- 
epithelial layer. 
Fig. 390.-Tuberculous Laryngitis. 
lenticular ulcers are shallow, oval areas, and are especially abundant 
on the epiglottis. The process may extend so as to involve the walls of 
the larynx, and necrosis of the cartilages may follow. Adjacent ulcers 
may become confluent so that considerable areas of the mucous mem- 
brane may be destroyed (Fig. 391). Lupus, also, may occur in the larynx. 
Syphilitic Laryngitis.-This form of inflammation may have the ordi- 
nary characters of an acute or chronic catarrhal inflammation, or may be 
productive in character with the formation of new tissue in the stroma 
of the mucous membrane. The new tissue is principally composed of 
small cells which often degenerate and become necrotic. In this way the 
mucous membrane of the larynx and the tissues beneath are thickened 
in some places and destroyed in others, giving rise to erosions and ulcers. 
At one stage, the lesion may be papillary. These changes are especially 
marked in the upper portion of the larynx. If the perichondrium be 
involved there may be necrosis of the laryngeal cartilages. Gummata 668 
THE RESPIRATORY SYSTEM 
are infrequent. Owing to the cicatricial contractions of healed syphilitic 
ulcers there may be great deformity of the larynx. 
Lesions of the trachea are often associated with those of the larynx 
and are in general similar in character. 
TUMORS OF THE LARYNX AND TRACHEA. 
Larynx.-Retention cysts of the mucous glands of the larynx may 
form sacs projecting into its cavity. 
Papilloma, single or multiple, is the most common form of benign 
tumor of the larynx (Fig. 392); it is most frequent upon the vocal cords 
(singers' nodes') and is usually associated with chronic inflammation. 
Adenoma, fibroma, lipoma, myxoma, and angioma occasionally occur. 
An extremely rare lesion is the amyloid tumor which is found most fre- 
The posterior surface of therepiglottis and the adjacent tissue are involved in tuberculous ulcers. 
Fig. 391.-Tuberculous Laryngitis. 
quently in the larynx and next most commonly in the tongue.1 Remains 
of thyroid tissue have been found in the larynx. 
Enchondromata grow from the normal cartilages and are usually 
multiple and sesshe; they may project into the cavity of the larynx.2 
Fusiform or spheroidal-cell sarcomata of the larynx have been seen 
in a considerable number of cases, both in children and in adults. 
Carcinoma, which is usually of the epitheliomatous type, may origi- 
nate in the larynx, most commonly upon the false vocal cords. Its 
1 Seckel, Arch. f. Laryngol. u. Rhino!., 1912, xxvi, 1 (bibl. covering amyloid tumors in general); 
Mannasse, Virchows Arch., 1900, clix, 117; Pollak, Ztschr. f. Laryngol., Rhinol., etc., 1914-15, vii, 24 
(bibl.); Willimann, Arch. f. Laryngol. u. Rhinol., 1912, xxvi, 395. 
2 Salomonsen, Arch. f. Laryngol. u. Rhinol., 1913-14, xxviii, 454 (bibl.). 669 
THE RESPIRATORY SYSTEM 
spread is very slow, and it usually involves only the lymph-nodes in its 
immediate neighborhood. 
Primary carcinoma of the epiglottis is extremely rare, but has been 
described.1 
A unique case of metastatic hypernephroma in the larynx has been 
reported.2 
Cysts of the larynx have been described.3 
Trachea.-Tuberculous or otherwise altered bronchial lymph-nodes 
may enter the trachea by ulcera- 
tion and obstruct the passage. 
Tumors of the trachea are of 
rare occurrence, but growths simi- 
lar to those in the larynx have 
been occasionally found.4 
The Bronchi and Lungs. 
The Bronchi. 
HEMORRHAGE. 
In hemorrhage from the 
bronchi the source of the blood is 
often to be sought in the paren- 
chyma of the lung (see page 679) 
or in a ruptured aneurysm. But 
hemorrhage from the bronchial 
walls may occur in tuberculous 
or other forms of ulceration, 
chronic bronchitis, malignant 
tumors, etc. 
Acute Catarrhal Bronchitis.- 
This is frequently associated with 
a similar process in the trachea. 
It is characterized by hyperemia 
and swelling of the mucous mem- 
brane. with the formation of exudate, which usually consists largely of 
mucus formed by the hypersecretion of the mucous glands or degenera- 
tion of the epithelial cells. Mingled with this are exfoliated and more 
or less degenerated epithelium from the mucous membrane, leucocytes 
from the dilated vessels of the submucosa, varying numbers of red blood- 
cells, and bacteria. 
The microscopic appearances differ in different parts of the bronchial 
tubes in accordance with the differences in structure. Mucous glands, 
INFLAMMATION. (Bronchitis.) 
Fig. 392.-Papilloma of the Larynx. 
The left vocal cord is involved in the lobulated 
growth. A tracheotomy opening is seen below the 
tumor. 
1 Mayer, Arch. f. Laryngol. u. Rhinol., 1913, xxvii, 588 (bibl.). 
2 Menzell, Arch. f. Laryngol. u. Rhinol., 1912, xxvi, 264. 
* Glas, Arch. f. Laryngol. u. Rhinol., 1906-07, xix, 285 (bibl.). 
4 See Heymann, Ztschr. f. Laryngol., Rhinol., etc., 1913-14, vi, 735 (bibl.). 670 
THE RESPIRATORY SYSTEM 
when these are present, may reveal great functional activity, and their 
ducts may be distended with mucus which, often mingled with exfoliated 
and degenerated cells, streams out upon the surface. Swelling and 
proliferation of the connective-tissue cells and endothelium of the vessels 
of the submucosa, edema, and emigration from the dilated vessels are 
often marked. The leucocytes may be seen making their way through 
the epithelium into the other exudates upon the surface. The epithelium 
may be loosened, single or clustered cells falling off here and there, or 
shreds of cells may exfoliate together (see Fig. 393).1 The deeper sphe- 
roidal epithelia, the so-called mother cells from which the new ciliated 
cells on the surface are formed in both physiological and pathological 
regeneration, usually remain in place upon the basal membrane. In the 
small bronchi whose walls are thin, little else may be seen than an irregu- 
lar exfoliation of the epithelium. On the other hand, the smaller 
Fig. 393.-Acute Catarrhal Bronchitis. 
This section of a small portion of the bronchial wall shows considerable exfoliation of the epithe- 
lium, but many of the deeper so-called "mother cells" remain in place. There are swelling of the 
connective-tissue cells and congestion of blood-vessels in the submucosa, with edema and emigration 
of leucocytes. Some of the leucocytes are passing through the epithelium to mingle with the mucous 
exudate and exfoliated cells in the lumen of the bronchus. Some of the ciliated cells show the "beaker" 
shape with a homogeneous interior indicating the production of mucus within them. 
bronchi may be much involved and their lumina filled with exudate; 
when this, which has been called "capillary bronchitis," occurs, the 
inflammatory process usually involves the adjacent and associated terri- 
tories of lung tissue, constituting one of the important forms of broncho- 
pneumonia. In some forms of bronchitis the exudate may consist 
largely of pus-"purulent bronchitis." 
Atelectasis of corresponding tracts of the lung may follow the occlu- 
sion of the bronchi with exudate. As recovery advances, the submucosa 
assumes its normal thickness and character and the epithelium is regener- 
ated from the cells of the deeper layers. 
1 For a study of physiology and pathology of ciliated epithelium of the respiratory organs, see 
Lommel, Deutsch. Arch. f. klin. Med., 1908, xciv, 365. 671 
THE RESPIRATORY SYSTEM 
Various forms of bacteria may be associated with acute bronchitis, and 
under favorable conditions are presumably the excitants of the lesions; 
the etiological relationship has, however, not yet been experimentally 
established. The most common forms of bacteria are Streptococcus 
pyogenes, the pneumococcus, Staphylococcus aureus, and the influenza 
bacillus.1 
Chronic Catarrhal Bronchitis.-This form of bronchitis may be the 
sequel of one or more attacks of acute bronchitis. More frequently it is 
associated with emphysema, heart disease, interstitial pneumonia, 
phthisis, pleuritic adhesions, or the inhalation of irritating substances. 
There is in most cases a constant production of mucus, pus, and serum 
in considerable quantities, and these inflammatory products may have a 
very foul odor. Less frequently these products are very scanty-dry 
catarrh. The epithelium is. deformed and desquamating, with a pro- 
duction of new cells in the deeper layers. There may be epithelial 
Fig. 394.-Chronic Bronchitis with Moderate Bronchiectasia. 
This transverse section of a portion of the wall of a dilated bronchus shows atrophy of the epithe- 
lium; fibrous hyperplasia of the submucosa with the formation of longitudinal ridges on the interior 
of the tube (cut across in this section); thickening of the wall of the bronchus and atrophy of the mucous 
glands. 
hyperplasia or atrophy; the mucous glands are large or atrophied; there 
may be hyperplasia or atrophy of the submucosa; the muscularis may 
show hypertrophy or atrophy. These changes in the fibrous and mus- 
cular elements of the walls lead to the so-called 11 trabeculation " of their 
inner surfaces (Fig. 394). Obliterating arteritis of the associated vessels 
may occur. These changes in the walls of the bronchi may lead to 
bronchiectasia. 
Acute Pseudomembranous Bronchitis-Croupous Bronchitis-may 
occur with croupous laryngitis, as a lesion of diphtheria, with lobular 
pneumonia, and sometimes without these associations. The bronchi 
1 For a study of the bacteria found in bronchitis, see Ritchie, W. T., Jour. Path, and Bacteriol., 
1901, vii, 1; also Karcher, Deutsch. Arch. f. klin. Med., 1905, Ixxxiii, 244. 672 
are lined or filled with a mass of fibrin, pus, and desquamated epithelium. 
Fibrin and pus may also be found beneath the epithelium and infiltrated 
in the stroma. 
Chronic Fibrinous Bronchitis is attended with the formation in one or 
more bronchi of masses of fibrin which are expectorated by the patient 
in the form of branching casts of the bronchi (Fig. 395). After death 
the bronchi are said to be but little altered from the normal.1 
Curschmann has described under the name 11 bronchiolitis exudativa" 
a form of bronchitis in which small threads and bands of gray or yellow, 
partly transparent, coagulated material are formed in the small bronchi 
-"Curschmann's spirals." These sometimes occur in pneumonia. In 
different forms of bronchitis, especially in those associated with asthma. 
THE RESPIRATORY SYSTEM 
Fibrinous casts of the bronchi, similar to those shown in the photograph, were coughed up at irregular 
intervals for several years. 
Fig. 395.-Chronic Fibrinous Bronchitis. 
the exudation may contain numerous octahedral bodies-Charcot-Ley- 
den crystals-and also a very large number of eosinophile cells. 
Tuberculous Inflammation of the bronchi frequently occurs in con- 
nection with pulmonary tuberculosis. The lesion may be miliary or 
larger involvement of the walls may lead to ulceration. 
Syphilitic Inflammation may lead to ulcers and to distortions and 
stenosis through cicatrization. 
BRONCHIECTASIA. 
Dilatations of the bronchi may be cylindrical, fusiform, or sacculated. 
The sacculated dilatations are usually the largest, and communicate 
with one side of the bronchus. The peripheral portion of the bronchus 
may be obliterated; the bronchus leading to the cavity may be of normal 
size, or dilated, or stenosed, or even completely obliterated. Such sac- 
culated dilatations may reach a very large size and may communicate 
with each other. Dilatations are apt to occur under conditions which 
1 For a rfisumfi and bibliography, see Bettmann, M., Am. Jour. Med. Sc., 1902, cxxiii, 304. THE RESPIRATORY SYSTEM 
673 
interfere with the integrity of the bronchial wall and also those which 
partially close a bronchus, such as thoracic aneurysm. 
In acute general bronchitis and bronchopneumonia in children, 
cylindrical dilatation of a number of the medium-size bronchi often 
occurs. 
In the persistent bronchopneumonia of children such dilatations may 
reach a still greater development.1 Chronic bronchitis may lead to cylin- 
drical or sacculated dilatations, sometimes of great size. 
Occlusion of some of the bronchi, consolidation of portions of the 
lung, and extensive pleuritic adhesions may also lead to bronchiectasia 
(Fig. 396). 
Fig. 396.-Multiple Bronchiectasis with Interstitial Pneumonia. 
Portion of anterior free border of lungs. From an adult after unresolved lobar pneumonia. 
The walls of bronchiectatic cavities may be lined with mucous mem- 
brane, which, however, is apt to undergo various changes as the process 
advances. Thus the subepithelial layer may be vascular and cellular and 
thrown into folds, or it may be thin and dense. The epithelium is often 
irregular, sometimes irregularly thickened, sometimes thin, or it may be 
largely absent. The glands, muscle, and cartilages of the walls of the 
bronchi may disappear through atrophy. The presence of certain forms 
of bacteria in the exudate in bronchiectasia may lead to an offensive 
putrefactive process and even to gangrene, especially if the drainage 
1 For a study of bronchiectasia in children, see Lapin, Arch. f. Kinderh, 1903, xxxvii., 406. 674 
THE RESPIRATORY SYSTEM 
is not good. Moulds maybe present, and acid-fast bacilli of the smegma 
group are often found in the sputum. 
In acute and chronic phthisis the tuberculous inflammation of the 
walls of the bronchi often gives rise to sacculated dilatations, which 
expand with time and become still larger by the destruction of the adja- 
Fig. 397.-Lung Stones. (From a case of Tuberculous Bronchitis.) 
cent lung tissue-tuberculous bronchiectasis. These are most frequent 
in the upper lobes, while the non-tuberculous form is most often seen in 
the lower portion of the lung. Enlargement of the tips of the fingers 
and toes is not infrequent in chronic bronchiectasis either simple or of 
tuberculous origin. (See p. 1046 under pulmonary dystrophy.) 
These calcified masses were found in the dilated bronchi. 
Fig. 398.-Primary Adenoma of the Bronchi. 
Occlusion of the bronchi, either partial or complete, may be caused by 
tumors, parasites, especially ascaris, foreign bodies, exudates, etc., or 
by destructive lesions in the walls. Calcified masses called "lung stones" 
(Fig. 397) may be found. (See also p. 726 ref.) 675 
THE RESPIRATORY SYSTEM 
TUMORS. 
Primary tumors of the bronchi are rare. Lipoma, chondroma, and 
fibroma have been observed. Sarcoma is rare, but may occur, especially 
in its spheroidal-cell form or as an extension of sarcomata from the 
mediastinum. Adenoma (Fig. 398) and primary carcinoma1 are also un- 
common. Epithelioma occurs, and is assumed to be derived from bron- 
chial epithelium which has undergone a metaplasia into the squamous 
type. Such tumors may remain small and be noticeable clinically only 
from the metastases which they 
produce. When the bronchus is ob- 
structed by the tumor, secondary 
dilatation below the point of closure 
occurs, with the production of large 
bronchiectatic cavities.2 Secondary 
carcinoma is not unusual and may 
involve also the trachea or the lungs. 
Plasmocytoma of the upper air 
passages has been described.3 
LESIONS OF THE TRACHEAL AND 
BRONCHIAL LYMPH-NODES. 
The tracheal and bronchial lymph- 
nodes may be the seat of a variety of 
lesions which, owing to their situa- 
tion, as well as for other reasons, 
are of considerable practical impor- 
tance. They may be enlarged from 
hyperplasia in acute infectious dis- 
eases; by the development in them 
of tumors; in leukemia, in Hodgkin's 
disease, and with especial frequency 
in tuberculosis (Plate V). They may 
become pigmented from inhaled coal 
or other dust and may atrophy or be- 
come fibrous or calcified.4 In cheesy 
degeneration following tuberculosis 
(Fig. 399), or in suppurative inflammation, perforation may take place 
into the air passages, the esophagus, the pulmonary blood-vessels, or 
aorta, or into the pericardial or pleural cavities;5 in this way hemorrhage 
or secondary inflammatory processes or gangrene may occur. Death 
may occur from pressure upon the trachea by tumors of the adjacent 
Fig. 399.-Tuberculous and Gaseous 
Bronchial Lymph-nodes. 
The nodes are much enlarged and press 
upon the larger bronchi. 
1 Weller, Arch. Int. Med., 1913, xi, 314 (bibl.); Kreglinger, Frankfurt. Ztschr. f. Path., 1913, xii, 
135; Davis, Tr. Chicago Path. Soc., 1913-15, ix, 156. 
2 Ernst, P., Zieglers Beitr., 1896, xx, 155. 
3 Wachter, Arch. f. Laryngol. u. Rhinol., 1913-14, xxviii, 69 (bibl.). 
4 For the association of pigmentation and tuberculosis of the bronchial lymph-nodes and the pleura, 
see p. 728. For a study of alleged intestinal origin of lung pigment, see Montgomery, E. M., Jour. Med. 
Research, 1910, N. S. xviii, 111. 
6 See Sternberg, C., Wien. klin. Wchnschr., 1905, xviii, 1214. 676 
THE RESPIRATORY SYSTEM 
lymph-nodes. Sudden death may occur from perforation into the 
trachea. Pressure upon the pulmonary veins may lead to pulmon- 
ary edema. The bronchial lymph-nodes are very important as distribut- 
ing centers of infectious microorganisms, and particularly as points of 
lodgment of tubercle bacilli, which have been gathered from the pulmon- 
ary air spaces, from the pharynx, or elsewhere.1 
The Lungs. 
One or both lungs may be wanting or only partially developed. One lung is some- 
times converted into a number of sacs formed of dilated bronchi, while the lung 
parenchyma is undeveloped. Supernumerary bronchi are recorded. 
The lobes may be subdivided by deep fissures, accessory lobes may be present, or 
an accessory lung may be present. An accessory lung in the abdominal cavity has 
been described.2 There may be, with absence of part of the wall of the thorax, hernia 
of the lung. There may be transposition of the lungs, with similar changes in the 
position of the heart and the abdominal viscera. 
Malformations. 
INJURIES-PERFORATIONS. 
Severe contusions of the thorax may produce rupture of the lungs, 
with extravasations of blood into the pleural cavities. 
The lungs may be wounded by puncture from a fractured rib and by 
penetrating weapons and projectiles. Such injuries often lead to bleed- 
ing into the lung tissue, followed by inflammatory changes. The lungs, 
however, exhibit a considerable degree of tolerance for such injuries, 
many perforating bullet wounds healing in a few days unless a large 
vessel has been severed. 
Collections of pus in the pleural cavities, the mediastinum, the liver, 
the spleen, the kidneys, and the peritoneal cavity may perforate the lungs. 
See also Hydropneumothorax. 
DISTURBANCES OF CIRCULATION 
It is very useful to anticipate a study of the diseases of the lungs by an examina- 
tion of the circulation in the lung of a curarized frog on the Thoma frog-plate (see 
page 129). In no other way can one gain so vivid a conception of the complexity and 
abundance of the circulatory mechanism. 
Anemia.-The lungs may be anemic in connection with a general 
anemia of the body; or from compression of a part or a whole organ, as 
by pleural exudates, tumors, or new-formed fibrous tissue; from occlu- 
sions of blood-vessels or in atrophy of these in emphysema. 
1 Consult for summary of lesions of bronchial lymph-nodes, Hall, J. N., Philadelphia Med. Jour., 
1900, vi, 1059 (bibl.). See also Northrup, W. P., New York Med. Jour., 1891, liii, 203; Bovaird, D., 
ibid., 1899, Ixx, 1; and Harbitz, Jour. Infect. Dis., 1905, ii, 143. See also statistics of Hand, Proc. 
Philadelphia Path. Soc., 1903, vi, 132. For an excellent resume concerning normal and pathological 
tracheal and bronchial lymph-nodes, see Marfan, A. B., Bouchard and Brissaud, TraitG de Mddicine, 
Paris, 1901, vii, 525; also Zuber, Grancher, Comby, and Marfan, TraitS des maladies de 1'enfance, 
Paris, 1904, iii, 578. For a study of the relation of the bronchial lymph-nodes to the lymph-vessels 
of the thorax see Weleminsky, F., Berl. klin. Wchnschr., 1905, xlii, 743. For a study of the relation- 
ship of the cervical and bronchial lymph-nodes, see Beitzke, H., Virchows Arch., 1906, clxxxiv, 1. 
2 Consult Vogel, R., Virchows Arch., 1899, civ, 235; and Hammer, J., Zieglers Beitr., 1904, xxxvi 
518. Pathology-Delafield and Prudden. 
Plate V. 
The nodes are enlarged and caseous, with areas of commencing softening. An isolated 
tubercle in the lung tissue above the enlarged nodes indicates a local dispersion of the 
tubercle bacilli. The lung was hardened in alcohol. 
Tuberculous Bronchial Lymph-Nodes. THE RESPIRATORY SYSTEM 
677 
Hyperemia and Edema. 
Hyperemia may occur as the result of the inspiration of irritating 
gases; from the presence of toxic substances in the blood; in early phases 
of inflammation, or as the result of such an occlusion of vessels in one 
part as causes the accumulation of blood in another. 
On the other hand, hyperemia of the lung is often due either to some 
hindrance to the exit of blood through the pulmonary vein, such as 
mitral stenosis or insufficiency, or to enfeeblement of the ventricular 
contractions, as in fatty degeneration of the heart muscle or interstitial 
myocarditis. In the last hours of life the feeble action of the heart dis- 
poses to pulmonary congestion. The position of the body upon the back 
in bed favors an accumulation of blood in the posterior portions of the 
lungs-hypostatic congestion. Hyperemic lungs are in varying degrees 
Showing dilated capillaries of th'e walls of the air vesicles and hematogenous pigment in the exfoliated 
epithelial cells of the air vesicles. 
Fig. 400.-Chbonic Congestion of the Lung. (Brown Induration.) 
darker and heavier than normal; an unusual amount of blood flows from 
the cut surface. Edema fluid also is often present. Red blood-cells 
often pass through the capillary walls in hyperemia, and these with more 
or less exfoliated epithelium may be found in the air vesicles. 
Chronic Congestion.-In prolonged hyperemia of the lungs, notably in 
connection with lesions of the mitral and aortic valve, or degeneration 
or dilatation of the left ventricle, the veins and capillaries, especially 
the capillaries, become permanently distended, pouched, and elongated, 
so that they often stretch in loops into the air spaces (Fig. 400). Red 
blood-cells find their way from the contorted vessels by diapedesis or small 
hemorrhages into the air vesicles or interstitial tissue of the lung. Here 
decomposition of the hemoglobin leaves brownish pigment particles 678 
THE RESPIRATORY SYSTEM 
which may remain free or be taken into cells. In the air vesicles the 
epithelial cells usually desquamate in considerable numbers, and take up 
the pigment in varying amount. This pigment gives to the lungs a pecu- 
liar brownish pink or salmon color. The appearance of these lungs may 
be modified by hemorrhagic infarctions, by preexisting emphysema or 
edema, or by exudative inflammation. Associated with these changes 
there is usually a new formation of fibrous tissue, so that the lung becomes 
indurated, leathery, and dry, and collapses less readily than normal. 
This condition is often called brown induration of the lung. This for- 
mation of fibrous tissue is analogous with that which occurs in other 
organs, such as the kidney and liver in chronic congestion. Emigration 
of leucocytes is not infrequently associated with diapedesis from the 
dilated capillaries, and these, with the desquamated epithelium, may 
accumulate in the air vesicles. 
EDEMA OF THE LUNGS. 
This condition is rarely independent, but is usually associated with 
other lesions of the circulatory or respiratory systems. It may be 
circumscribed or involve one or both lungs. The lungs in pronounced 
edema do not collapse, as is usual on opening the thorax. They may 
appear translucent. Fluid runs or is readily squeezed from the cut 
surfaces. 
In edema of the lungs the vesicles contain a clear, sometimes foamy 
albuminous fluid, occasionally tinged with blood, usually mixed with 
exfoliated vesicle epithelium. Leucocytes and red blood-cells may also 
be present. The edematous fluid may be present in the bronchi and 
in the interstitial tissue of the lungs. Edema is often associated with 
hyperemia, and like this may vary in different parts of the lung. On 
the other hand, there may be extensive edema without overfilled blood- 
vessels; these in excessive edema may indeed be nearly empty and 
compressed. Edema of the lungs may occur in general infections and 
intoxications, or in association with local inflammatory processes. 
It may be associated with cardiac and renal lesions. It may be a 
part of general dropsy or exist independently of this. It frequently 
occurs in the last hours of life-agonal edema. Edema of the lung may 
occur suddenly without the obvious inciting accompaniments above 
noted and may be fatal. In such instances the edema is due to an 
increased permeability for fluid of the pulmonary capillaries.1 Fatal 
edema of the lungs may be associated with fat embolism.2 
The studies of Welch3 show that with diminished force exerted by 
the left side of the heart, the vigor of the right remaining unimpaired, 
edema of the lungs may follow.4 
1 See Krehl, Clinical Pathology, Eng. trans. Philadelphia, 1905, p. 122. 
2 Connell, Jour. Am. Med. Assn., 1905, xliv, 612. 
3 Welch, W. H., Virchows Arch., 1878, Ixxii, 375; r6sum6 by Meltzer, Am. Med., 1904, viii, 391. 
4 For a study of edema of the lungs based on numerous cases, see Coplin, Proc. Path. Soc., Phila- 
delphia, 1906, ix , 77; also Riesman, Am. Jour. Med. Sc., 1906, cxxxiii, 88. For a study of the disturb- 
ances of circulation in the lungs under various abnormal conditions see Esser, J., Centralbl. f. inn. Med., 
1901, xxii, 97 (bibl.). THE RESPIRATORY SYSTEM 
679 
HEMORRHAGE AND INFARCTIONS. 
Hemorrhage. 
Hemorrhage into the lung tissue and air spaces of the lungs may occur 
from trauma, from pulmonary infarction, from rupture of aneurysm, in 
acute infectious diseases and intoxications, in scurvy and hemophilia, in 
asphyxia from brain lesions or other conditions, or from tuberculous 
ulcerations involving the blood-vessels. Multiple ecchymoses may occur 
in fat embolism. 
Hemorrhage is of frequent occurrence in excessive hyperemia of the 
lungs, notably in connection with mitral stenosis and insufficiency. 
Under these conditions the extravasation of blood may take place by 
diapedesis or by rhexis. The accumulations of blood may be single or 
multiple, localized or diffuse, dense and firm, or, when edema is present, 
soft and fluid in character. During the last hours of life, owing to 
enfeeblement of the heart, extravasation of blood may occur which sinks 
to the posterior dependent portions of the lungs. 
Thrombosis, Embolism, Infarcts. 
As a result of thrombosis or embolism of the pulmonary artery, 
hemorrhagic infarcts may be formed. They are not very common in the 
lungs because the supply of blood is through both the pulmonary and 
bronchial arteries, so that even with stoppage of the pulmonary artery 
by a thrombus or embolus, hemorrhagic infarcts are not necessarily 
formed. When, however, the pulmonary circulation is faulty as in var- 
ious cardiac lesions, hemorrhagic infarcts are more apt to form as the 
result of embolism or thrombosis of the pulmonary artery. 
These infarcts are often multiple, usually circumscribed, and rounded 
or wedge-shaped, from the size of a walnut to that of an orange. They 
are of dark red color, hard and unaerated, with the air spaces distended 
with blood, and are often surrounded by a zone of inflammatory exudate. 
They may be situated in any part of the lungs, but are most common 
in the lower lobes. At the apices of the infarcts, the occluding throm- 
bus or embolus may be discovered. When, as is usually the case, they 
are near the surface of the lungs, a circumscribed inflammation of the 
pleura often occurs. The air spaces within the infarcts are filled with 
blood and the capillaries distended. 
Such infarcts may be followed by death; they may become gan- 
grenous, or if the emboli or thrombi be not infectious, the blood may 
become absorbed, and, especially in the smaller forms which are more 
often due to embolism, they may be gradually changed into a smaller 
mass of pigmented fibrous tissue.1 
A large part of the lungs may be involved in hemorrhage due to 
thrombosis of large trunks of the pulmonary artery. Hemorrhagic 
1 For a study of experimental infarction of lung, see Karsner and Ash, Jour. Med. Research, 1912 
N. S. xxii, 205. Also Mann, F. C., Jour. Exper. Med., 1917, xxvi, 387. 680 
THE RESPIRATORY SYSTEM 
infarctions from thrombosis or embolism are most frequent in lungs 
which are the seat of chronic congestion. The most common source of 
the emboli of the pulmonary artery is the right heart or peripheral 
thrombi.' After surgical operations especially in the pelvic region, and 
also after injury, thrombi may form in the veins with subsequent em- 
bolism of the pulmonary artery. Such embolism is a frequent cause of 
sudden death (see page 38). 
ATELECTASIS. 
In atelectasis the walls of the air spaces lie together, either because 
they are collapsed or compressed, or because, as in congenital atelectasis, 
the lungs, or portions of them, have not been expanded in respiration. 
Fig. 401.-Vesicular Emphysema. 
In fetal or congenital atelectasis, defects in the respiratory mechanism 
or blocking of the air passages may be responsible for the unaerated 
condition which may affect only parts of a lung or a whole organ. The 
atelectatic portions of the lungs are dark red in color and of fleshy con- 
sistence.2 
Atelectasis may, on the other hand, be acquired, either in childhood 
or in adult life. In young children collapse of portions of the lung is 
of frequent occurrence, through occlusion of bronchi by inflammatory 
exudate. The region thus cut off is gradually deprived of air, and as the 
blood continues to circulate, becomes dark red and firm in texture. 
Compression atelectasis may be due to exudates, tumors, etc., in the pleu- 
ral cavities. Under these conditions the portion of lung involved may 
Showing enlargement of the air spaces and thinning of their walls. 
1 For a fuller consideration of embolism and thrombosis of the pulmonary artery consult Welch, 
Albutt, System of Medicine, 1909, vi, 691. See also Keen, System of Surgery, 1906, i, 444; also 
Aschoff, de la Camp, von Beek, and Kronig, Beitrage zur Thrombosefrage, Leipzig, 1912. 
» Collapsed lungs, from their red color and fleshy consistence, are often spoken of as " carnified." THE RESPIRATORY SYSTEM 
681 
be paler than normal from the pressing out of the blood. In adults, 
large or small portions of lung tissue may collapse from occlusion of 
a bronchus by exudate or stenosis, by paralysis of the vagus, or in long- 
continued feebleness of respiration. Edema may be associated with 
collapse. 
Atelectasis may resolve by an early admission of air to the collapsed 
region. On the other hand, if prolonged, fibrous tissue may form and 
the involved portion may be 
finally converted into a cicatri- 
cial mass, sometimes containing 
bronchiectatic cavities. 
EMPHYSEMA. 
Vesicular Emphysema.-In 
forcible inspiration or expiration 
through obstruction of the air 
passages, in coughing, in the use 
of wind instruments or in glass- 
blowing, or with consolidation 
or compression of portions of the 
lungs, the walls of the air spaces 
of the lungs may be more or less 
distended, either in circum- 
scribed regions or over large 
areas of the lungs. Inasmuch, 
however, as every performer on 
wind instruments or every glass 
blower does not develop emphy- 
sema2 the assumption has to be 
made that other factors than 
mere increased intrapulmonary 
pressure play a part, even though 
subordinate. The occurrence of 
emphysema in families points 
in the same direction; hence, a 
defective lung structure is often 
assumed as a precursor to the 
final change. Whether such de- 
fects in the elastic or connective 
tissue of the lung parenchyma 
exist has not yet been proved. 
The distention of the lung tissue 
may develop rapidly producing an acute emphysema. 
If the conditions which induce emphysema are persistent, as in chronic 
bronchitis with difficult respiration and coughing, atrophy of the walls 
Fig. 402.-Interlobular Emphysema of Lung. 
Child two months old. After whooping-cough.1 
1 For a fuller description of this case, see Northrup, IF. P., Am. Jour. Med. Sc., 1883, Ixxxvi, 147. 
2 Hoffman, F. L., Jour. Industrial Hygiene, 1920, ii, 1. 682 
of the air vesicles and alveolar passages may take place-chronic emphy- 
sema. The walls become thinner and are often perforated; adjacent air 
spaces coalesce, so that larger and smaller irregular, thin walled cavities 
are formed (Fig. 401). Destruction of the capillary network of the 
atrophied walls occurs, and the lung may thus become pale and anemic. 
As a rule, the distention of the air spaces is most marked along the 
anterior margins of the lungs, but it may be more general. Through 
the atrophy of the elastic tissue of the lungs, when the lesion is general 
and advanced, these organs do not collapse when the chest is opened. 
They appear pale, are dry and soft, and pit on pressure by the finger. 
THE RESPIRATORY SYSTEM 
The irregular darker areas in the lower lobe indicate the air largely in the interlobular septa. 
Fig. 403.-Interstitial Emphysema of the Lung of a Child. 
In addition to the changes in the lung, deformation of the thorax is 
evident if the emphysema is of long standing. The sternum arches for- 
ward, the ribs are held in a position of full inspiration, and there is often 
a kyphosis. Premature ossification of the costal cartilages occurs.1 
Hypertrophy of the accessory muscles of respiration is not infrequent. 
The heart may be pushed upward. Some pathologists consider that the 
emphysema is secondary to the thoracic changes and possibly consequent 
alteration in the pulmonary circulation.2 
1 Loschcke, Deutsch, med. Wchnschr., 1911, xxxvii, 916; Verhandl. d. deutsch. path. Gesellsch., 
1913, xvi, 435; and Salis, H. V., Frankfurt. Ztschr. f. Path., 1910, iy, 399. 
2 For bibl. of the newer views on emphysema, see Pdssler, H., Uber Lungen Emphysem, Deutsch. 
Klin., 1909, xii, 409. 683 
THE RESPIRATORY SYSTEM 
The microscopic picture is that of varying degrees of atrophy; des- 
quamation and fatty degeneration of the vesicle epithelium are common. 
As already indicated, emphysema of the lungs is often associated with 
chronic bronchitis and with chronic asthma. With this may be more or 
less hyperplasia of the interstitial tissue. Dilatation or hypertrophy of 
the wall of the right ventricle is common. Chronic endarteritis of the 
pulmonary vessels may be associated with emphysema. There may be 
chronic venous congestion of the abdominal viscera and dropsy. Dela- 
field held that the more esssential lesion in some forms of emphysema is 
the development of new connective and elastic tissue with which dilata- 
tion of the air vesicles and atrophy of their walls are in varying degrees 
associated.1 
In old age, atrophic processes in the lungs may be associated with 
dilatation and mergence of the air spaces. This is called senile emphy- 
sema. The lungs contract when the thorax is opened, the tissue is 
friable, and the elastic and connective tissues are diminished. Excessive 
emphysema, however, may be present in young children following whoop- 
ing-cough (Fig. 402), or in some instances may be congenital in origin. 
Interstitial Emphysema.-Rupture of the walls of the air spaces 
may permit the escape of air into the interstitial tissue of the lungs 
(Fig. 403). It is seen after whooping-cough and laryngeal diphtheria, 
or when artificial respiration has been violently applied in conditions 
where the bronchi are contracted, such as anaphylaxis consequent upon 
injection of antitoxic sera. Rupture of the pulmonary pleura may 
admit air into the mediastinum and thence into the tissues of the neck. 
Gas may form after death in the interstitial tissue of the lungs, from the 
presence of the Bacillus aerogenes capsulatus or other putrefactive 
bacteria. 
GANGRENE. 
Circumscribed gangrene occurs in the form of one or more rounded 
or irregular masses of variable size. The gangrenous portion of lung is 
at first brown and dry. The surrounding lung tissue is congested or 
edematous, or infiltrated with blood, or inflamed. If the gangrenous 
focus is near the pleura, the latter will be coated with fibrin. Gradually 
the gangrenous portion of lung assumes a dirty green color and a putrid 
odor. It becomes soft, disintegrated, and separated from the surround- 
ing lung. The blood-vessels may be obliterated by thrombi, or eroded 
so that there are profuse hemorrhages. 
Such a gangrenous process may extend to the adjacent lung tissue, or 
a zone of gray or red hepatization or of connective tissue may be formed. 
The fluid from the gangrenous lung may pass into the bronchi and be 
expectorated; or it may run from one bronchus into another and incite 
new gangrenous foci or diffuse gangrene. The pulmonary pleura may be 
perforated and a gangrenous pleurisy produced. Gangrene may follow 
lobar or bronchopneumonia, especially such phases of the latter as result 
from the inspiration of foreign material containing microorganisms from 
1 See also Ors6s, Zieglers Beitr., 1907, xli, 95. 684 
THE RESPIRATORY SYSTEM 
the mouth; it may arise from infectious emboli in the lungs, or by an 
extension of a gangrenous process from an adjacent part. It may be 
associated with esophageal diverticula.1 
Diffuse gangrene may follow the circumscribed form; it may compli- 
cate lobar pneumonia or occur as an independent condition. A large 
part of a lobe or of an entire lung becomes greenish, putrid, and soft, 
and the pulmonary pleura is inflamed. There may be hemorrhages from 
eroded vessels. There may be general septicemia. 
Various forms of bacteria may be present in gangrenous areas of 
the lungs. Among the more common are Streptococcus pyogenes, 
Staphylococcus pyogenes, pneumococcus, and various saprophytic 
microorganisms,2 among them the fusiform bacilli and the spirochete of 
Vincent.3 
INFLAMMATION. (Pneumonia, Pneumonitis.) 
General Considerations. 
Before commencing the study of inflammation of the lungs it is well to recall some 
of those features of structure and function which influence the local manifestations of 
disease in these organs and largely determine the special character of its lesions. In 
the first place, the lungs, like the gastrointestinal canal, while in a topographic sense 
within the body, are still in open communication with the exterior, and are thus more 
directly exposed to various deleterious agencies than are those structures and organs 
wholly inclosed by living tissues. Notwithstanding this vulnerability of location, the 
recesses of the lungs are guarded by protective mechanisms of great efficiency. 
Since many of the lesions of the lungs, as we shall presently see, are induced by 
the entrance of foreign material into them in the form of dust, it will be useful here to 
glance at some of the ways in which the body is protected against the entrance of dust 
and the means by which this is disposed of when it does pass, as is frequently the case, 
even the most effective barriers. 
In normal breathing through the nose, the air impinging upon the moist surface of 
the tortuous passages loses a considerable part of its dust and bacteria. In the 
throat, larynx, and trachea, a similar clearing occurs, so that at the end of 
inspiration the air has been so far freed from its floating particles that it emerges in 
the expiration practically dust- and germ-free. 
If the nasal passages are not normal, or if breathing through the mouth is practised, 
the air contaminations may pass more deeply into the recesses of the lungs, or may 
still remain to a certain extent suspended in the expired air. 
Many of the dust particles which may lodge upon the walls of the deeper air pas- 
sages are swept upward by the ceaseless ciliary movement and cast out, as are the 
secretions and dust accumulations from the nose and throat. The growth of many 
microorganisms is inhibited by the mucus of the air-passages. Many inert dust 
particles which are taken into the tissues at the tonsils or in the deeper recesses of the 
air tubes are carried in the lymphatics to places of temporary or permanent deposit. 
Many microorganisms within the tissues are destroyed by phagocytes or by the body 
fluids. 
Thus it is that although large numbers of dust particles may enter the respiratory 
passages at every breath, the larger proportion are usually safely disposed of, most of 
them through the secretions of the throat and nose. 
But it has long been known that a certain number of inert dust particles from the 
inspired air, in spite of the tortuous and narrow passages which they must pass in the 
deeper recesses of the lungs, do reach the air vesicles, from which they may be largely 
1 See Stark, Arch. f. Verdauungskr., 1901, vii, 1. 
2 See for "acid-proof" bacilli in gangrene, Ophuls, IF., Jour. Med. Research, 1902, N. S. iii, 242. 
3 Buday, Zieglers Beitr., 1910, xlviii, 70 (bibl.). THE RESPIRATORY SYSTEM 
685 
removed to the adjacent tissues or to the bronchial lymph-nodes by way of the pleural 
and other lymph-vessels. 
Whether living bacteria can reach the air vesicles under the ordinary conditions of 
respiration is a much discussed question, which has given rise to many painstaking 
researches. One group of workers has concluded that the lungs, except for the larger 
air passages, are usually germ-free. On the other hand, many have concluded from 
equally careful studies that the lungs of both men and animals often, if not always, 
contain a moderate number of living microorganisms. The technical difficulties in 
this research are so great, and the conditions under which they have been undertaken 
are so various, that this difference of opinion is not surprising. 
Without attempting to marshal the evidence adduced on both sides of the question 
it appears that in most of the earlier studies on the artificial introduction of living 
microorganisms into the lungs, the time which was allowed to elapse between the 
introduction of the germs and the examination of the lungs was too long, so that the 
possibility that the lungs might rapidly dispose of germs lodged in their deeper 
recesses by lysis or phagocytosis, was overlooked. 
In fact, it has been found that in experiments in which animals are exposed to an 
atmosphere laden with bacteria-containing dust or spray, if the animals are killed at 
once after the exposure, living microorganisms may be found even in the deepest 
portions, while if even a short time be allowed to elapse they will have entirely 
disappeared. 
While, however, in the air passages and lungs we have a most efficient protective 
mechanism against the entrance and permanent lodgment under ordinary conditions 
of both inert dust particles and living microorganisms in such situations as would 
involve serious damage to these delicate organs, it should be remembered that the 
efficiency of these safeguards may be greatly diminished if they are overworked and 
abused. 
The lungs of practically all persons who live indoors contain a considerable amount 
of soot, which blackens them (see page 703). The irritation incited by this foreign 
stuff leads in most adults to some part of the lungs becoming dense and useless. The 
overworking of the delicate mechanism for filtering the foreign matter out of the lymph 
flowing from the lungs to the interior blood channels leads to serious damage of this 
mechanism and to an increased vulnerability to infection which the healthy body 
should and could resist. 
The responses of the lung tissue to the excitants of inflammation are not funda- 
mentally as distinct nor as variable as the common classifications of pneumonia would 
seem to indicate. Exudation from the smaller blood-vessels is one of the most com- 
mon features of the acute phases of pulmonary inflammation. 
The formation of exudates is favored by the extensive capillary network which is 
almost directly exposed to such deleterious agents as may gain access to the air spaces; 
while a great accumulation of exudates is possible owing to the spongy structure of the 
organs. The transitional character of the epithelium lining the air vesicles predis- 
poses to cell proliferation and exfoliation, and thus to the formation of exudate. On 
the other hand, the abundant blood and lymph-channels1 favor the speedy removal 
from the air spaces in the lungs of large quantities of exudate. 
There are two sets of lymph-vessels in the lung; first, those which accompany the 
pulmonary artery and pour their lymph into the bronchial nodes at the hilum of the 
lung; second, those which ramify in the interacinous and interlobular tissue of the lung 
(Fig. 404) and join the branches of the pleural plexus between the lobules. It is 
evident from this arrangement of the pulmonary lymphatics that a close relationship 
is maintained between even the deeper recesses of the lung and the pleura.2 
Along the subpleural lymph-vessels are numerous islets of lymphoid tissue and 
often a few small lymph-nodes.3 
1 See Miller, Arch. f. Anat. u. Physiol., Anat. Abth., 1900, p. 197 (bibl.). 
2 Councilman, W. T., The Lobule of the Lung and Its Relation to the Lymphatics, Boston Jour. 
Med. Sc., 1900, iv, 165. For a study of the comparative histology of the lungs of domestic animals, 
see Muller, Arch. f. mikros. Anat., 1906, Ixix, 1. 
3 See for a study of pleural lymph-nodes and lymphoid tissue Heller, Deutsch. Arch. f. klin. Med., 
1895, Iv, 141. 686 
THE RESPIRATORY SYSTEM 
While the abundant lymphatics of the lungs aid in the rapid disposal of exudates, 
they, on the other hand, favor the absorption of toxic substances into the body at 
large when bacteria, for example, are the excitants of the local inflammation. So that 
although exudative pneumonia is commonly considered a local disease, it is often 
Fig. 404.-Lung Showing Tubercles with Pigmentation in the Pleura. 
At the lower left-hand portion the lobules of the lung are outlined by the thickening of the 
walls of the lymph-channels and of the interlobular septa. 
rather a local expression of a general infection or is doubly significant on account of the 
associated toxemia. In addition to the development and accumulation of exudates, 
necroses and the formation of fibrous tissue are the most noteworthy general pathologi- 
cal processes in the lungs. THE RESPIRATORY SYSTEM 
687 
While the conspicuous differences in the various forms of pneumonia are largely 
due to differences in the nature, virulence, and distribution of their excitants, predis- 
posing factors dependent upon age, constitutional condition, and the protective 
mechanism of the lungs are of great significance. 
The common classifications are based partly upon etiology, partly upon morphol- 
ogy, and the names used suggest now the topography of the lesions or the character of 
the tissue which is especially affected, and again the species of the bacterial excitant. 
Thus the term lobar pneumonia is topographical; tuberculous pneumonia emphasizes 
the excitant; while interstitial pneumonia suggests the form of tissue involved.1 
Acute Lobar Pneumonia. (Fibrinous Pneumonia- 
This is an infectious disease incited most frequently by the Diplo- 
coccus pneumoniae1. It is especially characterized by an exudative 
inflammation in which red and white blood-cells, serum, and fibrin 
accumulate in the air spaces of the lungs, usually involving, especially in 
adults, the whole of one lobe or lung or portions of both lungs.3 Toxe- 
mia from the absorption of poisons formed locally in the lungs is an 
important and often most significant factor in the disease. The pneumo- 
coccus is usually widely disseminated in the blood. 
During the first hours of the inflammation the capillaries of the air 
spaces are congested, the lung is edematous, firmer than normal, but 
not markedly consolidated. The air spaces contain varying numbers of 
leucocytes, red blood-cells, serum, and fibrin (Fig. 405). The epithelial 
cells lining the air vesicles may be swollen, they sometimes proliferate, 
and are usually detached in considerable numbers. Catarrhal bronchitis 
and pleuritis may at this time develop. This is called the stage of " con- 
gestion " or 11 engorgement " and may last for a few hours or for several 
days. 
As the process continues, red blood-cells, but especially polymor- 
phonuclear leucocytes, and fibrin accumulate in the air spaces and smaller 
bronchi, so that the portion of lung involved becomes solid and friable, 
somewhat resembling the liver in color and consistence; hence the term 
11 red hepatization" which has been used to indicate this condition. The 
cut surface of the consolidated portion is dry and coarsely granular, 
the granules being plugs or casts of exudate in the air spaces. A light 
scraping of the cut surface of the lung with the knife readily removes 
these granules or plugs of exudate, which consist largely of fibrin and 
leucocytes with red blood-cells and exfoliated epithelium (Fig. 406). The 
relative amount of leucocytes, red blood-cells, and fibrin in the air spaces 
Croupous Pneumonia.) 
1 For a comprehensive resume of the normal and pathological physiology of the lungs, see Heinz, R., 
Handbuch der exper. Path. u. PharmakoL, Jena, 1906, ii. 
2 We shall use here as synonymous the names Diplococcus pneumoniae and pneumococcus; when 
pneumococcus is used the pneumococcus of Fraenkel is referred to. For a description of this organism 
and methods of grouping for therapeutic purposes, see Avery, Chickering, Cole, and Dochez, Acute Lobar 
Pneumonia: Prevention and Serum Treatment, Monograph No. 7, Rockefeller Inst., New York, 1917; 
and p. 248. 
3 The clinical course and the morphological characters of the inflammation of the lungs associated 
with the Diplococcus pneumoniae are so typical that we seem justified in limiting the term lobar or 
fibrinous pneumonia to this condition, even though inflammations of the lungs due to other excitants 
are occasionally lobar in extent and may have a fibrinous exudate, and though exceptionally the pneu- 
mococcus inflammation itself fails to reach lobar proportions. 688 
THE RESPIRATORY SYSTEM 
varies greatly, sometimes one, sometimes the other, preponderating 
(Fig. 407). The fibrin fibrils often coalesce or swell, forming homogene- 
Fig. 405.-Acute Lobar Pneumonia-Early Stage. 
This single air vesicle shows congestion of the capillaries in the walls, and a small amount of exu- 
date, fibrin, leucocytes, red blood-cells, and exfoliated epithelium. 
ous, irregular masses. On staining, large numbers of pneumococci may 
be found mingled with the other elements or within the cells of the 
exudate. While the general appearance of the lung in this stage is red, 
The air vesicles are filled with exudate consisting largely of leucocytes, fibrin, and serum with a 
few epithelial cells. 
Fig. 406.-Acute Lobar Pneumonia-Stage of " Red and Grat Hepatization." 
it is often mottled with gray and frequently is not uniformly solid. 
Although the capillary blood-vessels are compressed, they for the most 
part remain pervious; but thrombosis is not infrequent. Fibrinous THE RESPIRATORY SYSTEM 
689 
pleuritis is commonly present, and the interstitial tissue of the lung, 
while usually free from exudate, may be edematous and contain a few 
leucocytes and some fibrin. 
Fig. 407.-Acute Lobar Pneumonia. 
Showing fibrinous exudate stained by Weigert's method. 
The quantity of exudate in the 
lung is often very large, sometimes 
three to four or even six pounds in 
weight. 
In the usual course of events the 
red blood-cells now lose their hemo- 
globin, the exudate begins to soften, 
and the lung assumes a grayish color 
-gray hepatization or commencing 
resolution. The leucocytes and ex- 
foliated epithelium undergo granu- 
lar and fatty degeneration1 or necro- 
sis, and these with the fibrin soften 
and disintegrate (Fig. 408). The 
cut surface of the lung is now 
moister and less granular, and is 
often covered with a grumous fluid. 
Fig. 408.-Exudate from the Lung in 
Resolving Lobar Pneumonia. 
The cells show various phases of granular 
and fatty degeneration with fragmentation ot 
the nuclei and disintegration of the cell bodies. 
1 See, on fatty degeneration of pneumonic exudates, Christian, H. A., Jour. Med. Research, 1903, 
N. S. v, 109 (bibl.). 690 
THE RESPIRATORY SYSTEM 
In view of the new studies on cytolysis it seems probable that here, as 
in the removal of alien and dead organic material elsewhere in the body, 
the exudate is softened and rendered capable of solution by an exag- 
geration of the normal autolytic processes (see page 122).1 The softened 
exudate is gradually absorbed or may be in part expectorated. The in- 
volved portion of lung again contains air; the epithelium of the air spaces 
is regenerated. 
While it is customary and convenient to describe definite stages of 
lobar inflammation of the lung-red and gray hepatization and resolution 
-these in fact not only merge gradually into each other, but often co- 
exist in different parts of the lung. The process of reparation also usu- 
ally occurs irregularly, so that a lung in resolution may show side by 
side in neighboring air spaces well-formed cellular and fibrinous exudate, 
degenerated exudate, and various phases of epithelial cell repair.2 
The nature of the characteristic crisis in pneumonia, marked by a 
sudden fall in the temperature and improvement of the general symp- 
toms, is not clear. It is not accompanied by obvious changes in the 
pulmonary exudate. Many studies have been made on this subject, 
upon wrhich we cannot enter here.3 
For the evidence of communicability of the infectious agent in lobar 
pneumonia see page 249.4 
Associated Lesions in Other Organs.5-Fibrinous or serofibrinous pleu- 
ritis, usually with slight but often with voluminous exudate, commonly 
accompanies lobar pneumonia. Catarrhal and fibrinous bronchitis is also 
usually associated with the pneumonic process. Pericarditis and endo- 
carditis are not infrequent complications; meningitis occasionally occurs. 
The excitant of these complications is usually the pneumococcus.6 
Chromatolysis of the ganglion cells, albuminous degeneration in the 
kidney, liver, and heart, hyperplasia of the bronchial lymph-nodes, 
together with leucocytosis, fever, and frequent serious enfeeblement of 
the heart action, are marks of toxemia. The bronchial lymph-nodes may 
contain, especially in the perifollicular sinuses, and often within phago- 
cytes, red blood-cells, cell detritus, and pneumococci brought from the 
lungs; fibrin is frequently also present. 
In lobar pneumonia in young children, in those enfeebled by acute 
and chronic disease, and in the aged, the lungs are often less uniformly 
consolidated and less dense and hard than in vigorous adults. When 
lobar pneumonia occurs in lungs already the seat of chronic lesions, such 
as chronic congestion, emphysema, interstitial pneumonia, or tuberculo- 
1 For a study of the chemistry of resolution of the exudate, see Simon, Deutsch. Arch. f. klin. Med. 
1901, xx, 604. See also Levene, Jour. Am. Med. Assn., 1906, xlvi, 774, 866. 
2 For a study of the histology of acute lobar pneumonia with bibl., see Pratt, J. H., Johns Hopkins, 
Hosp. Rep., 1900, ix, 265. 
3 See for a study of the crisis, Tchistovitch, Ann. Inst. Pasteur, 1904, xviii, 304 (bibl.); also, for discus- 
sion of opinion, p. 249. 
4 See, for a general study of communicability, Edsall and Ghriskey, Tr. Col. of Phys., Philadelphia, 
1904, xxvi, 6; and Dochez and Avery, Jour. Exper. Med., 1915, xxii, 105. 
6 See for r6sum6 of statistics of complications Kerr, Tr. Chicago Path. Soc., 1903, v, 274. Also, for 
an analysis of four hundred and eighty-six cases, McCrae, Fyshe, and Ainley, Am. Med., 1904, vii, 135. 
6 For a study of pneumococci in the blood in pneumonia see Rosenow, Jour. Infect. Dis., 1904, i, 
280 (bibl.); also Dochez, A. R., Jour. Exper. Med., 1912, xvi, 680. 691 
THE RESPIRATORY SYSTEM 
sis, the gross appearances of the organs may differ in various ways from 
those of uncomplicated pneumonia. 
While Diplococcus pneumoniae is the regular excitant of lobar pneu- 
monia, other bacteria-see below-are not infrequently associated with 
it, sometimes, though by no means always, leading to clinical complica- 
tions and to modifications of the appearance of the lesion. Predisposition 
of the individual is an uncommonly conspicuous and important factor 
in the etiology of this as other forms of pneumonia, so that, as is well 
known, exposure, fatigue, etc., may induce the favoring bodily condi- 
tions under which the pneumococcus becomes harmful. The experiments 
upon animals are most conclusive in demonstrating that intrapulmonary 
injections of pneumococcus cultures, which may be entirely without 
obvious effects in a healthy animal, may induce exudative inflammation 
or become quickly fatal after such exposure to cold or fatigue or injury, 
or to the action of drugs, as interferes with the integrity of the blood or 
locally damages the pulmonary tissues.1 
Delayed Resolution after Lobar Pneumonia ("Organizing Pneumonia"). 
-Instead of undergoing resolution, the fibrinous and cellular exudate 
in the air spaces in lobar pneumonia may persist, and by a process similar 
to that which is called organization of a thrombus (page 34) may be 
gradually replaced by new vascular fibrous tissue. New connective- 
tissue cells grow out from the walls of the air spaces into the exudate; 
these cells become elongated. Intercellular fibrils develop, and long 
masses or bands of this new tissue, often containing blood-vessels, may 
extend for considerable distances through the air channels of the lung 
(Fig. 409). These may gradually coalesce with the walls, and together 
with an interstitial connective-tissue growth may lead to a fibrous con- 
solidation of the lung. 
Delafield described such an intra-alveolar formation of connective 
tissue leading to fibrous induration of lobes of the lung and occurring as 
an independent lesion apart from the exudative form of lobar pneumonia. 
Concurrent Infection and Suppurative Inflammation of the 
Lung Following Lobar Pneumonia. 
Although, as stated above, Diplococcus pneumoniae usually occurs 
alone in typical lobar pneumonia, it may be accompanied by the Strepto- 
coccus pyogenes or hemolyticus, by the Staphylococcus pyogenes, and 
occasionally by other microorganisms. The exact significance of these 
mixed or concurrent infections in lobar pneumonia is not always clear. 
But instead of the usual resolution there may be gangrene; or suppuration 
of the interstitial lung tissue with the formation of abscess may occur. 
In such cases Streptococcus pyogenes and Staphylococcus pyogenes 
aureus or putrefactive bacteria may be present with the pneumococcus 
in the exudate. 
1 For a comprehensive resume of studies on experimental pneumonia, see Wadsworth, A. B., Jour 
Exper. Med., 1912, xvi, 54, 78 (bibl.). For experimental pneumonia in dogs by bronchial insufflation, 
see Lamar and Meltzer,ibid., 1912, xv, 133. For study of lesions produced by bronchial insufflation 
of streptococci, see Wollstein and Meltzer, ibid., 1913, xviii, 548. 692 
THE RESPIRATORY SYSTEM 
The clinical type of pneumonia caused by the Friedlander bacillus 
does not differ greatly from that due to the pneumococcus, except in its 
almost regularly fatal course, the mortality being about 85 per cent. 
The organism can be found in the sputum and in the blood. 
The lung, when incised, is not granular, as in pneumococcus pneu- 
monia, but is slimy, and a stringy, clear or bloody mucus can be scraped 
from the cut section This consists chiefly of the bacteria with their 
mucoid capsules. There is less fibrinous exudate and fewer leucocytes 
and red blood-cells in the alveolar exudate, than in pneumococcus pneu- 
monia. The center of the consolidated area frequently undergoes soft- 
ening, but, as a rule, does not break into the large bronchi and give rise 
to bronchiectases.1 
Fig. 409.-"Organizing" Pneumonia-Delayed Resolution After Lobar Pneumonia. 
Anastomosing fascicles of fusiform connective-tissue cells lie within the air vesicle and are con- 
tinuous with similar new formations in adjacent air spaces. 
Suppurative inflammation of the interstitial tissue of the lungs may 
involve not only the larger fibrous-tissue bands, but the walls of the air 
vesicles and other air spaces. It is often called "purulent infiltration." 
From the cut surface of the lungs in resolving lobar pneumonia a gru- 
mous fluid resembling pus often exudes, and this is sometimes mistaken 
for a mark of interstitial suppuration of the lung. 
Suppurative inflammation of the interstitial tissue of the lung may 
occur without association with lobar pneumonia. 
Lobular Pneumonia and Bronchopneumonia. 
In distinction from, that common form of pulmonary inflammation 
induced by the Diplococcus pneumoniae, which as we have seen is usu- 
ally lobar in character, there are exudative inflammations of the lungs, 
due to many different excitants, which are "patchy" or "lobular" in 
extent, the consolidated areas varying in size from such as are scarcely 
visible to those several centimeters in diameter.2 These patches of lobu- 
1 Toenniessen, Munchen, med. Wchnschr., 1911, Iviii, 2608. 
2 The term lobular does not refer exclusively to the anatomical "lobule" of the lung, since the 
masses or patches of consolidation often embrace several lobules or parts of these. THE RESPIRATORY SYSTEM 
693 
lar consolidation often join and merge, so that solidification of whole 
lobes or lungs is not uncommon. But the mottled, uneven surface and 
color of the lungs on section, and the Usual absence of the peculiar granu- 
lation ordinarily suffice for the distinction, even to the naked eye, of the 
lobar from the coalescent lobular forms of exudative pneumonia. 
It is convenient to recognize several types of lobular exudative pneu- 
monia, although the character of the exudate is not distinctive. 
Bronchopneumonia.-Lobular Pneumonia with Inflammation of the Smaller Bronchi. 
This most important type of lobular pneumonia frequently develops 
in connection with, and as an extension of that form of inflammation of 
the smaller bronchi commonly called 11 capillary bronchitis." At first 
dark red in color, the lobular areas of consolidation in bronchopneumonia 
become more gray at the center through degeneration of the exudate, 
while the advance of the process in the periphery is marked by a less 
solid, redder zone. On section of the fresh lung these areas (Fig. 410) 
Showing several areas of consolidation with the central bronchus filled with exudate-stained 
dark in the section from which the photograph was made. 
Fig. 410.-Bronchopneumonia in an Adult. 
usually project somewhat above the general surface, and at their cen- 
ters the involved bronchi may appear as lighter spots, from which pus 
may exude or be easily pressed out. Such areas may coalesce, forming 
larger consolidations. The exudate, which more or less completely fills 
the air spaces (Fig. 411), consists of serum, old and new-formed epithe- 
lial cells from the walls of the air spaces, red blood-cells, and often fibrin 
and polymorphonuclear leucocytes (Fig. 412) with various forms of 
microorganisms. As a rule, however, fibrin and leucocytes are not so 
abundant as in the exudate of lobar pneumonia. Giant cells are fre- 
quently found in the alveoli in the bronchopneumonia of children.1 
1 Hecht, Zieglers Beitr., 1910, xlviii, 263 (bibl.). 694 
THE RESPIRATORY SYSTEM 
Mucus and bronchial epithelium may be aspirated into the air spaces 
and mingled with the exudates. 
Bronchopneumonia involves a direct extension of the inflammatory 
process from the bronchi to the contiguous lung tissue, so that there is 
both an interstitial and an exudative pneumonia about the bronchial tubes, 
the whole forming the lobular areas of consolidation (Fig. 413). This 
The section shows a single lobular area of consolidation with its bronchus whose thickened wall 
merges with the surrounding zone of exudative pneumonia. 
Fig. 411.-Bronchopneumonia in a Child. 
involvement of the bronchial wall in inflammation with a direct exten- 
sion of the process to the surrounding lung tissue has been urged especially 
by Delafield as the process to which the term bronchopneumonia should 
be par excellence applied. 
Between the consolidated areas there may be atelectasis of lung tissue 
from the occlusion of the smaller bronchi 
with exudate. When the consolidated 
areas are situated at the surface of the 
lungs, fibrinous pleuritis may be present 
over the affected regions. 
This form of bronchopneumonia is 
frequent in children, sometimes as an 
independent process, but often associated 
with or following diphtheria, scarlatina, 
measles, etc.1 It occurs also in adults, 
either as a complication of infectious 
diseases such as typhoid fever, smallpox, 
influenza, measles, etc., or as a primary 
process. It may occur in the aged or in 
those enfeebled by wasting diseases. 
Resolution may take place in the areas of bronchopneumonia by proc- 
Fig. 412.-Bronchopneumonia-Exu- 
date in a Single Air Vesicle. 
1 MacCallum has recently called attention to the frequent occurrence of this type of pneumonia 
among soldiers. See Cole and MacCallum, Jour. Am. Med. Assn., 1918, Ixx, 1146 and MacCallum, 
Rockefeller Institute Monographs No. 10, New York, 1919. THE RESPIRATORY SYSTEM 
695 
esses of cell degeneration and absorption identical with those through which 
restoration is secured in lobar pneumonia. If, however, resolution in 
bronchopneumonia does not presently take place, and the lesion persists, 
dense connective tissue is apt to form about the bronchi and in the inter- 
stitial tissue of the lungs, which may lead to induration and distortion 
of the organs, atelectasis, chronic bronchitis with dilatation of the bron- 
chi, etc. A photograph of a section of such a chronic or "persistent" 
bronchopneumonia is reproduced in Fig. 414. Empyema due to the 
Streptococcus hemolyticus is a frequent complication. 
Other Forms of Lobular and Bronchopneumonia.-There are forms 
or types of lobular pneumonia in which serum and epithelial cells with 
more or less fibrin and leucocytes collect in the air spaces of a limited 
Fig. 413.-Bronchopneumonia-Child. 
Showing slight change in the epithelium of the bronchus; a purulent exudate in the lumen; thickening 
of the wall of the small bronchus, and exudate in the adjacent air vesicles. 
region without primary bronchitis and without involvement of the walls 
of the bronchi and air spaces. 
In one type of lobular pneumonia and bronchopneumonia the exu- 
date may consist largely of pus cells which infiltrate the walls of the air 
spaces and bronchi as well as fill the air spaces theinselves. This type 
of inflammation may be induced by the aspiration In feeble persons of 
irritating substances or bacteria-containing material of various kinds, 
particles of food, saliva, etc. This is called aspiration pneumonia and 
may result in necrotic or gangrenous processes in the involved regions 
of the bronchi and lungs. Again there may be circumscribed areas of 
exudative pneumonia, often suppurative in type and involving the walls 
of the air spaces, called lobular pneumonia of hematogenous origin, or 
pyemic or septic pneumonia. Thus, abscesses of the lungs may be formed. 
Such abscesses are of occasional occurrence after tonsilectomy.1 
1 Clendening, L., Jour. Am. Med. Assn., 1920, Ixxiv, 941; and Fisher, L., and Cohen, A. J., ibid, 1921, 
Ixxvii, 1313. 696 
THE RESPIRATORY SYSTEM 
In the lobular pneumonia of bubonic plague the exudate consists 
largely of blood and plague bacilli.1 
In the aged or those long in bed in an enfeebled condition, hyperemia 
and edema with more or less exudate, usually epithelial in character, 
may develop in the dependent posterior portions of the lungs-hypostatic 
congestion and hypostatic pneumonia. 
There is a peculiar and rare form of bronchopneumonia associated 
with necrosis in which forms of streptothrix have been isolated which 
Fig. 414.-Persistent-Chronic-Bronchopneumonia 
are undoubtedly the excitants of the disease.2 Actinomyces is also an 
occasional excitant of bronchopneumonia. 
In all these forms of lobular pneumonia edema and atelectasis of 
uninvolved portions of the lung may occur.3 
It is evident that in lobular pneumonia the infectious agent may reach 
the lungs either through the air passages or through the blood- or lymph- 
vessels, and that differences in the portals of entry as well as in the 
nature and virulence of the excitant and the susceptibility of the indi- 
1 Consult Flexner, S., Tr. Assn. Am. Phys., 1901, xvi, 481. 
2Consult Norris and Larkin, Jour. Exper. Med., 1900, v, 155; see also discussion on page 262. 
3 For a type ofhobular pneumonia in which the alveolar contents simulate giant cells, see Karsner 
and Meyers, Arch. Int. Med., 1913, xi, 534. THE RESPIRATORY SYSTEM 
697 
vidual have an important bearing upon both the course of the disease 
and the morphology of the lesion. 
The Excitants of Lobular and Bronchopneumonia.-The exci- 
tants of bronchopneumonia and other types of lobular pneumonia are 
most frequently Streptococcus pyogenes (Fig. 415), the pneumococcus, 
Staphylococcus pyogenes, the typhoid, diphtheria, influenza, and 
plague bacilli, and the pneumobacillus of Friedlander; the streptothrix, 
above mentioned, and other bacteria have been occasionally found.1 
Pathogenic moulds may be excitants of acute forms of lobular pulmonary 
inflammation. 
Fig. 415.-Aib Vesicle in Bronchopneumonia with Streptococci. 
This specimen is from a case of bronchopneumonia complicating a pseudomembranous inflam- 
mation of the larynx in scarlatina. Exfoliated epithelium, leucocytes, and a little fibrin with the strep- 
tococci form the scanty exudate. 
It will thus be seen that while it is convenient to group the exudative 
forms of pulmonary inflammation on the basis of distinctions which are 
in part morphological, in part etiological, the types in fact frequently 
merge or concur. This should not lead to confusion if we remember 
that these are infectious diseases whose most conspicuous lesion is located 
in the lungs, and that they are not species in the natural history sense, 
for which fixed and definite characters must be established, but that the 
groups only indicate various forms and phases of response of a living 
organ in various conditions of susceptibility to the damage inflicted by 
one or another, and not infrequently by two or more combined forms of 
microorganism. These pneumonias are not considered among the 
infectious diseases where they logically belong, partly because there are 
practical advantages in grouping pulmonary lesions together and partly 
because our knowledge of the relative frequency and significance of the 
bacterial excitants of the various types is still in many cases too incom- 
1 For a study of the bacteriology of lobular pneumonia, especially in adults, see Blumer, G., Albany 
Med. Ann., 1901, xxii, 424. 698 
THE RESPIRATORY SYSTEM 
plete to permit the establishment of a distinctive and clearly defined 
form of infection.1 
Chemical Pneumonia. 
The inhalation of atmospheres rich in oxygen incites, in twenty-four 
to forty-eight hours, congestion and edema of the lungs with desquama- 
tion of the alveolar epithelium, fibrinous exudate into the alveoli, and, 
finally, a fibrinous pneumonia.2 
The inhalation of irritating gases, especially chlorine, ammonia, 
nitrogen tetroxide, bromine, and a large number of the corrosive organic 
Fig. 416.-Chemical Pneumonia. 
Large phagocytic cells with pigment in the alveoli of lung in case of poisoning with nitric oxide. 
products now used as destructive agents in war, gives rise to a character- 
istic type of pneumonia due solely to the chemical action and not neces- 
sarily accompanied by bacterial infection,3 although this may occur. 
The inhalation of dilute corrosive vapors may cause no symptoms 
for six or eight hours, or there may be immediate dyspnea, a feeling of 
pressure on the chest, cough, cyanosis, and vomiting. These early 
1 For a study of experimental cooling of the body which may induce changes in the blood, predispos- 
ing to infection with the pneumococcus, see Reineboth and Kohlhardt, Deutsch. Arch. f. klin. Med., 
1900, Ixv, 192. For a study of the effects of cooling in general as a predisponent to infection, see Lode, 
Arch. f. Hyg., 1897, xxviii, 344; also Kisskalt, ibid., 1901, xxxix, 142 (bibl.). 
For a study of the portals of entry in lung infection, with special reference to the pleura, see Grober, 
Deutsch. Arch. f. klin. Med., 1900, Ixviii, 296 (bibl.). 
Concerning circulatory changes in the lungs under various pathological conditions, see Esser, 
Centralbl. f. inn. Med., 1901, xxii, 97 (bibl.). 
2 Karsner, H. T., Jour. Exper. Med., 1916, xxii, 149; Jour. Lab. and Clin. Med., 1917, ii, 254. 
3 See, for report of case with experiments on animals and bibl., Wood, F. C., Arch. Int. Med., 1912, 
x, 478. The best bibl. on nitrogen tetroxide poisoning is contained in Witthaus and Becker, Medical 
Jurisprudence and Toxicology, New York, 1911, iv, 301. THE RESPIRATORY SYSTEM 
699 
Fig. 417.-Chemical Pneumonia. 
Thrombus in vessel of lung in case of poisoning with nitric oxide. 
Fig. 418.-Chemical Pneumonia. 
Wall of bronchus from case of poisoning with nitric oxide, showing loss of surface epithelium and pig- 
mentation of connective tissue. 700 
THE RESPIRATORY SYSTEM 
symptoms occur only when the gas is fairly concentrated. At the end of 
six to eight hours of comparative comfort, the patient is suddenly at- 
tacked with extreme dyspnea and cyanosis; death may occur within 
forty-eight hours or, rarely, after five to eight days. If the attack is 
survived, the lungs remain sensitive to infections, and there is usually 
chronic cough and a tendency to hemoptysis. The sputum is tenacious 
and of a yellowish or brownish color; in nitrogen tetroxide poisoning this 
color may be due to staining by the gas itself; in other cases it is due to 
blood pigment derived from the bronchi or alveoli. At autopsy the 
larynx, trachea, and bronchi are congested and of a reddish or brownish 
color; the lungs of those who live for several days are full of emphysema- 
Fig. 419.-Chemical Pneumonia. 
Solid portions of lung with remnants of alveolar epithelium in case of poisoning with nitric oxide. 
tons areas, and the alveoli contain pigmented cells (Fig. 416). Many of 
the vessels contain thrombi (Fig. 417); and from the cut surface reddish 
or brownish fluid exudes. Ecchymoses in the lungs are present in the 
early stages; there is also an early exudation of fibrin and blood into 
the alveoli; and the bronchial mucous membrane is almost entirely de- 
stroyed (Fig. 418). After a few days, reaction sets in with regeneration 
of the alveolar epithelium in the form of large blocks or syncytial masses 
of cells with the growth of new connective tissue in the edematous and 
collapsed lung (Fig. 419 and 420). The patient may die in this stage. 
If he survives the bronchial mucous membrane regenerates to a certain 
extent, but considerable portions of the lung are irreparably damaged 
by the interstitial inflammation. THE RESPIRATORY SYSTEM 
701 
Interstitial Pneumonia. 
This name is given to a chronic productive inflammation, which 
involves the connective-tissue framework of the lung and the walls of the 
air spaces, and results in the formation of new connective tissue and the 
obliteration of the air spaces (Fig. 421). 
Such an interstitial pneumonia may follow acute lobar pneumonia 
with the production of new intra-alveolar connective tissue, broncho- 
pneumonia, chronic pleurisy, chronic bronchitis, and atelectasis, or may 
be induced by the inhalation of the dust of coal, stone, or other inor- 
ganic substances. Diffuse interstitial pneumonia may occur in syphilis. 
The topography of the lesion varies considerably in the different con- 
ditions under which the new tissue growth occurs. If it follows acute 
Fig. 420.-Chemical Pneumonia. 
Fibrinous and cellular exudate in lung after poisoning with nitric oxide. 
lobar pneumonia, one lobe or the whole of one lung may be involved and 
covered with pleuritic adhesions. The lobe or the lung is small, smooth 
on section, and firm in texture. The air spaces and small bronchi may 
be largely obliterated by the new connective tissue. If it follows broncho- 
pneumonia, one or more lobes are studded with fibrous nodules, which 
correspond to the affected bronchi and the associated lung territory; or 
a large part of a lobe is converted into dense fibrous tissue; the pleura 
may be thickened; there may be chronic bronchitis and bronchiectasia. 
If interstitial pneumonia is associated with thickening of the pleura, 
bands of connective tissue extend from the pleura into the lung, the 
bronchi are inflamed and often dilated. When associated with chronic 
bronchitis there are fibrous nodules around the bronchi, with more or 
less diffuse connective tissue. 702 
THE RESPIRATORY SYSTEM 
The changes in interstitial pneumonia may occur by a slow hyperpla- 
sia of the fibrous tissue or by the formation of granulation tissue, which 
Fig. 421.-Interstitial Pneumonia. 
With emphysema. The walls of the enlarged air vesicles and spaces are converted into dense 
fibrous tissue. 
gradually becomes denser with contraction. Although this process is 
primary in the interstitial tissue, exudates are often present in the air 
Fig. 422.-Chronic Interstitial Pneumonia. Reversion of Epithelium in 
Isolated Air Vesicles. 
spaces; atelectasis may occur, while emphysema and bronchiectasia are 
common. THE RESPIRATORY SYSTEM 
703 
Sometimes a noteworthy change occurs in the epithelium lining air 
vesicles which have been cut off from their neighbors by the new fibrous 
tissue. The epithelial cells increase in number and become thicker, and 
finally the small or distorted cavities may be lined with a complete 
investment of cuboidal cells (Fig. 422). This reversion of the epithelium 
of the air vesicles to a less differentiated type occurs in many chronic 
processes in the lungs. 
Pigmentation of the Lung.-The inhalation of dust and smoke is so 
continuous among those who live much indoors that the lungs of nearly 
all persons from the earliest years are more or less pigmented. The for- 
eign particles which get into the deeper recesses of the lungs are in part 
taken up by the epithelium of the air spaces, in part are carried by 
phagocytes or otherwise to the interstitial tissue of the lungs (Fig. 423). 
Here, either within cells or without, they are deposited along and within 
the lymph-channels or in the lymph-nodules of the pleura and interstitial 
Fig. 423.-Anthracotic Pigmentation of the Lung. 
Showing pigment beneath the thickened pleura and in the thickened septa of the emphysematous 
lung. 
tissue (Fig. 424), or they may be carried to the lymph-nodes at the root 
of the lungs. Rarely, this inhaled dust passes the tracheal and bron- 
chial lymph-nodes and may be deposited in the viscera, especially in the 
liver and spleen. 
Under ordinary conditions a moderate deposit of inhaled pigment 
particles in the lungs does not seem to be of great significance, but it does 
lead, if present in amounts as large as are frequently found in the air 
of many private houses, stores, factories, theaters, and other places of 
public assembly, to obliteration of lymph-channels and conversion of 
lymph-nodes into masses of pigmented fibrous tissue; and there is little 
doubt that in this way it may predispose to more serious lesions.1 On 
the other hand, miners and others working or confined in smoky air, 
stone or metal workers, and the like, are liable to excessive pigmentation 
and to develop interstitial pneumonia, especially marked at first along 
the interlobular septa and frequently associated with chronic bronchitis, 
emphysema, atelectasis, or bronchiectasia. This condition of the lung 
when due to the inhalation of coal dust is called anthracosis; when due 
to dust of various minerals, chalicosis; when due to iron dust, siderosis.2 
1 For a study of the significance of pulmonary anthracosis, see Haythorn, S. R., Jour. Med. Research, 
1913, N. S. xxiv, 259. 
2 For a study of the condition of iron pigment in cells and tissues see Arnold, J., Virchows Arch., 
1900, clxi, 284. 704 
THE RESPIRATORY SYSTEM 
The general process has been called pneumokoniosis. The color varies 
in these lungs with the character and amount of the deposited material, 
which is frequently quite unevenly distributed, though usually there is 
more in the upper than in the lower lobes. The amount of foreign mate- 
rial in such lungs is sometimes large,1 but in the normal urban dweller it 
amounts to only a few milligrams.2 
'Tuberculous Pneumonia. 
General Considerations.-Tuberculous inflammation of the lungs is 
similar in nature to tuberculous inflammation in other parts of the body.3 
But since the morphological features of the response of a tissue to injury 
are largely dependent upon the form and capacities of its cells, it is not 
surprising that in such complex organs as the lungs, the lesions of tuber- 
culosis should present many variations from the usual type elsewhere. 
The bronchial passages and the connecting air spaces, the numerous 
blood- and lymph-channels, especially favor the distribution of the 
tubercle bacillus within these organs; the open texture of the lungs per- 
mits, as in other forms of pneumonia, of great accumulation of exudate, 
while the delicacy and thinness of the air chambers favor extensive 
disintegration of the old or new-formed tissues or exudates when these 
have become necrotic under the influence of the poisons of the tubercle 
bacilli. 
Thus the variety of cells and tissues involved and their peculiar rela- 
tionships to one another and to the invading organisms render the lesions 
of pulmonary tuberculosis more complex in morphology than are tuber- 
culous lesions in any other part of the body. 
The classification of these lesions is largely based upon topographic 
considerations and is not to be regarded as indicating fundamental differ- 
ences in the reaction of the tissues. 
Portals of Entry.-Tubercle bacilli may enter the lungs through the 
blood- and lymph-vessels, being brought from a focus of tuberculous 
inflammation in another part of the body, or, as is frequently the case, 
may be introduced through the air passages by the inhalation of floating 
dust particles, among which are living tubercle bacilli. There is evidence 
that tubercle bacilli mav enter the body through the nasal and buccal 
mucosa or the tonsils or through the gastrointestinal mucous membrane 
without the development of tuberculous lesions at the point of entry.4 
Reaction of Tissue.-The introduction of tubercle bacilli into the 
lungs may induce an exudative inflammation with the accumulation of 
fibrin, leucocytes, and exfoliated epithelium in the air spaces; a produc- 
tive inflammation with the growth of epithelial cells, or of round-cell 
tissue, or of a tissue composed of basement substance, large and small 
1 For a study of the lungs in extreme anthracosis see Hodenpyl, E., Proc. New York Path. Soc., 
1899, p, 79. For a summary of the protective mechanism of the respiratory passages see p. 684. For 
summary of dusty trades and consumption, see Hoffman, Bureau of Labor, Dept, of Commerce and 
Labor, U. S. A., Bull. 79, 1908, and Bull. 82, 1909 (bibl.). 
2 Boer, Arch. f. Hyg., 1911, Ixxiv, 73. 
3 A complete review of the subject of pulmonary tuberculosis will be found in Bauer, Schroder, and 
Blumenfeld, Handbuch d. Tuberkulose, Leipzig, 1914. 
4 For a discussion of the sources and portals of entry of the tubercle bacillus, see p. 297. THE RESPIRATORY SYSTEM 
705 
Fig. 424.-Anthracosis of the Lung. 
A few tubercles are seen at the centers of the pigmented areas. There are slight pleuritic adhe- 
sions between the lobes. This is from a photograph of the lung of an actor who had been for many 
years upon the stage in the nearly always dusty air of theaters. 706 
THE RESPIRATORY SYSTEM 
cells, and giant cells, called tubercle tissue (see page 282); or there may be 
added necrosis of the new tissue and of portions of the lung. All of these 
phases of tuberculous lesions may and usually do occur together. 
The character of the inflammation in each case seems to be governed 
by the type of cells especially involved, by the number, virulence, and 
proliferative capacity of bacilli which are introduced into the lungs, and 
the way in which these enter, as well as by the susceptibility of the indi- 
vidual. If a large number of virulent tubercle bacilli are inhaled or 
aspirated through the bronchi, or if the bacilli grow with great rapidity, 
both productive and exudative inflammations may be set up in a consid- 
erable portion of the lungs. If, on the other hand, but few bacilli enter 
and their proliferation or virulence is not extreme, or if these find their 
way in small numbers into the lungs through the blood-vessels or lym- 
phatics, then there may be small foci of productive inflammation with 
but little exudation. The tuberculous alterations in the lungs are usually 
accompanied or followed by a series of secondary processes which often 
complicate the condition of the patient as well as the morphological 
appearances of the organs. The obliteration or destruction of the 
smaller blood-vessels of the lungs in the tuberculous areas contributes to 
the gray or whitish appearance of the lesions, due largely to new-formed 
tissue or accumulated exudate. The formation of fibrous tissue in the 
attempts at repair of the damage wrought by the tubercle bacillus often 
dominates the structural picture. 
Classifications.-The traditional distinctions between acute and 
chronic forms of pulmonary tuberculosis are often morphologically not 
at all well defined and are of value chiefly for clinical purposes. 
It has been customary to set apart those forms of acute tuberculosis 
of the lungs in which the lesions are in the form of small discrete so- 
called " miliary" foci, calling the condition Acute Miliary Tuberculosis. 
The other tuberculous lesions involving in varying degree the lungs and 
the bronchi with associated and often extensive exudative, necrotic, and 
reparative processes have been commonly jumbled together as Acute and 
Chronic Phthisis, many phases of which have been elaborately described 
as if they were the expression of independent processes. 
With our present knowledge of the nature and etiology of tuberculosis 
it seems better, however, to review the lesions of pulmonary tuberculosis 
under the following primary headings: 
1. Focal or miliary tuberculosis. 
2. Tuberculous bronchopneumonia. 
3. Complex forms of nodular and diffuse tuberculous lesions. 
4. The formation of cavities. 
5. Secondary lesions in pulmonary tuberculosis. 
6. Concurrent infection. 
Focal Tuberculosis. {Miliary Tuberculosis). 
Acute Miliary Tuberculosis.-The rapid and widespread development 
of miliary tubercles in the lungs is often a part of general tuberculosis, THE RESPIRATORY SYSTEM 
707 
although the lesion may be most extensive in the lungs. Both lungs are 
apt to be involved, but the distribution, number, size, and character of 
the miliary tubercles differ in different cases. The tubercles are found 
in the parenchyma of the lung, in the connective tissue forming the 
septa, along and in the walls of the bronchi and blood-vessels, and in the 
pulmonary pleura. They may be scattered singly through the lungs 
(Plate VI), or aggregated in groups (Plate VIII and IX). They may 
be separated by considerable interspaces, or so close together that the 
lung is rendered nearly solid. Some are so small and transparent that 
they can hardly be seen with the naked eye; others are larger and more 
opaque and may have a lighter center marking the area of necrosis. 
In many cases it is evident that the lungs are infected through the 
blood-vessels or the lymphatics, for the general tuberculous infection 
This tubercle has replaced several air vesicles whose walls are obliterated. In the center is an 
area of coagulation necrosis; outside of this is a zone of organized tubercle tissue; the surrounding air 
vesicles contain a cellular exudate. 
Fig. 425.-Miliary Tubercle of Lung. 
is secondary to a localized tuberculosis either in the lungs or in some 
other part of the body. In a considerable proportion of cases of miliary 
tuberculosis of the lungs, tuberculous lesions of the bronchial lymph- 
nodes or of the lung tissue at the apex of much longer standing indicate 
the probable immediate source of origin of the widely distributed tubercle 
bacilli. Very often in miliary tuberculosis of the lungs the tubercles in 
one part of the lungs are larger and appear to be older than those in 
other parts. Thus it is not infrequent to find the tubercles in the upper 
portion of the lungs more abundant, larger, and more fibrous than in the 
lower lobes (see Plate IX). It is in fact probable that in many cases 708 
THE RESPIRATORY SYSTEM 
of acute miliary tuberculosis of the lung, either associated or not with 
older local tuberculous lesions from which the distribution of bacilli may 
have taken place, the generalization has occurred, not at once, but by 
successive fresh infections.1 
Miliary tubercles in the lungs are in structure essentially similar to 
those formed elsewhere in the body, except that the filling of the air 
spaces with exudate makes the lesion somewhat more complex. 
Involving only two air vesicles, of which the walls are infiltrated and the cavities filled with tuber- 
cle tissue. The blood-vessels of the air vesicles are injected, except where these are obliterated by the 
tuberculous involvement of their walls. 
Fig. 426.-A Miliary Tubercle of the Lung. 
The tubercles may be composed of small spheroidal cells or of larger 
polyhedral cells with more or less fibrous stroma, or of small and large 
cells and stroma. Giant cells may be present, coagulation necrosis is 
usual (Fig. 157, page 286). Such forms of miliary tubercles may be and 
commonly are associated with the presence of an exudate in the adjacent 
or involved air vesicles (Fig. 425). This exudate may be largely made 
up of exfoliated epithelial cells which have proliferated; or with these 
there may be serum, leucocytes, and fibrin. The blood-vessels within 
1 For references to the origin of miliary tuberculosis see Benda, C., Lubarsoh-Ostertag, Ergebn. d. 
allg. Path., 1898, v, 447; see also Ribbert, H., Deutsch, med. Wchnschr., 1906, xxx i, 5. Pathology-Delafield and Prudden. 
Plate VI. 
Miliary Tuberculosis (Acute) of the Lung. 
The miliary tubercles, small and irregular in shape, are distributed 
throughout the lung-more abundantly in the upper and middle thirds. 
The blood-vessels are injected with blue gelatin, so that in this 
photographic reproduction of the specimen the uninvolved portions of 
the lung are dark, while the tubercles-in which the blood-vessels are 
compressed or obliterated-are light. THE RESPIRATORY SYSTEM 
709 
the tubercles which replace the lung tissue are partially or wholly oblit- 
erated (Fig. 426). 
But the miliary foci of tuberculous inflammation in the lungs may 
consist wholly of inflammatory exudate which early becomes necrotic, 
often with necrosis of the walls of the involved air spaces. Such tuber- 
cles of the exudative type are apt to occur in children and usually con- 
tain large numbers of tubercle bacilli. They may occur in connection 
with various other phases of acute and chronic pulmonary tuberculosis. 
When miliary tubercles are situated in the parenchyma of the lung 
the walls of the air spaces may be visible in the new growth or they 
may be largely or wholly obliterated (Fig. 427). 
In the obliteration of the walls of the air vesicles, their former situa- 
tion may be indicated by structureless bands or streaks of necrotic 
material, or they may disappear altogether. 
Fig. 427.-A Miliary Tubercle of the Lung. 
This tubercle is largely caseous, the walls of the involved air vesicles being merely indicated in 
the dead mass by slightly stained streaks or bands. There is cellular exudate in the surrounding air 
vesicles. 
Chronic and "Healed" Miliary Tubercles.-The small foci of tubercu- 
lous inflammation which are called miliary tubercles may, as we shall 
see later, extend and coalesce so that with more or less exudative pneu- 
monia large areas of the lung may become consolidated, thus developing 
one of the forms of pulmonary tuberculosis called phthisis. 
On the other hand, small tuberculous foci in the lungs may with or 
without extensive necrosis become surrounded by or converted into 
masses of dense fibrous tissue. These fibrous-tissue masses, which are 
often called "healed tubercles" (Fig. 428 and 429), may contain necrotic 
material, are often mottled black from anthracotic pigment, or they may 
be calcified at the center. Tubercle bacilli may be absent from them, or 
the bacilli may remain alive within them for a long time quiescent but 
still virulent. When such circumscribed masses of more or less fibrous 
tubercle tissue are scattered through the lungs, although the individual 710 
THE RESPIRATORY SYSTEM 
The central portion is necrotic and irregularly pigmented. The periphery is composed of dense 
pigmented fibrous tissue. There are emphysema and distortion from cicatricial contraction of the 
fibrous tissue. 
Fig. 428.-An Old Fibrous Tubercle of the Lung-"Healed Tubercle.'' 
Fig. 429.-A Fibrous Tubercle-"Healed Tubercle" of the Lung. 
The center is caseous, the fibrous tissue surrounding this is dense, the walls of the surrounding 
air spaces are thickened. A giant cell at the right is calcified. THE RESPIRATORY SYSTEM 
711 
masses may be of considerable size, the process is sometimes called 
"chronic miliary tuberculosis." 
It should be remembered that the new fibrous tissue which forms in 
and about miliary tubercles, as well as other tuberculous lesions, is the 
result of a distinctly reparative process in which the already formed 
tubercle tissue or its products apparently act somewhat as foreign bodies 
may in inducing fibrous-tissue growth. 
Tuberculous Bronchopneumonia. 
In another most important phase of tuberculous inflammation of the 
lung there is an involvement of the walls of the smaller bronchi and the 
Fig. 430.-Tuberculous Inflammation of the Lung with Cheesy Degeneration about the 
Bronchi in a Single Lobule of the Lung-Tuberculous Bronchopneumonia. 
associated groups of air spaces. This may occur through inhalation of 
bacilli or by their aspiration from an established tuberculous focus; for 
example, from a lesion at the apex, or, as is often the case in children, 
from tuberculous bronchial lymph-nodes; or infection may take place 
through the blood- or lymph-vessels. In the early stages of tuberculous 
bronchopneumonia the cut surface of the fresh lung may present small 
gray or yellowish white areas of consolidation with necrosis clustered 
about the small or terminal bronchi (Plate VII). The process is at first 
largely exudative, involving a catarrhal and necrotic inflammation of the 
mucous membrane of the bronchus with more or less exudate-which also 
may soon become necrotic-in the associated groups of air spaces (Fig. 
430). Sometimes organized tubercle tissue may form in the walls of 712 
THE RESPIRATORY SYSTEM 
Fig. 431.-Tuberculous Bronchopneumonia. 
The walls of the bronchi are thickened and caseous and are surrounded by zones of exudative and 
caseous pneumonia. This cut shows a small region, more highly magnified, of a lesion similar to that 
shown in Plate VII. 
Fig. 432.-Tuberculous Bronchopneumonia. 
The wall of this medium-sized bronchus is caseous, tubercle tissue is formed about it and is extending 
into the surrounding lung tissue A cellular exudate is seen in the contiguous air vesicles. Pathology-Delafield and Prudden 
Plate VII. 
Tuberculous Broncho-Pneumonia. 
The walls of the smaller bronchi are involved, being thickened and 
caseous, while the ulceration of many of them has led to the formation 
of numerous small cavities. 
The blood-vessels are injected with blue gelatin, so that the less 
affected and the intact parts of the lungs are the darker. THE RESPIRATORY SYSTEM 
713 
the bronchi, with thickening of the walls and obliteration of the blood- 
vessels of the adjacent air spaces. 
By the extension of the process from one and another affected bron- 
chus, and the coalescence of these, large areas of the lungs may become 
involved. In this more advanced stage of bronchopneumonia the larger 
and smaller consolidated areas may be dark red with firmer gray or yel- 
lowish gray central portions, in which the blood-vessels are obliterated, 
or the whole area may be solid and in the fresh lung grayish white. This 
new-formed tissue may undergo necrosis and ulceration so that with an 
advancing consolidation of the lung tissue about the bronchi numerous 
Fig. 433.-Tuberculous Bronchopneumonia. 
Showing the formation of cavities in the lung in acute phthisis. To the right are small, in the 
center large, tuberculous bronchiectatic cavities. At the left are areas of tuberculous consolidation 
with caseation in their central portions. 
larger and smaller, rough, irregular cavities may be formed (Fig. 431). 
The walls of the larger bronchi also may become the seat of a tubercu- 
lous inflammation with more or less necrosis (Fig. 432). Ulceration 
of these necrotic bronchial walls may lead to the formation of ragged 
cavities (Plate XI and Fig. 433). 
The secondary development of dense fibrous tissue in connection with 
tuberculous bronchopneumonia is a marked feature of the persistent or 
chronic forms. Tuberculous bronchopneumonia is one of the most 
important of that complex of pulmonary lesions called phthisis, and is 
commonly associated with other forms of tuberculous involvement of the 
organ-miliary tubercles, larger areas of consolidation, etc. 714 
THE RESPIRATORY SYSTEM 
Complex Forms of Nodular and Diffuse Tuberculous Lesions. 
With or without the various well-defined forms of tuberculous bron- 
chopneumonia and miliary tubercles above described, there may be 
more or less circumscribed small or large areas of productive and exuda- 
tive tuberculous inflammation of the lung with necrosis, both of the lung 
tissue, the new-formed tissue, and the exudate (Plate XIV). These may 
develop as the result of fresh infections of the lung through the lym- 
phatics or otherwise. These areas or nodules may coalesce so that whole 
lobes or parts of lobes of the lungs may become consolidated (Plates IX 
and X). Microscopically, these consolidated areas may be composed 
of tubercle tissue more or less necrotic, with partial or total obliteration 
of the walls of the air spaces. On the other hand, when the process has 
been exudative as well as productive in character, one may see in the solid 
areas the outlines of the air vesicles and larger spaces; but these, to- 
gether with the inclosed exudate, may be necrotic and granular with 
few stained nuclei and fragments of chromatin. Much of the exudate 
which fills the air vesicles either within or about these more densely con- 
solidated areas may not be caseous or necrotic, but may consist of well- 
preserved or fatty epithelial cells, or of these with varying quantities 
of leucocytes and fibrin. 
Aside from these complex forms of nodular and diffuse tuberculous 
lesions one may recognize a Diffuse Exudative Tuberculous Inflammation 
of the Lungs of Acute and of Chronic Type.-Cheesy Pneumonia; Pneu- 
monic Phthisis. 
1. Acute Type.-Sometimes large areas or whole lobes or the whole 
lung may be the seat of an exudative process by which the affected region 
becomes solidified, the exudate consisting of epithelium with more or less 
fibrin and pus. This exudate, together with the lung tissue, soon under- 
goes necrosis, so that the solidified lung becomes dense, mottled, and 
gray in color. Extensive disintegration (Fig. 434) of the consolidated 
and necrotic portions of the lung may take place, with the formation of 
large ragged cavities (see Plate XII). In many cases enormous numbers 
of tubercle bacilli are present in the exudate of the involved region in 
this type of exudative and necrotic pulmonary tuberculosis. 
2. Chronic Type.-There may be a more gradual development of 
the exudate, involving larger or smaller areas, often with tuberculous 
thickening and necrosis of the walls of the air spaces. With this as with 
other forms of pulmonary tuberculosis there may be associated a growth 
of simple fibrous tissue with the formation of cavities. 
Not infrequently the exudate in such forms of diffuse tuberculous 
inflammation of the lung is less cellular and more serous or serofibrinous 
in character, when the appearance of the consolidated region is trans- 
lucent and gelatinous. 
Obliteration of the larger blood-vessels by thrombosis or inflamma- 
tion of the wall often plays an important part in most forms of tubercu- 
lous lesions of the lungs. When large trunks are involved, extensive lung Pathology-Delafield and Prudden. 
Plate VIII. 
Miliary Tubercles and Tuberculous Broncho-Pneumonia with 
Diffuse (Chronic) Tuberculous Lesions in the Apex. 
There is in the apex tuberculous consolidation with coagulation 
necrosis (caseation), new fibrous tissue, and a small cavity. The middle 
third of the lung contains many small single and clustered miliary tuber- 
cles and foci of tuberculous broncho-pneumonia. The lower third con- 
tains a few similar small tuberculous foci, also scattered and in clusters. 
The appearance of the lung leads to the conjecture that tubercle 
bacilli may have been gradually disseminated from the earlier lesion in 
the apex. The blood-vessels are injected with blue. THE RESPIRATORY SYSTEM 
715 
areas, supplied by the occluded vessels, particularly those in which exu- 
date is present, may become necrotic en masse, then often appearing on 
section smooth, shining, grayish-white in color, and bloodless. 
Fig. 434.-Acute Pulmonary Tuberculosis-Exudative Type (Acute Phthisis-Cheesy Pneu- 
monia) ; with Extensive Disintegration and Formation of Cavities. 
The pleura is much thickened. 
The Formation of Cavities in Pulmonary Tuberculosis. 
We have seen that in tuberculous bronchopneumonia ragged cavities 
may form by a progressive necrosis and disintegration of the thickened 
walls of the affected bronchi and the adjacent lung tissue (Plate XI 716 
THE RESPIRATORY SYSTEM 
and Fig. 433). Similar destructive alterations may occur in the areas 
of tuberculous and necrotic tissue which involve larger and smaller 
portions of whole lobes (Plate 
XIII). This is most often 
rapid and extensive in solidified 
and necrotic areas of the exuda- 
tive type (Plate XII and Fig. 
434). These ragged cavities 
may communicate with one 
another as well as with the 
bronchi. 
While at first without dis- 
tinct limiting walls, if the ne- 
crotic process be not too active 
and extensive, new fibrous tis- 
sue may gradually form about 
tuberculous cavities (Plate XIV, 
and Fig. 435); and these may 
become lined with granulation 
tissue or a layer of new-formed 
tubercle tissue. Here an enor- 
mous proliferation of tubercle 
bacilli may occur for long pe- 
riods. These may be cast out 
in the sputum or aspirated into 
other parts of the lungs. The 
old blood-vessels of the in- 
volved portion of the lung may 
lie upon the walls or stretch 
across these cavities, sometimes 
with obliterated lumina, some- 
times still permeable; and from 
these hemorrhages may occur. 
There may be continuous and 
prolonged suppuration of the 
walls of the cavities and putre- 
factive processes may be incited 
by the advent through the air 
passages of various forms of bacteria. The walls of cavities may become 
fibrous with an arrest of the tuberculous process, and they may be shut 
off from bronchial communication. 
Fig. 435.-Chronic Pulmonary Tuberculosis 
(Chronic Phthisis), with Cavities. 
There is much dense fibrous tissue in the upper lobe 
surrounding and between the cavities, as well as in the 
upper portion of the lower lobe. 
Secondary Lesions in Pulmonary Tuberculosis. 
A variety of secondary processes may be associated with the various 
phases of pulmonary tuberculosis which we have briefly reviewed. The 
blood-vessels in affected regions may be intact, or, as we have seen, their 
walls may be involved in the productive and necrotic processes, with 
thrombosis or obliteration of the lumen; or more or less extensive hemor- Pathology-Delafield and Prudden 
Plate IX. 
Diffuse and Focal (Chronic) Pulmonary Tuberculosis- 
"Chronic Phthisis." 
In the upper third of the lung there is tuberculous broncho-pneu- 
monia with commencing ulceration of small bronchi: nearly complete 
consolidation from the extension and coalescence of small tuberculous 
foci and diffuse formation of fibrous tissue. 
In the lower third of the lung are irregular, dense, sharply outlined 
tuberculous foci (chronic miliary tubercles). 
In the middle third there is tuberculous pneumonia of the exudative 
type, the incompletely consolidated areas having become, in part, caseous. 
The less involved portions of the lung in this, as in the other in- 
jected specimens, are the darker. THE RESPIRATORY SYSTEM 
717 
rhages may occur. If the consolidation be not complete, lung tissue, 
often in a condition of atelectasis or emphysema and with more or less 
cellular or granular exudate, may remain between the tuberculous 
areas. Miliary tubercles may be scattered among the larger consolidated 
masses or in parts of the lung otherwise free. 
In chronic forms of pulmonary tuberculosis the anthracotic pigment 
is often conspicuous, particularly in the cheesy and fibrous areas, stand- 
ing out in masses and streaks in contrast to the new or dead tissue. 
Furthermore, there may be associated with the lung lesions acute exu- 
dative or chronic fibrous pleuritis with adhesions; tuberculous pleuritis 
of varying extent; empyema; and pneumothorax. There is nearly always 
more or less chronic catarrhal bronchitis or bronchopneumonia and fre- 
quently bronchiectasia. 
Tuberculous inflammation in the bronchial lymph-nodes frequently 
accompanies and often precedes the development of pulmonary tuber- 
culosis. In children the tuberculous lymph-nodes often extend far into 
the lung and may on softening give rise to cavities at a considerable 
distance from the hilus of the lung. 
Tuberculosis in other parts of the body is common in connection with 
pulmonary tuberculosis. 
In all these various processes new-formed fibrous tissue, not tuber- 
culous in character, may develop, variously distorting the lungs and 
sometimes inclosing the tuberculous areas. There is much reason for 
the belief that the characteristic tubercle-tissue formation in all phases 
of tuberculosis is a response of the living cells to injury, which as in 
other types of inflammation is fundamentally conservative (see page 
123). But whether this be so or not, it is certain that it is through the 
development of fibrous tissue, which is so important a feature in persist- 
ent phases of pulmonary tuberculosis, that the delimitation or replace- 
ment of tuberculous foci, the encapsulation of tuberculous cavities, etc., 
occur. While, therefore, fibrous-tissue formation in the lung is fre- 
quently associated with the necrotic and other destructive tuberculous 
lesions, and is often a very conspicuous factor, it should be remembered 
that the healing which takes place in the majority of cases in man after 
moderate infection is achieved through its agency. 
It is especially upon the presence or absence of fibrous tissue in the 
lesions that the distinction between acute and chronic phthisis is based. 
It will be seen from this brief outline of various prominent phases 
of pulmonary tuberculosis that the gross appearances of the lungs are 
most diverse, although the processes by which these changes are induced 
are few and comparatively simple. While no two lungs are quite simi- 
lar in the complex phases of the lesion, systematic gross and micro- 
scopical examinations soon enable the student to recognize the type of 
lesion under great complexity of detail. 
The Distribution of the Lesions in Pulmonary Tuberculosis. 
Aside from, general miliary tuberculosis in which the tubercles are 
widely distributed throughout one or both lungs, the most common seat 718 
THE RESPIRATORY SYSTEM 
and starting-point of tuberculous lesions in adults is the apical region or 
the depth of the lung, particularly the right, somewhat below the apex.1 
In children, the tuberculous process more frequently commences in the 
bronchial lymph-nodes (Plates V and XIII). 
From the apex the tuberculous process may extend downward, and 
with various forms of lesions involve more or less of the lungs. It is 
common to find at autopsies older fibrous lesions about the apices while 
marks of more active processes are to be seen below (Plate XIV). In a 
considerable percentage of bodies examined at autopsies, small and often 
healed tuberculous foci are found at the apex or in the bronchial lymph- 
nodes without evidence of extension of the process. 
Concurrent Infection in Pulmonary Tuberculosis. 
While it has been definitely established that tubercle bacilli are the 
excitants of both the productive and the exudative forms of tuberculous 
inflammation, these bacilli are not infrequently associated in pulmonary 
tuberculosis with other organisms, especially with the Streptococcus and 
Staphylococcus pyogenes, with Diplococcus pneumoniae, and with the 
influenza bacillus. 
There is reason to believe that in many cases at least the concurrent 
infection of tuberculous lungs with the Streptococcus pyogenes may be an 
important factor in the formation of cavities in areas of consolidation 
already established.2 The pyogenic cocci apparently play an important 
part in the bronchitis which so often accompanies acute and chronic 
phthisis. 
Bacteriemia has been shown to exist in a certain proportion of cases 
of active progressive pulmonary tuberculosis, but in many such cases 
the blood is sterile.3 
Much light may be gained upon the successive steps in the development of the 
lesions of pulmonary tuberculosis as well as upon the rapidity with which in a suscepti- 
ble animal the lesion may develop, by the study of the tuberculosis artificially induced 
in rabbits with pure cultures. 
By the injection of tubercle bacilli alone and associated with streptococci into the 
lungs of rabbits through the trachea, it has been possible to reproduce very closely the 
lesions of pulmonary tuberculosis in man.4 
If a small quantity of a pure culture of the tubercle bacillus in very minute flocculi 
be mixed with a considerable quantity of salt solution and introduced into the lungs 
of rabbits through the trachea, a number of small areas of consolidation are produced 
which have the gross appearance of miliary tubercles (Fig. 436). These small areas of 
consolidation are composed of epithelial cells and leucocytes. After the development 
of these cell masses, which may occur within a few hours, they may remain with little 
apparent change, or become more or less infiltrated with leucocytes, or become cheesy, 
Artificial Pulmonary Tuberculosis in Animals. 
1 For a suggestive consideration of apical vulnerability, see Hutchinson, Studies in Human and 
Comparative Pathology, 1901, p. 81. 
2 For bibliography of concurrent infection in tuberculosis, see Avery and Lyall, Jour. Med. Research, 
1913, N. S. xxiii, 111; Pettit, Jour. Infect. Dis., 1911, ix, 237; also Prudden, New York Med. Jour., 
1894, lx, 1. 
3 For a study of bacteriemia in pulmonary tuberculosis, see Jochmann, Deutsch. Arch. f. klin. Med., 
1905, Ixxxiii, 558. 
4 Prudden, New York Med. Jour., 1894, lx, 1. Pathology-Delafield and Prudden 
Plate X. 
Diffuse (Chronic) Pulmonary Tuberculosis-"Chronic Phthisis." 
In the upper half of the lung there are scattered miliary tubercles 
and irregular areas of consolidation, with a diffuse formation of fibrous 
tissue; the pleura is thickened. A large portion of the lower lobe is 
densely consolidated from tubercle tissue and exudate with coagulation 
necrosis of the involved regions. These regions are light in color, 
dense, hard, and bloodless. Such dead caseous areas may persist for 
some time, or may soften and disintegrate, giving rise to cavities. Pathology-Delafield and Prudden. 
Plate XT. 
Tuberculous Bronchiectatic Cavities in Pulmonary Tuberculosis. 
The advancing tuberculous involvement of the walls of the larger 
bronchi in the upper lobe is associated with ulceration, so that the bron- 
chiectatic cavities gradually become larger. In the upper portion of the 
upper lobe there is diffuse consolidation with caseation: the lower por- 
tion of the lobe shows miliary tubercles and partial consolidation of the 
lung about them by exudate. 
The lower lobe is free save for a few scattered tubercles. The 
blood-vessels are injected with blue so that the uninvolved portions of 
the lung are dark. THE RESPIRATORY SYSTEM 
719 
or be surrounded by a dense zone of small spheroidal cells; or small foci of new tissue 
with more or less exudate, and necrosis, may form. 
When larger quantities of the tubercle bacillus are introduced into the lungs 
through the trachea, large areas of consolidation are formed (Fig. 437), which may 
involve whole lobes or whole lungs. 
Microscopically, these consolidated areas are practically identical with those which 
are found in man in various forms of tuberculous bronchopneumonia. A later fibrous- 
tissue development may occur, and blood-vessels may be obliterated. 
Fig. 436.-Experimental Tuberculous Inflammation (Miliary) in the Lung of a Rabbit. 
Fig. 436. 
Fig. 437. 
The rabbit's lung shows miliary foci of tuberculous inflammation twenty-two days after the 
injection through the trachea of a small quantity of broth culture of the tubercle bacillus. 
Large areas of solidification, in the lung twenty-eight days after the injection through the trachea 
of a considerable quantity of a pure culture of the tubercle bacillus. The lesions resemble those of 
acute phthisis in man. 
Fig. 437.-Experimental Tuberculous Inflammation in the Lunq of a Rabbit. 
In the presence of the tubercle bacillus alone the consolidated and caseous areas 
rarely soften and break down so as to form cavities. If, however, after the tubercu- 
lous lesion of the lung has been induced and allowed to continue for a number of days, 
a culture of Streptococcus pyogenes be introduced into the trachea of the rabbit, 
within twenty-four hours the caseous areas often begin to soften. The softening may 
begin at the center, or may surround a central portion of the necrotic mass. The 
softening is soon followed by absorption, and so cavities are formed of varying sizes 
and shapes (Fig. 438). 
It will thus be seen that in the rabbit a concurrent infection with the tubercle 720 
THE RESPIRATORY SYSTEM 
bacillus and the streptococcus has an important bearing upon the breaking down of 
lung tissue which leads to the formation of cavities. While it would not be wise to 
assume from these experiments on the rabbit that a similar condition is always 
present when cavities form in man, we have seen that in fact a similar concurrent 
infection in man in acute phthisis actually does often exist. 
Fig. 438.-Experimental Tuberculous Inflammation in the Lung of a Rabbit, with the 
Formation of Cavities 
The lung was injected with a considerable quantity of tubercle bacillus culture through the trachea, 
followed after twenty-eight days by the injection of the broth culture of the Streptococcus pyogenes. 
Animal killed seven days after the streptococcus injection. The specimen shows large areas of consoli- 
dation with cavities. The lesions resemble those of acute phthisis with cavities in man. 
Syphilitic Pneumonia. 
Persons suffering from inherited or acquired syphilis sometimes 
develop inflammations of the lungs which seem to be due to the syphilitic 
infection. The lungs may then be affected in several different ways. 
There may be well-defined large or small gummata with or without 
interstitial and more or less exudative pneumonia. There may be a 
formation of new fibrous tissue in the walls of the bronchi and in the lung 
tissue about them, often with ulceration of the mucous membrane and 
distortion of these structures. There may be, particularly in the new- 
born, lobular or lobar hepatization, the affected region appearing reddish 
or gray or white. This is due to a growth of new cellular tissue in the Pathology-Delafield and Prudden. 
Plate XII. 
Pulmonary Tuberculosis-Exudative Type-with Large Cavities. 
The entire lung is solid from new-formed tubercle tissue and exudate which are both 
largely in a condition of coagulation necrosis. 
The thickened trunks of the larger pulmonary vessels are exposed in the depths of 
the ragged communicating,cavities. 
This lung was hardened in alcohol without injection of the blood-vessels. THE RESPIRATORY SYSTEM 
721 
walls of the air spaces and to an exudate largely of epithelial cells in the 
air spaces. Infarctions of the lung from obliterating endarteritis may 
be present. It is often difficult to determine in many cases of interstitial 
inflammation of the lungs whether the lesion be syphilitic or not.1 
TUMORS. 
Fibroma and osteoma are rare; enchondroma may occur as a primary 
tumor originating in the cartilages of the bronchi. Teratoma is an occa- 
sional finding.2 Sarcoma3 is not common and is usually secondary.4 
The primary tumor involved the gall-ducts, liver, and pancreas. The metastatic tumors in the 
lung were in part white, in part dark red from interstitial hemorrhage. 
Fig. 439,-Secondary Carcinoma of the Lung. 
Mesothelioma (page 442), which is sometimes called sarcoma or endo- 
thelioma, is of infrequent occurrence on the surface of the lung, and, fol- 
1 For a bibliography of pulmonary syphilis, consult Flockemann, Centralbl. f. Path., 1899, x, 449. 
2 Katase, Centralbl. f. allg. Path., 1912, xxiii, 146 (bibl.). 
3 For a study of sarcoma and carcinoma of the lungs, see Packard, Am. Jour. Med. Sc., 1917, cliv, 
351. For primary sarcoma, see Eckersdorff, Centralbl. f. allg. Path., 1906, xvii, 355; Pater and Rivet, 
Arch, de med. exp6r., 1906, xviii, 85; Boschowsky, Frankfurt. Ztschr. f. Path., 1912, ix, 239. 
4 Holt and Ratterman, Jour. Am. Med. Assn., 1916, Ixvi, 171; Jackson, ibid., 833. 722 
THE RESPIRATORY SYSTEM 
lowing the subpleural lymph-vessels may form a reticular raised white 
network (Fig. 440 and 441). Adenoma is rare.1 Primary carcinoma of 
the lung, usually originating in the bronchi and therefore generally of 
Fig. 440.-Mesothelioma of the Pleura. 
The inner surface of a segment of the costal pleura, containing three of the ribs, is shown in the cut. 
the cylindrical-cell type, though squamous-cell cancer2 has been described, 
is also uncommon.3 Carcinoma, and particularly lymphosarcoma, ap- 
Showing the growth of the tumor along the superficial lymph-vessels. 
Fig. 441.-Mesothelioma of the Pleura. 
pear to be not infrequent among workers in the cobalt mines in the region 
about Schneeberg.4 Carcinoma may be associated with exudative pneu- 
1 For a discussion of primary adenoma of the lung in mice, see Tyzzer, E. E., Jour. Med. Research, 
1909, N. S. xvi, 479. 
2 Hermann, Ztschi. f. Krebsforsch., 1913, xiii, 446 (bibl.). 
8 Adler, Primary Malignant Growths of the Lungs and Bronchi, New York, 1912; Henrici, Jour. 
Med. Research, 1912, N. S. xxi, 395 (bibl.); Scott and Forman, Med. Rec., 1916, xc, 452 (bibl.); Lambert, 
R. A., Proc. New York Path. Soo., 1915, xv, 117. 
For a discussion of the clinical aspect of primary carcinoma of the lungs, see v. Wiczkowski, Wien, 
klin. Wchnschr., 1913, xxvi, 1067 (bibl.); McMahon and Carman, Am. Jour. Med. Sc., 1918, civ, 34. 
4 Arnstein, Wien. klin. Wchnschr., 1913, xxvi, 748, Verhandl. d. deutsch. path. Gesellsch., 1913, 
xvi, 332; Centralbl. f. allg. Path., 1913, xxiv, 408; Risel, ibid., 409. Pathology-Delafield and Prudden. 
Plate XIII. 
Pulmonary Tuberculosis (Chronic), with Large Cavities. 
The ragged communicating cavities involve a large part of the lung and are bronchiec- 
tatic in origin. The bronchial lymph-nodes are enlarged, tuberculous, and caseous. The 
pleura and interlobar septum are thickened by the formation of dense fibrous tissue. Pathology-Delafield and Prudden 
Plate XIV. 
Chronic Pulmonary Tuberculosis with a Fibrous-Walled Cavity at the Apex. 
The fibrous wall of the cavity is dense and is continuous with the 
greatly thickened pleura and with the diffuse new-formed connective 
tissue throughout the upper lobe. The upper lobe is greatly reduced in 
size by the cicatricial contraction of the fibrous tissue. The lower lobe 
shows two areas of tuberculous consolidation; both are caseous in the 
central portions; the upper shows commencing tuberculous bronchiec- 
tasia. The upper part of the fibrous wall of the cavity, firmly adherent 
to the thoracic wall, has been cut away. THE RESPIRATORY SYSTEM 
723 
monia and involve large portions of the lungs as well as the pleura. It 
sometimes develops in the wall of a tuberculous cavity.1 Secondary 
carcinoma of the lung is very common, particularly in connection with 
mammary carcinoma; the secondary growths may appear as circum- 
scribed nodular masses displacing the lung tissue (Fig.'439), or may infil- 
trate the lung, often following the bronchi and larger blood-vessels. The 
cells of such tumors often invade and fill the air spaces over larger areas, 
though without immediate involvement of their walls.2 
Dermoid cysts have been found in the lung. 
THE MEDIASTINUM. 
Inflammation.-Suppurative inflammation may occur in either the anterior or 
the posterior mediastinum. It may be caused by fractures, caries, or necrosis of the 
sternum and vertebrae, by perforation of the esophagus, by suppuration of the lymph- 
nodes, or by pleurisy, or may occur without discoverable cause. 
The pus may infiltrate the connective tissue, or may form abscesses which attain 
a large size. The inflammation may extend to the pleura or the pericardium, the 
abscesses may displace the heart, the lungs, or the sternum; or they may perforate 
through the skin, into a pleural cavity, the esophagus, the trachea, or a bronchus.3 
A few cases of chronic inflammation of the tissues of the mediastinum have been 
reported-chronic mediastinitis.4 Lesions of the tracheal and bronchial lymph-nodes 
are considered on page 675. 
Tumors.-The most common form of new growth in the mediastinum is that 
known by the names of lymphoma, lymphosarcoma, and lymphadenoma. 
These tumors are confined to the mediastinum, or they are associated with similar 
growths in other parts of the body in the disease called pseudoleukemia. Persons 
between the ages of twenty and thirty years seem to be the most liable to the growth, 
but it is not uncommon in children. It begins in the lymph-nodes in the medias- 
tinum, and at the root of the lung. It increases at first slowly, then more rapidly, and 
gradually infiltrates the adjoining tissues. In this way the walls of the trachea, 
bronchi, aorta, the pericardium, the pleura, and the lung, become infiltrated with 
compression of the surrounding organs. 
The growth is composed of a fibrous stroma associated with small round cells, the 
relative quantity of cells and stroma varying in the different cases. 
Besides this form of tumor there may also occur in the mediastinum tumors similar 
to those which grow in the pleura and behind the peritoneum-tumors which resemble 
both the sarcomata and carcinomata, and which it is difficult to classify. Aberrant 
thyroid-gland tissue may be found in the mediastinum. 
Complex tumors belonging among the fetal inclusions or teratomata are of occa- 
sional occurrence in the anterior mediastinum.5 They may contain bone, cartilage, 
connective tissue, muscle, hairs, skin, and even chorionepithelioma, etc. Cysts, 
sometimes lined with ciliated epithelium, may form in such tumors.6 
1 For bibliography, see Wolff, Die Lehre d. Krebskrankheit, Jena, 1911, Teil ii, 817; Hermann, 
Ztschr. f. Krebsforsch., 1913, xiii, 446; and Oertel, H., Jour. Med. Research, 1911-12, N. S. xx, 503; 
for a discussion of the relation in general between carcinoma and tuberculosis, see Layman, Frankfurt. 
Ztschr. f. Path., 1914, xv, 360 (bibl.); Bundschuh, Zieglers Beitr., 1914, Ivii, 64 (bibl. with special ref- 
erence to the mamma). 
2 For a consideration of the diagnosis of malignant tumors of the lungs, consult Adler, New York 
Med. Jour., 1896, Ixiii, 173, 204; Fraenkel, Deutsch, med. Wchnschr., 1911, xxxvii, 531; Pick, ibid., 570. 
3 For tuberculous lesions of the tracheobronchial lymph-nodes see reference, p. 675. 
4 Whipham, Lancet, 1899, i, 882, 947 (bibl.). 
5 See Mandlebaum, F. 8., Am. Jour. Med. Sc., 1900, cxx, 64. 
8 Consult Hare, Tumors of the Mediastinum, Philadelphia, 1889; also Zahn, Virchows, Arch., 1896, 
cxliii, 170 and 416; also Lohrisch, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1900, vii, 912 (bibl.); 
also, for a study of dermoid cysts of the mediastinum, see Morris, Med. News, 1905, Ixxxvii, 404, 438, 
494, 538; Lambert, S. W., and Knox, L. C., Intrathoracic teratomata, Trans. Am. Phys., 1920, xxxv, 17. 724 
THE RESPIRATORY SYSTEM 
The Pleura. 
Non-inflammatory accumulations of clear serum in the pleural cavi- 
ties are of frequent occurrence. They occur under conditions similar 
to those which lead to dropsy in other parts of the body-lesions of the 
heart, liver, and kidneys, and changes in the circulation and in the com- 
position of the blood. 
If the amount of serum be large it may compress the lower lobes of 
the lungs. 
HYDROTHORAX. 
HYDROPNEUMOTHORAX-PYOPNEUMOTHORAX. 
The presence of air in the pleural cavities is usually associated with 
a serous or purulent exudate. It may occur as the result of perforation 
of the lung, of rupture, of ulceration of tuberculous lesions at the pleural 
surfaces, of injuries to the chest wall, and of perforation of the diaphragm 
by suppurative or cancerous lesions of the esophagus, stomach, or intes- 
tine, as well as in a variety of other conditions. Gas may form in the 
pleural cavities in infection by the Bacillus aerogenes capsulatus.1 
HEMORRHAGE. 
Subpleural ecchymoses may occur in asphyxia or during infectious 
diseases or intoxications. More extensive extravasations of blood- 
hemothorax-may be the result of injuries to the wall of the thorax or 
the rupture of an aneurysm. 
Hemorrhagic exudates (hemothorax) are usually associated with in- 
juries, with malignant tumors of the lungs or pleura, with infarctions of 
the lungs, with tuberculous pleurisy, or with infectious diseases of a 
hemorrhagic type, and are occasionally seen in cases of cirrhosis of the 
liver. 
Inflammation of the pleura may occur as an independent lesion, but 
it is commonly associated with pathological processes in the lungs, peri- 
cardium, abdomen, or chest wall. It may be exudative in character, 
usually associated with more or less proliferation of the mesothelial 
("endothelial") and connective-tissue cells, or it may be productive 
with the formation of new connective tissue. These phases of inflamma- 
tion may be associated. Through the production of new connective 
tissue, repair of the acute inflammatory lesion is commonly effected. 
In the exudative forms of pleurisy the exudate may consist of fibrin, or 
of serum and fibrin, or of serum, fibrin, and pus. 
Simple Fibrinous Pleurisy (Dry Pleurisy; Pleuritis Sicca).-This may 
involve circumscribed areas of the costal, mediastinal, diaphragmatic, 
or pulmonary pleura, less frequently the entire pleura of one side of the 
chest. The affected portions of pleura are dull and lustreless and coated 
INFLAMMATION. (Pleuritis, Pleurisy.) 
1 For a study of pneumothorax, see Emerson, Johns Hopkins Hosp. Rep., 1903, xi, 1. THE RESPIRATORY SYSTEM 
725 
with fibrin, opposing surfaces often being joined by bands of fibrin. 
There are swelling, degeneration, proliferation, and exfoliation of the 
mesothelium, with swelling and proliferation of the connective-tissue 
cells beneath. Exceptionally, there is involvement of the entire pleura 
of one side, with the production of such a large amount of fibrin as 
seriously to compress the lung.1 
Serofibrinous Pleurisy (Pleurisy with Effusion).-This is the most 
common form of pleurisy. As a rule, it involves the greater part of the 
pleura of one side of the chest. Sometimes, however, the pleura of both 
sides of the chest is involved, and then the pericardium also is often 
inflamed. 
While the inflammation is in progress the surface of the affected 
pleura is coated with fibrin, and bands of fibrin stretch between the 
parietal and pulmonary pleurae. In the pleural cavity is serum in vari- 
able quantity. This serum is clear, or turbid from the presence of 
exfoliated mesothelium, leucocytes, and flocculi of fibrin or red blood- 
cells. The lung is compressed in different degrees and positions, accord- 
ing to the quantity of the serum and the character of the adhesions. The 
heart may also be displaced by the accumulated exudate. 
The natural termination of such a pleurisy is the recovery of the 
patient, with thickenings of the pleura and adhesions. The irregular 
terminations are: The death of the patient, the protracted existence of 
the fibrin and serum, and the change of the character of the inflammation 
so that pus is produced. 
If the patient recovers, the serum is absorbed, the fibrin disappears, 
and repair is effected, as in simple fibrinous pleurisy, by the formation 
of granulation tissue, which gradually becomes dense and cicatricial in 
character and may remain as local or general thickenings or firm adhe- 
sions of the opposed pleural surfaces. The lung may be distorted by 
contraction of the new-formed connective tissue. The exudates in the 
serofibrinous form of pleurisy do not usually infiltrate the pleura, but 
gather upon its surface and in the cavity. 
The Excitants of Serofibrinous Pleurisy.-Cultivations from 
the exudate give in the larger number of cases negative results; but 
the pneumococcus, Streptococcus pyogenes, Staphylococcus aureus or 
albus, and the typhoid bacillus have been isolated. When the inflam- 
mation of the pleura is consecutive to acute lobar pneumonia, the 
pneumococcus may still not be found in the exudate. The presence 
of the streptococcus is frequently followed by the formation of pus. 
The organisms named above may be present alone or in various associa- 
tions. Many cases with simple serofibrinous exudate prove on inocula- 
tion to be tuberculous.2 
Suppurative Pleurisy (Empyema).-Suppurative pleurisy may occur 
either with or without the formation of a considerable serofibrinous 
1 For a Study of the origin of fibrin and adhesions of the serous membranes, consult Heinz, R., 
Virchows Arch., 1900, clx, 365; also Gaylord, H. R., Jour. Exper. Med., 1898, iii, 1 (bibl.). 
2 For a study of the bacteria in exudative pleuritis, with the earlier bibliography, consult Prudden, 
New York Med. Jour., 1893, Ivii, 696. For fuller data see Netter, Bouchard and Brissaud, Trait 6 de 
Medecine, Paris, 1901, vii, 399. 726 
THE RESPIRATORY SYSTEM 
exudate. The exudate may be purulent from the beginning, or a sero- 
fibrinous exudate may assume this character. 
The pleural cavity in empyema is partly or completely filled with 
purulent fluid, and the lung is either compressed against the vertebral 
column or partly adherent to the chest wall. Sometimes, however, the 
purulent fluid is shut in by adhesions, either between parts of the lung 
and the thoracic wall, or between the lung and the diaphragm, or between 
the lung and the pericardium, or between the lobes of the lung. 
The fluid in the pleural cavity is usually a thin, purulent serum, 
composed of serum, pus cells, mesothelial cells, and flocculi of fibrin; 
but sometimes this fluid is thick and viscid. 
While in children the more or less active suppurative process in the 
pleural cavity may continue for a long time without deep involvement of 
the pleura, in adults granulation tissue may form upon the membrane, 
which thus becomes gradually thickened and may so remain for months 
with its inner vascular surface covered with pus and fibrin. In such cases, 
as well as in less chronic forms, the fibrin fibrils are often swollen and 
coalesce to form irregular homogeneous or finely granular masses. 
Resolution may occur in one region of the pleura while the exudate in 
another may become encapsulated by new-formed connective tissue. 
In old cases the thickening of the pleura may be great and it may 
become calcified.1 The perichondrium of the cartilages and the peri- 
osteum of the ribs may become inflamed, with necrosis of the cartilages 
and ribs or a production of new bone. Necrosis and gangrene of the 
involved pleura may occur and putrefactive process be set up in the exu- 
date. The suppurative process may extend from the pleura involving 
adjacent parts, such as the fasciae, the muscles, the skin, the diaphragm, 
or the lungs. Thus the pus may find an exit through the wall of the 
thorax, into the peritoneal cavity, or into the lungs. 
In inflammation of the pleura the process may extend to the lym- 
phatics in the interlobular septa, around the bronchi, and around the 
blood-vessels. This interlobular lymphangitis occurs more frequently in 
children than in adults. The lymphatics in the interlobular septa and 
those around the bronchi and blood-vessels are distended with pus cells, 
the septa are much thickened, and the lobules separated from each other. 
Serofibrinous pleurisy and empyema may occur as complications of 
infectious diseases, such as scarlatina, typhoid fever, and various forms 
of septicemia, or by an extension of an inflammatory process from such 
adjacent parts as the pericardium, lungs, mediastinum, etc.2 The vari- 
ous forms of pneumonia are frequently associated with local or general 
inflammation of the pleura. 
The Excitants of Empyema.-Streptococcus pyogenes is the most 
frequent excitant of suppurative inflammation of the pleura. According 
to the statistics of Netter this organism has been found in a little over 
1 For a resum6 of our knowledge of various calcifications in the lungs, and allied conditions often 
called "lung stones," consult Polaillon, Les Pierres de Poumon, Paris, 1891; or Legry, Arch. gdn. de 
m6d., 1892, i, 337 and 466. 
2 For a study of relation of esophageal diverticula to empyema, see Starck, Arch f. Verdauungskr., 
1901, vii, 1. 727 
forty per cent, of the cases examined of all ages. The pneumococcus 
has been found in over twenty-five per cent, of cases examined. The 
streptococcus and the pneumococcus are associated in a small proportion 
of cases. Of less frequent occurrence are Staphylococcus pyogenes, 
Bacillus typhosus, Bacillus coli communis, the gonococcus, the pneumo- 
bacillus of Friedlander, and the influenza bacillus. In empyema with 
fetid exudate, various forms of bacteria may be present. While in the 
adult the streptococcus is most often found in the empyemic exudate, 
in young children the pneumococcus is, according to Netter,1 most 
common. 
Chronic Pleurisy with Adhesions.-This form of pleurisy may follow 
one of the varieties of pleurisy just described, it may be associated with 
emphysema and chronic phthisis, or it may occur by itself. 
After death the pulmonary and costal pleura are found thickened and 
joined together by numerous adhesions. These changes may involve 
only a part or the whole of the pleura on one or both sides of the chest. 
The thickened pleura is covered with mesothelium; the new connec- 
tive tissue may be very dense and may contain few or many cells. 
Blood-vessels may be numerous and irregular in distribution or few in 
number. New lymph-vessels are formed with the growth of the new 
tissue.2 These, as well as the old lymph-vessels, may be dilated, forming 
small cysts. 
Tuberculous Pleurisy.-Acute general tuberculosis of the pleura is 
usually secondary to tuberculous inflammation elsewhere in the body, 
either in the lungs, which is most common, or the bronchial lymph-nodes, 
peritoneum, bones, etc., or it may be a part of a general miliary tuber- 
culosis. There may be localized or widely disseminated miliary tuber- 
cles upon or beneath the pleural surfaces, either in direct association 
with lesions beneath the pulmonary pleura or apart from these or upon 
the costal pleura. The tuberculous foci may be larger and more diffuse. 
The minute characters of the inflammation are not essentially different 
from those found in tuberculosis in connective tissue elsewhere, but the 
mesothelial cells covering the pleura may share largely in the early 
phases of the new growth. 
If the process is prolonged, much dense fibrous tissue may be formed 
in which are miliary tubercles in various stages of coagulation necrosis, 
or larger patches of necrotic tissue surrounded by miliary tubercles or 
diffuse tuberculous tissue. 
With acute types of tuberculous inflammation of the pleura more or 
less exudate may form. This may be serofibrinous, often with very 
little fibrin, or, as is frequently the case, it may be tinged or deeply colored 
with blood. The exudate may be purulent. The tubercle bacillus may 
be associated with other bacteria, most often with the Staphylococcus 
pyogenes in the purulent exudate. 
Many cases of pleuritis with a serofibrinous exudate giving no growth 
THE RESPIRATORY SYSTEM 
1 Netter, Bouchard and Brissaud, TraitS de MSdecine, Paris, 1901, vii, 445. For a study of the 
ways of infection of the pleura, see Grober, Deutsch Arch. f. klin. Med., 1900, Ixviii, 296 (bibl.). 
2 For a study of the formation of new lymph-vessels in pleurisy, see Guyot, G., Zieglers Beitr., 1905, 
xxxviii, 207. 728 
THE RESPIRATORY SYSTEM 
of bacteria on the ordinary culture media are found to be tuberculous, by 
the inoculation of guinea-pigs with the fluid. 
Miliary tubercles of the pleura, chronic in form, mostly composed of 
fibrous tissue, with cheesy degeneration or calcification, are very common, 
and are frequently associated with tuberculous bronchial lymph-nodes 
without tuberculosis in other parts of the body. These tubercles are 
usually widely scattered over the pleura and are almost always associated 
with anthracotic pigmentation. 
The dense fibrous tubercle or the cheesy or calcified portion may be 
seen as a lighter spot in the pigmented area (Fig. 404). Such tubercles 
are sometimes accompanied by minute cystic dilatations of the lymph- 
vessels on which they are formed. 
These pleural tubercles develop along the subpleural lymphatic 
vessels, or in the areas of lymphoid tissue or in the minute subpleural 
lymph-nodes. 
The presence of these healed tubercles, which rarely harbor stainable 
tubercle bacilli, together with the simultaneous involvement and pig- 
mentation of the bronchial lymph-nodes, affords strong evidence of the 
frequency of the direct infection of the lungs through the respiratory 
passages. They are formed along the lines of lymph drainage of the lungs 
which ultimately enter the bronchial nodes. Since in this drainage 
inhaled pigment particles and tubercle bacilli are deposited together, the 
frequent association of pigmentation and tuberculosis is comprehensible. 
Hodenpyl showed the great frequency of those chronic pleural pig- 
mented tubercles, and Ribbert1 believed that the tuberculous process 
precedes the local pigmentation and furnishes suitable conditions for it. 
TUMORS. 
Benign tumors of the pleura are rare, though fibroma and enchon- 
droma have been described;2 fibromata and lipomata developing in the 
The growth is in the subpleural lymph-vessels, which seen from the pleural surface in the fresh 
lung formed a white raised network over a considerable portion of one lung. The lymph-vessels in 
the cut are seen in transverse section. 
Fig. 442.-Mesothelioma (Endothelioma) of the Lung. 
subpleural tissues may encroach upon the pleural cavity. Small, white, 
slightly projecting, often pigmented elevations of the pleura, either single 
1 Ribbert, Deutsch. Med. Wchnschr., 1906, xxxii, 1615. 
2 For a discussion of tumors of the pleura in general, see Pallasse and Roubier, Ann. de m6d., 1916, 
iii, 243 (bibl.). 729 
THE RESPIRATORY SYSTEM 
or multiple, are common. These were formerly regarded as miliary fibro- 
mata, but Hodenpyl1 and others have shown that while some may be 
fibromata, lymphangiomata, or air cysts, the majority are fibrous masses 
replacing or inclosing miliary tubercles. 
A malignant growth of the pleura which is variously called mesotheli- 
oma, sarcoma, or endothelioma2 (page 441), is an occasional finding; it 
occurs in the form of flat or projecting irregular nodular masses of various 
size (Fig. 442), frequently most distinct and extensive upon the costal 
pleura (Fig. 439 and 440). This, as well as other neoplasms of the pleura, 
may be associated with exudative pleuritis. 
Carcinoma, primary in the thyroid, mamma, esophagus, or stomach, 
may invade the pleura. 
Echinococcus and other cysts of the pleura have been recorded.3 
1 Hodenpyl, Med. Record, 1899, Iv, 903. 
2 Bernard, Virchows Arch., 1913, ccxi, 156; Mehrdorf, ibid., 1908, cxciii, 92; Glockner, Ztschr. f. 
Heilk., 1897, xxviii, 209. 
For a discussion of both pathological and clinical aspects of these tumors, see Fraenkel, Deutsch, 
med. Wchnschr., 1911, xxxvii, 531; and Pick, ibid., 570. 
For a discussion mainly from the clinical side, see Keilty, Am Jour. Med. Sc., 1917, cliii, 888. 
3 For a description of ciliated cysts of the pleura, see Zahn, Virchows Arch., 1896, cxliii, 170. CHAPTER VII. 
THE DIGESTIVE SYSTEM. 
The Mouth. 
Malformations of the lips and cheeks are usually associated with defective forma- 
tion of the bones of the mouth. The entire process is generally due to an arrest of 
development, or a failure of the nasal and maxillary processes or of the branchial 
arches to fuse normally (see Fig. 185, 186 and 443). 
1. The lower jaw is absent; the upper jaw and hard palate are small and imper- 
fectly formed; the temporal bones nearly touch in the median line. The lower part of 
the face is, therefore, wanting; the mouth is absent, or small and closed posteriorly; 
the tongue is absent. Such a malformation is rare; the fetus is not viable. 
2. The face remains in its early fetal condition of a large cleft; the mouth and nose 
form one cavity; the orbits may be united in the same cavity. The fetus is not viable. 
3. There is a cleft in the upper lip, upper jaw, and hard palate. The cleft corre- 
sponds to the point of junction of the processes of the superior maxilla with the inter- 
• maxillary bone. There may be one cleft or two, one 
on either side of the intermaxillary bone. The cleft 
involves the lip alone,-harelip (Fig. 186 and 187)- 
or the lip and superior maxilla, or the lip, maxilla, 
and palate. There may be a single, or a double 
cleft in the palate, and the cleft may involve either 
the hard or soft palate, or both. If there are two 
clefts of the lip and maxilla the portion of lip and bone 
between them may be small, or entirely absent so as 
to leave a large open space. The soft palate maybe 
entirely absent. This is a common malformation and 
does not endanger life. 
4. Rarely there is a cleft involving the middle of 
the lower lip, and sometimes extending into the in- 
ferior maxilla. 
5. Either the inferior, or the superior, or both 
maxillary bones may be abnormally small. 
6. The edges of the lips may be partly or completely joined together. The open- 
ing of the mouth may be only a round hole. 
7. The lips may be absent or imperfectly developed. 
8. The corners of the mouth may be prolonged by clefts in the cheeks nearly to the 
ears. 
Malformations. 
Fig. 443.-Diagram of Lines of 
Embryonic Union in Face. 
Showing the position of clefts of 
the upper lip. (Merkel.) 
INFLAMMATION. (Stomatitis.) 
Catarrhal stomatitis is most frequent in children and occurs with a 
great variety of local and general disturbances. 
During life the congestion and swelling of the mucous membrane may 
be well marked and there are often white patches, produced by the death 
of the superficial epithelial cells. There may be an increased production 
of mucus, or, instead of this, the entire mucous membrane may be un- 
730 THE DIGESTIVE SYSTEM 
731 
naturally dry. In addition to hyperemia and local edema there may be 
proliferation, exfoliation, and degeneration of the epithelium. 
Extravasated leucocytes may infiltrate to a moderate degree the 
stroma of the mucous membrane and appear upon its surface. Small, 
clear vesicles may form beneath the epithelium from the collection of 
serous exudate. 
Croupous stomatitis is incited by local irritants, by local infection, or 
by the extension of the same form of inflammation from the pharynx; it 
frequently occurs with diphtheria and other infectious diseases. 
Portions of the mucous membrane are swollen and congested, and 
covered with a false membrane. This false membrane is composed of a 
thickened layer of epithelium in the condition of coagulation necrosis, 
and of fibrin and pus in variable relative quantity. The stroma of the 
mucous membrane may be infiltrated with pus and fibrin, and portions 
of it may become necrotic. 
Aphthous Stomatitis.-In this condition small whitish projecting 
patches surrounded by a zone of hyperemia may form upon the mucous 
membrane. These consist of a more or less fibrinous exudate beneath 
the epithelium which may exfoliate, leaving small ulcers. 
Ulcerative Stomatitis.-This form of stomatitis is apt to occur in 
ill-nourished children or in young adults, in scurvy, or in mercurial poison- 
ing. It usually begins at the margin of the gums of the lower jaw and 
extends to the cheeks and tongue. The affected parts are swollen and 
coated with a grayish, soft pellicle composed of bacteria and necrotic 
tissue. The gums may be destroyed around the teeth, and these may 
fall out. The surrounding soft parts are swollen, and there may be 
necrosis of the jaws. Chronic phosphorus poisoning, also, induces a 
severe inflammation with necrosis of the maxillary bones. 
In noma or gangrenous stomatitis similar changes may be associated 
with extensive gangrenous destruction of the cheeks. This most often 
occurs in young children in connection with measles, scarlatina, or 
typhoid fever. It has been asserted that a special microorganism is the 
excitant of this disease, but this has not yet been proved. 
Thrush (Soor; Parasitic Stomatitis).-In ill-nourished children or in 
adults suffering from chronic disease a fungus related to the yeasts- 
oidium albicans-may grow among the epithelial cells of the mouth, form- 
ing white membranous patches. These may involve large areas of the 
mouth and pharynx and extend to the esophagus or upper respiratory 
passages. 
Phlegmonous Stomatitis.-Exudative inflammation of the mouth may 
result from infected wounds, in connection with erysipelas or suppurative 
or other infectious process near the mouth. Various pyogenic bacteria 
may be its excitants. 
Chronic Stomatitis.-This may follow acute catarrhal or other inflam- 
matory processes, or most frequently syphilis, and may be due to per- 
sistent irritation-for example, from the use of tobacco. Owing to hyper- 
plasia of the epithelium and submucous tissue, white patches of varying 
extent may form on the tongue or elsewhere-lezicoplakia buccalis. 732 
THE DIGESTIVE SYSTEM 
These through excessive increase in the epithelium may project in wart- 
like form from the surface-ichthyosis. When the thickening is accom- 
panied by local inflammatory thinning it produces the condition known 
as geographic tongue. The inflammatory lesion is apt to be more extensive 
than in simple leucoplakia. 
Fig. 444.-Fibbous Epulis from Gum. 
This type contains only fibrous tissue with large vessels, in contradistinction to the more usual giant- 
cell type. 
Tuberculous stomatitis commences with the formation of miliary 
tubercles or of larger tuberculous masses in the stroma of the mucous 
membrane. These masses soon degenerate, soften, and form ragged 
ulcers. THE DIGESTIVE SYSTEM 
733 
Syphilitic Stomatitis.-As a result of syphilis there may be produced 
either the so-called mucous patches or gummata. In the mucous patches 
the epithelial layer is at first thickened and the papillae of the stroma 
are swollen and infiltrated with cells (see Fig. 167, p. 305 and Fig. 168, 
p. 306). This may be followed by desquamation of the epithelium and 
ulceration. 
TUMORS.1 
Fibroma, lipoma, and enchondroma have been seen in a few cases in 
the lips. When in the mouth they usually grow from the bones. Epulis, 
which may be congenital,2 is a tumor of the jaw, either fibrous (Fig. 444), 
sarcomatous, or epitheliomatous. The term is applied in a clinical sense 
to any tumor of the jaw, but the most frequent form is the giant-cell 
sarcoma (see page 433). 
Fig. 445.-Tumor of Hard Palate. 
These tumors are related both in morphology and in nature to those of the salivary glands. 
Papillomata occur most frequently at the edges of the lips, but are 
found also on the gums, the floor of the mouth, and the cheeks. They 
are composed of hypertrophied papillae covered with thickened epidermis, 
and often ulcerate. Angiomata may be formed in the mucous membrane 
covering the mouth, lips, or soft palate. These tumors are rounded, 
usually small, though sometimes as large as a hen's egg, and may be situ- 
ated in the mucous membrane or project from it as a polyp. 
Mixed tumors, like those found in the parotid gland (page 443 and 
798), sometimes arise in the palatine region (Fig. 445).3 
1 For a general discussion of tumors and other diseases of the mouth, see v. Mikulicz-Radetsky and 
Kummel, Die Krankheiten des Mundes, Jena, 1909; Blessing, Lubarsch-Ostertag, Ergebn. d. allg. 
Path., 1914, xvii1, 858; and Means and Forman, Jour. Am. Med. Assn., 1917, Ixviii, 180. 
2 Futh, Beitr. z. Gebiirtsh. u. Gynak., 1902, vi, 82. 
3 Sturgis, Surg., Gynec., and Obst., 1914, xviii, 456 (bibl.). 734 
THE DIGESTIVE SYSTEM 
Carcinoma is of frequent occurrence and is usually of the cpithelioma- 
tous form. It may originate from any part of the mucous membrane of 
the mouth, and often develops on the edge of the lower lip as a result of 
persistent irritation by a clay-pipe or in the mucous membrane of the 
cheek from the irritation of a rough or carious tooth. Carcinomata may 
originate in an ulcerating papilloma, as flat superficial growths from the 
deeper layers of the epithelium, or as deep nodules starting in the mucous 
glands. 
Dermoid tumors have been described1 in the floor of the mouth. 
Cysts.-Dermoid cysts and cysts of the embryonal branchial clefts 
may involve the mouth, the latter sometimes giving rise to carcinoma.2 
Simple cysts may form in the jaws from aberrations in the development 
of the teeth. Complex congenital tumors of the mouth are of rare occur- 
rence, apparently arising in some congenital anomaly.3 For a descrip- 
tion of adamantinoma, see page 448. 
Showing ciliated epithelium and remnants of thyroid tissue about the periphery. 
Fig. 446.-Thyroglossal Duct from Base of Tongue. 
The Tongue. 
Malformations. 
Absence of the tongue may be associated with the extreme defects of development 
of the face already mentioned. 
The anterior portion of the tongue may be absent while its base remains. The 
lower jaw is then small. The tongue may be cleft or lobulated. 
It may be partly or completely adherent to the floor of the mouth. The frenulum 
may be abnormally short, or may extend to the tip of the tongue. In rare cases the 
1 Hassel, Beitr. z. klin. Chir. (Bruns), 1913, Ixxxiii, 332 (bibl); Gilman, Surg., Gynec., and Obst., 
1916, xxii, 672. 
2 Powers, Ann. Surg., 1898, xxvii, 187 (bibl.). 
3 For a study of complex tumors of the mouth, see Schorr, Zieglers Beitr., 1906, xxxix, 82. THE DIGESTIVE SYSTEM 
735 
sides of the tongue are adherent, or its upper surface may be adherent to the roof of the 
mouth. 
Ciliated or colloid-containing cysts at the base of the tongue are derived from 
remnants of the thyroglossal duct (Fig. 446). 
HYPERTROPHY AND INFLAMMATION. 
Macroglossia, or hypertrophy of the tongue, is almost always a con- 
genital lesion, and is especially common in cretins. The tongue may be 
so large that it protrudes through the lips. The lips may also be simi- 
larly enlarged. There is hyperplasia of the fibrous and other tissues of 
the tongue, and in addition to this there may be a dilatation of the lym- 
phatic vessels. Macroglossia is seen, also, in acromegaly. 
Inflammations of the tongue-glossitis-may be associated with sim- 
ilar changes in the mouth, or may occur by themselves. In catarrhal 
inflammation the accumulation of epithelium may give rise to the 
"furred tongue." Most of the inflammatory processes above indicated 
as occurring in the mouth may affect the tongue also, especially leuko- 
plakia, which is important as a possible precancerous condition. 
Tuberculous lesions in the form of shallow ulcers are not infrequent in 
those suffering from pulmonary tuberculosis. Primary and tertiary 
syphilitic lesions, also, are occasionally seen, and especially an atrophy 
of the papillae and glands at the base of the tongue which is thought to 
be diagnostic of syphilis. In addition to the smooth atrophy a sclerotic 
process may ensue which renders the organ very hard and stiff. 
TUMORS. 
Hyperkeratosis linguae {black hairy tongue) is an occasional finding,1 
and papillomata are not rare. 
Cysts.-The most common forms of cysts are the sacs beneath or 
partly in the substance of the tongue {ranula). They are formed by 
dilatation of the ducts of the mucous glands or of the submaxillary and 
sublingual glands. Amyloid or colloid tumors of the tongue have been 
reported,2 as well as thyroid and parathyroid tumors.3 If the thyroid 
gland is atrophic, these tumors may act vicariously and prevent myx- 
edema.4 
Lipoma and fibroma are rare. They form nodules in the substance 
of the tongue or project in a polypoid form. Composite tumors, com- 
posed largely of fat, are found on the tongue as a congenital condition. 
Angioma.-Cavernous vascular tumors are found in the substance of 
the tongue or projecting from its surface. 
Sarcoma5 is not common in this situation. Carcinoma,6 usually of 
the epitheliomatous type, is a much more frequent growth, affecting 
1 Arrowsmith, Laryngoscope, 1909, xix, 545 (bibl.). 
2 Helter, Wien. klin. Wchnschr., 1908, xxi, 1383 (bibl.). See Schmidt, Virchows Arch., 1896, cxliii, 
369, for bibl. of amyloid tumors in general. For additional bibl. of amyloid tumors, see page 668. 
3 Wood, Proc. New York Path. Soc., 1916, xvi, 84 (bibl.). 
4 Ungermann, E., Virchows Arch., 1907, clxxxvii, 58 (bibl.). 
6 Baastrup, Arch. f. Laryngol. u. Rhinol., 1912, xxvi, 379 (bibl.). 
6 For the differential diagnosis of various ulcers of the tongue, see Howell-Evans, Brit. Med. Jour,, 
1912, i, 1283. 736 
THE DIGESTIVE SYSTEM 
particularly the male sex, perhaps because of the irritation to which the 
tongue is subjected during the use of alcohol and tobacco. Syphilis is 
said to be an important predisposing factor. 
Microorganisms of various forms-bacteria, moulds, and yeasts-are 
always present in the mouth, often in enormous numbers. They are for 
the most part not of significance save for the putrefactive processes 
which they initiate and maintain in mouths not properly cleansed. On 
the other hand, Staphylococcus and Streptococcus pyogenes and the 
pneumococcus are of frequent occurrence in the mouths especially of 
those who live in towns and crowded dwellings, and, while usually harm- 
less, they may under favorable conditions become excitants of serious 
disease. 
The tubercle bacillus may be present in the mouth as well as in the 
nose of those who care for uncleanly consumptives. 
The fungus of thrush (soor), and leptothrix, which under usual 
conditions are not harmful, may incite serious local disease. 
The so-called Mycosis pharyngis is apparently due to the growth in 
susceptible persons of a form of leptothrix not yet thoroughly studied, 
on account of the technical difficulties in the way of its artificial cultiva- 
tion.1 
Two cases of granulomata of the tongue, thought to be due to blasto- 
mycetes, have been described.2 Actinomycosis, also, has been reported. 
MICROORGANISMS OF THE MOUTH. 
The Pharynx and Tonsils. 
Malformations. 
Branchial Fistula and Cysts.-When, as not infrequently occurs, the embry- 
onal gill clefts do not close properly, fistulas may remain.3 These may in rare cases be 
complete, so that an opening exists from the pharynx, larynx, or trachea to the side of 
the neck (see Fig. 185, p. 357). More frequently, however, these fistulae are incom- 
plete and shallow, and open either inward into one of the above-named organs or 
outward on to the neck. Small portions of the gill clefts may persist without external 
openings, and from these subcutaneous cysts of the neck are often developed. Or a 
portion of the cleft may be cut off, forming a cyst, while the fistula persists with its 
external opening. The possibility that some, if not all, of these cysts and fistulae 
may be derived from the embryonic ducts of the lateral lobes of the thyroid and the 
thymus bodies, has been suggested.4 
The walls of these fistulas and cysts may be covered with mucous membrane having 
cylindrical or flattened or ciliated surface cells. Or, when formed from the outer 
clefts, they may be lined with skin. 
Not infrequently the walls of these cysts and fistulse are embedded in lymphatic 
tissue, which may be diffuse or gathered in nodular form (see Fig. 447 and 448).8 
Diverticula of the pharynx have been observed. 
1 For methods of cultivating spirochetes (Treponema) found in the mouth, see Noguchi, Jour. Exper. 
Med., 1912, xv, 81; and 1912, xvi, 194. 
2 New, G. B., Jour. Am. Med. Assn., 1917, Ixviii, 186. 
3 For details of the formation of fissures in the cervical region from incomplete closure of the branchial 
clefts, see Thoma, Text-book of General Pathology, Eng. trans., 1896, p. 201; and Grosser, Keibel and 
Mall, Human Embryology, Philadelphia, 1912, ii., 446. 
4 Wenglowski, Arch. f. klin. Chir. (Langenbeck), 1913, c, 789 (bibl.). 
6 For bibliography of branchial cysts and fistulae, see Coplin, IF. L., Proc. Path. Soc., Philadelphia, 
1901, N. S. iv, 109. THE DIGESTIVE SYSTEM 
737 
INFLAMMATION. (Pharyngitis, Angina, Tonsillitis.) 
Catarrhal pharyngitis is usually associated with the same form of 
inflammation in the mouth and has similar characters. 
Formed from the imperfect closure of an embryonal gill cleft. The cyst is lined with ciliated epithe- 
lium, and the wall is largely formed of diffuse lymphoid tissue. 
Fig. 447.-Section of the Wall of a Branchial Cyst of the Neck. 
This cyst, like that shown in Fig. 447, has much lymphoid tissue in the wall, but is nodular in character, 
while the epithelial lining is squamous in type. 
Fig. 448.-Section of the Wale of a Branchial Cyst of the Neck. 
In catarrhal inflammation involving the tonsils and those portions of 
the pharynx richly supplied with the so-called submucous adenoid- 
lymphoid-tissue, leucocytes may in considerable numbers pass through 738 
THE DIGESTIVE SYSTEM 
the thin epithelial layer and mingle with the exudate upon the exposed 
surface. 
In chronic inflammation of the pharynx there may be a large and 
permanent hyperplasia of the lymphoid tissue, with more or less dense 
fibrous tissue, leading to diffuse or circumscribed nodular or peduncu- 
lated masses of vascular new tissue in the vault or elsewhere in the 
pharynx, called "adenoids."1 
Phlegmonous pharyngitis may occur with inflammations of the 
mucous membrane, with caries of the cervical vertebrae, with inflammation 
of the cervical and parotid glands, and with periostitis of the cranial 
bones, or it may occur independently. It may result in swelling and 
edema, in induration, or in suppuration. It is most important when it 
affects the posterior wall of the pharynx and forms retropharyngeal 
abscesses. Such abscesses may cause death by suffocation. 
Diphtheritic pharyngitis is the form of pseudomembranous or croup- 
ous inflammation of which the Bacillus diphtherias is the excitant. The 
general characters of the diphtheritic infection have been considered in 
an earlier part of this book. The local process, often affecting the fauces, 
pharynx, and tonsils, may involve the mouth as well as the larynx and 
trachea (for details of the local lesion see page 313). 
Tonsillitis.-The tonsils may share in the inflammatory processes of 
the pharynx or be independently affected. The structural characters 
of the tonsils render them liable to infection and involve certain pecu- 
liarities in the lesions.2 
In Follicular Tonsillitis the swollen organ shows upon section an 
increase in the number of the lymphoid cells of the nodules and a hyper- 
plasia of the endothelium of the reticulum. These new-formed and 
often exfoliated endothelial cells are similar to those found in the lymph- 
nodes in general in the presence of bacterial or other toxic substances. 
There may be an increase in the cells of the stroma of the tonsil. The 
epithelial cells of the surface and the crypts may increase in number 
and exfoliate. Epithelial cells and leucocytes and other forms of exudate 
may gather in the crypts or over the surface of the tonsil, forming white 
plugs or a whitish pellicle.3 
In Exudative Tonsillitis {suppurative or phlegmonous tonsillitis, 
quinsy) there are, in addition to hyperplasia and catarrhal inflammation, 
edematous swelling and suppuration often leading to abscess. 
Acute inflammation of the pharynx and tonsils is usually infectious 
in character, and may be due to various forms of pyogenic and other 
organisms. Thus in tonsillitis and other forms of acute angina, the most 
common microorganisms concerned are Streptococcus4 and Staphylo- 
1 See page 664. For a study of the uvula in various abnormal conditions, see Hoen, A.G., Jour. 
Exper. Med., 1898, iii, 649. 
2 Consult Dobrowolski, Z., Zieglers Beitr., 1894, xvi, 43. 
8 See Hodenpyl, E., Am. Jour. Med. Sc., 1891, ci, 257; also Packard, Philadelphia Med. Jour., 1900, 
v, 914, 957. For a study of the lymph drainage of the faucial tonsils, see Wood, G. B., Am. Jour. Med. 
Sc., 1905, cxxx, 216. For a study of absorption in the tonsils, see Wright, New York Med. Jour., 1906, 
Ixxxiii, 17. 
4 See, for study of milk-borne epidemic of tonsillitis due to streptococci, Smith and Brown, Jour. Med. 
Research, 1914-15, N. S. xxvi, 455. 739 
coccus pyogenes, the pneumococcus, and the Micrococcus tetragenus. 
Many other forms have been isolated.1 
In Chronic Tonsillitis (the so-called hypertrophy of the tonsils) 
there is hyperplasia of the lymph-nodules with increase in the fibrous 
stroma. The mouths of the crypts may be occluded and distended with 
exfoliated cells and cell detritus; these deposits may become calcified.2 
Tuberculous Pharyngitis.-Tuberculous inflammation of the pharynx 
may be primary or secondary to tuberculous lesions elsewhere; ulcers 
THE DIGESTIVE SYSTEM 
Fig. 449.-Tuberculosis of Tonsil. 
may form and the tonsils may be involved. This tonsillar infection may 
be primary and may be due to either the human or the bovine type of 
bacilli (Fig. 449).3 
The hyperplasiae of the pharyngeal mucosa in children, commonly 
called "adenoids," have been found in a considerable number of cases to 
be tuberculous. The fact should be borne in mind that from tuberculous 
adenoids and tonsils tubercle bacilli may pass through the lymph-channels 
to the bronchial and cervical lymph-nodes, and that the pharynx may 
thus be a more important portal of entry in tuberculosis than has hitherto 
1 For a study of actinomyces-like structures in the tonsillar crypts, see Gappisch, Verhandl. d. deutsch. 
path. Gesellsch., 1905, ix, 130; also Wright, J., Am. Jour. Med. Sc., 1904, cxxviii, 74. For study of 
bacteriology and pathology of tonsils with reference to articular rheumatism and cardiac disease, see 
Davis, O., Jour. Infect. Dis., 1912, x, 148. 
2 For r6sum£ of tonsillar calculi with bibliography, see Robertson, Brit. Med. Jour., 1899, i, 14. 
3 For a study of primary tonsillar tuberculosis, see Mitchell, A. P., Jour. Path, and Bacteriol., 1917, 
xxi, 248 (bibl.); and Cobbett, C., Causes of Tuberculosis, London, 1917, p. 590. 740 
THE DIGESTIVE SYSTEM 
been recognized.1 These nodes, when tuberculous, have frequently been 
shown to contain bacilli of the bovine type, an observation pointing to 
infection by means of food. 
Fibromata grow from the periosteum of the bones at the base of the 
skull and project into the cavity of the pharynx and posterior nares in 
TUMORS OF THE PHARYNX.2 
the form of large polypoid tumors. Other retropharyngeal tumors,3 both 
benign and malignant and of various types, occur (myxofibroma, fibro- 
lipoma, fibrochondroma, sarcoma, etc.). 
Lipomata4 and amyloid tumors0 are occasionally discovered in the 
pharynx and larynx. 
Fig. 450.-"Adenoid" Polyp of Pharynx. 
1 For a study of the tonsils as portals of entry of tubercle bacilli, see r. Scheibner, Zieglers Beitr., 
1899, xxvi, 511; also Friedmann, F., ibid., 1900, xxviii, 66. Also bibliography in Wood, G. B., Univ. 
Pennsylvania Med. Bull., 1903, xvi, 368. For relation of cervical and bronchial lymph-nodes to 
tuberculous infection, see Beitzke, H., Virchows Arch., 1906, clxxxiv, 1. 
For general bibliography on the tonsils, see Ullman, Med. News, 1901, Ixxviii, 137. 
2 For general discussion of tumors of the pharynx, see Schellong, Geschwiilste des Pharynx, Diss, 
med., Gottingen, 1897; of malignant tumors of the nasal pharynx, see Opikofer, Arch. f. Laryngol. u. 
Rhinol., 1913, xxvii, 526. 
3 Brunner, Beitr. z. klin. Chir. (Bruns), 1903, xxxvi, 689 (bibl.); Hellendall, ibid., 1903, xxxix, 666 
(bibl.). 
4 Goebel, Deutsch. Ztschr. f. Chir., 1904, Ixxv, 196 (bibl.). 
6 Seckel, Arch. f. Laryngol. u. Rhinol., 1912, xxvi, 1 (bibl.). THE DIGESTIVE SYSTEM 
741 
Soft polypoid masses consisting largely of loose succulent connective 
tissue and lymphoid tissue and often called adenoid polyps (Fig. 450), 
are of frequent occurrence. They are usually to be regarded rather as 
hyperplasiae than as true tumors. 
Hairy polyps (teratomata) of the pharynx have been described.1 
Sarcoma, carcinoma,2 and various tumors of mixed type are of fre- 
quent occurrence in the pharynx. 
Cavernous angiomata3 may develop in the posterior pharyngeal wall. 
TUMORS OF THE TONSIL. 
Aberrant islets of cartilage, bone, and marrow are sometimes dis- 
covered in the tonsil (Fig. 451) ;4 these, however, are not in any sense 
true tumors. 
Fig. 451.-Cartilage, Bone, and Bone-marrow in Peritonsillar Tissue. 
Lipoma5 has been described. Malignant tumors6 are comparatively 
rare, though both carcinoma and sarcoma7 have been found. Terato- 
mata8 also occur. Metastatic carcinoma is distinctly uncommon.9 
1 Reuter, Arch. f. Laryngol. u. Rhinol., 1905, xvii, 233 (bibl.). 
2 For a study of carcinoma originating in the branchial clefts, see Powers, Ann. Surg., 1898, xxvii, 187. 
3 Blau, Arch. f. Laryngol. u. Rhinol., 1912, xxvi, 270 (bibl.). 
4 Cary, E. G., Proc. New York Path. Soc., 1916, xvi, 173 (bibl.). 
5 Sommer, Arch. f. Laryngol. u. Rhinol., 1906-07, xix, 523 (bibl.). 
6 Mathews, Laryngoscope, 1912, xxii, 737 (bibl.); Honsell, Beitr. z. klin. Chir. (Bruns), 1895, xiv, 
736. 
7 Berry, Boston Med. and Surg. Jour., 1912, clxvi, 376. 
8 Jewett, Laryngoscope, 1909, xix, 366; Quarella, Policlinico, 1917, xxiv, 60 (abstr. in Jour. Am. 
Med. Assn., 1917, Ixviii, 1441). 
9 Stoll, Arch. f. Laryngol. u. Rhinol., 1913-14, xxviii, 267 (bibl.). 742 
THE DIGESTIVE SYSTEM 
The Esophagus. 
Malformations. 
Malformations of the esophagus are rare. The esophagus may be entirely absent 
or its lower portion may be present and joined to the pharynx by a solid cord; or 
the pharynx, or the lower part of the esophagus, may be continuous with the trachea; 
or the entire esophagus may be represented by a solid cord. Dilatations of the esoph- 
agus and division of the middle portion of the esophagus into two branches have been 
observed.1 The mucosa may be folded across the lumen partially occluding it. 
PERFORATION AND RUPTURE. 
Foreign bodies in the esophagus may perforate its wall. Perforation 
of the esophagus from without may be produced by inflamed bronchial 
glands, by the extension of cavities and gangrene of the lungs, by abscesses 
in the mediastinum, by abscesses accompanying caries of the vertebrae, 
and by aneurysms of the aorta. Rupture of the wall of the esophagus 
by violent coughing and vomiting has been described, but it seems im- 
probable that this should occur without some previous local lesion.2 A 
few cases of perforating ulcer of the esophagus have been recorded. 
HEMORRHAGE. 
Aside from injuries, ulceration, etc., hemorrhage may take place from 
the lower veins of the esophagus, which, in obstructed circulation, espe- 
sially in atrophic cirrhosis, may be much dilated-esophageal varices.3 
DILATATION. 
Simple Cylindrical Dilatations of the esophagus are usually the result 
of long-continued stenosis of the esophagus or of the cardiac end of the 
stomach, although not nearly all the stenoses are followed by dilatation. 
These dilatations are formed at first immediately above the stenosis and 
then extend upward. Dilatation may occur below the stricture. Only 
in rare cases does the dilatation involve the whole length of the tube. 
The entire wall of the dilated portion of the esophagus is thickened, and 
there may be polypoid growths from the mucous membrane. 
In rare cases there is symmetrical dilatation of part or of the whole of 
the esophagus without a stenosis or other discoverable cause. In these 
cases the dilatation is usually greatest near the middle of the esophagus 
and diminishes upward and downward, so that the esophagus has a fusi- 
form shape. The dilatation may reach a very considerable degree, the 
walls of the esophagus may be thickened, and its mucous membrane may 
be covered with papillary outgrowths or ulcerated. 
The Sacculated Dilatations of the esophagus are of two kinds: those 
due to pressure, and those due to traction. 
1 For a study of aberrant islets of gastric mucosa in the upper end of the esophagus, see Schaffer, J., 
Virchows Arch., 1904, clxxvii, 181. 
1 For a study of rupture of esophagus, see McWeeney, Lancet, 1900, ii, 158 (bibl.). 
3 See Preble, R. B., Am. Jour. Med. Sc., 1900, cxix, 263. THE DIGESTIVE SYSTEM 
743 
The dilatations due to pressure are situated in the posterior wall of 
the pharynx, just at its junction with the esophagus. The smaller sacs 
are from the size of a pea to that of a hazelnut; the larger sacs may 
reach a large size and hang down between the esophagus and the verte- 
bral column, the opening into the esophagus remaining comparatively 
small. It is supposed that a limited area of the wall of the esophagus 
loses its power of resistance against the pressure exercised upon it in 
each act of swallowing; it then is forced outward by the pressure, and 
so there is formed first a protrusion and then a sac. When a sac is 
formed the food enters it, and accumulates there, and the sac becomes 
larger and larger. 
The dilatations due to traction are situated on the anterior wall of 
the esophagus, at a point nearly corresponding to the bifurcation of the 
trachea. They are of funnel shape, with the small end outward. Their 
length varies from two to twelve millimeters; the width of the opening 
into the esophagus is from six to eight millimeters. 
These dilatations are due to inflammation of the parts adjoining the 
esophagus, especially of the bronchial nodes, followed by adhesions to 
some part of the anterior wall of the esophagus. These adhesions then 
contract and draw the wall of the esophagus outward, and in this way 
the dilatations are formed. 
At a later time these sacs may perforate into the bronchi, the lungs, 
the pleural cavity, the pericardium, the aorta, or the pulmonary artery.1 
STENOSIS. 
Congenital Stenosis.-Besides the defects of development of the 
esophagus which are incompatible with life, there may be a congenital 
stenosis of some part of it which causes difficulty in swallowing, but yet 
does not destroy life. 
Compression Stenosis is not uncommon. Tumors of the neck and 
mediastinum, and aneurysms of the aorta are the usual causes. Stenosis 
from vertebral ecchondroses has been reported.2 
Obstruction Stenosis.-Foreign bodies may be lodged in the esopha- 
gus. Tumors may hang down from the pharynx into the esophagus, or 
may be situated in the wall of the esophagus. Inflammation of the 
esophagus, due to the ingestion of irritating poisons, may induce cica- 
tricial stenosis. A few cases of stenosis due to syphilitic inflammation 
have been reported. 
INFLAMMATION. (Esophagitis.) 
Catarrhal Esophagitis may be either acute or chronic. The chronic 
form may lead to ulceration, or relaxation and dilatation of the walls, 
or to hypertrophy of the muscular coat. Leukoplakia is not uncommon. 
Pseudomembranous Esophagitis may occur with a similar process in 
the pharynx, with the exanthemata and other severe diseases, or under 
1 For bibl. of esophageal diverticula, see Brosch, Deutsch. Arch. f. klin. Med., 1900, Ixvii, 44; and 
Starck, Arch. f. Verdauungskr., 1901, vii, 1. For later cases, see Pfaff, Tr. Assn. Am. Phys., 1901, xvi, 
656. 
2 See Zahn, H., Munchen, med. Wohnschr., 1906, liii, 906. 744 
THE DIGESTIVE SYSTEM 
other conditions. It may be diphtheritic in character or due to other 
excitants than the diphtheria bacillus. 
Other Forms of Inflammation of the Esophagus.-Foreign bodies 
which are swallowed and become fixed in the esophagus may incite 
inflammation of the mucous membrane and of the adjoining soft parts. 
Abscesses may form around the esophagus, or destroy the wall of the 
canal, and the foreign body may find its way into the trachea, aorta, or 
pericardium. 
Inflammation of the submucous tissue of the esophagus, apart from 
the cases just mentioned, is not common. It may result in abscess or 
the formation of fibrous tissue, causing stenosis. 
Irritating and caustic acids and alkalies may destroy larger or smaller 
portions of the mucous membrane. The necrosed portions are of a black 
or whitish color, surrounded by a zone of intense congestion. If the 
patient recovers, the patches of membrane which have been destroyed 
slough and fall off, leaving a surface covered by granulation tissue. As 
this assumes cicatricial characters and contracts, serious stenosis of the 
esophagus may be produced. 
Tuberculous Esophagitis may occur in generalized miliary tuberculo- 
sis or by local infection from tuberculous sputum, either with or without 
obvious predisposing local lesion, or through an extension of a tubercu- 
lous process from adjacent structures. Ulceration is apt to occur.1 
Syphilitic Esophagitis.-There may be gummata which encroach upon 
the lumen, or ulceration followed by cicatrices may lead to stenosis. 
Small papillomata may occur singly or in considerable numbers 
throughout the entire length of the esophagus; large ones are more rare. 
Submucous fibromata, lipomata, angiomata, myomata,2 leiomyomata, 
rhabdomyomata,3 fibromyomata,4 may develop in the esophagus. Mixed 
tumors5 sometimes arise, and adenomata and myxomata have been 
observed. 
As for malignant growths, sarcomata are rare.6 Carcinomata, which 
are more common, may originate at any part of the wall of the pharynx 
and esophagus. The growth may encircle the tube; it may remain as a 
flat infiltration (Fig. 452), or may project inward in large fungous masses. 
In any case it is prone to ulceration. It may extend up and down the 
esophagus and involve even the pharynx or stomach; or the ulceration 
may extend outward and perforate into the air passages, lungs, pleura, 
pericardium, or large blood-vessels.7 Carcinosarcoma sometimes in- 
volves the esophagus.8 
TUMORS. 
1 For bibliography of tuberculous esophagitis see Flexner, Bull. Johns Hopkins Hosp., 1893, iv, 4, 
and also Cone, ibid., 1897, viii, 229. 
2 Itlig., Inaug.-Diss., Giessen, 1894 (abstr. in Centralbl. f. allg. Path., 1897, viii, 920); Anitschkow, 
Virchows Arch., 1911, ccv, 443 (bibl.). 
3 Wolfensberger, Zieglers Beitr., 1894, xv, 490 (bibl.). 
4 Hall, Quart. Jour. Med., 1916, ix, 409 (bibl.); Anitschkow, Virchows Arch., 1911, ccv, 443 (bibl.). 
6 Glinski, Virchows Arch., 1902, cxlvii, 383 (bibl.). 
6 v. Hacker, Mitt. a. d. Grenzgeb. d. Med. u. Chir., 1908, xix, 396 (bibl.); Donath, Virchows Arch., 
1908, cxciv, 446 (bibl.). 
' For a resum6 of tumors of the esophagus, see Coplin, Am. Med., 1904, vii, 773 
8 Herxheimer, Zieglers Beitr., 1908, xliv, 150 (bibl.); Herzog, Verhandl. d. deutsch. path. Gesellsch., 
1914, xvii, 346 (bibl.); Saltykow, ibid., 351 (bibl.). THE DIGESTIVE SYSTEM 
745 
Cysts.-Small retention cysts of the follicles of the mucous membrane 
are sometimes found. Larger cysts lined with ciliated epithelium have 
been described.1 
Fig. 452.-Infiltrating Carcinoma of the Esophagus. 
The Stomach. 
Malformations. 
Malformations of the stomach arc not common. The organ may be entirely want- 
ing in acephalous fetuses. It may be of various degrees of smallness, sometimes no 
larger than the duodenum. It may be divided into two parts by a deep constriction 
in the middle. It may be vertically placed. Diverticula are noted. The stomach 
may be outside of the abdominal cavity from a hernial protrusion through the dia- 
phragm or at some point in the abdominal wall. It is found on the right side, instead 
of the left, when the other viscera are transposed, and the position of the cardiac and 
pyloric orifices is correspondingly inverted. 
Congenital stenosis of the pylorus in infants is of occasional occurrence. It is com- 
monly due to hypertrophy of the muscular layers, which often involves the fibrous 
coats, also.2 
Cadaveric Changes. 
The mucous membrane of the stomach is liable to undergo considerable alterations 
soon after death, owing to changes in the distribution and composition of the blood and 
to the action of the digestive fluids. The blood is apt to collect in the small veins, 
especially at the fundus, while, by diffusion of the coloring matter, red or brown or 
black streaks and patches form in the mucous membrane. 
Those portions of the mucosa on which the food and digestive fluids collect, usually 
at the fundus and on the posterior aspect of the stomach, frequently appear gray and 
turbid, and are soft and easily rubbed off. The epithelium in these regions is unusu- 
1 Stoebe, Zieglers Beitr., 1912, lii, 512 (bibl.); Staehelin-Burckhardt, Arch. f. Verdauungskr., 1909, 
xv, 584 (bibl.); Pappenheimer, Proc. New York Path. Soc., 1913, xiii, 60 (bibl.). 
2 See Wachenheim, F. L., Am. Jour. Med. Sc., 1905, cxxix, 636; Holt. L. E., Jour. Am. Med. Assn., 
1917, Ixviii, 1517 (bibl.); Ibrahim, J., Ergebn. d. Med. u. Kinderheilk., 1908, i, 208 (bibl.) and 
Strauss, A., Jour. Am. Med. Assn., 1918, Ixxi, 807. 746 
THE DIGESTIVE SYSTEM 
ally granular or disintegrated, and is often detached. Sometimes this post-mortem 
softening involves the entire thickness of the stomach wall, which is converted into a 
gray or yellow or brown gelatinous pulp. Thus large or small post-mortem perfora- 
tions may occur. 
INJURIES. 
Perforating wounds of the stomach usually give rise to a fatal perito- 
nitis. It is possible, however, for the wound to heal, or for a gastric 
fistula to form. 
Rupture of the stomach may be produced by severe blows or falls. 
Minor degrees of injury may produce ulcer. 
Small extravasations of blood in the wall of the stomach are fre- 
quently found in persons who have died from one of the infectious 
diseases. 
Hemorrhage into the cavity of the stomach may occur in a variety 
of ways. It may take place from injuries or poisons; from ulcers or 
HEMORRHAGE. (Hematemesis.) 
Fig. 453.-Fatty Degeneration of the Epithelium of the Gastric Tubules in Phosphorus 
Poisoning. 
carcinoma; from rupture of small aneurysms of the stomach, or from the 
rupture into the stomach of aneurysms elsewhere. It may occur in 
infectious diseases, especially in yellow fever, or in diseases of the blood. 
It may be associated with passive congestion of the stomach in hepatic 
cirrhosis of the liver, with obstruction of the portal vein, chronic disease 
of the heart and lung, an enlarged spleen, and chronic gastritis. In the 
new-born and in young infants hemorrhage into the stomach not infre- 
quently occurs without apparent lesions which would account for it; or 
there may be ulcers of the mucous membranes, or cardiac disturbances, 
or infection. While the source of hemorrhage into the stomach is often 
evident, in many cases none can be discovered. Considerable bleeding 
can evidently take place by diapedesis from congested vessels. 
Some cases of chronic gastritis are characterized by general bleeding 
from the mucous membranes of the stomach.1 
1 For a study of occult hemorrhage in the gastrointestinal canal, see Jaworski and Korolewicz, Wien, 
klin. Wchnschr., 1906, xix, 1129. 747 
THE DIGESTIVE SYSTEM 
ATROPHY AND DEGENERATION. 
Atrophy of the stomach occurs in a variety of cachectic conditions, 
in chronic inflammation, and in stenosis of the cardiac orifice. 
Albuminous degeneration of the epithelium may occur in infectious 
diseases and in inflammation of the stomach. 
Fatty degeneration is often associated with arsenic and phosphorus 
poisoning (Fig. 453). 
Amyloid degeneration of the small vessels is associated with a similar 
process in other parts of the body. 
INFLAMMATION. (Gastritis.) 
Acute Catarrhal Gastritis is usually due to the ingestion of irritating 
decomposing or infectious substances and may accompany general 
infectious diseases. 
Fig. 454.-Acute Catarrhal Gastritis. 
Showing the open ends of two gastric tubules. There is a considerable formation of mucus by the 
epithelial cells, many of which have the so-called "beaker" form. There is exfoliation of epithelium 
which, with mucus and a few leucocytes and red blood-cells, covers the surface of the mucous mem- 
brane. 
After death the mucous membrane may be congested and swollen, 
or the congestion may have disappeared. The mucous membrane is 
coated with an increased amount of mucus, especially at the pyloric end 
of the stomach. 
The structural changes in the mucous membrane consist chiefly in 
swelling and albuminous degeneration, and sometimes exfoliation of the 
epithelium with an increase in the production of mucus by the cylindrical 
cells (Fig. 454), while the intertubular tissue and the submucosa may be 748 
THE DIGESTIVE SYSTEM 
edematous and contain a few emigrated leucocytes. The solitary lymph- 
nodules may be enlarged from hyperplasia, and hemorrhagic erosions 
may be present. 
Chronic Gastritis.-This, with the continuance of the exciting condi- 
tions, may follow the acute form. It is often associated with the persist- 
ent use of alcohol, with ulcers and carcinoma, with venous congestion 
from heart lesions, cirrhosis of the liver, obstruction of the portal vein 
or ascending vena cava, or chronic diffuse nephritis. These are doubtless 
predisposing conditions rather than actual excitants of the disease. 
The stomach may be normal in size or small or dilated. Its inner 
surface is usually covered with tenacious mucus. The mucous mem- 
brane may be congested with minute hemorrhages or erosions, or it may 
be pale and gray or pigmented from former hemorrhages. It may be 
thickened or thinner than normal. Often, owing to irregular thickening, 
it projects in places in the form of minute granules, or it is irregularly 
Showing a small portion of the new-fonned tissue between the gastric tubules. There are many large 
polyhedral cells in the new tissue. 
Fig. 455.-Chronic Gastritis. 
roughened-etat mamelonne-or there may be distinct polypoid out- 
growths. These alterations are usually most marked in the pyloric 
region. Microscopical examination shows alterations varying in differ- 
ent parts of the organ and in different stages of the disease. The surface 
epithelium may be degenerated and exfoliated. The detached epithe- 
lium with leucocytes may be mingled with the mucus covering the surface. 
The gastric glands may be variously altered. They may be dilated, or 
elongated and tortuous, or hyperplastic1 or atrophied; their epithelium 
may be flattened, degenerated, or detached. The interstitial tissue and 
the submucosa may be infiltrated with small spheroidal cells or new- 
formed larger polyhedral cells (Fig. 455), and new fibrous tissue may 
form (Fig. 456), thus often greatly thickening the mucous membrane 
and causing atrophy of the glands. The lymph-nodules at the base of 
the glands may be enlarged from hyperplasia. On the other hand, the 
mucous membrane, as contraction takes place in the new-formed intersti- 
1 See Cone, Welch Anniversary Contributions to the Science of Medicine, 1900, p. S77 (bibl.). THE DIGESTIVE SYSTEM 
749 
tial tissue, may undergo great atrophy (Fig. 457), so that it is pale, thin, 
often gray in color, with more or less pigmentation. 
The formation of new fibrous tissue may later involve the muscularis 
also, leading to various distortions of the stomach. 
A much more extensive form of chronic cirrhosis of the stomach 
{linitis plastica) is occasionally seen, in which there is a formation of 
dense connective tissue in the pyloric region or involving the entire organ, 
and causing a shrinkage of the whole viscus.1 The affected portions are 
cartilaginous in texture. Microscopically, the sclerotic process is found 
mainly in the submucosa, but it may invade the muscularis and even the 
serosa. In the last instance, the disease usually affects more or less ex- 
tensively all the serous membranes {fibrous polyserositis). It is sometimes 
Fig. 456.-Chronic Gastritis. 
Fig. 457.-Chronic Gastritis. 
Showing the new-formed fibrous tissue 
between the gastric tubules. 
Showing atrophy of the mucous membrane 
with much new-formed fibrous tissue. 
difficult to distinguish linitis plastica from a scirrhous carcinoma of the 
stomach wall which does not involve the mucosa. 
Croupous Gastritis (Membranous or Diphtheritic Gastritis).-This 
form of gastric inflammation, most common in children, may be asso- 
ciated with diphtheria or with other infectious diseases, but may occur 
independently. In adults it is usually secondary to typhus fever, 
pneumonia, pyemia, typhoid fever, the exanthemata, and other infec- 
tions, or may follow the ingestion of irritant poisons. The excitants 
are thus of the most varied kinds, as is the case in pseudomembranous 
inflammation elsewhere in the body. 
Exudative Gastritis (Suppurative or Phlegmonous Gastritis).-This 
process is characterized by the formation of purulent and other exudate 
in the connective tissue of the mucosa and submucosa. The exudate may 
be diffuse or localized in the form of abscess. As an independent affec- 
tion it is rare. It is more frequent in connection with puerperal fever 
1 Krompecher, Zieglers Beitr., 1910, xlix, 384; v. Sury, Arch. f. Verdauungskr., 1907, xiii, 1. Lyle, 
H. H. M., Linitis plastica (cirrhosis of stomach), Ann. Surg., 1911, liv., 625, complete bibl. 750 
THE DIGESTIVE SYSTEM 
and other infectious diseases; it has been ascribed to injury and also to 
alcoholism. 
The accumulation of exudate may be slight, the interglandular and 
submucous tissue being edematous with few pus cells. The mucous 
membrane may under these conditions remain intact or show slight 
catarrhal lesions. When this relatively slight accumulation of exudate 
occurs in the pyloric region it may apparently occasion temporary 
stenosis. On the other hand, a considerable or large amount of exudate 
may form, and the process may involve diffusely a large part of the wall 
of the stomach; or the process may be circumscribed and abscesses may 
form. The suppurative process may extend to the mucous membrane, 
or to the serosa, and thus perforations may occur with the incitement 
of peritonitis. Little is known of the direct excitants of phlegmonous 
gastritis.1 Streptococcus pyogenes has been found in the exudate.2 
Toxic Gastritis.-The mineral acids, the caustic alkalies, arsenic, 
corrosive sublimate, and the metallic salts, phosphorus, camphor, and 
other irritating materials, induce different lesions of the stomach, accord- 
ing to their quantity, their strength, and the length of time which has 
elapsed before death. 
In large quantities they destroy and convert into a soft, blackened 
mass both the mucous membrane and the other coats, so that perforation 
may take place. In smaller quantities they produce black or white 
sloughs of the mucous membrane, surrounded by a zone of intense con- 
gestion. If death does not soon ensue, the ulcerative and cicatricial 
processes which follow such sloughs may contract and deform the stom- 
ach in various ways. 
If the poisons are of less strength they may induce a diffuse conges- 
tion of the mucous membrane, with catarrhal or croupous exudation on 
its surface and serous infiltration of the submucous coat (see chapter on 
Poisons). 
Tuberculous Inflammation of the stomach is rare and is usually sec- 
ondary to tuberculous lesions elsewhere. There may be miliary tubercles 
or small or large, single or multiple ulcers involving especially the mucosa 
and submucosa.3 
Syphilitic Inflammation of the stomach with ulceration has been 
occasionally observed.4 The lesion is often not very characteristic as 
the changes due to the syphilitic poison are superimposed on those due 
to ulceration; but usually a few giant cells are present, and these with 
the perivascular infiltration, the absence of tubercle bacilli, and a positive 
Wassermann reaction permit of a diagnosis. 
1 Reference to the bibliography of microorganisms of the normal stomach may be found in an 
article by Weiss, Bacteria in the Stomach of the Cat, Jour. App. Microscopy, 1900, iii, 827; also Coyon, 
Flore microbienne de 1'estomac, Th^se de Paris, 1900 (bibl.). For bibl. of phlegmonous gastritis, see 
Leith, Edinburgh Hospital Reports, 1896, iv, 51. For a later study, see Schnarrwyler, Arch. f. Ver- 
dauungskr., 1906, xii, 116 (bibl.). 
2 See Kinnicutt, F., Tr. Assn. Am. Phys., 1900, xv, 127 (bibl.) For a study of lesions of the stomach 
as portals of entry of bacteria see James, Tr. Assn. Am. Phys., 1901, xvi, 72. 
8 For tuberculosis of the stomach, see Dewey, Jour. Infect. Dis., 1913, xii, 236; Winternite, Bull. 
Johns Hopkins Hosp., 1908, xix, 223; Pertik, O., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1902, viii2, 
273. 
4 Consult for bibliography, Smithies, F., Jour. Am. Med. Assn., 1915, Ixv, 572. THE DIGESTIVE SYSTEM 
751 
ULCERS OF THE STOMACH. 
Simple or Peptic Ulcer.-This form of ulceration of the stomach is 
often seen. It occurs in males nearly three times as frequently as in 
females; and the peak of the age distribution, as shown by surgical mate- 
rial rather than by post-mortem statistics, is between twenty and thirty 
years, the average age for males being a trifle higher than that for females. 
The disease is almost unknown in children. Clinically, the ulcers are 
found in about 1 per cent, of general hospital admissions, and in about 
4 per cent, of post-mortem examinations.1 
They are most frequent on the posterior surface of the stomach, 
especially close to the pylorus and along the lesser curvature. On the 
anterior wall, the cardia, the fundus, and the greater curvature only a 
small percentage of ulcers occur. 
In size they vary from one-quarter inch to five or six inches. They 
are usually of circular shape, but occasionally they are oval, and some- 
times two or more ulcers fuse. The lesion is most extensive in the mucous 
membrane, and the ulcers may be confined to this or may extend outward, 
involving the connective tissue, and the muscular and, finally, even the 
peritoneal coats, the diameter becoming less as the ulcer progresses 
Showing a section through the stomach wall at the central part of the round ulcer. 
Fig. 458.-Chronic Ulcer of the Stomach. 
through the wall (Fig. 458). The ulcer looks like a clean hole punched 
out of the wall of the stomach (Fig. 459). 
There are probably three different etiological factors in the production 
of ulcers of the stomach: (1) Some type of injury to the mucous mem- 
brane; (2) a disturbance of circulation; and (3) hyperacidity of the gastric 
juice. Nevertheless, the actual conditions underlying the production of 
simple ulcers are still obscure, though it seems probable that in some 
fashion the nutrition of a circumscribed portion of the wall of the stomach 
is interfered with and that then, and only then, is the mucous membrane 
of the wall destroyed by action of the gastric juice. But we are still 
ignorant of the way in which are produced the vascular changes which 
lead to the primary injury of nutrition. Nervous influences can appar- 
ently be excluded.2 Gastric ulcer is frequently seen in chlorotic or 
1 Welch, W. H., Pepper, System of Practical Medicine, 1885, iii, 504. Many important data are to 
be found in this excellent article. 
2 Kawamura, Deutsch. Ztschr. f. Chir., 1911, cix, 540 (bibl.). See, however, Ophuls, W., Jour. 
Exper. Med., 1906, viii, 181. 752 
THE DIGESTIVE SYSTEM 
anemic persons, and examination of the tissues about the ulcer often 
shows a good deal of vascular thickening and in some places a chronic 
obliterating endarteritis. Emboli have been found in branches of the 
gastric artery in cases of simple ulcer. 
Recently, the possibility of a bacterial origin of the preliminary 
ischemic necrosis which permits of digestion of the mucous membrane 
by the gastric juice has been stressed, but the difficulties of producing 
such an ulceration with any constancy in the stomach of animals by any 
means has prevented a successful approach to the solution of the problem.1 
There is usually but little active inflammatory change about the 
ulcer, though the edges are occasionally thickened by the growth of con- 
nective tissue. A moderate cellular infiltration is seen near the eroded 
surface. The mucous membrane of the remainder of the stomach is apt 
Fig. 459.-Chronic Perforating Ulcer of the Stomach. 
to be in a condition of catarrhal inflammation. The ulcer may perforate 
directly through the wall of the stomach, the contents of the latter being 
discharged into the peritoneal cavity, and this may be the first evidence 
of the presence of the lesion. On the other hand, if the ulcer is more 
chronic dense adhesions may be formed between the wall of the stomach 
and the neighboring viscera, so that the bottom of the ulcer is closed and 
only a large tumor-like mass of inflammatory tissue is the result. Again, 
the liver, the intestine, and abdominal wall may adhere to the stomach, 
and these tissues be invaded by the ulcerative process, and cavities be 
formed which communicate with the lumen of the stomach. Local peri- 
tonitis and collections of pus may develop. Perforation may take place, 
also, into the duodenum or into the pericardial or pleural cavities. 
Repeated small hemorrhages occur regularly from the erosion of small 
1 For experimental production of gastric and duodenal ulcer, especially with reference to injections 
of bacteria, see Rosenow, E. C., Jour. Infect. Dis., 1916, xix, 333 (good bibl.). See, also, Steinharter, 
E. C., Boston Med. and Surg. Jour., 1917, clxxvi, 461; and Celler, H. L., and Thalhimer, W., Jour. 
Exper. Med., 1916, xxiii, 791. THE DIGESTIVE SYSTEM 
753 
blood-vessels on the surface of the ulcer. This blood may be vomited 
or passed in the stool and can almost always be detected by modern 
laboratory methods. If a larger vessel is eroded quantities of blood will 
be vomited or passed as a black tarry mass from the anus. 
Occasionally, a gaping vessel of considerable caliber is found in the 
floor of a gastric ulcer during operation or at autopsy, but usually the 
blood seems to come from the capillaries rather than from the larger 
arterial trunks. 
The ultimate course of such ulcers is unquestionably toward cicatriza- 
tion with the final restoration of the mucous membrane. This is espe- 
cially the case if the irritation of the ulcer by food is avoided either by 
placing the patient on a diet or by the performance of a gastroenteros- 
tomy. Such cicatrization may produce various deformities of the stom- 
ach by production of the dense connective tissue formed during the 
process of repair.1 
A not infrequent alteration in the very chronic ulcers is the appear- 
ance in the edges of changes suggestive of carcinoma. Opinions are still 
at variance as to the interpretation and relative frequence of this occur- 
rence, some observers thinking that as many as 60 to 70 per cent, of 
chronic ulcers in persons of advanced years show microscopical carcin- 
omatous changes, while others believe that at a maximum 10 per cent, 
of ulcers may become malignant.2 The question must be settled by the 
observation of surgical material, because at the time of autopsy it is 
difficult or impossible to differentiate an extensive ulcerated carcinoma 
from an ulcer with carcinomatous changes, and thus to determine 
whether or not the growth began primarily as an ulcer. 
Follicular Ulcers, similar to those in the small intestine, are of occa- 
sional occurrence in the stomach. They are formed by the degenerative 
changes and necrosis in the solitary lymph-nodules of the stomach. 
For Tuberculous Ulcers, see above. 
Hemorrhagic Erosions occur as rounded spots or narrow streaks, 
formed by a loss of substance of the mucous membrane. The mucous 
membrane at these points may be congested, soft, and covered by small 
blood-clots. The destruction of the mucous membrane is usually super- 
ficial, but may involve its entire thickness. The internal surface of the 
stomach may be studded with these erosions. They give rise to repeated 
hemorrhages, and are accompanied by catarrhal inflammation of the rest 
of the mucous membrane. 
They occur at all periods of life, even in infants. Their usual seat is 
the pyloric portion of the stomach. They may occur independently of 
other obvious lesions, but are most frequent in connection with chronic 
1 For general surveys of the subject, see Martin, C. F., Osler and McCrae, Modern Medicine, 2d 
edition, Philadelphia, 1914, iii, 168; Smithies, F., Cancer of the Stomach, Philadelphia, 1916; and 
Verse, Verhandl. d. deutsch. path. Gesellsch., 1909, xiii, 374. 
2 See Hauser, G., Das chronische Magengeschwiir, Leipzig, 1883; Wilson, L. B., and McDowell,.!. E., 
Am. Jour. Med. Sc., 1914, cxlviii, 796; Friedenwald, J., ibid., p. 660; MacCarty, W. C., and Broders, 
A. C., Arch. Int. Med., 1914, xiii, 208; Mayo, W. J., Jour. Am. Med. Assn., 1915, Ixv, 1069 (bibl.); 
Ochsner, A. J., ibid., p. 1073; Smithies, F., Cancer of the Stomach, Philadelphia, 1916; Wilensky and 
Thalheimer, Ann. Surg., 1918, Ixvii, 215; Ewing, J., Relation of gastric ulcer to cancer. Ann. Surg., 
1918, Ixvii, 715. 754 
THE DIGESTIVE SYSTEM 
congestion of the mucosa, chronic gastritis, infectious diseases, and 
intoxications. 
DILATATION AND DISPLACEMENT. 
Very considerable degrees of dilatation of the stomach are found at 
autopsies usually in persons with enteroptosis, without stenosis of the 
pylorus or other mechanical cause to account for them. It is usually 
difficult to determine how long these dilatations have existed and their 
influence in the illness or death. 
Acute dilatation of the stomach, with vomiting of very large quanti- 
ties of thin fluid, has been observed in a few cases, the dilatation being 
developed suddenly and without discoverable cause. 
Of the mechanical factors which lead to dilatation of the stomach a 
stenosis of the pylorus is the most common. Such a stenosis may be 
effected by a tumor, by chronic inflammation and thickening, and by the 
cicatrization of ulcers. Less frequently obstructions of the small and 
large intestines act in the same way. Postoperative dilatation is not in- 
frequent, and is due in some instances to atony, in others to mechanical 
closure of the duodenum by direct pressure or indirectly by traction on the 
mesentery. Some forms of chronic gastritis are attended with dilatation 
of the stomach without stenosis. In rare cases circumscribed, sacculated 
dilatations are produced by the presence of foreign bodies-portions of 
wood, metal, etc. 
The stomach may be variously displaced by pressure from without. 
TUMORS. 
Papillomata.-It has already been mentioned that some cases of 
chronic gastritis are accompanied by small polypoid hypertrophies of the 
mucous membrane; but besides these, polypoid tumors are found which 
may reach a considerable size and may number as many as two hundred.1 
They are composed of a connective tissue stroma arranged in tufts and 
covered with cylindrical epithelium. In some places tubules lined with 
cylindrical epithelium are found, so that the growth has partly the struc- 
ture of an adenoma (Fig. 460). 
Fibromata of small size are sometimes found in the connective tissue 
coat, and lipomata may develop in the same situation and assume the 
form of rounded or polypoid neoplasms. They usually project inward, 
but sometimes push outward beneath the peritoneum. Leiomyomata 
develop as rounded tumors in the muscular coat, but may gradually 
separate themselves from it and project either inward or outward.2 The 
submucous myomata are at first small tumors lying loosely attached 
in the submucous coat, but as they grow larger they push the mucous 
membrane inward and become polypoid. Small multiple angiomata may 
be found in the stomach in connection with similar tumors in the sub- 
1 Finney and Friedenwald, Am. Jour. Med. Sc., 1917, cliv, 683 (bibl.); Meulengracht, Virchows Arch., 
1913, ccxiv, 438. 
2 James and Sappington, Surg., Gynec., and Obst., 1915, xxi, 744 (bibl.). THE DIGESTIVE SYSTEM 
755 
mucosa throughout the gastrointestinal canal.1 Lymphomata in the wall 
of the stomach are seen in some cases of leukemia and lymphosarcoma. 
Sarcomata of the stomach are rare, though all types have been 
recorded.2 
Adenoma.-Besides the papillomata discussed in a preceding para- 
graph, there are found in the submucous coat circumscribed tumors com- 
posed of tubules irregular in form and lined with one or more layers of 
cylindrical epithelium, like those of the gastric mucous membrane (see 
adenocarcinoma, below). 
Carcinoma of the stomach is usually primary, though it may occasion- 
ally be metastatic. It may develop from polyps or adenoma,3 though 
Fig. 460.-Small Papillary Adenoma of the Stomach. 
This is confined to the mucous membrane, forming a small polypoid growth into the cavity. En- 
larged about five diameters. 
the origin from ulcer is much more frequent. It is of relatively common 
occurrence, the stomach in Welch's4 analysis of over 30,000 cases being, 
next to the uterus, the organ most frequently affected. The common 
involvement of this structure shown in these figures is substantiated by 
more recent statistics;5 thus, of a total of 52,420 deaths caused by cancer 
throughout the United States in 1914, 12,768, or about 24 per cent, 
were the result of cancer of the stomach. 
1 Bennecke, Virchows Arch., 1906, clxxiv, 171; MacCallum, Bull. Johns Hopkins Hosp., 1906, xvii, 
258. For a review of the bibl. of benign growths of the stomach, see Basch, Surg., Gynec., and Obst., 
1916, xxii, 165 (bibl.). 
2 Dock, Tr. Assn. Am. Phys., 1900, xv, 165 (bibl.); Fenwick, Lancet, 1901, i, 463 (bibl.); Corner, 
and Fairbanks, Practitioner, London, 1904, Ixxii, 810; Flebbe, Frankfurt. Ztschr. f. Path., 1913, xii, 
311 (bibl.); Storch, Deutsch. Ztschr. f. Chir., 1904, cxxviii, 218 (bibl.); Hartz, Surg., Gynec., and Obst., 
1914, xviii, 502 (bibl.). 
3 Verse, Uber d. Entstehung, d. Bau u. d. Wachstum d. Polypen, Adenome u. Karzinome des Magen- 
Darmkanals, Arb. a. d. path. Inst. z. Leipzig, 1908, Erster Band. 
4 Welch, Pepper's System of Practical Medicine, 1885, ii, 561. 
5 Mortality from Cancer and Other Malignant Tumors, Department of Commerce, Bureau of the 
Census, Sam. L. Rogers, Director, Washington, 1916, p. 15. 756 
THE DIGESTIVE SYSTEM 
The situation of the tumor in Welch's summary of 1300 cases of 
carcinoma of the stomach was: pyloric region, 791; lesser curvature, 148; 
cardia, 104; posterior wall, 68; involving the greater part of the stomach, 
61; greater curvature, 34; anterior wall, 30; fundus, 19; multiple tumors 
were found in 45 cases. 
Carcinoma of the stomach is rare in childhood, though the physician 
must not lose sight of the fact that it may occur.1 
Carcinomata of the stomach occur in various forms. There may be 
large or small, flat or rounded or lobulated growths projecting from the 
inner surface (Fig 461); the mucous membrane overlying them may be 
Fig. 461.-Carcinoma of the Stomach. (Pyloric Region.) 
intact or ulcerated; and the destructive process may advance far enough 
for the ragged or smooth-edged ulcers to reach a considerable size The 
wall of the stomach may be involved; peritoneal adhesions may form; 
or perforation may occur. On the other hand, carcinoma may assume the 
form of a diffuse infiltration of the stomach wall; growths of this type are 
less liable to ulcerate and are, indeed, often overlooked or mistaken for 
a chronic inflammatory lesion. 
A large globular tumor projects into the cavity. 
1 Osler and McCrae, New York Med. Jour., 1900, Ixxi, 581; BrUning and Schwalbe, Handbuch d. 
allg. Path. d. Kindesalters, Wiesbaden, 1912, p. 422 (bibl.). THE DIGESTIVE SYSTEM 
757 
Metastatic tumors are most common in the liver, lymph-nodes, and 
peritoneum, but may arise in any part of the body. Many neoplasms 
described in the earlier literature as primary carcinomata of the liver 
are now regarded as metastatic carcinoma from the stomach. 
Showing the infiltrating form of tumor occupying the pyloric end of the stomach and advancing along 
the wall. 
Fig. 462.-Gelatinous Carcinoma of the Stomach. 
The most common variety of carcinoma of the stomach is the adeno- 
carcinoma, in which the glandular type is followed in many parts of the 758 
THE DIGESTIVE SYSTEM 
growth (Fig. 262, page 451); cylindrical or polyhedral epithelial cells 
line variously shaped alveoli which frequently maintain well-marked 
lumina that are sometimes distended. Other portions of the growth, 
however, often show a medullary structure. It forms early and distant 
metastases. 
Scirrhous carcinoma, the next most frequent type, is often of the infil- 
trating variety (Fig. 272, page 459). A third type, gelatinous carcinoma, 
frequently forms extensive growths and is also apt to invade adjacent 
structures and to establish metastases. Squamous-cell carcinoma of the 
stomach has been described.1 
This specimen consists largely of hairs, cotton and woolen threads, straws, etc. 
Fig. 463.-Hair Balls from Human Stomach. 
Stenosis of the pylorus, chronic gastritis, adhesions, fistulae, distortion, 
perforation, hemorrhage, and suppurative inflammation are among the 
most frequent secondary complications of gastric carcinoma. Of the 
relatively infrequent secondary cancers of the stomach, those originating 
in the breast are proportionately most numerous.2 
Cysts of the stomach wall have been recorded.3 
FOREIGN BODIES. 
Among the various foreign bodies which by accident or design may 
be present in the stomach may be mentioned hairs, thread, string, etc., 
which have been swallowed from time to time, usually by hysterical 
1 Borst, Die Lehre v. d. Geschwiilsten, Wiesbaden, 1902, p. 665; Fiitterer, Jour. Am. Med. Assn., 
1904, xliii, 1129. 
2 Welch, Pepper's System of Practical Medicine, 1885, ii, 561. 
3 Schultze, Proc. New York Path. Soc., 1899-00, p. 260. 
For general bibl. of lesions of the stomach, see Thorel, Lubarsch-Ostertag, Ergebn. d. allg. Path., 
1898, v, 142. 
For a study of retrograde metastases of carcinoma through thelymph-channels from the stomach to 
the liver, see Jacob, Arb. d. path.-anat. Inst., Tubingen, 1904, v, 121. 
For general information, bibl., etc., pertaining to tumors of the stomach and intestine, see the mono- 
graphs of Borrmann, Magencarcinoms, Mitt. a. d. Grenzgeb. d. Med. u. Chir., Erster Supplementband, 
Jena, 1910; Hauser, Das Cylinderepithel-Carcinom d. Magens u. d. Dickdarms, Jena, 1910; Versi, 
Uber d. Entstehung, d. Bau u. d. Wachstum d. Polypen, Adenome u. Karzinome d. Magen-Darm- 
kanals, Arb. a. d. path. Inst. z. Leipzig, 1908, Erster Band. THE DIGESTIVE SYSTEM 
759 
women. These may be closely packed together into a large mass nearly 
filling the cavity of the stomach, to which in shape it may correspond 
(Fig. 463).1 Masses of shellac have been found in the stomachs of those 
who have satisfied their desire for alcohol by drinking varnish. Glass 
and metallic articles have been removed in large numbers from the stom- 
achs of insane persons.2 
The Intestines. 
Atresia Ani.-Absence of the anal opening is frequent. This may be associated 
with partial or complete atresia of the rectum or of the colon, which may be represented 
by solid cords. Blind terminations of the small intestine may occur, or there may be 
complete closure of the gut. There may be absence 
of continuity between the large and small intestine. 
The appendix may be absent, but this is a very 
rare anomaly. 
Transposition.-The position of the intestines 
may be the opposite to that which is usually found. 
The transposition may affect all the abdominal vis- 
cera, or only a single viscus may be transposed. 
Anomalous Positions.-The intestines with the 
other abdominal viscera may be partly without the 
abdominal cavity in failure of the abdominal walls 
to close in development (see Fig. 188, p. 359). Dis- 
placements of the colon are not infrequent.3 
Diverticula.-Congenital Diverticula.-1These are 
most frequent in the lower part of the ileum, occur- 
ring in about 1 per cent, of autopsies. They spring 
usually from the convex surface of the intestine, 
more rarely from the attached border, at a distance 
of about one meter from the ileocecal junction in 
adults. In the latter case they are joined to the 
mesentery by a fold of peritoneum. The divertic- 
ulum forms a pouch from two to fifteen cm. long, of 
about the same diameter as the intestine, smallest 
at its free extremity. 
Such diverticula do not interfere with the func- 
tions of the intestines except in rare instances when 
the gut is stenosed.4 They occasionally form part 
of a hernia. Sometimes the remains of these intestinal diverticula-called Meckel's 
diverticula-form soft, projecting tumors at the umbilicus5 in children. Micro- 
scopical examination of such tumors often shows the structure of the intestinal mucosa 
and muscularis or even tissues resembling the pancreas at the tip.6 If they remain 
attached by a fibrous cord to the navel, this cord may be the cause of incarceration 
of a portion of the intestines.7 
Malformations. 
Fig. 464.-Diverticulum of the 
Small Intestine. 
1 Such a specimen, mentioned by Osler, is in the museum of McGill University; another, reported 
by Findler (see Fig. 463), is in the museum of the College of Physicians and Surgeons, New York. See 
Jacobson, N., Med. News, 1901, Ixxviii, 245; Fenwick, Brit. Med. Jour., 1902, ii, 1696 (bibl.), Heazlit, 
L., Jour. Am. Med. Assn., 1914, Ixii, 107 (bibl.), Matas, R., Surg., Gynec., and Obst., 1915, xxi, 594, 
and O'Brien, F. W., Boston Med. and Surg. Jour., 1918, clxxviii, 396. 
2 See, for example, a case with 452 foreign bodies, Eliason, E. L., Jour. Am. Med. Assn., 1917, 
Ixix, 2106; and another with 95 hairpins, Nix, J. T., ibid., 1917, Ixviii, 840. 
3 For bibliography of reported cases, see Shober, J. B., Am. Jour. Med. Sc., 1898, cxvi, 405. 
4 Doepfner, K., Deutsch. Ztschr. f. klin. Chir., 1911, cix, 396. 
6 For bibliography of umbilical tumors, see Giannettasio, Arch. g6n. de Med., 1900, iii, 65; and 
Cullen, The Umbilicus and its Diseases, Philadelphia, 1916. For diverticula of duodenum, see Davis, 
Tr. Chicago Path. Soc., 1913, ix, 1. 
3 Albrecht and Arzt, Frankfurt. Ztschr. f. Path., 1910, iv, 167. 
7 For bibliography, see Riesman, Proc. Path. Soc., Philadelphia, 1898, N. S., i., 193. For case of 
volvulus of Meckel's diverticulum, see Taylor, Bull. Johns Hopkins Hosp., 1901, xii, 326. For a study 
of the diseases connected with Meckel's diverticulum, see Griffith, J. P. C., Jour. Am. Med. Assn., 1914, 
xii, 1624 (bibl.). 760 
THE DIGESTIVE SYSTEM 
Acquired Diverticula.-Not infrequently one finds at autopsies either in the small 
or large intestine diverticula or hernise which project from the exterior of the gut, 
usually near its mesenteric attachment. These consist of the mucous membrane 
which has been crowded through the muscularis and is covered by serosa. They may 
form in connection with the appendix. These so-called "false diverticula" may be 
large, but are generally not larger than a pea; they may be single or numerous (Fig. 
465). They as a rule cause no functional disturbance, but may, through the accumu- 
lation of fecal material within them, be the seat of perforation, inducing abscesses or 
peritonitis; or they may lead to local adhesion to adjacent parts.1 Carcinoma may 
develop in such diverticula. 
Cloacae.- The rectum may open into the bladder, urethra, or vagina. Thus 
cloacae are formed which are often associated with other malformations of the abdomi- 
nal wall, intestines, and generative organs. 
Incarceration, Volvulus. 
1. The most common form is that in which a portion of intestine is strangulated by 
a fibrous band. Such fibrous bands are the result of peritonitis or may be of fetal 
origin. The intestine becomes in some way caught under one of these bands and is 
compressed by it. The stricture thus produced may lead to a gradual accumulation 
of feces in the intestine above it, and may last for a long time before death ensues. In 
other cases the stricture interferes at once with the circulation of the blood; the intes- 
Fig. 465.-Multiple False Diverticula of the Intestine. 
tine is intensely congested, becomes gangrenous, and death takes place with the symp- 
toms of general peritonitis. 
2. A portion of intestine becomes caught in some abnormal opening in the mesen- 
tery or omentum, or in the foramen of Winslow, or between the two layers of the mes- 
entery. We have seen a case in which twelve feet of intestine had passed through 
a small opening in the mesentery. 
3. A coil of intestine makes a half turn at its base, so that the two sides of the 
loops cross at its base. In this way the lumen of the intestine is completely closed 
and the vessels are compressed, so that congestion, peritonitis, and gangrene result. 
In the small intestine it may occur when the gut is fixed by old adhesions. This twist- 
ing of the gut is called volvulus. 
4. A portion of the intestine, with its mesentery, makes one or more complete 
turns on itself, closing the canal and compressing the vessels. 
5. A portion of the intestine makes a half or entire turn about its longer axis. 
6. The mesentery of a part of the intestine is long and loose, in consequence of a 
dragging down of the intestine by a hernia or by habitual constipation. The portion 
1 Consult Fischer, M. H., Jour. Exper. Med., 1901, v, 333 (bibl.); also Beer, E., Am. Jour. Med. So., 
1994, cxxviii, 135. For diverticula of appendix, see Corning, E., Albany Med. Ann., 1905, xxvi, 816. 
For studies of acute diverticulitis, see Rosenheim, Ztschr. f. klin. Med., 1904, liv, 475; t>. Hansemann, 
Virchows Arch., 1896, cxliv, 400; and the numerous publications from the Mayo Clinic, especially 
Mayo, W. J., Jour. Am. Med. Assn., 1917, Ixix, 781 (bibl.). 761 
THE DIGESTIVE SYSTEM 
of intestine thus permitted to hang down is habitually filled with feces, and by its 
pressure on some other part of the intestine produces an incomplete stricture. 
Intussusception. 
This change of position consists in the invagination of one portion of intestine in 
another portion (Fig. 466). Usually this takes place in the direction of the peristaltic 
movements, from above downward; more rarely in the opposite direction. 
Fig. 466.-Intussusception 
A portion of the gut is completely invaginated in the segment below and strangulated 
Fig. 467.-Intussusception---Agonal oh Post-mortem in Intestine of Infant. 
The parts are found in the following condition: There are three portions of intes- 
tine, one within the other. The inner portion is continuous with the intestine above 
the intussusception; its peritoneal coat faces outward. The outer portion is continu- 
ous with the intestine below; its peritoneal coat also faces outward. The inner portion 
is turned inside out, its mucous membrane is in contact with the mucous membrane of 
the outer portion. In rare cases the intussusception is complicated by the invagination 
of a second portion of intestine in the inner tube, and even by a third intussusception 
into the second one. These changes occur both in the large and small intestine; most 
frequently the lower part of the ileum is invaginated in the colon. The invaginated 762 
THE DIGESTIVE SYSTEM 
portion may be from a few inches to several feet in length. The lesion is most fre- 
quently found in early childhood. 
The intussusception, by the dragging and folding of the mesentery which it 
involves, may lead to intense congestion of the parts, and even to large hemorrhages 
between the coats of the intestine. The congestion may induce fatal peritonitis, or 
gangrene of the intestine, or chronic inflammation and adhesions, and the patient may 
live for a considerable time with symptoms of stricture. In other cases the invagin- 
ated portion of the intestine sloughs, the outer and inner portions become adherent, 
and the patient recovers, with or without stricture. 
Besides this grave form of intussusception we often find, especially in children, one 
or more small invaginations not attended with congestion or inflammation. These are 
agonal or are formed immediately after death (Fig. 467). 
Fig. 468.-Inguinal Hernia-Intestinal. 
Fig. 469.-Inguinal Hernia-Omental. 
The dislocation and protrusion of the whole or a part of an internal organ from its 
normal position is called hernia. This may occur in various parts of the body, but 
most frequently involves the abdominal viscera, especially the intestine or omentum. 
In the most common form of the so-called inguinal hernia, which is of frequent occur- 
rence in men, there is a descent into the inguinal canal of either a loop of intestine 
(Fig. 468) or a portion of the omentum (Fig. 469). For a description of the various 
forms of hernia we refer to works on surgery. 
Hernia. THE DIGESTIVE SYSTEM 
763 
DILATATION OF THE COLON. 
This may be congenital or acquired and is sometimes so extensive as 
to fill the abdominal cavity.1 
A special type of enlargement of the colon, seen chiefly in children, 
bears the name Hirschsprung's disease.2 The large intestine is enor- 
mously increased in diameter with extreme thickening of the wall, this 
thickening being greater the longer the disease has existed. The sigmoid 
flexure is long, but usually escapes dilatation, though children who sur- 
vive to adolescence may show dilatation of the small intestine and stom- 
ach, also, with thickening of the walls. Muscular hypertrophy is 
responsible for the increase in the mural dimensions, the mucous and 
serous coats showing little or no change. The etiology of the condition 
is still obscure, but it is generally assumed that it is due to obstruction 
based on a congenitally abnormal length of the sigmoid flexure in conse- 
quence of which the coils of the gut are more numerous than normal and 
a certain amount of kinking may occur with consequent partial obstruc- 
tion. 
WOUNDS-RUPTURES. 
Penetrating wounds of the intestine usually prove rapidly fatal, either 
from shock or from peritonitis. Sometimes, however, the wound 
becomes closed by the formation of adhesions with the neighboring parts. 
Sometimes the wound in the intestines becomes adherent at the position 
of the wound in the abdominal wall, and an intestinal fistula is formed. 
Rupture of the small intestine is not infrequently produced by severe 
blows on the anterior abdominal wall. It is noticeable that such blows 
may not produce marks or ecchymoses of the skin. Such ruptures 
usually prove fatal very soon, but sometimes the patient lives several 
days and the edges of the rupture undergo inflammatory changes. 
Strictures of the intestine are sometimes followed by rupture of the 
dilated intestine at some point above the stricture.3 
DISTURBANCES OF THE CIRCULATION-HEMORRHAGE. 
Hyperemia of the intestine may be inflammatory in character or it 
may be associated with disturbance of the portal circulation. Under 
both of these conditions ecchymoses may occur. Pigmentation may fol- 
low large or small interstitial hemorrhages. 
As a result of embolism or thrombosis of the mesenteric vessels 
hemorrhagic infarctions may occur, sometimes involving a considerable 
portion of the gut.4 Hemorrhage into the lumen may follow, or gangrene, 
or inflammation. The latter processes are readily induced in the injured 
regions by the bacteria constantly present in the intestinal contents. 
Septic emboli may induce suppurative inflammation in the mesentery 
and in the wall of the intestine. 
1 Fitz, R., Am. Jour. Med. Sc., 1899, cxviii, 125 (bibl.); Griffith, J. P. C., ibid., p. 283; Hubbard, 
Ann. Surg., 1916, Ixiii, 349. 
2 Puls, Beitr. z. klin. Chip. (Bruns), 1910, Ixix, 306; De Jong and Muskens, Mitt. a. d. Grenzgeb. d. 
Med. u. Chir., 1909-10, xxi, 647; Konjetzny, Beitr. z. klin. Chir. (Bruns), 1911, Ixxiii, 155; Cadwallader, 
R., Arch. Pediat., 1916, xxxiii, 665; Heller, Munchen, med. Wchnschr., 1911, Iviii, 1059. 
3 See summary of cases by Gallaverdin, L., Gaz. d. hop., 1901, Ixxiv, 929, 956 (bibl.). 
4 For a further consideration of thrombosis of the mesenteric veins, consult Welch, Allbutt's System 
of Medicine, 1909, vi, 218. See, also, study by Jackson, Porter, and Quinby, Jour. Am. Med. Assn., 
1904, xlii, 1469. 764 
THE DIGESTIVE SYSTEM 
Intestinal hemorrhage may occur in venous congestion, as in certain 
forms of cirrhosis of the liver. It may follow ulceration in typhoid fever, 
in chronic colitis, in malignant tumors, etc.; it may accompany infarction.' 
Amyloid degeneration may be associated with a similar process else- 
where in the body. The iodine test may reveal the existence of this 
alteration in the villi of the small intestine. 
DEGENERATION. 
INFLAMMATION. 
Acute Catarrhal Enteritis.-This may occur under conditions similar 
to those inciting catarrhal inflammation in the stomach. It may be local 
or general and may be associated with similar processes in the stomach 
and colon. In "ptomaine poisoning" the lesions are often severe. Com- 
paratively mild forms of the lesion may predispose the intestine to the 
incursions of intestinal bacteria and the development of more severe 
forms of destructive lesions. The mucosa may be reddened or ecchy- 
mosed, and covered with mucus 
mingled with degenerated epithelium 
and leucocytes. The epithelium may 
be degenerated and peeled off (Fig. 
470), and the cylindrical cells may be 
distended with mucus formed within 
them-"beaker cells." 
The solitary and agminated 
lymph-nodules may be swollen from 
hyperplasia. When this hyperplasia 
is marked (Fig. 471), the lesion is 
often called follicular or nodular en- 
teritis, and erosions and ulceration 
may occur (Fig. 479 and 480).2 This 
lesion is especially common in children 
suffering from various types of acute 
infection. For hyperplasia of the 
lymphoid tissue of the intestine in 
typhoid fever see page 266. 
Chronic Catarrhal Enteritis.-This 
may follow the acute form or occur 
independently. It often accompanies 
many forms of chronic disease of the 
heart, kidneys, lungs, etc. The 
mucous membrane may be covered 
with mucus; ecchymoses, erosions, 
and pigmentation are frequent. There is hyperplasia of the inter- 
Inflammation of the Small Intestine. {Enteritis.} 
Fig. 470.-Acute Catarrhal Enteritis. 
Showing the open end of one of the tubular 
glands with exfoliating and disintegrating 
epithelium. 
1 For reference to occult hemorrhage in gastrointestinal canal, see Jaworski and Korolewicz, Wien, 
klin. Wchnschr., 1906, xix, 1129. 
2 It is better to abandon the name nodular enteritis for this lesion and call it nodular hyperplasia THE DIGESTIVE SYSTEM 
765 
glandular tissue of the mucosa and the submucosa. In this way there 
may be atrophy of the glands, and the mucous membrane may be thin 
and fibrous. The muscularis may also be involved and atrophied. The 
submucosa and the muscular layer may, on the other hand, be thickened 
from the new-formed fibrous tissue. 
Pseudomembranous Enteritis may occur in connection with a similar 
condition in the colon, in infectious diseases, in chronic diseases of the 
Fig. 471.-Nodular Hyperplasia. 
From the intestine of a child. 
liver and kidney; in cachectic conditions, or as the result of the ingestion 
of irritant poisons. The mucous membrane may be the seat of superficial 
necroses, sometimes in patches, and the pellicle may consist largely of 
mucus with necrotic epithelium. Fibrin may be present, and fibrin and 
extravasated leucocytes and serous fluid may infiltrate the submucosa. 
In the larger ulcers the mucous membrane is almost entirely gone, leaving the muscularis exposed at 
the bottom. 
Fig. 472.-Tuberculous Ulcers of the Small Intestine. 
Exudative or Suppurative Enteritis is rare. Purulent foci, usually 
metastatic in origin, may form in the wall of the intestine. A more dif- 
fuse suppuration may follow infection after obstruction or strangulation.1 
Tuberculous Enteritis.-The lymph-nodules and Peyer's patches are 
1 See for a study of phlegmonous enteritis, MacCallum, Bull. Johns Hopkins Hosp., 1906, xvii, 
254 (bibl.). 766 
THE DIGESTIVE SYSTEM 
often involved in intestinal tuberculosis and may ulcerate (Fig. 472). 
Miliary tubercles may be present with cheesy degeneration (Fig. 473) and 
the subperitoneal lymphatic vessels are often involved and may appear 
as white, nodular, branching, slightly elevated cords, running around the 
gut (Fig. 474). Tuberculous ulcers are apt to extend most rapidly in a 
direction transverse to the axis of the gut (Fig. 475), differing in this 
Fig. 473.-Section of a Tuberculous Ulcer of the Small Intestine. 
Showing tubercle tissue with miliary tubercles and caseation at the bottom of the ulcer. There are 
miliary tubercles beneath the serosa. (See Fig. 474.) 
respect from typhoid ulcers (page 267). But to this there are frequent 
exceptions. Tuberculous ulcers rarely perforate. (See for other forms 
of tuberculosis of the intestine page 775.)1 
The mesenteric lymph-nodes are frequently involved in either active 
or inactive tuberculosis in any part of the body. They may not show 
Fig. 474.-Subserous Tubercles Following the Lymph-vessels at the Bottom of a Tuber- 
culous Ulcer of the Small Intestine. 
gross lesions, but microscopically characteristic lesions or tubercle bacilli 
may be found. Frequently, when neither lesions nor bacilli are demon- 
strable, inoculation of guinea-pigs shows that the nodes are infected. 
1 For statistics of intestinal tuberculosis see Zahn, F. W., Munchen, med. Wchnschr., 1902, xlix, 
49; Nebelthau, ibid., 1903, 1, 1246, 1300; Wagener, ibid., 1903, 1, 2036, 1095; and Ipsen, J., Berl. klin. 
Wchnschr., 1906, xliii, 791. For presence of tubercle bacilli in mesenteric lymph-nodes, see MacFadyen 
and MacConkey, Brit. Med. Jour., 1903, ii, 129. THE DIGESTIVE SYSTEM 
767 
The mesenteric nodes are frequently infected without other tuberculous 
lesions in the body.1 The bovine type of bacillus is often present. 
Syphilitic Ulcers, originating in the lymphatic structures, are some- 
times found in infantile syphilis.2 
Duodenal ulcers, while usually simple, may be tuberculous; it has 
been stated that they may follow extensive burns, but apparently this is 
often only a coincidence.3 They may occur under a variety of other 
conditions, and are much more frequent than was at one time supposed.4 
Carcinoma almost never develops on a duodenal ulcer. The sex distribu- 
tion is the same as in the case of gastric ulcer, that is, the lesion is about 
three times as frequent in males as in females.5 
Other Forms of Ulcers.-The solitary and agminated lymph-nodules 
frequently undergo hyperplasia in infectious diseases, after extensive 
Showing the extension of the ulcers in a direction transverse to the axis of the gut. 
Fig. 475.-Tuberculous Ulcers of the Small Intestine. 
burns,6 and in various forms of inflammation of the intestine. Hyper- 
plasia of the lymphatic tissue-see page 764-with ulceration is especially 
frequent in children. 
Inflammation of the Large Intestine. {Colitis.) 
The mucous membrane of the large intestine is frequently the seat of 
acute and chronic inflammatory and necrotic processes known clinically 
as dysentery.1 The rectum is most often involved, but sometimes the 
upper part of the colon and sometimes the whole colon is affected. 
Acute Catarrhal Colitis.-This process is frequently limited to the 
lower end of the colon and presents several types. There may be an 
1 See Rosenberger, R., Am. Jour. Med. Sc., 1905, cxxx, 95. For discussion of intestines as portals 
of entry of tubercle bacilli, see p. 791. 
2 For study of acquired syphilitic ulcers of intestine, see Arken, Tr. Chicago Path. Soc., 1912, viii 
224. 
3 Busse, Verhandl. d. deutsch. path. Gesellsch., 1914, xvii, 290. 
4 Mayo, W. J., Ann. Surg., 1911, liv, 313, 427; Moynihan, Sir Berkeley, Brit. Med. Jour., 1912, i, 
346; Melchior, E., Ergebn. d. Chir., 1911, ii, 290. 
6 For a study of duodenal ulcers, see Weir, Med. Record, 1900, Ivii, 749 (bibl.); Gruber, Mitt. a. d. 
Grenzgeb. d. med. u. Chir., 1912, xxv, 465; and Moynihan, Sir Berkeley, Duodenal Ulcer, Philadelphia, 
1910. 
6 Bardeen, C. R., Jour. Exper. Med., 1897, ii, 501. 
' The classification of these lesions is with our present knowledge unsatisfactory, and is largely 
based upon morphology. In some phases of so-called dysentery-infectious colitis-however, the 
nature of the excitant is taken into the account. Consult for a special study of forms of colitis seen in 
New York, Delafield, Am. Jour. Med. Sc., 1897, cxiv, 401. 768 
THE DIGESTIVE SYSTEM 
increased production of mucus, which coats the surface of the mucous 
membrane and is mixed with exfoliated and fatty or disintegrated epithe- 
lium and red blood-cells. The surface epithelium may be degenerated 
and exfoliate, many " beaker cells " being present, indicating the source 
of over-production of mucus (Fig. 476). The mucous membrane may 
be congested and infiltrated with serum and leucocytes. Again, with 
conditions similar to those just described, there may be a purulent 
exudate in the mucous membrane. There is a form of catarrhal colitis 
in which there is a more or less extensive formation of new connective 
tissue between the glands and in the submucosa. Finally, there may 
be small or extensive ulceration in the involved areas of the mucosa. 
The epithelium of the tubular glands, especially near their mouths, is forming an excessive amount 
of mucus with destruction and exfoliation of the cells. The tubules are dilated with mucus which 
covers the surface. The mucosa at the right is necrotic and forms the edge of an ulcerated area. 
Fig. 476.-Acute Catarrhal Colitis. 
Acute Infectious Colitis (Tropical Dysentery) is of especially frequent 
occurrence in warm countries and is often epidemic. In one group of 
cases (a) the disease is probably incited by protozoa-Entamoeba histo- 
lytica; while in the other (6), bacteria, some apparently related to the 
typhoid-colon bacillus group, and possibly others, are believed to be the 
excitants. 
(a) Amebic Colitis.-This form of colitis is apparently incited by 
the presence of the wall in the intestine of the Entamoeba histolytica. 
The amebas are found in the gelatinous masses which are common in 
the stools. They are of rounded shape, and, when alive, change their 
position and shoot out and retract little projections (pseudopodia). 
Their outer portion is composed of a pale hyaline or homogeneous sub- 
stance; the inner contains vacuoles and is more refractive (see Fig. 78). THE DIGESTIVE SYSTEM 
769 
In the colon the amebas are found in the connective-tissue coat (Fig. 
477) and in the floors of the ulcers. 
Ameba excites at first a moderate exudative and productive inflam- 
mation followed by necrosis. Thus ulcers are formed. The ulcers may 
be superficial or deep, sometimes extending to the peritoneum; they 
enlarge by infiltration and necrosis at their edges, so that extensive 
destruction of the mucous membrane may occur. The amebas may be 
present in the connective tissue at the base or sides of the ulcers. Not 
infrequently, owing to bacterial infection from the intestinal contents, 
varying degrees of suppurative inflammation may complicate the lesion. 
Necrotic and suppurative processes may be set up in the liver (see 
page 822) and in the right lung, and in these lesions the ameba may be 
found.1 In the later stages, the amebas may disappear from the liver 
Showing amebas in the submucous fibrous tissue. 
Fig. 477.-Amebic Colitis. 
abscesses, and a partial cure be effected by inspissation of the pus and 
dense connective tissue formation about the abscesses. 
(6) Acute Infectious Colitis with Bacterial Excitants.- 
Another type of acute infectious colitis or dysentery occurs epidemic- 
ally, especially in hot climates, and is most often seen among soldiers 
under war-time conditions, and in children during the hot weather. 
There is also a sporadic form which may occur at any time in temperate 
or hot climates. The lesions are variable. In the acute diarrheas of 
infants, congestion of the intestine and swelling of the follicles may be all 
that is found post mortem. Usually there is a small amount of blood 
mixed with thick mucus which covers the surface of the intestinal mucosa. 
The more severe types, especially in adults, show a pseudomembranous 
or ulcerative colitis, varying according to the extent and duration of the 
infection. Abscess of the liver, so frequently seen in the amebic type, 
is rare in the bacillary form. In the milder cases the process may be 
confined to the mucous membrane; in the more severe the inflammatory 
lesions involve the submucosa which may show extensive edema with 
1 See, for details and bibliography, Kartulis, Kolle and Wassermann, Handbueh d. path. Mikro- 
organismen, 2d edition, 1913, vii, 651. 770 
THE DIGESTIVE SYSTEM 
hemorrhages and, in the later stages, ulceration extending down to the 
muscular coats. In the chronic stage, the whole coat is thickened and 
dark in color from blood pigment deposited in the cells, and microscopical 
examination shows that the epithelium has largely disappeared and that 
only a few glands of the original mucous membrane are left. A large 
amount of connective tissue is found in the submucous and muscular 
coats. 
The disease is due to a group of bacilli (page 277) whose differentia- 
tion depends upon fermentation reactions. The bacilli are found only 
in the intestines, and do not invade the rest of the body. The disease 
is unquestionably spread by carriers, those who are suffering from mild 
forms of infection, as well as those who are convalescent or healthy. In 
treatment excellent results have been obtained by the use of polyvalent 
antitoxic sera.1 
Fio. 478.-Nodular Colitis-Follicular Colitis. 
Showing commencing necrosis of the mucosa over the hyperplastic lymph-nodule. 
Bacillus pyocyaneus has been repeatedly found in the discharges in 
cases of dysentery as well as in other intestinal disorders under conditions 
which justify the conjecture that it is sometimes, at least, an excitant of 
intestinal inflammation and necrosis. Streptococcus pyogenes has been 
repeatedly found in association with enteritis and colitis. Intestinal 
infection with streptococcus is more frequent and significant in children 
than in adults.2 
Nodular Hyperplasia.-In many cases of catarrhal and croupous 
inflammation of the colon and of acute infections, especially in children, 
the solitary follicles (lymph-nodules) become more or less swollen and 
necrotic. Besides these cases, however, there are others in which the 
1 An excellent review of the bacteriology, clincial course, and lesions of the disease will be found in 
a monograph by Ruge, R., Mense, Handbuch der Tropenkrankheiten, 2d edition, Leipzig, 1914, iii, 158. 
For a general statement of forms and lesions of dysentery and its relationship to microorganisms, 
see Flexner, S., Philadelphia Med. Jour., 1900, vi, 414; see also Lentz, Kolle and Wassermann, Hand- 
buch d. path. Mikroorganismen, 2d edition, 1913, iii, 899. 
For a study of experimental colitis, see Flexner and Sweet, Jour. Exper. Med., 1906, viii, 514. 
2 See v. Lingelsheim, Kolle and Wassermann, Handbuch d. path. Mikroorganismen, 2d edition, 
1912, iv, 451. THE DIGESTIVE SYSTEM 
771 
changes in the nodules form the principal part of the lesion, while the 
catarrhal or croupous inflammation is but slightly developed. The 
lesion is similar to that in nodular hyperplasia in the small intestine. 
The nodules are first swollen-hyperplastic-(Fig. 478), then necrotic, 
then slough away and leave little circular ulcers with overhanging 
edges (Fig. 479). These ulcers are usually numerous (Fig. 480) and 
Fig. 479.-Nodular Colitis with Ulceration. 
Showing necrosis and ulceration of the lymph-nodule with opening into the lumen of the gut. 
may be scattered over a large part of the colon. The ulcers are apt to 
show but little disposition to heal, and the acute colitis often becomes 
chronic. 
Nodular Colitis.-In rare cases of typhoid fever and occasionally 
under other conditions there are foci of inflammation with necrosis and 
ulceration irregularly scattered and involving primarily not the mucous 
membrane but the underlying tissue. These lesions are not to be iden- 
Fig. 480.-Nodular Colitis. 
From the intestine of a child, showing numerous ulcers involving solitary nodules. (Compare Fig. 471.) 
tified with hyperplasia of the solitary lymph-nodules with ulcerations 
which occur with especial frequency in children suffering from acute 
infections.1 
Pseudomembranous (Croupous) Colitis.-This form of inflammation 
may involve the rectum alone, or the entire length of the colon, or only 
its upper portion. The mucous membrane is congested and swollen, and 
coated with a layer of false membrane; the connective tissue between and 
1 See Whipple, Bull. Johns Hopkins Hosp., 1906, xvii, 281. 772 
THE DIGESTIVE SYSTEM 
Fig. 481.-Pseudomembranous (Croupous) Colitis. 
Circumscribed congestion and necrosis of the glandular and connective-tissue coats. 
Fig. 482.-Necrotic Colitis. THE DIGESTIVE SYSTEM 
773 
beneath the gland tubules is infiltrated with fibrin and pus, and in severe 
cases the inflammation involves the muscular and peritoneal coats also. 
The inflammation is usually more intense at some places than at others, 
so that the surface of the mucous membrane shows the false membrane 
in isolated patches (Fig. 481). Less frequently there is a uniform coat- 
ing with the false membrane. In mild cases, as the inflammation sub- 
sides, the products of inflammation are absorbed and the wall of the 
intestine returns to its normal condition. In more severe cases the 
quantity of the inflammatory products is so great that portions of the 
wall of the intestine become necrotic. This necrosis may involve only 
the glandular coat, or it may extend deeper into the wall of the intestine. 
The necrosed tissue after a time sloughs away, leaving behind ulcers of 
different sizes and depths. After this 
the ulcers may cicatrize, or their floors 
and walls may remain in the condi- 
tion of granulation tissue for an in- 
definite length of time. When the 
latter is the case there is added a 
chronic inflammation of the wall of 
the intestine between the ulcers, with 
changes in the mucous membrane and 
thickening of the connective-tissue 
and muscular coats. This form of 
colitis is observed after bacterial inva- 
sion, following the ingestion of mer- 
curic chloride,1 and as a terminal con- 
dition in nephritis. 
Necrotic Colitis.-There is a form 
of inflammation of the colon in which 
considerable areas of the connective- 
tissue coat become necrotic, leaving 
the glandular coat undermined and 
separated from the muscular coat. 
In this way large ulcers with over- 
hanging edges are developed. This 
form of colitis is very often fatal. 
There is another very serious and 
obscure form of necrotic colitis which 
appears to be septic in character. 
After death the inner surface of the 
colon is found studded with little 
blackish areas in which the blood- 
vessels are gorged with blood. The 
glandular and connective-tissue coats 
are infiltrated with pus cells and there 
is a superficial necrosis (Fig. 482). 
Various forms of microorganisms have been found in connection with 
Fig. 483.-Chronic Ulcerative 
Colitis-Dysentery. 
There are small erosions of the swollen 
mucous membrane. 
1 Weiler, F., Virchows Arch., 1913, ccxii, 200 (bibl.). 774 
THE DIGESTIVE SYSTEM 
suppurative and necrotic lesions of the ileum and colon-Streptococcus 
pyogenes, Staphylococcus pyogenes, Bacillus coli communis, Bacillus 
proteus, Bacillus pyogenes, and others. The significance of these organ- 
isms is not yet clear.1 
Mucous Colitis (Membranous Colitis).-Under a variety of obscure 
conditions, probably sometimes inflammatory in character, shreds or 
sheets or even cylindrical casts of the interior of the gut are passed from 
the bowels. These consist of dense mucus often mingled with degener- 
ated epithelium.2 While the phenomenon may occur in connection with 
chronic dysentery, chronic appendicitis, constipation, or tumor of the 
bowel, it is seen most frequently without evident cause in persons of a 
neurotic temperament; and as the disease is never of itself fatal, little is 
known of the underlying anatomical alterations, if such regularly exist. 
Chronic Colitis.-In prolonged inflammation of the colon, marked 
structural alterations may take place. The glandular coat may be 
uniformly thickened or thrown into the form of polypoid tumors, or atro- 
phied, or destroyed by ulcers of various sizes and shapes (Fig. 483 and 
Fig. 484.-Chronic Colitis with Extensive Ulceration of the Mucous Membrane. 
In places only a few ragged islets of mucous membrane are left, the muscularis forming the bottomof 
the ulcers. 
484). Small cysts may form from the retention of mucus in the follicles. 
The connective-tissue and muscular coats may be thickened or thinned. 
Apparently chronic colitis may follow any of the forms of acute colitis.3 
Repair may follow even considerable losses of substance in the intes- 
tinal mucous membrane. The new-formed connective tissue may un- 
1 See Kruse and Pasquale, Ztschr. f. Hyg. u. Infectionskrankh., 1894, xvi, 1; also Cerenville, Tavel, 
and others, Ann. Suisses des Sc. M6d., 1895, ii, 531. 
See, for consideration of Streptococcus enteritidis in infants, Hirsch, Centralbl. f. Bakteriol., Orig., 
I., 1897, xxii, 369 (bibl.). 
For a study of intestinal bacteria, see van Ermengem, Kolle and Wassermann, Handbuch. d path. 
Mikroorganismen, 1st ed., 1903, ii, 637; Ford, Studies Royal Victoria Hospital, Montreal, 1903, vol. i„ 
(r6sum6 and bibl.); Kendall, A. I., Bacteriology, General, Pathological and Intestinal, Philadelphia, 
1916; and Am. Jour. Med. Sc., 1918, clvi, 157; and Cammidge, P. J., Feces of Children and Adults, 
New York, 1914. For a study of the permeability of the intestinal wall for bacteria, see Klimenko, 
Ztschr. f. Hyg. u. Infectionskrankh., 1904, xlviii, 67; and Uffenheimer, A., Deutsch, med. Wchnschr., 
1906, xxxii, 1851 (bibl.). See, for a study of absorption in the large intestine, Bremer, J., Jour. Med. 
Research, 1906, N. S. x, 89. For a study of the cause of death of bacteria in the small intestine, see 
Rolly and Liebermeister, Deutsch. Arch. f. klin. Med., 1905, Ixxxiii, 413. 
2 For observations and bibliography of membranous enteritis or colitis consult Butler, G. R., New 
York Med. Jour., 1895, Ixii, 824 (bibl.); or Akerland, Arch. f. Verdauungskr., 1896, i, 396. 
3 For reference to syphilitic ulcers, see Arken, Tr. Chicago Path. Soc., 1912, viii, 224. THE DIGESTIVE SYSTEM 
775 
dergo slight or marked cicatricial contraction. The denuded surfaces may 
become covered anew with epithelium derived from the intact cells.1 
Anthrax Infection of the Intestine (Mycosis Intestinalis).-The anthrax 
bacillus may lodge in the intestinal mucosa either through food contain- 
ing the germ or by metastasis through the blood from some infective 
focus, especially the skin.2 
The intestinal lesions are most apt to occur in the small intestines and 
in the upper part of the colon. The mucous membrane is studded with 
larger and smaller brown or black, frequently elevated patches, or areas 
of local congestion, or hemorrhage, or necrosis. The mucous membrane 
near the inflammatory and necrotic foci may be edematous. Hyper- 
plasia of the spleen and lymph-nodes is apt to accompany the intestinal 
anthrax. The anthrax bacillus may be found about the seat of local 
lesion in the intestine, in the associated lymph-nodes; and when secondary 
to local infection elsewhere it may be found in the primary lesion and in 
the blood. 
It is believed that other forms of bacteria may cause intestinal lesions 
somewhat similar to those of anthrax, but the researches in this direction 
are not yet sufficiently numerous to permit of very definite statements. 
Actinomycosis of the intestine is rare. It may give rise to tumor-like 
masses of inflammatory tissue, in which the fungi can be demonstrated. 
The portal of entry is through the mucous membrane, most often of the 
appendix, and there is presumably a previous slight injury of the mucosa 
by sharp particles of food.2 
The Cecum. 
Catarrhal Inflammation, of the cecum is not uncommon. It is usually 
produced by an habitual accumulation of feces in this part of the intes- 
tine. The course of the inflammation is usually chronic, but marked by 
acute exacerbations. At first the mucous membrane undergoes the ordi- 
nary changes of chronic catarrhal inflammation. To this may succeed a 
slow suppurative inflammation which extends through the wall of the 
intestine and gives rise to ulcers and perforations. 
Through these perforations the feces may pass into the peritoneal 
cavity, or the perforations may be partly closed by adhesions, and ab- 
scesses, or sinuses into the surrounding soft parts may be formed. 
Chronic Hyperplastic Tuberculosis of the Ileocecal Region and Other 
Parts of the Intestine.-Attention has recently been called to a peculiar 
form of tuberculous inflammation of the intestine which is characterized 
by the extensive formation of small spheroidal-cell and fibrous tissue, 
especially in the submucosa and often involving the muscular wall and 
the subserous layer. Miliary tubercles, cheesy degeneration, and ulcera- 
tion are not usually conspicuous features of the lesion. The ileocecal 
region is most often involved, the rectum less frequently, while the lesion 
is rarely limited to the ileum. Both the large and small intestines may 
1 For a study of regeneration of intestinal epithelium, see Quenu and Branca, Arch. d. m6d. exper., 
1902, xiv, 405. For a study of the association of the crypts of Lieberkuhn with lymph-nodules in the 
colon, see Schultze, W., Centralbl. f. allg. Path., 1905, xvi, 99. 
2 Brumbaugh, A. S., Jour. Am. Med. Assn., 1919, Ixxii, 482. 
3 Harbitz and Grbndahl, Zieglers Beitr., 1911, 1, 193. 776 
THE DIGESTIVE SYSTEM 
be involved together. The new tissue may form a circumscribed annular 
thickening of the wall of the gut, or it may occur as a distinct tumor or 
as polypoid projections of the mucous membrane. The intestine in the 
vicinity of the involved portion may be inclosed in a mass of fibrous fat 
tissue. Owing to the thickening of the wall of the intestine the lumen 
may be much narrowed or nearly completely stenosed. On section of the 
thickened areas, caseous foci may be revealed; ulcerations, in rare cases, 
may be absent; more often they are moderate or extensive. 
The microscopical examination shows that while miliary tubercles and 
cheesy degeneration are commonly to be detected, the new tissue consists 
in the main of collections of small spheroidal cells with more or less 
fibrous stroma and occasionally giant cells, and of moderately cellular or 
dense fibrous tissue. The polyhedral cells common in tuberculous 
inflammation are not as a rule conspicuous. The new tissue is usually 
most abundant in the submucosa. The mucosa may be similarly thick- 
ened, usually in polypoid form, or unchanged; it may show simple 
catarrhal alterations or may contain miliary tubercles or be ulcerated. 
The muscular coat also may be infiltrated and much thickened by the 
new-formed cellular and fibrous tissue and there may be muscular hyper- 
trophy. The associated lymph-nodes may be involved. Tubercle bacilli 
are present in the lesions, sometimes in enormous numbers. The process 
appears to be sometimes primary in the intestine; sometimes it occurs 
with or follows tuberculous lesions of the lungs. Hyperplastic tubercu- 
lous lesions limited to the cecum have frequently been operated upon 
because the process was thought to be cancerous.1 
The Rectum. 
Besides inflammatory changes similar to those already described as 
occurring in the colon, we sometimes find a suppurative inflammation of 
the connective tissue which surrounds the rectum, either associated with 
lesions of the mucous membrane or occurring by itself. 
In adults the lower end of the rectum is the part of the intestine 
which is the most frequent seat of syphilitic ulceration.2 Most of these 
ulcers seem to be the result of unnatural coitus, or of infection from 
specific sores of the vulva; but some of them seem to be due to the 
softening of gummy tumors. The gonococcus, also, is an occasional ex- 
citant of inflammation of the rectum, and some of the lesions previously 
classed as syphilitic may be due to this agent.3 Microscopically, an ex- 
tensive and diffuse plasma-cell infiltration is found, with perivascular 
collections and swelling of the endothelium. 
Strictures of the rectum may be due to tumors, to cicatrices following 
trauma, or to inflammation.4 
1 Wiener, J., Ann. Surg., 1914, lix, 698; Gage and Hunt, Boston Med. and Surg. Jour., 1917, clxxvi, 
259; De Nancrede, C. B. G., and Butterfield, E. E., Surg., Gynec., and Obst., 1906, iii, 302. 
2 Herxheimer, G., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1906, x1, 1; 1908, xii, 499. 
3 Exner, A., Ztschr. f. Chir., 1911, cix., 261. 
4 For bibliography of non-malignant rectal strictures see Peterson, Jour. Am. Med. Assn., 1900, 
xxxiv, 259. 777 
THE DIGESTIVE SYSTEM 
Hemorrhoids (Piles).-Ectasias of the hemorrhoidal veins are of fre- 
quent occurrence. They are most frequent in adults and are usually due 
to venous obstruction in cirrhosis, chronic constipation, pelvic tumors, 
chronic inflammation of the rectum, etc. The enlarged veins may be 
within or without the sphincter-internal or external hemorrhoids. The 
dilated veins may have thickened walls and may be surrounded by new- 
formed connective tissue. The projecting mass in external hemorrhoids 
may consist in part of dilated vessels, in part of fibrous tissue, and is 
covered by thickened epithelium (Fig. 485). Considerable hemorrhage 
may take place from hemorrhoids, and they may afford a portal of entry 
of bacteria leading to local or general infection. 
Fig. 485.-Hemorrhoid. 
Section of an external hemorrhoid consisting of fibrous tissue and dilated vessels. Covered with 
epithelium except at the upper right portion where it was attached. 
The Appendix Vermiformis. 
Inflammation-Appendicitis.-Inflammation of the appendix may- 
present various phases. 
1. The mucous membrane may be the seat of acute catarrhal inflamma- 
tion. This is of mild type and short duration, with congestion, swelling, 
and an increased production of mucus; or it is of severer type, of longer 
duration, and the cavity of the appendix is distended by mucus and pus. 
2. The entire thickness of the wall of the appendix may be the seat 
of an acute exudative inflammation. The appendix is very much increased 
in size, sometimes to the size of a man's finger (Fig. 486). This increase 
in size is due, not to a dilatation of the cavity of the appendix, but to a 
thickening of its walls. The walls are congested, swollen, infiltrated with 
fibrin and pus, the peritoneal coat is covered with fibrin. There is 
neither necrosis nor perforation. If the appendix is behind the cecum, 
or if adhesions are formed early, there is only a localized peritonitis. If 
the appendix projects freely into the peritoneal cavity and no adhesions 
are formed, a general peritonitis may be soon established. 
3. At one or more points in the wall of the appendix there is an exu- 
dative inflammation with necrosis. In this way small or large portions of 778 
THE DIGESTIVE SYSTEM 
the wall of the appendix are destroyed, large or small perforations are 
formed, and the contents of the appendix escape into the abdominal cav- 
ity. In these cases the appendix often contains a fecal concretion. 
Such perforations are usually followed by the collection of pus around 
the appendix (Fig. 487). The pus may extend from this abscess-like 
collection in any direction and for long distances, so that collections may 
be found deep in the pelvic cavity, or under the diaphragm, or abscesses 
may form at other remote points. 
A posterior view of the caput coli. The appendix is swollen and a pellicle of exudate covers 
it and the adjacent intestine. 
Fig. 486.-Acute Appendicitis. 
4. The entire appendix may become gangrenous within one or two 
days, with the formation of an abscess, or general peritonitis. This is 
the most usually fatal form of appendicitis. 
5. Inflammation of the appendix may be secondary to catarrhal or 
croupous colitis. 
6. In typhoid fever there may be changes in the wall of the appendix 
of a character similar to those in the wall of the small intestine; that 
is, hyperplasia of the lymphoid tissue and endothelial cells with necrosis 
(page 265). 
7. There may be a tuberculous inflammation of the appendix, with the 
ormation of ulcers. 
As the result of chronic inflammation in the appendix, atrophy of the THE DIGESTIVE SYSTEM 
779 
glands and lymphoid tissue with increase of the fibrous tissue (Fig. 488) 
and strictures or obliteration of its lumen may occur (Fig. 489) often corre- 
Appendix removed by operation twelve hours after first symptoms. Streptococcus was found in 
the exudate. 1, Mucous membrane of the appendix; 2, lymphatic nodules in the mucous membrane; 
3, submucosa; 4, muscularis; 5, mesentery of the appendix; 6, pus and fibrin covering the appendix; 
7, dense infiltration of the wall of the appendix with pus; 8, pus exudate in lumen. 
Fig. 487.-Acute Suppurative Appendicitis. 
Fig. 488.-Chronic Appendicitis. 
Showing obliteration of the glands and lymphoid tissue with new fibrous tissue in the mucosa 
and submucosa. 
lated with extensive arterial changes. Such chronic inflammation does 
not always lead to obliteration of the appendix, but may cause only a 780 
THE DIGESTIVE SYSTEM 
Fig. 489.-Appendix with Oblitebation of the Lumen by Fibrous Tissue. 
Fig. 490.-Eosinophilia in Submucosa of Appendix. 
No parasites were present. THE DIGESTIVE SYSTEM 
781 
thickening of the wall and extensive infiltration with eosinophiles and 
plasma cells (Fig. 490).1 
Cystic dilatation of the appendix may be formed by obstruction of 
the lumen. The cysts thus formed may be of considerable size-from 
one to fifteen centimeters in diameter or larger-and contain mucous, 
gelatinous, or watery fluid often turbid or colored.2 
The lumen of the appendix frequently contains concretions of fecal 
material which have been mistaken for foreign bodies. Foreign bodies, 
Fig. 491.-Appendix with Oxyuris Vermicularis in Cross Section. 
such as grape and apple seeds, shot, pins, and various other small objects 
which have been swallowed, sometimes, though rarely, find their way 
into the appendix.3 Both the fecal concretions and the foreign bodies 
may act as important predisposing agents of inflammation and perfora- 
tion of the appendix, through pressure, erosion, etc., of the mucous 
membrane, affording portals of entry to various forms of pathogenic 
microorganisms. 
1 Weir, W. H., Jour. Am. Med. Sc., 1903, cxxv, 74. 
2 See, for a study of cysts and diverticula of the appendix, Corning, Albany Med. Ann., 1905, xxvi, 
816; and Winkier, Erkrankungen des Blinddarmanhanges, Jena, 1910. 
8 For a study of foreign bodies in appendix, see Mitchell, Bull. Johns Hopkins Hosp., 1899, x, 35 
For report of cases in which concretions were demonstrated by Roentgen rays, see Douglas and LeWald 
Jour. Am. Med. Assn., 1916, Ixvi, 1919. 782 
THE DIGESTIVE SYSTEM 
The bacteria most commonly found associated with the lesions of 
acute appendicitis and its accompanying peritonitis are Streptococcus 
pyogenes, Staphylococcus pyogenes, the B. coli communis, B. proteus, 
and B. pyocyaneus. Anaerobic forms are also important.1 
Oxyuris and trichocephalus are frequently found in the appendix in 
children, and may by their destruction of the mucosa permit the entry of 
bacteria (Fig. 491).2 
TUMORS OF THE INTESTINE. 
Primary tumors of all types, both benign3 and malignant, are com- 
paratively rare in the small intestine. Malignant growths are perhaps 
more common than benign, sarcomata being the most frequent malignant 
tumor found; in the large intestine, however, it 
is carcinoma which occurs most often. 
Fibromata4 and lipomata5 may be developed 
from the submucous coat and grow inward, or 
from the subserous coat and project outward 
into the peritoneal cavity. 
Small multiple cavernous hemangiomata are 
of occasional occurrence in the submucosa of the 
small intestine, to which they may be limited; 
on the other hand, they may be found through- 
out the whole gastrointestinal tract.6 
Myoma may originate in the muscular coat and 
project inward, diminishing the lumen; in the 
duodenum such tumors may obstruct the com- 
mon bile duct. Less frequently these growths 
project outward into the peritoneal cavity. 
Adenomyoma has been described, and 
referred to congenital pancreatic remnants7 or to 
developmental displacements of fragments of 
the mucous membrane.8 
Polypoid growths, projecting into the cavity 
of the intestine and composed of connective tis- 
sue covered by epithelium, are frequently found 
Fig. 492.-Small Polyp of 
the Mucous Membrane of 
the Small Intestine. 
1 Hodenpyl, E., New York Med. Jour., 1893, Iviii, 777. Consult also Kelynack, Pathology of the 
Vermiform Appendix, London, 1893; Berry, R., Jour. Path, and Bacteriol., 1895, iii, 160 (bibl.); Ribbert, 
Virchows Arch., 1893, cxxxii, 66. For bacterial reports, see Low, Reports of Boston City Hosp., 
1900, Ser. 11, p. 173; Lanz and Tanel, Rev. de chir., 1904, xxx, 43; and Perrone, Ann. Inst. Pasteur, 1905, 
xix, 367. For comprehensive treatise, see Kelly and Hurdon, Diseases of the Vermiform Appendix, 
Philadelphia, 1905; Aschoff, Die Wurmfortsatzenziindung, Jena, 1908; and v. Brunn, Ergebnisse der 
Chir., 1911, ii, 32. 
2 Cecil and Bulkley, Jour. Exper. Med., 1912, xv, 225; Aschoff, Berl. klin. Wchnschr., 1914, 1, 1504; 
and Suzuki, K., Surg., Gynec., and Obst., 1915, xxi, 702. 
3 For an extensive discussion and bibl. of benign tumors of the intestine, see King, Surg., Gynec., 
and Obst., 1917, xxv, 54. 
4 James and Sappington, Ann. Surg., 1917, Ixv, 109 (bibl.); King, Surg., Gynec., and Obst., 1917, 
xxv, 54. 
5 Harrigan, Boston Med. and Surg. Jour., 1917, clxxvi, 535 (bibl.); Tromp, Munchen, med. 
Wchnschr., 1915, Ixii, 1215 (bibl.); Stetten, Surg., Gynec., and Obst., 1909, ix, 156 (bibl.). 
6 Bennecke, Virchows Arch., 1906, clxxxiv, 171; MacCallum, Bull. Johns Hopkins Hosp., 1906, xvii, 
258 
7 Trappe, Frankfurt. Ztschr. f. Path., 1907, i, 109 (bibl.); Saltykow, Zieglers Beitr., 1912, liv, 559. 
(bibl.). 
s Meyer, R., Verhandl. d. deutsch. path. Gesellsch., 1908, xii. 148. THE DIGESTIVE SYSTEM 
783 
(Fig. 492).1 They are associated with catarrhal inflammation or occur 
in its absence; they are found throughout the intestinal tract and may 
be single or multiple They are most common in the large intestine and 
the rectum, springing from the submucous coat and projecting inward.2 
Some are solid connective tissue tumors, while others are spongy and 
contain tubules lined with cylindrical epithelium giving to the growth 
the character of an adenoma. 
Lymphoma.--Growths somewhat resembling the lymphatic tissue of 
the lymph-nodes may originate in the solitary and agminated nodules 
and in the intestinal wall in cases of leukemia and pseudoleukemia (Fig. 
493). Similar growths are found as independent lesions in both the large 
and the small intestine; they are irregular diffuse nodules infiltrating the 
wall, the mesentery, and the neighboring lymph-nodules and may reach 
The growths are polypoid, many are pigmented, and they were in this case widely 
distributed over the intestinal mucosa. 
Fig. 493.-"Lymphomata" of the Intestine in Pseudoleukemia. 
a considerable size. They often ulcerate internally and sometimes lead 
to dilatation and stenosis. 
Carcinoid Tumors.3-These are small nodules, a few millimeters in 
diameter and often multiple, which are found in middle-aged people in 
the submucous coat of the small intestine opposite the attachment of 
the mesentery. They are whitish in color, freely movable, and covered 
by intact mucous membrane. They grow slowly and rarely metastasize. 
Upon morphological examination they are found to consist of anastomos- 
ing nests and columns of closely packed cells with round nuclei and some- 
times arranged after the manner of a gland. They are sharply encapsu- 
lated and exhibit no tendency to penetrate the muscular coat. Their 
acellular stroma may contain smooth muscle fibers. This type of growth 
has given rise to much controversy. Certainly they can hardly be called 
1 For a general discussion of these and their relation to carcinoma, see Verse, Uber die Entstehung, 
den Bau u. das Wachstum der Polypen, Adenome u. Karzinome des Magen-Darmkanals, Arb. a. d. 
path. Inst. z. Leipzig, 1908, Erster Band; and Hauser, Das Cylinderepithel-Carcinom des Magens u. d. 
Dickdarms, Jena, 1910. 
2 Carroll, Surg., Gynec., and Obst., 1915, xx, 412 (bibl.). 
3 Oberndorfer, Frankfurt. Ztschr. f. Path., 1907, i, 426 (bibl.); Saltykow, Zieglers Beitr., 1912, liv, 
559 (bibl.); Dietrich, Frankfurt. Ztschr. f. Path., 1913, xiii, 390 (bibl.); Vance, Proc. New York Path. 
Soc., 1916, xvi, 158 (bibl.). 784 
THE DIGESTIVE SYSTEM 
carcinomata, and the name carcinoid tumor will do as well as any other 
until their true nature is determined. They have been compared to 
basal-cell carcinoma,1 and by another observer have been referred to mis- 
placed remnants of pancreas.2 Similar tumors are found in the appendix 
(page 786). 
Sarcomata3 are of occasional occurrence in the intestine, as has already 
been said. They are rare in the large intestine, with the exception of 
the rectum.4 Melanotic sarcoma has been described in the small intes- 
tine5 and in the rectum.6 
While various types of sarcoma have been recorded, lymphosarcoma'1 
is the most common; this sometimes gives the clinical symptoms of 
appendicitis.8 
Fig. 494.-Adenoma of the Rectum. 
The glands, as is not uncommon in polypoid adenomata of the intestine, are seen in the submucosa, 
although the tumor is benign. 
Adenomata are found in the duodenum, colon, and rectum. They 
form superficial infiltrations of the intestinal wall or project inward as 
polypoid tumors. They are composed of tubular follicles like those of 
the mucous membrane, and of a connective tissue stroma. In some, the 
tubules have a regular shape and arrangement and do not infiltrate the 
surrounding tissue; the tumor is of benign nature. In others, however, 
the tubules are irregular in shape and arrangement, and the growth 
infiltrates the neighboring parts (Fig. 494). As with the bladder, it is 
1 Bunting, Bull. Johns Hopkins Hosp., 1904, xv, 389. 
2 Oberndorf er, Frankfurt. Ztschr. f. Path., 1907, i, 426 (bibh); Saltykow, Zieglers Beitr., 1912, liv, 
559 (bibl.). 
3 Storch, Deutsch. Ztschr. f. Chir., 1904, cxxviii, 218 (bibl.); Douglass, Ann. Surg., 1912, Iv, 400 
(bibl.); Miller, Surg., Gynec., and Obst., 1913, xvii, 210 (bibl.); Libman, Am. Jour. Med. Sc., 1900, 
cxx, 309. 
4 For bibl. of sarcoma of the large intestine, see Jopson and White, Am. Jour. Med. Sc., 1901, cxxii, 
807. 
6 Vander Veer and Kellert, New York State Jour. Med., 1917, xvii, 335 (bibl.). 
6 Weiner, Zieglers Beitr., 1899, xxv, 322. 
7 Eisenbrey, Proc. New York Path. Soc., 1913, xiii, 116; Schmidt, Frankfurt. Ztschr. f. Path., 
1915, xvi, 131 (bibl.) 
* Libman, Proc. New York Path. Soc., 1913, xiii, 119 (discussion of Eisenbrey's paper). THE DIGESTIVE SYSTEM 
785 
sometimes difficult to decide whether polypoid tumors of the rectum are 
benign or malignant. 
Carcinoma develops most often in the colon and the duodenum.1 
Forms which have been described in the stomach occur here also; i.e., 1, 
The variety with relatively little stroma and epithelial cells arranged in 
solid masses {medullary type) or maintaining in a measure the glandular 
arrangement {adenocarcinoma Fig. 495 and 496). 2. Scirrhus. 3. The 
gelatinous type, which is more common here than in the stomach. 4. 
Epithelioma, which often involves the rectum and anus. 
Fig. 495.-Adenocarcinoma of the Rectum. 
Shows a portion of normal mucous membrane invaded by the new growth. This type of tumor 
is frequently, but improperly, called malignant adenoma. 
Cysts of the intestine are uncommon.2 One type {gas cyst) appears 
as multiple cavities containing gas and scattered through the intestinal 
wall.3 
Dermoid cysts are most frequently observed in the small intestine, 
where they may be subserous, intramuscular, or submucous.4 
TUMORS OF THE APPENDIX.5 
Tumors of the appendix are not frequent; fibroma, lipoma, myoma, 
and sarcoma6 have been found.7 
1 Rolleston, Lancet, 1901, i, 1121. For a general discussion of various types of intestinal carcinoma, 
see Hauser, Das Cylinderepithel-Carcinom d. Magens u. d. Dickdarms, Jena, 1910. 
2 Ayer, Am. Jour. Med. Sc., 1906, cxxxi, 89. 
3 Thalhimer, Proc. New York Path. Soc., 1913, xiii, 5 (bibl.); Schnyder, Cor.-Bl. f. schweiz. Aerzte, 
1917, xlvii, 289. 
4 Jepson, Surg., Gynec., and Obst., 1905, i, 319. 
5 For a general discussion of tumors and other diseases of the appendix, see Oberndorfer, Lubarsch- 
Ostertag, Ergebn. d. allg. Path., 1909, xiii1, 527 (bibl.); Winkler, Die Erkrankungen des Blinddarman- 
hanges, Jena, 1910. 
6 Jones, Surg., Gynec., and Obst., 1911, xii, 131 (bibl.). 
7 For bibl. of tumors of the appendix, see Kelly, Proc. Path. Soc., Philadelphia, 1900, N. S. iii, 109; 
Miloslavich and Namba, Ztschr. f. Krebsforsch., 1913, xii, 14; Crouse, Surg., Gynec., and Obst., 1910, xi, 
457. 786 
THE DIGESTIVE SYSTEM 
Carcinoid Tumors.1-There is sometimes found in the appendix a 
peculiar and characteristic growth, the nature of which is as yet unde- 
termined (Fig 497). It usually involves the muscularis or submucosa 
and is discovered in about 0.5 per cent, of all appendices removed,2 par- 
ticularly in younger patients. It consists of alveoli filled with rather 
large clear cells of uniform size, packed closely together and bearing ves- 
icular nuclei with prominent nucleoli; mitotic figures are not often found. 
The condition is rarely diagnosed during life, but is discovered accident- 
Fig. 496.-Glandular Carcinoma of Intestine. 
ally in appendices extirpated for other reasons. By some observers the 
growth is regarded as a carcinoma, though only an occasional one proves 
to be malignant.3 Other writers prefer some such term as pseudocarcin- 
oma, carcinoid tumor* (on account of its morphological resemblance to 
carcinoid tumors of the intestine (see page 783), or nuvus.5 
Cylindrical-cell cancer, sometimes forming much mucoid material 
and of a morphological type similar to that found in any other part of 
the gastrointestinal tract, may develop in the appendix,6 though it is 
extremely rare (Fig. 498). 
1 Rolleston and James, Am. Jour. Med. Sc., 1906, cxxxi, 951 (bibl.); Whipham, Lancet, 1901, i, 
319; Jessup, Med. Rec., 1902, Ixii, 289; Moschcowitz, Ann. Surg., 1903, xxxvii, 89 (bibl.); Norris, 
Univ. Pennsylvania Med. Bull., 1903, xvi, 334; McWilliams, Am. Jour. Med. Sci., 1908, cxxxv, 822; 
Gerlach, P., Frankfurter Ztschr. f. Path., 1920, xxiv, 515 (bibl.); Vance, Proc. New York Path. Soc., 
1916, xvi, 158 (bibl.). 
2 Meyer, Surg., Gyn., and Obst., 1915, xxi, 354 (bibl.); Rogg, Ztschr. f. Krebsforsch., 1913, xii, 12 
(bibl.); Mayo, C. H., Jour. Am. Med. Assn., 1910, Iv, 1605. 
3 Luce, Beitr. z. klin. Chir. (Bruns), 1912-13, Ixxxii, 155 (bibl.). 
4 OberndoMer, Frankfurt. Ztschr. f. Path., 1907, i, 426 (bibl.). 
6 Aschoff, Pathologische Anatomie, 3d ed., Jena, 1913, p. 831. 
6 Miloslavich, Frankfurt. Ztschr. f. Path., 1913, xiii, 138; Miloslavich and Namba, Ztschr. f. Krebs- 
forsch., 1913, xii, 14 (bibl.). THE DIGESTIVE SYSTEM 
787 
Cysts.1-A rather uncommon condition (pseudomucinous cyst, hydrops 
spurius) is the result of obliteration of the lumen of the appendix near 
Fig. 497.-Carcinoma of Appendix. 
Carcinoid type. 
Fig. 498.-Gelatinous Carcinoma of Appendix. 
its proximal end and dilatation of the remainder; the wall of the resulting 
cyst may undergo calcification.2 Sometimes the wall ruptures and par- 
1 For bibliography see Crouse, Surg., Gynec., and Obst., 1910, xi, 457. 
2 Ogilvie, Jour. Am. Med. A.ssn., 1915, Ixiv, 657 (bibi.). 788 
THE DIGESTIVE SYSTEM 
tides of the mucous membrane escape into the peritoneal cavity, where 
they have the power to grow1 (see page 797). 
INTESTINAL CONCRETIONS. (Enteroliths.) 
The intestines may contain round, oval, or irregular masses of firm 
consistence, usually small, but sometimes as large as a man's fist. They 
consist of fecal matter, mucus, bile, the carbonate and phosphate of 
lime, and triple phosphate. They may induce inflammations, ulceration, 
and perforation. Small brown concretions-intestinal sand-may be 
found. A large part of such bodies are derived from the ligneous "stone 
cells" contained in some fruits, upon which calcium salts collect. 
PIGMENTATION OF THE INTESTINE. 
A moderate amount of pigmentation is frequently noted in the large 
intestine after bleeding from any portion of the gut, after severe inflam- 
Fig. 499.-Pigmented Intestine. 
matory lesions, and, also, following chronic intoxication with silver, mer- 
cury, and bismuth. The Peyer's patches may be blackened by absorp- 
tion of coal-dust or soot.2 There is, in addition, a somewhat rare form 
of melanosis of the large intestine which is limited to that portion of the 
gut. The color of the mucous membrane varies from dark brown to pure 
black; and the pigment is, as a rule, confined to the mucous membrane, 
the remainder of the wall being free, while the lymph-nodes of the meso- 
colon and all the other organs of the body, also, are free from any abnor- 
mal pigmentation. Very infrequently the pigment-bearing cells may be 
found in the submucosa or the mesenteric nodes. The pigment itself is 
1 Oberndorfer, Verhandl. d. deutsch. path. Gesellsch., 1906, x, 235. 
2 Lubarsch, Deutsch, med. Wcshnchr., 1915, xli, 1025. THE DIGESTIVE SYSTEM 
789 
amorphous, and composed of minute granular masses, and lies within 
large mononuclear pigment cells (Fig. 499), though occasionally it is set 
free in the tissues on the death of the cells of this type. It gives no iron 
reaction and is not affected by concentrated acid. It is probably due 
to the local formation of melanin from some of the decomposition products 
of the proteins during their absorption through the intestinal wall.1 
The Peritoneum. 
Malformations. 
Arrest in development of the peritoneum may be manifested in fissures in the 
mesial line or external to it; in partial2 or complete absence of the diaphragm; in 
fusion with the pleura; and in incomplete formation of the mesentery, the omentum, 
or the other folds of the peritoneum. 
Excess of development occurs in the shape of unusual length of the mesentery, 
the omentum, or the other folds of the peritoneum; or of supernumerary folds and 
pouches. These are chiefly found in the hypogastric, iliac, and inguinal regions and 
near the fundus of the bladder. There may be access to these sacs by a well-defined 
fissure or ring, which is frequently surrounded by a tendinous band lying in the dupli- 
cature. These may give rise to internal incarceration of the intestines. 
The left half of the diaphragm may have an abnormally high position with up- 
ward displacement of the abdominal viscera, particularly the stomach, on the left 
side, and displacement of the heart to the right. This has been called eventration of 
the diaphragm. It may be mistaken in diagnosis for diaphragmatic hernia.3 
HEMORRHAGE. 
Large hemorrhage into the peritoneal cavity may result from injuries 
to the abdominal viscera, ruptured aneurysm, etc. Punctate hemor- 
rhages may accompany various acute infections and toxemias. Hemor- 
rhage may occur in acute localized or general peritonitis, in obstruction 
of the portal circulation, in thrombosis and in embolism of the mesenteric 
vessels. 
ASCITES. 
The collection of transudate in the peritoneal cavity may accompany 
chronic venous congestion, especially with obstruction of the portal cir- 
culation in cirrhosis from thrombi, emboli, etc., or with chronic heart 
and kidney diseases. It often accompanies similar conditions in the 
pleura and pericardium. It may accompany chronic peritonitis. 
Chylous ascites may result from a rupture of the thoracic duct or 
from a transudation from the chyle vessels.4 
Chyliform Ascites.-Most frequently in abdominal carcinoma and 
tuberculosis, but also in other forms of chronic peritonitis with serous 
exudate, the peritoneal cavity may contain fluid, milky from cell detritus 
i Pick, Berl. klin. Wchnschr., 1911, xlviii, 840, 884; McFarland, Jour. Am. Med. Assn., 1917, Ixix, 
1946; Bland-Sutton, Brit. Med. Jour., 1914, ii, 656. Henschen, F., and Bergstrand, H., Studien uber 
die Melanose der Darmschleimhaut, Zieglers Beitr., 1913, Ivi, 103. 
2 Vogel, K. M., Am. Jour. Med. Sc., 1913, cxlv, 206. 
3 See Sailer and Rhein, Am. Jour. Med. Sc., 1905, cxxix, 688. 
* Shaw, Jour. Path, and Bacterio!., 1900, vi, 339. 790 
THE DIGESTIVE SYSTEM 
and fat derived from the disintegration of degenerated mesothelial and 
other cells. This condition is called chyliform ascites. 
INFLAMMATION. (Peritonitis.) 
Acute Peritonitis.-Acute inflammation of the peritoneum may occur 
as a primary process, but is much more often secondary. In the latter 
case it may be associated with wounds and contusions of the wall of the 
abdomen; wounds, ulcers, new growths, incarcerations, intussusceptions, 
There are swelling and proliferation of the mesothelial cells as well as of the cells of the 
fibrillar tissue forming the omental trabeculae. 
Fig. 500.-Acute Cellular Peritonitis-Human Omentum. 
ruptures, perforations, and inflammations of the stomach and intestines; 
inflammation of the vermiform appendix; injuries, ruptures, and inflam- 
mations of the uterus, ovaries, and Fallopian tubes; rupture and inflam- 
mation of the bladder; inflammation of and about the kidneys; abscesses 
and hydatid cysts of the liver; inflammation of the gall-bladder and 
large bile ducts; thrombosis of the portal vein; inflammations of the 
spleen, pancreas, lymph-nodes, retroperitoneal connective tissue, verte- 
brae, ribs, and pelvic bones; pyemia and other infectious diseases. The 
inflammation is at first either local or general. A local peritonitis may 
remain circumscribed, or it may spread and become general. 
We may distinguish two anatomical forms of acute peritonitis. THE DIGESTIVE SYSTEM 
791 
1. Cellular Peritonitis.-This form of peritonitis may be induced 
by any irritant which does not act too energetically. It can be excited 
in dogs by intraperitoneal injections of very small quantities of a solution 
of chloride of zinc. In the human subject we find it with perityphlitis, 
with circumscribed abscesses in the peritoneal cavity, in puerperal fever, 
and in other infectious diseases with early death. 
At the autopsy the entire peritoneum may be congested; but there 
are no exudates and no other lesions visible to the naked eye. Minute 
examination, however, shows a very marked change in the mesothelial 
(endothelial) cells. These are increased in size and number and the 
new cells coat the surface of the peritoneum and project outward in little 
masses (Fig. 500). This form of inflammation, in many cases, at least if 
life be prolonged, passes into the exudative phase, next to be considered. 
2. Exudative Peritonitis.-This, which is the common form of 
acute peritonitis, presents lesions similar to those which have been already 
described in pleuritis and pericarditis. Thus there is a form in which 
fibrin is the chief exudate with but little serum; or the exudate is sero- 
fibrinous, or purulent, or hemorrhagic.1 When fibrin is present, the 
intestinal coils may be more or less firmly adherent to the abdominal 
walls or to each other. If putrefactive bacteria are present, as in peri- 
tonitis from perforation of the intestine, the exudate may be foul. 
In local inflammation of the peritoneum the position may be indicated 
by the name, thus perihepatitis, perisplenitis, perityphlitis, pelvic, sub- 
phrenic, etc. 
Acute exudative peritonitis may terminate in recovery with absorp- 
tion of the exudate, permanent connective-tissue adhesions and thicken- 
ings of the peritoneum often remaining. Chronic peritonitis may follow 
the acute phase. 
Bacteria are the usual excitants of acute exudative peritonitis. In 
primary forms of peritonitis the Streptococcus and Staphylococcus pyo- 
genes are the bacteria most frequently present. 
In secondary exudative peritonitis the pyogenic cocci and the colon 
bacillus have been most frequently found. Of the other bacteria which 
have been found in the exudate we may name the pneumococcus,2 the 
gonococcus,3 B. pyocyaneus, B. proteus, B. aerogenes capsulatus, B. 
typhosus. 
There is abundant evidence that bacteria can pass from the intes- 
tinal cavity through its wall into the peritoneum without perforation, 
especially in regions where the integrity of the tissues is impaired by 
disturbances in circulation and nutrition, or in necrosis, as in strangula- 
tion of the gut.4 
1 For a study of the forms of cells in exudative peritonitis, see Lossen, Deutsch. Arch. f. klin. Med., 
1906, xxxvi, 217. 
2 Rischbieth, H., Quart. Jour. Med., 1911, iv, 205. 
3 See Cushing on gonococcus peritonitis, Bull. Johns Hopkins Hosp., 1899, x, 75.. 
4 Consult, for studies and bibliography of various phases of peritonitis, Tavel and Lanz, Peritonitis, 
Mitt. a. d. kl. u. med. Inst. d. Schweiz, I Reihe, 1893, i, 1; Silber schmidt, ibid., 1894, v, 342; Flexner, S., 
Philadelphia Med. Jour., 1898, ii, 1019; Cullen, T. S., Johns Hopkins Hosp. Rep., 1895, iv, 411; 
Abramow, Zieglers Beitr., 1898, xxiii, 1; Buttner, ibid., 1899, xxv, 453. 
For special studies on the entrance of microorganisms into the body from the gastrointestinal canal, 
see Opitz, Ztschr. f. Hyg., 1898, xxix, 505; Birch-Hirschfeld, Zieglers Beitr., 1898, xxiv, 304; Buchbinder, 792 
THE DIGESTIVE SYSTEM 
Absorption from the Peritoneum.-In connection with inflammation, recent 
studies which have been made of the absorption of alien substances injected into the 
peritoneal cavities of animals, especially rabbits and guinea-pigs, are of extreme in- 
terest and importance. Living bacteria as well as various kinds of inert particles may 
be rapidly disposed of through the action of the body fluids or phagocytic cells. The 
studies of Buxton and Torrey1 indicate that after an intraperitoneal injection of sus- 
pensions of inert particles there may be an immediate rush of these to the lymphatics 
of the diaphragm, whence they are carried almost immediately by the anterior medias- 
tinal lymph-trunks through the lymph-nodes to the thoracic duct and general circula- 
tion. In the earlier stages the transported particles may be free, but later may be 
taken up by phagocytes in the mediastinal lymph-nodes. But the omentum appears 
to be of significance in the disposal of inert particles injected into the peritoneal cavity. 
Buxton and Torrey showed that almost immediately after the injection of such particles 
in the guinea-pig, fibrin is formed on the surface of the omentum in which the parti- 
cles and phagocytic cells become entangled. The phagocytes taking up the particles 
may then enter the tissues. These observers have furthermore shown that after intra- 
peritoneal injections of typhoid bacilli in the rabbit, the bacilli may become fixed upon 
the surface of the omentum where they may be destroyed.2 
Chronic Peritonitis may follow the acute exudative form or may occur 
independently. The lesions vary. In one group of cases the peritoneum 
is beset with minute translucent nodules, sometimes visible, sometimes 
invisible to the naked eye. These are apparently formed by a local 
proliferation of the mesothelial and connective-tissue cells. Associated 
with this there may be a general irregular proliferation of the peritoneal 
mesothelium. This has been called chronic cellular peritonitis. 
In other cases there are local or general fibrous adhesions, sometimes 
firm, sometimes loose, between the intestinal coils or between the intes- 
tine-and the abdominal wall or the viscera (Fig. 501). In this way sac- 
culated collections of serofibrinous or purulent exudate may form in the 
abdominal cavity. Finally chronic peritonitis may result in a dense 
fibrous thickening of the peritoneum, either local or widespread. 
In some cases the parietal peritoneum is principally involved, in 
others the peritoneum of the stomach, intestines, liver, and spleen. The 
thickening of the capsule of the liver may be attended with a diminution 
in the size of that viscus. There may or may not be adhesions;serous 
or other exudate may be present. Great distortion of the omentum, 
mesentery, and other abdominal viscera may occur. 
When the condition is very marked the peritoneal covering of the 
abdominal organs may form a thick white translucent coating, resembling 
the icing of a cake; hence, the term 11 iced liver" sometimes employed. 
Another name is polyserositis fibrosa. This coating can be peeled off the 
organ, leaving a more or less normal peritoneum. There is usually ex- 
treme ascites with a palpable spleen, so that clinically the resemblance 
to hepatic cirrhosis is quite striking. In some instances the pericardium 
and pleura, also, are involved. 
Deutsch. Ztschr. f. Chir., 1900, Iv, 458; Marcus, Ztschr. f. Heilk., 1899, xx, 427; also Wien. klin. 
Wchnschr., 1901, xiv, 11; Ravenel, M. P., Jour. Med. Research, 1903, N. S. v, 460; and Calmette, 
Med. Record, 1908, Ixxiv, 741. 
1 Buxton and Torrey, Jour. Med. Research, 1906, N. S. x, 5. 
2 For a study of the local accumulation of eosinophile leucocytes after intraperitoneal injections of 
bacteria, see Opie, Tr. Assn. Amer. Phys., 1904, xix, 136. THE DIGESTIVE SYSTEM 
793 
The course of the disease is progressive, and death results from ileus, 
cardiac or renal disease (which often occurs with polyserositis), or a 
terminal infection. The etiological factor is supposed to be of toxic or 
bacterial origin, but there is as yet no positive evidence in this regard.1 
Tuberculous Peritonitis may occur in acute general miliary tuberculo- 
sis or it may be secondary to tuberculous inflammation elsewhere, as in 
the lungs or genitourinary organs or intestines; or it may be an inde- 
pendent process. The process may be local or general in the peritoneum. 
The lesions may be miliary in character (Fig. 502) or there may be large 
foci of the new-formed tubercle tissues with considerable necrosis. There 
may be more or less serous or serofibrinous or purulent or hemorrhagic 
Fig. 501.-Old Peritoneal Adhesions between the Under Surface of the 
Liver and the Intestine. 
L is the liver turned over to expose the inferior surface. Many delicate fibrous cords and bands 
pass from the liver to the intestine, I. The gall-bladder, G. B., is distended. 
exudate. Fibrous adhesions may form between the intestinal coils and 
the peritoneal walls with the encapsulation of exudate. Ulceration of the 
tubercle tissue may occur, or it may become dense and fibrous and is then 
often pigmented. The tuberculous inflammation may be limited to the 
vicinity of tuberculous ulcers of the intestine. It may involve the omen- 
tum, which is converted into a hard, thick, dense mass at the upper part 
of the abdominal cavity.2 
i For review and bibl. see Kelly, A. O. J., Am. Jour. Med. Sc., 1903, cxxv, 116- and Evans G H 
bid., 1918, civ, 553. ' ' ' " 
2 For bibl. with reference to operative treatment, see Bottomley, Reports of Boston City Hosp., 
1900, Series 11, p. 118. For a full critical summary of the literature of peritonitis from 1885 to 1900, 
see Brunn, M., Centralbl. f. allg. Path., 1901, xii, 65. For review of tuberculous peritonitis, see 
Beitzke, H., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1910, xiv, 169; and Mayo, W. J., Jour. Am. 
Med. Assn., 1918, Ixxi, 6. 794 
THE DIGESTIVE SYSTEM 
TUMORS. 
Many of the growths loosely referred to as peritoneal tumors actually 
arise in the subperitoneal tissue. Among these the commonest is the 
lipoma, and the least common, the fibroma. 
Lipoma.1-This arises most often in the mesentery and frequently 
undergoes fibrous or calcareous change. The pedicle may atrophy, leav- 
ing the tumor free in the peritoneal cavity. When lipomata grow beneath 
the parietal peritoneum they may form fat hernia;; thus, at the umbilicus, 
in the inguinal canal, along the vas deferens, in the crural ring, and in 
the obturator foramen, they may project outward under the skin and by 
Fig. 502.-Miliary Tubercles of the Omentum. 
drawing the peritoneum after them open the way for a future intestinal 
hernia. 
Very large perirenal lipomata are of occasional occurrence.2 
Myxoma, chondroma, osteoma, and angioma3 have been described. 
Fibroma.-Fibromata4 originating in the subperitoneal connective tis- 
sue may be found beneath either the parietal or the visceral peritoneum. 
Retroperitoneal sarcomata5 are found in both children and adults, 
sometimes extending between the folds of the mesentery.6 Some of those 
1 Voeckler, Deutsch. Ztschr. f. Chir., 1909, xcviii, 149 (bibl.). 
2 Adami, Montreal Med. Jour., 1896-97, xxv, 529 (bibl.). 
3 For a discussion of angioma of the mesentery, see Takano and Manser, Zieglers Beitr., 1912, liii, 
105 (bibl.). 
4 Sympson, Lancet, 1916, ii, 188. 
6 Steele, Am. Jour. Med. Sc., 1900, cxix, 311. For a study of sarcoma and mixed tumors of the 
great omentum, see Conforti, Centralbl. f. allg. Path., 1906, xvii, 817. 
6 For a discussion of tumors of the mesentery, see Bowers, Ann. Surg., 1906, xliv, 892 (bibl.). For 
sarcoma of the omentum, see Cobb, ibid., 16 (bibl.); Nash, Lancet, 1911, i, 117 (angiosarcoma); McLean, 
Surg., Gynec., and Obst., 1911, xii, 588 (myxoma). For a review of primary malignant tumors of 
the omentum, see Litchkous, Ann. de gyn6c. et d'obst., 1909, Ixvi, 338 (bibl.) (abstr. in Surg., Gynec., 
and Obst., 1910, x, 218). For a study of retroperitoneal lymph-nodes and retrograde metastases of 
bacteria, dust, and tumor cells from the thorax into the abdomen, see Tenderloo, Munchen, med. 
Wchnschr., 1904, li, 1537. THE DIGESTIVE SYSTEM 
795 
reported in the past may have been ganglioneuromata.1 They may be 
of the small round-cell or spindle-cell type, and are often very vascular. 
They metastasize in the omentum, mesentery, intestinal wall, liver, lungs, 
and other viscera. The fibrosarcoma is relatively benign in this situation.2 
Fig. 503.-Cystic Papilloma of the Omentum. 
Secondary to papilloma of the ovaries. 
Tumors of the peritoneum itself are rare. They include the meso- 
thelioma,3 which is similar in all respects to that found in the pleura 
(page 729). Many of the so-called primary peritoneal tumors are meta- 
1 Dunn, Jour. Path, and Bacteriol., 1914-15, xix, 456 (bibl.); Bland-Sutton, Lancet, 1918, i, 429. 
2 Bland-Sutton, Lancet, 1918, i, 429. 
3 Miller and Wynn, Jour. Path, and Bacteriol., 1908, xii, 267 (bibl.); Herzog. Zieglers Beitr., 1914, 
Iviii, 390 (bibl.). 796 
THE DIGESTIVE SYSTEM 
stases from small carcinomata overlooked at autopsy, though it is said 
that endotheliomata may arise from the lymph-vessels.1 
Cysts of the mesentery or omentum are not particularly uncommon.2 
Various types are found-blood cysts, chyle cysts,3 serous cysts, dermoid 
cysts,4 echinococcus cysts, gas cysts, etc. Multiple cysts of the omentum 
may result by the transplantation of papillary cystadenomata from the 
ovary (Fig. 503). 
This growth was secondary to a similar tumor originating in the ovary and connected with that 
organ (see Fig. 631). Detached portions of the original tumor were transplanted to various regions 
of the peritoneum. 
Fig. 504.-Papilloma of Peritoneum. 
Secondary tumors of the peritoneum include the papillary cystade- 
noma (Fig. 504) which is metastatic from the ovary (Fig. 631, page 960). 
It often involves the peritoneum, and although technically a benign tumor 
not infrequently causes death from the widespread involvement. 
Secondary carcinoma'' of the peritoneum is sometimes a complication 
of this disease in adjacent regions such as the stomach, liver, uterus, etc., 
and its structural characters, therefore, correspond with those of the 
1 e.g., Kaufmann, Lehrbuch d. spez. Path., Berlin, 1911, ii, 560. 
2 Kayser, Beitr. z. klin. Chir. (Bruns), 1914, xciv, 52 (bibl.); Jones, Surg., Gynec., and Obst., 1915; 
xxi, 56 (bibl.); Funk, ibid., 1914, xviii, 70 (bibl.); Frazier, Jour. Am. Med. Assn., 1913, Ixi, 97 (bibl.), 
Dowd, Ann. Surg., 1911, liv, 617 (bibl.). 
3 Benedict, Surg., Gynec., and Obst., 1913, xvi, 606 (bibl.); Friend, ibid., 1912, xv, 1 (bibl.); Hadley, 
ibid., 1916, xxii, 174. 
4 Jepson, Surg., Gynec., and Obst., 1905, i, 319 (bibl.). 
6 Misumi, Virchows Arch., 1909, cxcvi, 371. THE DIGESTIVE SYSTEM 
797 
primary growth. It is apt to appear in the form of whitish nodules, 
sometimes local, sometimes widely disseminated over the peritoneal sur- 
faces. Such tumors, when small and numerous, may readily be mistaken 
for tubercles. 
Pseudomyxoma Peritonei.-This obscure disease, in which the peri- 
toneum is thickened and covered with a gelatinoid material, is also called 
morbus gelatinosus or colloid, mucoid, muciparous, gelatinous, or gelatinoid 
carcinoma. It is often accompanied by ascites, attacks the entire peri- 
toneum and the underlying musculature, and appears to be in many 
cases a secondary carcinosis in which the invading cells suffer edematous 
disintegration.1 The primary carcinoma may be in the stomach, gall- 
bladder, appendix or ovary.2 In the case of the organs last named, how- 
ever, the source may not be a carcinoma at all, but a mucocele, a benign 
cystadenoma with gelatinous contents, or a teratoma.3 Whether in such 
an event the condition in the peritoneum is simply a foreign-body reac- 
tion to the gelatinous material,4 or 'whether it consists of actual metastasis, 
is still an unsettled question.5 It may be that two distinct processes 
have been included under one name. In the appendix, also, a benign 
process (pseudomyxomatous cyst, hydrops spurius, page 788) sometimes 
leads to pseudomyxoma of the peritoneum6 or even of the retroperitoneal 
tissues.7 
Various forms of tumors of the umbilicus have been described,8 and 
some half dozen of the umbilical cord itself,9 such as myxosarcoma, 
angioma, and hematoma.10 
PARASITES. 
Echinococcus cysts may be formed in their regular way at any part of 
the visceral and parietal peritoneum, or be free in the peritoneal cavity. 
These cysts may be small, or so large as nearly to fill the abdominal 
cavity. 
Cysticercus cellulosae may also be developed in the subperitoneal 
connective tissue. 
The Salivary Glands-The Parotid, Submaxillary, and Sublingual. 
INFLAMMATION. 
Acute Parotitis, occurring as an epidemic disease known as mumps, 
is usually confined to the parotid gland of one side; the submaxillary and 
sublingual may be at the same time involved. The gland is swollen and 
1 McCrae and Coplin, Am. Jour. Med. Sc., 1916, cli, 475 (bibl.). 
2 Lewis, Surg., Gynec., and Obst., 1914, xix, 757 (bibl.). 
3 Roth, Zieglers Beitr., 1916, Ixi, 42 (bibl.). 
* Werth, Arch. f. Gynak., 1884, xxiv, 100; Marchand, Munchen med. Wchnschr., 1907, xxxiv, 1704. 
s Fraenkel, Munchen, med. Wchnschr., 1901, xlviii, 965 (bibl.). 
6 Fraenkel, Munchen, med. Wchnschr., 1901, xlviii, 965 (bibl.); Tomita, Centralbl. f. allg. Path., 
1907, xviii, 849 (bibl.); Merkel, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1903, ix2, 328 (bibl.); 
Hueter, Zieglers Beitr., 1907, xli, 517 (bibl.); Bailey, Surg., Gynec., and Obst., 1916, xxiii, 219 (bibl.). 
7 Sturm, Frankfurt. Ztschr. f. Path., 1915, xvi, 464. 
8 Cullen, The Umbilicus and its Diseases, Philadelphia, 1913, p. 351 ff. 
9 Herweg, Arch. f. Gynak., 1909, Ixxxix, 317 (bibl.). 
10 Cooper, Practitioner, 1917, xcviii, 389; Ritter, Centralbl. f. Gynak., 1912, xxxvi, 641 (bibl.). 798 
THE DIGESTIVE SYSTEM 
there is often edema of the mucous membrane of the mouth and pharynx. 
Very little is known of the minute changes which the gland undergoes in 
this disease.1 
Suppurative Parotitis may occur as a secondary lesion in many 
diseases, typhoid and scarlet fever, pyemia, pneumonia, etc., and by 
bacterial invasion or extension of inflammation from the mouth. Under 
these conditions the process is usually suppurative and frequently results 
in abscess or sloughing. The interstitial tissue of the gland is more or 
less densely infiltrated with pus cells, and the parenchyma cells may 
undergo fatty degeneration and disintegration. The inflammation may 
be confined to the gland or it may spread to adjacent parts, sometimes 
causing much destruction of tissue, and may give rise to inflammation of 
the brain or of the inner ear, or even to metastatic pyemic abscesses in 
different parts of the body. Healing may occur, with formation of 
salivary fistulae. 
The submaxillary gland may be involved with the parotid in the 
suppurative inflammation. Acute suppurative inflammation of the 
connective tissue about the submaxillary gland is sometimes of serious 
import. Sloughing and gangrene may occur and are apt to spread to 
adjacent parts. Septicemia, edema of the glottis, or pneumonia may 
complicate the process and cause death. 
The sublingual gland is not often the seat of inflammation. 
Chronic inflammation, leading to the formation of dense interstitial 
tissue, sometimes occurs in the salivary glands. This may occur by 
itself or follow an acute inflammation. Tuberculous inflammation of the 
parotid is not infrequent.2 
The excretory ducts of the salivary glands may become inflamed from 
the presence of foreign bodies or of concretions formed in them. They 
may become occluded from the presence of calculi or as the result of 
inflammation, and may thus become widely dilated both in the main 
branches and in the finer ramifications. The dilatation of Wharton's 
duct to form larger and smaller cysts containing salivary fluid sometimes 
gives rise to very large and troublesome tumors which constitute one of 
the forms of ranula.3 
TUMORS OF THE SALIVARY GLANDS. 
Fibromata sometimes occur in the parotid; chondromata, myxomata, 
and sarcomata, including fibrosarcomata and melanosarcomata, have 
been described. A more common growth, however, is the mixed tumor, 
containing fibrous connective tissue, epithelium, cartilage, and cylindro- 
matous portions (Fig 505). Similar neoplasms are occasionally dis- 
1 See Herb, I. C., Jour. Infect. Dis., 1909, iv, 201; Wollstein, M., Jour. Am. Med. Assn., 1918, Ixxi, 
639. 
2 Consult Meslay and Parent, Gaz. d. hop., 1899, Ixxii, 156 (bibl.); also Wood, G. B., Univ. Pennsyl- 
vania Med. Bull., 1903, xvi, 368. 
For bibliography of lesions of the salivary glands, see Thorel, Lubarsch-Ostertag, Frgebn. d. allg. 
Path., 1898, v, 221. For a very complete survey from a surgical point of view, see Heineke, Deutsch. 
Chir., Stuttgart, 1913, Lief, xxxiii. THE DIGESTIVE SYSTEM 
799 
Fig. 505.-Complex Tumor of Parotid. 
Containing fat and mucoid tissue and a few cellular areas not showing the gland type. 
Containing cartilage, bone, and myxomatous and glandular tissue. 
Fig. 506.-Complex Tumor of Parotid. 800 
THE DIGESTIVE SYSTEM 
Fig. 507.-Adenoma of Parotid. 
Fig. 508.-Tumor of Parotid. 
Composed of cellular areas embedded in mucoid tissue. While tumors of this type are unquestionably 
epithelial in nature, they very closely resemble the sarcomata. THE DIGESTIVE SYSTEM 
801 
covered in the submaxillary gland also. These complex or mixed tumors, 
which are sometimes called adenochondromata (Fig. 506), originate more 
frequently in the salivary glands than in any other part of the body, and 
are sometimes rendered still more complex in structure by the formation 
of cysts and by what has been usually regarded as an atypical glandular 
growth lending to them an adenomatous character (Fig. 507). Earlier 
studies upon these tumors led to the belief that a large proportion were 
endotheliomata1 (see page 441); but more recent studies indicate that 
many cell types formerly interpreted as endothelium are actually epi- 
thelium (Fig. 508).2 
Although it has been asserted3 that the growths under discussion 
should be classed as basal-cell carcinomata, the more general opinion is 
that they are derived from congenital remnants of the glandular struc- 
tures.4 The majority are benign, malignant examples being exceptional. 
Other benign growths of the salivary glands include angioma5 and 
rhabdomyoma.6 
Primary carcinoma and squamous-cell epithelioma are very rare. 
The Pancreas. 
Malformations and Displacements. 
The pancreas may be entirely absent in acephalous and double monsters. The 
pancreatic duct may be double; it may open into the duodenum at some distance from 
the biliary duct, or into the stomach. The head of the pancreas may be unduly 
developed and sometimes even completely separated from the rest of the organ, 
opening into the duodenum with a duct of its own. The gland may be variously lobed 
and distorted. Occasionally there is a small accessory pancreas situated beneath the 
serosa of the duodenum or stomach.7 
The pancreas is so firmly bound down that its position is not often changed. 
Sometimes, however, it is found pressed downward by tight lacing, displaced by 
aneurysms, or contained in umbilical and diaphragmatic herniae. 
ATROPHY, DEGENERATION, AND NECROSIS. 
Atrophy of the pancreas may occur in old age and as a result of pres- 
sure from tumors or other adjacent structures, and may be associated with 
fatty infiltration. It occurs in a certain proportion of cases of diabetes 
mellitus. 
1 Volkmann, Deutsch. Ztschr. f. Chir., 1895, xli, 61; Hansemann, Ztschr. f. Krebsforsch., 1910, ix, 
379, Trendelenburg and Heineke, Deutsche Chirurgie, Lief. 33. Stuttgart, 1886-1913. 
2 For a critical study of the mixed tumors of the salivary gland, see Wood, F. C., Ann. Surg., 1904, 
xxxix, 57 (bibl.); Wilson and Willis, Am. Jour. Med. Sc., 1912, cxliii, 654; Lowenstein, Frankfurt., 
Ztschr. f. Path., 1910, iv, 187. 
3 Krompecher, Der Basalzellenkrebs, Jena, 1903, p. 204; and Zieglers Beitr., 1908, liv, 51. 
4 For an admirable series of studies along this line, see Huntington, Schulte, and Car malt, Anatomy 
and Development of the Salivary Glands in the Mammalia, Studies in Cancer and Allied Subjects, 
George Crocker Special Research Fund, vol. iv, New York, 1913. 
6 v. Haberer, Arch. f. klin. Chir. (Langenbeck), 1910, xciii, 817 (bibl.). For a discussion of angioma 
with particular reference to tumors of the parotid in children, see, Grulee, Surg., Gynec., and Obst., 
1906, ii, 31 (bibl.). 
6 Prudden, Am. Jour. Med. Sc., 1883, Ixxxv, 438. 
7 For obliteration of pancreas and ducts with congenital obliteration of gall-ducts, see Hess, A., 
Arch. Int. Med., 1912, x, 37. 802 
THE DIGESTIVE SYSTEM 
Autodigestion of portions of the pancreas, intra vitam, has been 
described, and may, it is believed, lead to localized formation of fibrous 
tissue in the organ.1 
Albuminous Degeneration may occur in acute infectious diseases. 
The organ may be red, swollen, and edematous. The most marked 
Fig. 509.-Fatty Infiltration with Atrophy of the Pancreas. 
minute lesions are swelling and albuminous degeneration of the gland 
epithelium with hyperemia and interstitial edema. 
Fatty Degeneration may follow albuminous degeneration and is most 
common in poisoning, especially by phosphorus. 
Fatty Infiltration, which should be distinguished from fatty degenera- 
tion, consists in the accumulation of fat in the interstitial tissue of the 
i Chiari, H., Prag. med. Wchnschi., 1900, xxv, 29. THE DIGESTIVE SYSTEM 
803 
gland (Fig. 509). This when excessive may be associated with almost 
complete atrophy of the gland structures. Under these conditions the 
outline of the organ may be preserved, the fat being inclosed by the 
capsule. It occurs in obesity and in atrophy and fibrosis of the gland. 
Amyloid Degeneration.-This usually occurs in connection with 
similar degeneration in other organs, and is confined to the walls of the 
blood-vessels and the interstitial tissue. 
Fig. 510.-Fat Necrosis in the Mesentery. 
From a case of acute hemorrhagic pancreatitis. 
Hyaline Degeneration, involving and limited to the islands of Langer- 
hans, has been described by Opie and others in diabetes without other 
marked lesions of the pancreas.1 
Fat Necrosis.-This is a peculiar lesion of the fat tissue, most fre- 
quently seen about the pancreas or between its lobules, but sometimes in 
fat tissue in other parts of the body. White or yellowish nodules (Fig. 
i Opie, E. L., Jour. Exper. Med., 1901, v, 527; also Disease of the Pancreas, 2d ed., Philadelphia, 
1910, on structure, function, and lesions of the pancreas with bibl. For development of the islands of 
Langerhans in human embryo, see Pearce, R. M., Am. Jour. Anat., 1903, ii, 445. For morphology 
and physiology of these structures, see Dewitt, L., Jour. Exper. Med., 1906, viii, 193. For hypertrophy 
of the islands of Langerhans, see MacCallum, W. G., Am. Jour. Med. Sc., 1907, cxxxiii, 432, and Cecil, 
R. L., Jour. Exper. Med., 1911, xiv, 500. For adenoma of islands of Langerhans, see Cecil, R. L., 
Jour. Exper. Med., 1911, xiii, 595; and LeComte, R., Jour. Med. Research, 1913, N. S. xxiv, 251. 804 
THE DIGESTIVE SYSTEM 
510), varying from the size of a pin's head to that of a pea or larger, are 
seen embedded in the fat, the central portion being often soft and grumous. 
They are sometimes calcified and sometimes surrounded by a connective- 
tissue capsule. Microscopical examination shows necrosis, degeneration, 
and disintegration of the fat tissue (Fig. 511). 
Fat necrosis is usually associated with lesions of the pancreas-hem- 
orrhagic infiltration, necrosis, gangrene, and acute and chronic inflam- 
matory processes. The lesion has been shown to be due to some ferment 
in the pancreatic secretion which splits the fat molecule into fatty acids, 
which may crystallize, and soluble substances; calcification is of later 
occurrence. Experimental studies have shown that fat necrosis can be 
induced by such operative procedures as direct the pancreatic secretion 
into fat tissue either immediately about the pancreas or elsewhere.1 
Fig. 511.-Fat Necrosis in the Pancreas. 
Hemorrhage into the substance of the pancreas may occur as the 
result of injury; in the hemorrhagic diathesis; in connection with valvu- 
lar diseases of the heart or interference with the portal circulation; or 
in connection with extensive fatty degeneration, or with local necrosis, 
or with fat necrosis of the organ. Such hemorrhages may be minute or 
extensive. Several cases of sudden death are recorded in which the only 
discoverable lesion was an extensive hemorrhage into the substance of 
the gland and the tissue about it. The hemorrhage may be moderate 
HEMORRHAGE. 
1 For studies in fat necrosis with bibl., see Opie, Disease of the Pancreas, 2d ed., Philadelphia, 1910, 
also Wells, H. G., Jour. Med. Research, 1903, N. S. iv, 70. THE DIGESTIVE SYSTEM 
805 
and limited to the pancreas, or it may extend into the subperitoneal 
tissue for a considerable distance. 
Hemorrhage of the pancreas may be associated with acute inflamma- 
tory changes and with more or less extensive gangrene of the organ.1 
INFLAMMATION. (Pancreatitis.) 
Hemorrhagic Pancreatitis.-In this form of disease hemorrhage similar 
to that above described is associated with suppurative inflammation or 
gangrene or both. The gangrenous pancreas may be more or less encap- 
sulated; it may be surrounded by pus. Hemorrhagic pancreatitis is 
often associ ated with fat necrosis. 
The conditions leading to pancreatic hemorrhage and hemorrhagic 
pancreatitis are not yet fully clear, but in some cases at least the presence 
of intestinal juice or of bile and bacteria in the pancreatic duct is of 
importance. The frequent association of gall-stones in the ampulla with 
hemorrhagic pancreatitis is significant,2 the obstruction by the stone 
leading to a regurgitation of bile up either the main pancreatic duct or 
one of the accessory ducts. 
Suppurative Pancreatitis is not very common, and may be primary or 
due to the extension of a suppurative inflammation from adjacent or 
distant parts of the body. There may be a diffuse infiltration of the 
organ with pus cells or larger and smaller abscesses. The abscesses may 
open into the gastrointestinal canal or into the peritoneal cavity. The 
causes of primary suppurative pancreatitis are often obscure. It may 
accompany fat necrosis and hemorrhage and gangrene of the pancreas. 
It is probably usually due to bacterial invasion through the duct. 
Various forms of bacteria have been found in the necrotic, hemor- 
rhagic, and inflammatory lesions of the pancreas, but in most cases the 
significance of their presence is not clear, since necrotic and hemorrhagic 
foci may afford regions favorable to the lodgment and proliferation of 
microorganisms which are secondary invaders and whose lesions, if such 
be induced,- are complicating and not primary.3 
Chronic Interstitial Pancreatitis.-This lesion consists in an increase of 
interstitial connective tissue, which may be general or confined to some 
particular portion of the gland. The new-formed tissue may be inter- 
lobular or interacinar in distribution. 
The organ is sometimes enlarged, sometimes smaller than normal. It 
is usually dense and hard; secondary atrophy of the parenchyma regu- 
larly occurs. It may be associated with chronic inflammatory processes 
in the vicinity of the organ, and obstruction of the pancreatic duct. It 
iFor a study of hemorrhagic necrosis of the pancreas, see Opie and Meakins, Jour. Exper. Med., 
1909, xi, 561 (bibl.). 
2 For a study of the relationships between cholelithiasis and diseases of the pancreas, see Opie, Dis- 
ease of the Pancreas, 2d ed., Philadelphia, 1910. For a study of experimental pancreatitis, see Flexner, 
S., Univ. Med. Mag., 1901, xiii, 780; and Jour. Exper. Med., 1906, viii, 167; also Flexner and Pearce, 
Tr. Assn. Am. Phys., 1901, xvi, 348; also Opie, loc. cit. 
3 For a detailed consideration of acute hemorrhage, gangrene, and fat necrosis of the pancreas, with 
bibl., consult Fitz, R. H., Tr. New York Path. Soc., 1889, p. 3. For later bibl. see Warthin, Philadelphia 
Med. Jour., 1898, ii, 1067; Eve, Brit. Med. Jour., 1915, i, 7; and Opie, E. L., Diseases of the Pancreas, 
2d ed., Philadelphia, 1910. 806 
THE DIGESTIVE SYSTEM 
may accompany cirrhosis of the liver.1 It regularly follows acute hem- 
orrhagic pancreatitis, if the patient survive.2 
Tuberculous Inflammation.-Larger and smaller tubercles and tuber- 
culous cheesy nodules are occasionally found in the pancreas in con- 
nection with acute general miliary tuberculosis or with tuberculous 
inflammation in some other organ, particularly with that of adjacent 
lymph-nodes, the lungs, and the intestine. 
Syphilitic Inflammation.-Chronic interstitial pancreatitis is frequently 
found in congenital syphilis of the new-born. The fibrous tissue is 
increased with atrophy of gland parenchyma, but the islands of Langer- 
hans persist.3 It is not definitely established whether or not a similar 
lesion may be caused by acquired syphilis. Gummata are very rare in 
the pancreas, but have been described in congenital syphilis in very 
young children. 
Benign tumors of the pancreas are extraordinarily rare, and only a 
few have been described; these include adenoma,5 which sometimes 
originates in the islands of Langerhans, fibroadenoma,6 and fibroma.7 
Lipoma, myxoma, and chondroma have been found.8 
The most common neoplasm of the pancreas is carcinoma,9 which 
makes up about 0.5 per cent, of all carcinomata. In two thirds of the 
cases the growth originates in the head of the gland, and most often from 
the ducts. 
Sarcoma of the pancreas is a very rare tumor;10 like carcinoma it most 
often involves the head of the gland. The growth may be of the small 
round-cell, spindle-cell, or polymorphous-cell variety. As with carcin- 
oma,11 even though large areas of the pancreas are involved many of the 
islands of Langerhans may be spared. The observation that even in 
wide-spread involvement of the gland there may be no diabetes12 suggests 
that the preservation of the islands of Langerhans may perhaps have 
something to do with the absence of sugar in the urine. Sarcoma may 
metastasize widely or not at all. 
TUMORS.4 
1 See reference to Lando, Ztschr. f. Heilk., Abth. f. path. Anat., 1906, xxvii, 1. 
2 For experimental evidence of this, see Whipple, Chaffee, and Fisher, Bull. Johns Hopkins Hosp., 
1910, xxi, 339. 
3 For a study of the pancreas in congenital syphilis, see Pearce, Am. Med., 1903, vi, 1020. 
4 For a general discussion of tumors of the pancreas and bibl., see Heiberg, Die Krankheiten des 
Pankreas, Wiesbaden, 1914, p. 152 ff. 
6 Heiberg, Centralbl. f. allg. Path., 1911, xxii, 532 (bibl.); Cecil, Proc. New York Path. Soc., 1910, 
x, 135; ». Beust, Virchows Arch., 1915, ccxix, 191; Rollett, Frankfurt. Ztschr. f. Path., 1912, x, 268 
(bibl.); Helmholtz, Bull. Johns Hopkins Hosp., 1907, xviii, 185 (bibl.); Nicholls, Jour. Med. Research, 
1902, N. S. iii, 385 (bibl.); Koch, Virchows Arch., 1914, ccxvi, 25. 
6 Biondi, cited by Heiberg, Die Krankheiten des Pankreas, p. 179. , 
7 Kdrte, Deutsch, med. Wchnschr., 1909, xxxv, 2153. 
8 Kaufmann, Lehrbuch d. spez. Path., Berlin, 1911, i, 651. 
' Heiberg, Centralbl. f. allg. Path., 1911, xxii, 233; Baldwin, Philadelphia Med. Jour., 1900, vi, 
1195 (bibl.); Leriche, Lyon chir., 1910, iv, 261 (French bibl.); Arch. f. klin. Chir., 1910, xcii, 1048 
(French bibl.). 
10 Kakeis, Am. Jour. Med. Sc., 1902, cxxiii, 471 (bibl.); Schirokogoroff, Virchows Arch., 1908, cxciii, 
395 (bibl.); Haldsz, Wien. klin. Wchnschr., 1908, xxi, 1807 (bibl.); Constantini, Tumori, 1911-12, i, 
735 (bibl.); Boyd, Jour. Am. Med. Assn., 1901, xxxvi, 1461 (bibl.). 
11 Herxheimer, Verhandl. d. deutsch. path. Gesellsch., 1904, vii, 215. 
12 Schirokogoroff, Virchows Arch., 1908, cxciii, 395. THE DIGESTIVE SYSTEM 
807 
Cysts of the pancreas,1 which are rather uncommon, are usually 
divided into three classes: 1. Retention cysts, due to obstruction of the 
duct of Wirsung from within by a concretion or from without by gall- 
stones, neoplasms, etc., may involve the entire passage in a uniform dila- 
tation. Or the smaller tributary ducts alone may be dilated, perhaps 
from the presence of chronic fibrotic changes in the organ, so as to form 
a number of small cysts. The wall of a retention cyst is fibrous and may 
or may not have an epithelial layer. The contents may exhibit any or 
all of the pancreatic ferments or none of them. 
2. Pseudocysts (apoplectic cysts').-These are the result of trauma,2 or 
of acute hemorrhagic pancreatitis. They project from the surface of the 
gland (peripancreatic) or, less commonly, are situated within its substance 
(endopancreatic). As in the preceding variety, the wall is fibrous and 
may or may not have an epithelial lining. The contents are often blood 
stained and usually lacking in ferments. 
3. Proliferative Cysts.-These include such lesions as cystadenoma,3 
cystoma, either multiple or papilliferous, cystic carcinoma, etc. Their 
contents may be hemorrhagic and may exhibit any or all of the pancreatic 
ferments. 
To these three varieties may be added echinococcus cysts.4 
Concretions of carbonate and phosphate of lime are frequently found 
in the pancreatic ducts. They are usually multiple, small, whitish, 
smooth, or rough and of irregular shape. Sometimes, however, they 
reach a diameter of more than an inch. They consist chiefly of calcium 
phosphate and carbonate. Besides these free concretions the walls of 
the ducts are sometimes encrusted with salts of lime. Such concretions 
may produce dilatation of the pancreatic ducts and large cysts, or more 
rarely abscesses. 
Foreign Bodies.-Gall-stones sometimes find their way into the 
pancreatic duct. Ascarides have been found in the ducts in a consider- 
able number of cases. 
1 Willis and Budd, Surg., Gynec., and Obst., 1915, xx, 688 (bibl.); Heiberg, Die Krankheiten des 
Pankreas, Wiesbaden, 1914, p. 130. 
1 Graf, Munchen, med. Wchnschr., 1910, Ivii, 2529 (bibl.). 
* Roman, Virchows Arch., 1912, ccix, 234 (bibl.). 
4 Hanser, Beitr. z. klin. Chir. (Bruns), 1912, Ixxvii, 360 (bibl.). CHAPTER VIII. 
THE LIVER. 
Congenital malformations of the liver are not common and are of little practical 
importance. The organ may be entirely wanting; it may be very small;1 the lobes 
may be diminished or increased in number; its form may be altered, so that it is 
rounded, flattened, triangular, or quadrangular. The gall-bladder or gall-ducts may 
be absent; the ductus choledochus may be double, both ducts emptying into the duo- 
denum, or one emptying into the duodenum, the other into the stomach. The single 
ductus choledochus may also empty into the stomach. Owing to abnormal openings 
in the diaphragm or the abdominal parietes, the liver may suffer displacement upward 
or forward. In congenital transposition of the viscera the liver is found on the left 
side, the stomach and spleen on the right side. 
Small, isolated bodies, having the same structure as the liver, have been a few 
times found in the suspensory ligament, on the surface of the gall-bladder, and in the 
lesser omentum. 
Malformations. 
Acquired Changes in Size, Form, and Position. 
As a result of tight lacing very marked changes are sometimes produced in the 
shape of the liver. By the narrowing of the base of the thorax the organ is compressed 
from side to side, and its convex surface is pressed against the ribs. In consequence 
of this there are found ridges and furrows on its convex surface. In consequence also 
of the circular constriction, a part of the right, and usually a part of the left lobe, be- 
come separated by a depression (Fig. 17). Over this depressed and thinned portion 
of the liver the capsule is thick and opaque. In extreme cases the depression and 
thinning reach such an extent that there is only a loose, ligamentous connection 
between the separated portion and the liver. 
A series of depressions are sometimes found on the upper surface of the right lobe 
of the liver, running from front to back, apparently caused by folds of the organ. 
These folds are most often found in patients who have suffered ±...... severe dyspnea 
before death; but in some instances they may be congenital.2 
Structural alterations in the liver may induce changes in its size and shape. It 
may be increased in size by tumors, hydatid cysts, abscesses, fatty and amyloid degen- 
eration, and congestion, and sometimes by cirrhosis, etc. 
It may be diminished in size by atrophy, by cirrhosis, by acute parenchymatous 
degeneration, etc. 
Changes in the position of the liver are produced by alterations in its size, by pres- 
sure downward from the thoracic cavity and upward from the abdomen, by the con- 
striction of tight lacing, by tumors or circumscribed serous exudation between the 
liver and diaphragm, by curvature of the spine. 
The liver is readily turned, by pressure from above or below, on its transverse axis. 
The transverse colon may be fixed above the liver so as to push it backward, down- 
ward, and to the right. There are a few cases recorded of dislocated and movable 
livers. These occurred in women who had borne children and whose abdominal walls 
were lax. With ascites it is not uncommon to find the liver quite movable.3 
WOUNDS, RUPTURE, AND HEMORRHAGE. 
Wounds of the liver may induce hemorrhage, which, if life continue, 
is followed by inflammation. Serious wounds of the liver are usually 
1 ZypKin, Virchows Arch., 1908, cxciv, 63. 
2 Chiari, Verhandl. d. deutsch. path. Gesellsch., 1899, ii, 107. 
3 For displacements of the liver, see Graham, Tr. Assn. Am. Phys., 1895, x, 258 (bibl.). 
808 THE LIVER 
809 
fatal, but recovery may occur even after the destruction of a considerable 
portion of the organ. 
Rupture of the liver may be produced by severe direct contusions or 
by falls. It may be produced in children by artificial delivery. The 
rupture usually involves both the capsule and a more or less consider- 
able portion of the liver tissue. It is commonly accompanied by large 
hemorrhage, and is usually fatal. 
Hemorrhage.-Extravasations of blood in the substance of the liver, 
or more frequently beneath the capsule, may be found in new-born chil- 
dren after tedious or forcible labors. In adults, hemorrhage, except as 
the result of injury, is uncommon. Extravasations of blood are some- 
times seen in malignant malarial fevers, especially in tropical climates; 
in scurvy, purpura, and phosphorus poisoning; and bleeding may occur 
in and about soft tumors, abscesses, and echinococcus cysts. It may 
also occur as a result of thrombosis of the hepatic vein. 
ANEMIA AND HYPEREMIA. 
Anemia of the liver may be general or partial. It may be due to 
general anemia or to local disturbances of the circulation, such as swell- 
Fig. 512.-Chronic Congestion of the Liver-"Nutmeg Liver." 
The liver cells are completely atrophied except in the peripheries of the lobules. The central 
portions of the lobules, which in the fresh organ are darker than the periphery, are lighter in the pre- 
served specimen from which this section was cut, because the hemoglobin has been dissolved out of 
the red blood-cells. 
ing of the cells in parenchymatous or other degeneration, pressure of 
tumors, etc. The organ appears pale, often of slightly yellowish or 
brownish color. It may be harder than usual, and smaller. 
Hyperemia of the liver is either an active or a passive process. In 
health the amount of blood in the liver varies at different times, being 
regularly increased during the process of digestion. When the digestive 810 
THE LIVER 
process is unduly influenced by the ingestion of spirits, spices, etc., 
the hyperemia assumes abnormal proportions, and when this is often 
repeated it may lead to structural changes in the organ. Severe contu- 
sions over the region of the liver sometimes cause a hyperemia, which 
may result in suppurative or in productive inflammation. In hot 
climates and in malarious districts active and chronic hyperemia of the 
liver are frequent and often incite structural lesions. In scurvy, also, 
the liver is sometimes congested. Cessation and suppression of the 
menses and of hemorrhoidal bleeding may be followed by hyperemia of 
the liver. In all these varieties of active congestion the liver is enlarged, 
and of a deep red color, and blood flows freely from its cut surface. 
Fig. 513.-Chronic Congestion of the Liver. 
Showing a single lobule. The capillaries about the central vein are widely distended with blood- 
decolorized; the liver cells on the borders nearest the dilated capillaries show various phases of pressure 
atrophy. 
Passive congestion of the liver is produced by an obstruction to the 
current of blood in the hepatic veins. Valvular diseases of the heart, 
emphysema and fibrous induration of the lungs, large pleuritic effusions, 
intrathoracic tumors, angular curvature of the spine, aortic aneurysms 
pressing on the vena cava, and constrictions of the vena cava and of the 
hepatic veins, may all lead to a chronic hyperemia of the liver. In such 
cases, since the congestion affects principally the hepatic veins, we find 
the center of each acinus congested and red, while its periphery is lighter 
in color. This gives to the liver a mottled or nutmeg appearance (nut- 
meg liver) (Fig. 512). The liver cells in the center of each acinus are 
frequently colored by little granules of red or black pigment, and the 
cells at the periphery become fatty, so that the nutmeg appearance is still 
more pronounced. A liver in this condition is usually of medium size, 
but may be smaller or larger than normal. 
When the congestion is long continued the veins at the center of each 
acinus may become permanently dilated, and the hepatic cells in their 
meshes become atrophied (Fig. 513 and 514), so that the center of each THE LIVER 
811 
acinus consists only of dilated capillaries or of these and new connective 
tissue; or the dilatation and atrophy of the liver cells may, in circum- 
scribed portions of the organ, involve the entire acinus. Whether the 
atrophy of the cells is due entirely to pressure or possibly in part to lack 
of nutrition owing to the sluggish blood-current in the vessels, is not yet 
clear. In long-continued congestion the liver is usually small and hard- 
cyanotic induration-and may be rough or uneven on the surface; but it 
is sometimes enlarged. The peculiar nutmeg appearance may be very 
well marked, or it may not be evident, the organ being of a dark-red 
color.1 
Fig. 514.-Chronic Congestion of the Liver. 
Showing atrophy of the liver cells. 
LESIONS OF THE HEPATIC VESSELS. 
The hepatic artery is in rare cases the seat of aneurysms which may 
attain a large size. Such aneurysms may displace the liver tissue, may 
compress the bile ducts so as to cause jaundice, and may rupture into 
the stomach or abdomen. 
Owing to its abundant anastomoses, emboli of the branches of the 
hepatic artery usually induce no marked lesions, but they sometimes 
result in single or multiple anemic infarcts.2 
The Hepatic Artery. 
The Portal Vein. 
Thrombosis, Embolism, and Inflammation.-Thrombosis of the 
branches of the portal vein may be produced by weakening of the circu- 
lation from general debility-marantic thrombi; by pressure on the vessel 
from without, as in cirrhosis, chronic peritonitis, tumors, gall-stones, 
dilatation of the bile ducts, etc.; by injury; by the presence of foreign 
materials within the vessel; and as a result of inflammation, especially 
1 For another view of chronic passive congestion of the liver, see Mallory, F. B., Jour. Med. Research, 
1911, N. S. xix, 455. 
2 For a critical summary of recorded cases of anemic infarcts of the liver, see Baldwin, F. A., Jour. 
Med. Research, 1902, N. S. iii, 431. For a study of experimental closure of the hepatic artery and the 
gall-ducts, see Tischner, R., Virchows Arch., 1904, clxxv, 90. 812 
THE LIVER 
syphilitic, of its wall-phlebitis-or of embolus. The thrombus may 
form in the vessels in the liver or be propagated into them from without. 
It may partially or entirely occlude them. The clot may become organ- 
ized as a result of endophlebitis, and a permanent occlusion of the vessel 
ensue. If the clot be a simple, non-irritating one, leading to occlusion, 
the consequences are usually more marked in the abdominal viscera 
than in the liver itself. The branches of the hepatic artery usually form 
sufficient anastomoses to nourish the liver tissue and prevent its necrosis 
even in complete occlusion of the portal vein; and if occlusion occur 
slowly, the organ may continue to perform its functions, though the pro- 
duction of bile is diminished, the amount formed by the liver depending 
directly upon the blood flow through the organ.1 But this obliterative 
form of thrombosis is usually attended by ascites, enlargement of the 
spleen, and dilatation* of the abdominal veins, and sometimes by hemor- 
rhage from the stomach and intestines. 
In another class of cases, in addition to the local and mechanical 
effects, the thrombus may be infectious; then there are necrotic changes 
and suppurative inflammation in the walls of the vessels or in the liver 
tissue about them. The thrombi are apt to soften and break down, and 
the fragments may be disseminated through the smaller trunks of the 
portal vein. In this way, by the distribution through the smaller vessels 
of a disintegrated thrombus from a large trunk, or by the introduction 
into the branches of the portal vein of purulent or septic material from 
some of the abdominal viscera or from wounds, multiple foci of purulent 
inflammation in the portal vein, and multiple abscesses involving the 
liver tissue, may be produced. In many cases the presence of bacteria 
may be detected in the inflammatory foci. 
These soft thrombi of the portal vein and the accompanying pyle- 
phlebitis and abscess are induced in a variety of ways. Ulceration of 
the appendix, intestines and stomach, abscesses of the spleen, inflam- 
mation of the mesentery and mesenteric glands, inflammation and ulcera- 
tion of the bile-ducts from gall-stones, inflammation of the umbilical 
vein in infants, may all induce local thrombi, which may be propagated 
to the portal vein or may give rise to purulent or septic emboli. Two 
cases are recorded in which a fish-bone in the portal vein induced sup- 
purative inflammation in that vessel.2 
In infants inflammation of the umbilical vein may induce not only 
inflammation of the portal vein and abscesses in the liver, but multiple 
abscesses in various parts of the body, and acute peritonitis may follow. 
Infarcts.-Infarcts of the liver seldom form, owing to the abundant 
anastomosis of its blood-vessels. But under exceptional conditions, 
as we have seen, anemic infarcts may occur as the result of the closure 
of the hepatic artery or of small branches of the portal vein. There 
may then be a larger or smaller mass of dead liver tissue surrounded by 
a zone of congestive or inflammatory reaction (Fig. 515). Occasionally 
also, owing usually to the occlusion of branches of the portal vein, lim- 
1 Voegtlin, C., and Bernheim, B. M., Jour. Pharmacol, and Exper. Therap., 1910, ii, 455. 
2 For a study of primary portal thrombosis, see Lewis and Rosenow, Arch. Int. Med., 1909, iii, 232 
(bibl.). THE LIVER 
813 
ited areas of liver tissue may suffer disturbance of the circulation leading 
to atrophy of the liver cells and the formation of fibrous tissue. This 
condition has been called hemorrhagic atrophic infarction. It is appar- 
ently rather localized atrophy of the liver than true infarction. 
It is probable that the rare occurrence of hepatic infarcts is closely 
The infarcts, multiple and large, are due to extensive thrombosis of branches of the portal vein. 
Fig. 515.-Inf auction of the Liver. 
dependent in most instances upon the development of local thrombosis or 
embolism, which commonly do not lead to infarction, together with gen- 
eral disturbances of the circulation which prevent the re-establishment 
of equilibrium in the hepatic vessels.1 
1 For a study of liver infarcts, see summary by Baldwin, Jour. Med. Research, 1902, N. S. iii, 431 
also Steinhaus, Deutsch. Arch. f. klin. Med., 1904, Ixxx, 364. 814 
THE LIVER 
Rupture of the Portal Vein, with fatty degeneration of its walls, has 
occurred in a few instances. 
Chronic Endophlebitis, with atheroma and calcification, may occur in 
the walls of the portal vein, giving rise to thrombosis. 
Dilatation of the Portal Vein, either uniform or varicose, may occur in 
various parts of the vessel or its branches. It may be caused by destruc- 
tion of the liver capillaries in cirrhosis, or by occlusion of the vein by 
thrombi, tumors, etc. 
The Hepatic Veins. 
The hepatic veins present lesions similar to those of the portal vein 
and its branches, but they are much less frequent. The veins may be 
dilated by obstruction to the passage of venous blood into the heart. 
They may be the seat of acute and chronic inflammation, and soft thrombi 
and suppurative inflammation may be produced by abscesses in the 
liver. Rarely there is a localized obliterating phlebitis in the hepatic 
vein followed by chronic congestion, interstitial inflammation, and 
thrombosis.1 When the obstruction of the hepatic veins is rapid, the 
liver enlarges slowly and is very tender. Ascites, cyanosis, and in some 
cases an acidosis have been noted.2 
ATROPHY OF THE LIVER. 
Atrophy of the liver may affect the entire organ or be confined to 
some part of it. General atrophy may occur in old age as a senile 
change, or may be induced by starvation or chronic exhausting diseases. 
The organ is diminished in size and is usually firm; and the acini appear 
smaller than usual. Microscopically, the change is seen to be due to a 
diminution in size of the liver cells, and hand-in-hand with this there 
occurs frequently an accumulation of pigment granules within the atro- 
phied cells. The cells may entirely disappear over circumscribed areas, 
leaving only shrivelled blood-vessels and connective tissue; or, in some 
cases, there may be an increase of connective tissue associated with 
the atrophy of the cells. When much pigment is formed in the cells the 
lesion is often called pigment atrophy. 
Essentially the same changes may occur in circumscribed portions of 
the liver, as the result of pressure from new connective tissue in cirrhosis, 
from tumors, hydatids, amyloid degeneration, gall-stones, etc. In 
atrophy from pressure the liver cells are apt to become very much flat- 
tened and squeezed together as they diminish in size. 
Necroses in the liver may occur under various conditions and in 
many forms.3 
Minute areas of necrosis of liver cells, focal necrosis (page 232), are 
NECROSIS. 
1 Consult, for obliterating phlebitis of the main trunks of the hepatic vein as a cause of death, 
Chiari, H., Zieglers Beitr., 1899, xxvi, 1 (bibl.). 
iThompson, T., and Turnbull, H. M., Quart. Jour. Med., 1912, v, 277; Jacobson, V. C., and Good- 
pasture, E. W., Arch. Int. Med., 1918, xxii, 86. 
8 For a study of necroses of the liver, see Mallory, F. B., Jour. Med. Research, 1901, N. S. i, 264. THE LIVER 
815 
found irregularly scattered through the organ in various acute infections, 
and may be artificially induced in animals by the injection of bacteria, 
diphtheria toxin, or vegetable toxins such as ricin and abrin.1 
More extensive necroses of liver cells, especially about the central 
vein, frequently occur, usually in acute infectious diseases-diphtheria, 
endocarditis, lobar pneumonia, peritonitis, cerebrospinal meningitis.2 
This has been called central necrosis. 
Necrosis in the liver may, however, be limited to the peripheral 
zone of the lobule, peripheral necrosis. This condition has been described 
in a few instances, especially in connection with eclampsia. 
Finally, the necrosis of parenchyma cells in the liver may be limited 
to the middle zone of the lobule, " midzonal necrosis." 
In most of these forms of so-called " zonal necrosis"3 bacterial toxins 
or infections appear to be the chief determining factor. 
Many of the necroses of the liver are doubtless due to the action of 
bacteria or bacterial toxins. The focal forms may be determined by the 
local growth of bacteria, by the occlusion of capillaries by swollen and 
proliferated endothelial cells, as in typhoid fever, or by fibrinous or 
agglutinative thrombi. 
The reason for the topography of the lesion in the various forms of 
" zonal necrosis," and the relation of these necroses to certain phases of 
eclampsia, chloroform poisoning, and acute yellow atrophy of the liver 
have not yet been definitely determined. 
It has been shown4 that by the injection into animals of hem agglutinative sub- 
stances contained in various cytolytic immune sera, agglutinative thrombi may form 
in the capillaries and smaller branches of the portal vein, leading to necrosis of the 
liver. The position and extent of these areas of hyaline necrosis vary with the amount 
of the serum administered. They are mostly superficial, and may be small and focal 
or involve nearly all the parenchyma of the lobule, except that in the vicinity of the 
portal spaces. 
It has been shown,5 also, that similar lesions may follow the injection of hemag- 
glutinins of bacterial origin. In these areas of hyaline necrosis the liver cells stain 
poorly with eosin; the nuclei do not stain and may be seen only as faint outlines, or 
may be shrunken. 
The occurrence has been described of multiple circumscribed necrotic and atrophic 
foci in the liver not associated with local infective processes and without marks of 
inflammation or connective-tissue hyperplasia. These are associated with stasis in 
the blood and bile capillaries, and local portal sclerosis; and the areas contain bile 
pigment. The lesion is most marked about the central vein, and may vary in extent. 
It is associated with jaundice. The condition is diffuse in the liver, often running in 
streaks which merge into normal liver tissue. Thus the liver becomes tough, pale, 
and bile-stained, with obscured markings. The liver cells in the affected areas appar- 
ently lose their cytoplasm, leaving a well-preserved outline, and may contain fat. 
For this lesion the designation multiple non-inflammatory necrosis of the liver with 
jaundice has been suggested.6 
1 Flexner, S., Johns Hopkins Hosp. Rep., 1897, vi, 259; Mallory, F. B., Jour. Exper. Med., 1898, iii 
611. 
2 Mallory, F. B., Jour. Med. Research, 1901, N. S. j, 264. 
3 For a study of "zonal necroses" of the liver, see Opie, E. L., Jour. Med. Research, 1904, N. S. vii, 
147. 
4 Pearce, R. M., Jour. Med. Research, 1904, N. S. vii, 329; 1906, N. S. ix, 541. 
3 Pearce and Winne, Amer. Jour. Med. Sc., 1904, cxxviii, 669. 
3 Oertel, H., Jour. Med. Research, 1904, N. S. vii, 75; Jour. Exper. Med., 1906, vii, 103, and Berl, 
klin. Wchnschr., 1912, xlix, 2019. For a study of changes in necrotic cells in cytolysis in the liver and 
elsewhere, see Symmers, D., Jour. Exper. Med., 1907, ix, 64. 816 
THE LIVER 
Experimental work has shown1 that chloroform anesthesia in animals repeated on 
several successive days induces fatty degeneration or hyaline necrosis or both, of the 
liver cells in the central portion of the lobules. It has been found,2 also, that animals 
may recover from the chloroform liver necroses with complete restitution of the cells 
after two or three weeks. 
The acute degenerations of the liver occurring in eclampsia, in which condition 
chloroform is often administered, require careful scrutiny in view of the striking lesions 
of necrosis induced by chloroform alone. 
DEGENERATION. 
Albuminous Degeneration.-In the infectious diseases and in certain 
cases of acute anemia and phosphorus poisoning, the liver is swollen 
and, on section, of a dull yellowish gray color, looking as if it had been 
boiled. It contains less blood than usual, and the outlines of the lobules 
are indistinct. Microscopical examination shows the lesion to consist of 
a swelling of the liver cells and an accumulation in them of moderately 
refractile, finer and coarser albuminous granules. These granules may 
disappear and the cells return to their normal condition, or fatty degen- 
eration may follow. Fatty and parenchymatous degenerations are often 
associated. 
Acute Yellow Atrophy (Acute Parenchymatous Degeneration).-This 
rare condition is characterized anatomically by a rapid diminution in the 
size of the liver as the result of a granular and fatty degeneration, 
necrosis, and disintegration of the liver cells. It is frequently associated 
with the clinical condition called icterus gravis. The liver, sometimes 
within a few days, may be reduced to one-half its normal size. On open- 
ing the abdominal cavity the organ may be found lying, concealed by 
the diaphragm, close against the vertebral column. The amount of 
diminution and the general appearance of the affected organ depend to a 
considerable extent upon its previous condition-i.e., whether or not it 
was the seat of other lesions-as well as upon the duration of the process 
and the degree of degenerative change. In general, if the lesion is well 
marked, the liver is small, flabby-sometimes almost fluctuating-and 
the capsule wrinkled. On section the cut surface may show but little 
trace of lobular structure, but present an irregular mottling with 
gray, ochre-yellow, or red; sometimes one, sometimes another color 
preponderating. 
Microscopical examination shows varying degrees of degeneration and 
destruction of the liver cells. Most evidently in those parts which have 
a grayish appearance, the outlines of the cells are preserved and the proto- 
plasm is filled with larger and smaller granules. In the yellow portions 
the outlines of the liver cells may be preserved, and they may contain 
varying quantities of larger and smaller fat droplets and granules of 
yellow pigment. Or the cells may be necrotic or disintegrated, and in 
their place be irregular collections of fat droplets, hyaline material, pig- 
ment granules, red and yellow crystals, and detritus, only the connective 
1 Howland, J., and Richards, A. M., Jour. Exper. Med., 1909, xl, 344; Opie, E. L., ibid., 1910, xii, 367; 
Cragin, E. B., and Hull, E. T., Jour. Am. Med. Assn., 1911, Ivi, 5; and Fraser, A., Am. Jour. Med. Sc., 
1916, clii, 202. 
2 Whipple, G. H., and Sperry, J. A., Bull. Johns Hopkins Hosp., 1909, xx, 278. THE LIVER 
817 
tissue and blood-vessels of the original liver tissue remaining (Fig. 516). 
The red areas may show nearly complete absence of liver cells and cell 
detritus, and sometimes irregular rows of cells which are variously 
interpreted as being new-formed gall-ducts or proliferated liver cells, 
marking a reparative process which may be extensive.1 In these areas it 
appears to be, in part at least, the blood contained in the vessels which 
imparts the red color. Sometimes the interstitial tissue is infiltrated 
with small spheroidal cells resembling leucocytes. Crystals of leucin and 
tyrosin are sometimes found intermingled with the cell detritus. In 
some cases the liver is not diminished in size. In early stages it may 
even be larger than normal. 
These lesions of the liver are frequently associated with enlargement 
of the spleen and parenchymatous degeneration of the kidney and of the 
Fig. 516.-Acute Yellow Atrophy of the Liver. 
The liver cells in the periphery of the lobule are little changed; those toward the center are 
largely destroyed. 
heart muscle. Multiple hemorrhages may occur in the gastrointestinal 
canal, kidneys, bladder, and lungs. There is frequently marked jaundice. 
The condition above described as acute yellow atrophy of the liver 
sometimes occurs in persons previously apparently well, but may accom- 
pany infectious diseases-typhoid fever, diphtheria, puerperal infection, 
etc.-and may be seen in eclampsia and pernicious vomiting in preg- 
nancy. While the nature of the condition is not well understood it 
seems probable that the lesion is essentially a necrosis and degeneration 
resulting from toxic substances produced either in bacterial infection or 
through faulty cell metabolism and followed by more or less pronounced 
autolysis by the ferments resident in the liver cells. The fatal nature of 
1 For a study of regenerative changes in the liver after acute yellow atrophy, see MacCallum, W. G. 
Johns Hopkins Hosp. Rep., 1902, x, 375; also Pearce, R. M., Jour. Med. Research, 1906, N. S. x, 99. 
See, also, for repair of liver, Muir, R , Jour. Path, and Bacterio!., 1908, xii, 287; and Milne, L. S., Proc. 
N. Y. Path. Soc., 1909, ix, 90. 818 
THE LIVER 
the disease is probably dependent more upon the destruction of the liver 
cells than upon the exogenous inciting infection or toxemia. It is prob- 
ably erroneous to consider the lesions of the liver described under the 
name of acute yellow atrophy as marking a single disease process. 
As to the details of the pathogenesis of this condition, opinions differ, 
and the whole subject is in urgent need of more exact research. 
In the forms of this liver lesion which mark the toxemia of pregnancy, 
whether these be clinically manifested in eclampsia, pernicious vomiting 
of pregnancy, or other well marked abnormal conditions, there appears 
to be a disturbance of nitrogenous metabolism in the liver, associated 
with the characteristic rapid destruction of the parenchyma.1 Un- 
doubtedly, however, some of the chemical abnormalities described as 
characteristic may be, in part at least, due to the accompanying inanition.2 
It should be borne in mind, finally, that while acute yellow atrophy 
of the liver has been regarded as an especially fatal lesion, there is abun- 
dant clinical and morphological evidence that various grades of the lesion 
may occur and that recovery from many forms, with regeneration of liver 
tissue, is not uncommon.3 
Portion of the periphery of a lobule, showing many liver cells distended with a single large drop of 
fat, while between these are liver cells with small fat droplets and others flattened by pressure. In 
this section, hardened by alcohol, the fat has been dissolved, leaving clear spaces. 
Fig. 517.-Fatty Infiltration of Liver. 
Experimental Studies.-The results of the experimental production in animals of 
lesions comparable with those of acute yellow atrophy in man are very suggestive.4 
It has been found that after the relatively slight injury of the liver parenchyma in- 
duced by repeated doses of chloroform in dogs, the injection of Bacillus coli-not 
itself especially virulent for these animals-may be followed by changes in the liver 
which neither the chloroform (page 816) nor the bacteria alone can induce. For 
under these conditions it appears that the liver cells may be largely destroyed by 
1 For discussion and bibl., see W/uZe, Boston Med. and Surg. Jour., 1908, clviii, 729. 
2 Underhill, F. P., and Rand, R. F., Arch. Int. Med., 1910, v, 61. 
3 For forms of acute yellow atrophy in the toxemia of eclampsia and other disturbances of pregnancy, 
see Strauss, Am. Jour. Obst., 1906, liii, 145 (bibl.); Ewing, J., ibid., 1905, li, 145; and Proc. Path. Soc., 
Philadelphia, 1910, xiii, 65. For acute yellow atrophy in children, see Philips, J., Am. Jour. Med. Sc., 
1912, cxliii, 177 (bibl..); also Graham, E. A., Jour. Exper. Med., 1912, xv, 307. 
4 Opie, E. L., Jour. Exper. Med., 1910, xii, 367. THE LIVER 
819 
necrosis, the remainder being fatty, while evidence of reparative changes-new fibrous 
tissue and new-formed gall-ducts, such as are often seen in acute yellow atrophy in 
man-is strikingly shown. In view of these experiments attention has been called to 
the possibility that some of the lesions of the toxemia of pregnancy and acute yellow 
atrophy in man may in fact be due to the action of bacteria or their poisons on liver 
cells already vulnerable from metabolic or other forms of intoxication. 
Fatty Infiltration.-In the normal human liver there is usually a cer- 
tain amount of fat in the liver cells, and this amount varies considerably 
under different conditions. 
The gross appearance of pathological fatty livers varies a good deal, 
depending upon the amount and distribution of fat and its association 
with other changes. If the lesion is un- 
complicated and considerable, the organ 
is increased in size, the edges are rounded, 
the consistence is firm, the color yellow- 
ish, and the cut surface greasy. The 
lobules are enlarged and their outlines 
indistinct, and the blood content is 
diminished. The liver is increased in 
weight. The lesion may be uniform 
throughout the organ or it may occur 
in patches. In the latter case the liver 
has a mottled appearance, irregular yel- 
lowish patches alternating with the brownish red, unaffected portions. 
Fatty infiltration is often associated with chronic congestion (nutmeg 
Fig. 518.-Fatty Infiltration of 
Liver Cells. 
Fig. 519.-Fatty Degenebation of Liver Cells. 
liver), with cirrhosis, and with amyloid degeneration; the picture may 
then present considerable complexity. Fatty livers may be stained 
brown or greenish with bile pigment. 
Microscopically the liver cells are seen to contain larger and smaller 
droplets of fat (Fig. 517), and frequently large drops of fat occupy nearly 820 
THE LIVER 
the entire volume of the cell, so that the protoplasm may be visible only 
as a narrow, nucleated crescent at one side, or it may disappear alto- 
gether (Fig. 518). 
Fatty infiltration of the liver may occur as a result of excessive 
ingestion of oleaginous food; in chronic alcohol, phosphorus, and arsenic 
poisoning; in certain exhausting diseases accompanied by malnutrition, 
as in pulmonary phthisis, chronic dysentery, etc.; and under a variety 
of conditions which we do not understand. It is common in children, 
especially in acute infectious diseases.1 
Fatty Degeneration.-In this condition, which in many cases cannot 
be distinguished morphologically from fatty infiltration, the fat is 
believed to be formed by a transformation of the protoplasm of the liver 
cells (page 49). The fat droplets are, for the most part, very small and 
abundant (Fig. 519), though this is not constant. Fatty degeneration 
The capillaries are much enlarged and occluded by the amyloid material; the liver cells 
between them are atrophied. 
Fig. 520.-Amyloid Degenebation of Liver Capillaries. 
of the liver cells frequently follows, and is associated with, cloudy 
swelling under the varying conditions in which this occurs, or it may 
appear in profound anemia and in acute phosphorus and arsenic 
poisoning.2 
Amyloid Degeneration.-In the liver amyloid degeneration may be 
general or local; so extensive as to give the organ very characteristic 
appearances, or so slight as to be unrecognizable without the aid of the 
microscope. It may be associated with other lesions. When the change 
is extensive and general, the liver is enlarged, sometimes to more than 
twice its normal size; the edges are thickened and rounded; the surface 
1 See Freeman, R. G., Arch. Pediat., 1900, xvii, 81. 
2 For a study of localization of fat in the liver, see McCrae and Klotz, Jour. Exper. Med., 1910, xii, 746. THE LIVER 
821 
is smooth; the tissue tough, firm, inelastic, more or less translucent, and 
of a brownish yellow color. The lobular structure may be more or less 
indistinct, or it may become very evident by an associated fatty degen- 
eration of the peripheral or central cells of the lobules. The translu- 
cency and peculiar appearance of the tissue may be best seen by slicing 
off a thin section and holding it up to the light. When the lesion is less 
considerable the liver may be of the usual size, and may feel harder than 
normal, and here and there a translucent mottling may be evident, or 
the degeneration may be apparent only on the addition of staining 
agents. When, as is frequently the case, it is associated with cirrhosis, 
the liver may be small and nodular, and the appearance of the cut sur- 
face may vary, depending upon the character of the cirrhotic change and 
the presence or absence of fat. 
This degeneration usually commences in the walls of the intralobular 
blood-vessels, causing them to become thickened and translucent (Fig. 
520). Their lumen may be nearly or entirely occluded. The liver cells 
may be squeezed by the thickening of the vessels and may become 
partially or completely atrophied, or they may be fatty. In advanced 
stages larger and smaller areas of liver tissue may be almost completely 
converted into the dense, re- 
fractile substance in which 
here and there flattened liver 
cells may be seen. 
Amyloid degeneration of 
the liver is usually associated 
with a similar lesion of other 
organs. 
Glycogen Degeneration.- 
This may occur in the liver 
cells in diabetes. 
PIGMENTATION OF THE 
LIVER. 
Pigmentation of the liver 
cells, from bile and blood de- 
rivatives, is to a certain extent 
normal, but may be greatly 
increased as a result of atro- 
phy, of localized hemorrhage, 
and of obstructive jaundice. Hemosiderin is present in large quantities 
in the liver cells and sinusoidal endothelium in pernicious anemia.1 Pig- 
mentation of the liver may be marked in hemochromatosis, both hemo- 
siderin and hemofuscin being found (page 65).2 
As a result of severe malarial poisoning a variable amount of brown, 
black, or reddish pigment is often found in the blood. This is usually 
mostly taken up by the leucocytes and deposited in various parts of the 
Fig. 521.-Malarial Pigmentation of the Liver. 
The pigment is largely in the exfoliated endothelium 
within the capillaries. Pigmented malarial parasites 
may be seen in some of the cells. 
1 Rossie, Verhandl. d. deutsch. path. Gesellsch., 1906, x, 157. 
2 Rossie, Zieglers Beitr., 1907, xli, 181 (bibl.); Opie, E. L., Jour. Exper. Med., 1899, iv, 279 (bibl.). 822 
THE LIVER 
body, chiefly in the liver, spleen, and marrow of the bones. In the liver 
it is usually found inclosed in the endothelial cells1 free or in place in the 
blood-vessels (Fig. 521), but sometimes in the tissue between them. 
The liver cells frequently contain bile pigment, but usually are free from 
the melanotic pigment characteristic of this malarial condition. As the 
result of this accumulation of pigment the liver may have a dark reddish 
brown, an olive brown, or a black color. 
Pigment similar in character to that which occurs in the lungs from 
the inhalation of coal dust may be found in the connective tissue along 
the portal vessels. Inhaled pigment particles may pass the lungs and 
bronchial lymph-nodes, and be deposited in the liver as they are in the 
spleen and hepatic lymph-nodes. In argyria, the silver granules may be 
found in the walls of the interlobular veins. 
This lesion of the liver is rare; but it has been seen in eclampsia, 
chronic nephritis, and tuberculosis. The deposit of lime may be in the 
vicinity of the arteries or the veins.2 
CALCIFICATION. 
Acute Exudative Hepatitis (Purulent Hepatitis).-Purulent or suppura- 
tive inflammation of the liver may be the result of injury; it may be 
secondary to inflammation of the gall-ducts or of the branches of the 
portal vein. It may occur as the result of the presence of tumors and 
parasites, or from propagation of an inflammatory process from without, 
as in ulcer of the stomach with adhesions to the liver and secondary 
involvement of the latter. It is not infrequent as a sequence of suppura- 
tive appendicitis with pyelophlebitis of the portal vein, and is often 
directly due to the introduction of bacteria into the organ, through the 
blood-vessels or gall-ducts or otherwise. Purulent inflammation in the 
liver almost always results in abscess. 
Large abscesses of the liver may be traumatic, but are often due to 
unknown causes. They are not infrequently associated with dysentery, 
and may then be due to the conveyance of microorganisms, through the 
veins, or lymph-channels, or peritoneum, or gall-ducts, from the intestinal 
ulcers. Such abscesses may be due to the presence of the Amoeba coli. 
They occur most frequently in tropical climates-hence the name tropical 
abscess-but are not very uncommon in the temperate zone. They are 
usually single, but there may be several of them. They are sometimes 
so large as to occupy a large part of the lobe; and are most frequent in 
the right lobe, but may occur in any part of the organ. They tend to 
enlarge, and as they do so they approach the surface of the liver, where 
the contents of the abscess may be discharged into the peritoneal cavity. 
More frequently, however, as they approach the surface a localized 
adhesive peritonitis ensues, so that the liver becomes bound to adjacent 
INFLAMMATION. (Hepatitis.) 
1 For a study of the phagocytic powers of the endothelial cells of the blood-vessels of the liver, see 
Heinz, Arch. f. mikros. Anat., 1901, Iviii, 576. 
2 See Brill and Libman, Jour. Exper. Med., 1899, iv, 541; Rollet, H., Frankfurt. Ztschr. f. Path., 
1909, iii, 715; and Ceelen, PF., Virchows Arch., 1910, cci, 361. THE LIVER 
823 
parts, and thus the abscess may open into the pleural cavity, or, owing 
to a secondary pleurisy with adhesions, into the lung tissue. They may 
open into the pericardium; externally through the abdominal wall; into 
the stomach, duodenum, colon, or pelvis of the right kidney; or into the 
hepatic veins, portal vein, vena cava, or gall-bladder or gall-ducts. 
The early stages in the formation of large abscesses of the liver are 
but little known. It is probable, however, that in many cases they are 
the result of the confluence of smaller abscesses (Fig. 539). Their con- 
tents, usually bad-smelling, may be thick and yellow like ordinary pus, 
but more commonly are thin, reddish-brown, or greenish in color from 
admixture with the pus of blood, gall-pigment, and broken-down liver 
Fig. 522.-Small, Abscess in the Liver Containing Bacilli. 
tissue. Microscopical examination shows the contents to consist of fluid 
with pus cells, more or less degenerated blood, degenerated liver cells, 
fragments of blood-vessels, and pigment granules and crystals. The 
walls of the abscess are usually ragged, shreds of necrotic liver tissue 
hanging from the sides. Microscopical examination of the liver tissue 
near the abscess shows infiltration with pus, flattening of the liver cells 
from pressure, cloudy swelling, and necrosis of those lying along the 
cavity.1 
The amebic abscesses are usually free from bacteria, but are occasion- 
ally infected secondarily with organisms of the colon group. Other 
abscesses may contain the Bacillus coli communis, the Streptococcus 
pyogenes, or the Staphylococcus pyogenes. 
1 See for a study of tropical abscess of the liver Howard and Hoover, Am. Jour. Med. Sc., 1897, 
cxiv, 150, 263 (bibl.). 824 
THE LIVER 
Not infrequently, however, especially in old abscesses, examination 
both morphological and cultural fails to reveal the presence of micro- 
organisms. 
After the discharge of the contents of the abscess or without this, if 
it be not very large, granulation tissue may form in the wall of the cavity 
and a fibrous capsule be produced. The contents which persist become 
thickened and often calcareous, and in this condition may remain for a 
long time. Or the connective-tissue walls may approach one another 
and join, forming a fibrous cicatrix at the seat of the abscess. 
Small multiple metastatic abscesses are not infrequent in pyemia. In 
these abscesses we can readily study the various stages of formation. 
Suppurative processes in any part of the body-in the head, upper and 
lower extremities, etc.-may act as distributing centers for micro- 
a, New-formed connective tissue; b, dilated blood-vessels of the new tissue; c, gall-duct. 
Fig. 523.-Chronic Interstitial Hepatitis-Cirrhosis. 
organisms.1 Entering the circulation, the bacteria may pass the heart 
and pulmonary capillaries, with or without inducing lesions in the lungs, 
and, lodging in the vessels of the liver, induce circumscribed necrosis of 
the liver tissue (.Fig. 61, page 105) and suppurative inflammation. Under 
these conditions we may find on section of the liver larger and smaller 
yellowish or grayish spots, the larger of which may be soft and present 
the usual characters of abscesses. The smaller, which may not be larger 
than a pin's head, may present the usual consistence of liver tissue with 
the lobular structure still evident; others may be softer, more yellow, 
and surrounded by a zone of hyperemic liver tissue. Microscopical 
examination of the earlier stages often shows the blood-vessels filled with 
bacteria, scattered and in masses. Around these the liver cells are found 
in various stages of necrosis; in many the nuclei do not stain and the 
bodies are very granular, or the entire cell is broken down into a mass 
1 Kruse and Pasquale, Ztschr. f. Hyg. u. Infectionskrankh., 1894, xvi, 1. THE LIVER 
825 
of detritus. About these necrotic islets of nver cells, pus cells collect 
and often form a zone of dense infiltration (Fig. 62, page 106). Thus, by 
the increase of pus cells and the necrosis of liver tissue, small abscesses 
are formed whose contents are intermingled with greater or less num- 
bers of bacteria (Fig. 522), which seem to increase in number as the 
process goes on. By the confluence of small abscesses larger ones may 
be formed. Death usually ensues, however, before the abscesses attain 
a very large size. 
Chronic Interstitial Hepatitis (Cirrhosis, Laennec Type).-Cirrhosis 
of the liver1 is a disease characterized by extensive toxic destruction of 
the liver cells and subseoxuent connective tissue replacement. There may 
Fig. 524.-Chronic Interstitial Hepatitis-Cirrhosis. 
On account of the rough surface such livers are sometimes called " hobnail livers." This cut is 
a photographic reproduction of a cirrhotic liver of a child. 
be also as the disease progresses a very considerable restoration of the 
liver substance by compensatory hyperplasia. 
1 Various names have been applied to the form of cirrhosis described under this head; Portal cirrhosis, 
Laennec's cirrhosis, fibrous liver, lacunar cirrhosis, hobnail liver, granular liver. For details of the liver 
lesions, see Rolleston, Diseases of the Liver, 2d ed., London, 1921; Quincke and Hoppe-Seyler, Krank- 
heiten der Leber, 2d ed., Vienna, 1912; and Kelly, A. 0. J., Am. Jour. Med. Sc., 1905, cxx, 951. The 
earlier bibl. is given by Paltauf, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1896, i2, 301; and Kretz, 
R., ibid., 1902, viii2, 473. 826 
THE LIVER 
The causes of cirrhosis of the liver are still imperfectly understood.1 
It is commonly a disease of adult life, but exceptionally occurs in children.2 
Congenital cirrhosis with obliteration of the bile ducts has occasionally 
been noted.3 Familial occurrence of cirrhosis has been observed in 
children and is probably related in most instances to progressive lenticular 
degeneration which is usually accompanied by cirrhosis.4 In adults, 
and in some instances in children, the disease seems to be correlated with 
the continued ingestion of large quantities of strong alcoholic liquor, 
hence the name "gin drinker's cirrhosis." Acute infectious disease, 
syphilis, tuberculosis, and malaria have also been regarded as additional 
Showing a portion of the section shown in Fig. 523, but more highly magnified, a, Portions of 
liver lobules; b, new-formed connective tissue; c, gall-ducts, apparently new-formed; d, blood-vessels 
in the new tissue. 
Fig. 525.-Chronic Interstitial Hepatitis. 
inciting factors. In all probability there is necessary a combination of 
toxic agents to produce the lesion. This has been suggested by the results 
of experimental attempts to produce cirrhosis of the liver in animals.5 
Interstitial lesions have been induced by the injection or inhalation of 
alcohol but the extent and character of them differ from cirrhosis in man. 
1 For genesis of liver cirrhosis, see Ribbert, Deutsch, med. Wchnschr., 1908, xxxiv, 1678, and a very 
interesting recent review by Chvostek. Wien. klin. Woch., 1922, xxxv, 381 and 408. 
2 For a resum6 of cirrhosis in childhood see Morse, J. L., Boston Med. and Surg. Jour., 1902, cxlvii, 
299; and Satre, Progrds m6d., 1917, xxxii, 73. 
3 See Rolleston and Hayne, Brit. Med. Jour., 1901, i, 758 (bibl.). 
4 Bramwell, Edinburgh Med. Jour., 1916, xvii, 90; Tilney and Mackenzie, Neurol. Bull., 1918, i, 
243; Geissmar, J., Frankfurter Ztschr. f. Path., 1916, xviii, 305. 
6 Grover, A. L., Jour. Am. Med. Assn., 1913, Ixi, 458 (r£sum6 and bibl.); Fischler, Deutsch. Arch. f. 
klin. Med., 1908, xciii, 427. An interesting type of cirrhosis is that produced in cattle by the eating of 
the rag-wort Senecio jacoboea, and related species. See Cushny, Jour. Pharmacol, and Exper. Therap., 
1910, ii, 531. THE LIVER 
827 
The repeated administration of chloroform to dogs by the stomach so as 
to cause continuous destructive lesions of the liver cells has, however, 
produced changes fairly comparable with those noted in man.1 
If injections of cultures of Bacillus coli are associated with the adminis- 
tration of chloroform, lesions may be induced still more nearly resembling 
those of advanced cirrhosis with the active new formation of gall ducts. 
Chronic protein intoxication, produced by the injection of moderate 
amounts of protein in sensitized animals has been shown also to produce 
lesions of the liver resembling those of cirrhosis.2 It is therefore probable 
that the complete picture is due to alcoholism, plus toxic materials 
absorbed from the intestinal tract, either through lesions induced by the 
alcohol, or in the direct course of absorption of food products acting in 
combination with the alcohol. It 
may be also that the type of alcoholic 
drink used or the presence of other 
alcohols or aldehydes in the fluid has 
some influence on the production of 
the disease, the general opinion being 
that the consumption of gin is espe- 
cially apt to lead to cirrhosis. Ex- 
cessive beer drinking may induce 
cirrhosis but more frequently causes 
extensive fatty degeneration. 
The various appearances which 
cirrhotic livers present to the naked 
eye depend largely upon the nature, 
amount and distribution of the new 
formed connective tissue, and upon 
the secondary changes in the liver. 
As a rule, the loss in volume of the 
organ is very considerable because the 
amount of connective tissue present 
as a replacement fibrosis is rarely 
in any way equivalent to the total 
volume of liver substance lost. The 
organ is therefore almost always 
smaller than normal. The surface 
may be very rough and uneven from the projection of smaller and larger, 
irregularly shaped, nodules of liver tissue, between which are depressed, 
contracted bands of new formed connective tissue. On the other hand, 
the surface of the liver may be smooth, when the new connective tissue 
bands are small, even if the liver is little contracted, or when the lesion is 
early. Again, the liver may be greatly distorted and misshapen by the 
atrophy of the parenchyma and the contraction of large and irregular 
Fig. 526.-New-formed Gall-ducts 
in Cirrhosis. 
The section shows the projection into the 
new connective tissue from the rows of old 
liver cells, of cell masses resembling gall-duct 
epithelium. This may be interpreted as an 
example of reversion of the differentiated liver 
cells to a simpler type. 
1 Opie, E., Jour. Exper. Med., 1910, xii, 367; and Fraser, A., Am. Jour. Med. Sc., 1916, clii, 202. 
2 For relation of cirrhosis to chronic protein intoxication, see Longcope, Tr. Assn. Am. Phys., 1913, 
xxviii, 427. 828 
THE LIVER 
bands or masses of new connective tissue. In a cirrhotic liver, the new 
tissue may not be easily visible to the naked eye, or it may appear as gray 
irregular streaks or bands, or patches, often sharply outlined against a 
dark red or brown or yellow or greenish-yellow parenchyma. When, as 
is often the case, fatty infiltration is associated with atrophic cirrhosis, 
the liver may not only not be diminished in size, but may be larger than 
normal, weighing as much as 4,000 grams. The consistence of the small 
livers is usually very firm, and they cut with a gritty feel. Large livers, 
on the other hand, while often firmer than normal, may not show an 
extraordinarily firm consistence. Microscopically the new connective 
tissue in cirrhosis is in some instances of loose texture and contains many 
types of wandering cells. In other examples, it may be extremely dense 
and contains comparatively few cells. It is usually however quite vascu- 
lar, and contains, a relatively large number of elastic fibrils.1 Connective 
tissue is most abundant between the lobular masses of liver parenchyma, 
but occasionally encroaches more or less upon their periphery. Small 
gall ducts, some of them at least new formed, are usually present in the 
connective tissue around the islets of parenchyma. Some of these gall 
ducts may be continuous with old ducts, or with strands of liver cells. 
By some it is thought that the picture may be interpreted as a reversion 
of the liver cell to a simpler type; others believe that it presents the forma- 
tion of new liver cells from the gall ducts, just as in the case of acute 
yellow atrophy, where an extensive reparative process goes on with 
reconstruction of new parenchyma.2 
The newly formed liver cells are characterized by their large size, 
pale cytoplasm, and wealth of chromatic material in the nuclei. Branches 
of the hepatic and portal veins, particularly the latter, often become 
obliterated by pressure from the new connective tissue or from chronic 
thickening of the vessel walls, so as to seriously interfere with the func- 
tions and nutrition of the liver cells.3 The branches of the hepatic artery 
are much less liable to alterations than the others. The central veins 
also persist longer than other portions of the capillary circulation. The 
bile ducts also may become obliterated or there may be catarrhal inflam- 
mation especially of the larger trunks. The capsule of the liver is usually 
thickened, either uniformly, or in irregular patches, or its surface may be 
roughened by larger or smaller papillary projections. The liver is fre- 
quently bound to the diaphragm or other adjacent organs by connective 
tissue adhesions. Obstruction to the portal circulation induced by cir- 
rhosis usually gives rise to a number of secondary lesions; since collateral 
circulation through the small veins of the ligamentum teres is rarely 
1 For a study of the character of the new connective tissue in cirrhosis, see Flexner, S., Univ., Med. 
Mag., 1900, xiii, 613. 
2 See Muir, R., Jour. Path, and Bacteriol., 1908, xii, 287; MacCallum, W. G., Jour. Am. Med. Assn., 
1904, xliii, 649; and Kretz, R., Wien. klin. Wchnschr., 1900, xiii, 271, and Verhandl. d. deutsch. path. 
Gesellsch., 1905, viii, 54; also Naunyn, ibid., p. 59. 
3 For a study of the increase of portal pressure in portal cirrhosis, see Herrick, F. C., Jour. Exper. 
Med., 1907, ix, 93. For a study of the lesions of the hepatic veins, see Hess, A. F., Am. Jour. Med. 
Sc., 1905, cxxx, 986. Pathology-Delafield and Prudden 
Plate XIV-A. 
Fig. 1. 
Fig. 2. 
Biliary Cirrhosis. THE LIVER 
829 
established in sufficient degree to afford much relief. The hemorrhoidal, 
oesophageal, and vesical veins may be greatly enlarged, and also the veins 
of communication between Glisson's capsule and the diaphragmatic 
veins. In rare instances a very peculiar dilation of the cutaneous veins 
above the umbilicus is observed-caput medusae. The enlarged veins 
may form a circular network around the umbilicus or a pyramidal tumor 
beside it, or all the veins in the abdominal wall, from the epigastrium 
to the inguinal region, are dilated. This condition is thought to be 
dependent upon the congenital nonclosure and subsequent dilatation of 
the umbilical vein and its anastomoses with the internal mammary, 
epigastric and cutaneous veins. Not infrequently a dilatation of the 
veins of the abdominal wall is seen, which has a different origin. This is 
produced by the pressure of the ascitic fluid often present in cirrhosis, 
on the vena cava, and is found not only with ascites from any cause, but 
also with large abdominal tumors.1 
The presence of ascites is a common secondary phenomenon in 
atrophic cirrhosis and is generally attributed to the portal obstruction 
through chronic peritonitis or cardiac failure may play a part. It usually 
begins at a fairly early stage of the disease, and is apt to increase incon- 
stantly. It generally precedes edema of the feet, but both may appear 
at the same time. The fluid is clear or more rarely cloudy, yellow 
brown or greenish in tone, or reddish. It is sometimes mixed with 
shreds of fibrin, and more rarely with blood. In exceptional instances 
ascites is not present and then there will usually be found extensive 
adhesions between the omentum and the abdominal wall. By this 
means a sufficient by-pass for the blood is offered from the portal system 
to the veins of the abdominal wall. The Talma operation, which is 
sometimes very effective, imitates this condition by suturing the omentum 
to the parietal peritoneum.2 
The peritoneum remains normal, or may become very opaque and 
thick. Lesions of the intestines and other viscera are not uncommon, 
nor is peritoneal tuberculosis a not infrequent complication. The 
spleen is enlarged in some 80 per cent, of cases of cirrhosis,3 sometimes 
to a very considerable degree. When it is not increased in size this 
may be due to previous atrophy of the organ, or to great fibrous thicken- 
ing of its capsule, or possibly to hemorrhages from the stomach or bowels 
which may occur just before death. The pancreas is usually the seat of 
a more or less marked interstitial hyperplasia.4 The stomach and 
intestines are often secondarily affected by the obstruction to the portal 
circulation. Profuse gastrointestinal hemorrhage may occur, and some- 
times causes sudden death. The mucous membrane is then found pale 
or congested, or with a hemorrhagic serosa. The hemorrhage not infre- 
1 Gilbert and Villaret, Rev. de m6d., 1907, xxviii, 305. 
2 Riesman, D., Jour. Am. Med. Assoc. 1921, Ixxvi, 288. 
3 Klopstock, Virchows Arch., 1907, clxxxvii, 111. 
4 For a study of pancreatic lesions in hepatic cirrhosis, see Lando, Ztschr. f. Heilk., Abt. f. path. 
Anat., 1906, xxvii, 1. 830 
THE LIVER 
quently results from rupture of esophageal varices which are frequently 
present, especially in the lower portions of the tube, in a considerable 
proportion of cases of atrophic cirrhosis.1 The blood may, in this in- 
stance, infiltrate the coats of the stomach and intestines. The mucous 
membrane of the stomach and the entire length of the intestines is fre- 
quently the seat of chronic catarrhal inflammation, and is sometimes 
intensely and uniformly congested, and coated with mucus. In other 
cases, both the mucous and muscular coats are pale but very markedly 
thickened. Cirrhosis of the liver is also not infrequently accompanied 
by chronic diffuse nephritis. The fever, which is seen in the later stages, 
is due in some instances at least to an accompanying tuberculosis, though 
it is probably more often an expression of the cholangitis which may form 
a part of the disease. Mild jaundice is the rule, but the color of the skin 
is more dull and muddy than in ordinary obstructive jaundice. The 
blood shows a cholemia. Anemia is the usual rule, but polycythemia has 
been observed in a few instances, and regularly occurs as a temporary 
phenomenon after the removal of large quantities of ascitic fluid. 
Hypertrophic Cirrhosis (Hanot Type).-There is a form of chronic 
interstitial cirrhosis in which the growth of new tissue not only occurs 
between the lobules, but extends into the lobule between the liver cells 
(Fig. 527). Under these conditions, in an advanced form of the lesion, 
Showing formation of connective tissue between the liver cells. 
Fig. 527.-Hypertrophic Cirrhosis of the Liver. 
the liver may be greatly enlarged; the surface may be smooth or slightly 
roughened, and the parenchyma is often deeply bile-stained. Islets 
of liver tissue are not seen as in the atrophic form. Microscopically 
there is the formation of a great deal of new connective tissue which 
1 For a critical summary of gastrointestinal hemorrhage in cirrhosis, with bibl., see Preble, Am. Jour. 
Med. Sc., 1900, cxix, 263. Pathology-Delafield and Prudden. 
Plate XIV B. 
Fig. 1. Liver. 
Fig. 2. Lymph-Node. 
Fig. 3. Testicle. 
H EMOCH ROM ATOSIS THE LIVER 
831 
separates individual liver cells or small groups of the latter from each 
other. The disease is rare and is much more rapidly fatal than the 
atrophic cirrhosis. Extreme jaundice is frequent. 
Biliary Cirrhosis.-Under this title are grouped a series of lesions of 
the liver which develop from chronic bile stasis, with or without infection.1 
The liver is usually large, smooth, and intensely stained with bile. The 
cut section is of a deep green color. The amount of connective tissue is 
not as a rule great, and is chiefly in the region of the bile ducts, though 
it may spread between the individual lobules, and even separate groups 
of cells (Fig. 1, Plate XIV A). The microscopic lesions vary. When the 
lesion is due to bile stasis alone inflammatory effects may be minimal 
and the chief feature a plugging of the bile capillary with inspissated 
bile. Even the delicate channels in the liver cells may show a natural 
injection. Small block concretions of bile pigment may fill the larger, 
bile capillaries (Fig. 2, Plate XIV A). In other types the inflammatory 
aspects are dominant and the new formed connective tissue about the 
bile capillaries is filled with wandering cells. Patients with this disease 
usually die early, but in case they survive atrophy of the liver tissue 
may be extensive, and the liver become small and hard. Clinically a 
deep jaundice of the skin is an almost constant symptom, while ascites 
is moderate or absent. The spleen is not as greatly enlarged as in the 
atrophic type. 
Hemochromatosis.-A very rare type of cirrhosis, usually hyper- 
trophic in form and occurring almost wholly in males is seen in a disease 
of as yet unknown etiology whose characteristic lesion is a pigmentation 
of the tissues by hemosiderin and hemofuscin. Fibrosis of many of the 
organs and often, though not always, a diabetic condition with hyper- 
glycemia and glycosuria accompanies the pigmentation. Hemosiderin 
is the predominant pigment and may be present in large quantities, 
the liver containing for example a hundred times its normal amount of 
iron. It is deposited in the parenchyma cells of the glandular organs 
(Fig. 1, Plate XIV B), the interstitial cells and tubules of the testis 
(Fig. 3, Plate XIV B), and in the heart muscle. When the paren- 
chyma cells degenerate from an overload of pigment the latter is set free 
and is picked up by the cellular phagocytes of the stroma and the vascular 
endothelium. The hemofuscin is usually contained in the smooth 
muscle fibers. The endothelial cells of the lymph-nodes also contain 
much pigment (see Fig. 2, Plate XIV B). The cause of the disease is as 
yet uncertain.2 
Syphilitic Hepatitis.-Chronic interstitial inflammation of the liver 
1 Ogata, T., Zieglers Beitr., 1913, lv, 236. 
2 The recent literature on the subject may be found in Sprunt, Arch. Int. Med., 1911, viii, 75; and 
Banton, W. B., and Healy, W., ibid., 1921, xxvii, 406. See also Rossie, Zieglers Beitr., 1907, xli, 181 
(bibl.); Opie, E. L., Jour. Exper. Med., 1899, iv, 279 (bibl.). The discussion in the Brit. Med. Jour., 
1921, ii, 783-786, contains some interesting viewpoints. For experimental investigation of the problem,, 
see Rous, P., and Oliver, J., Jour. Exper. Med., 1918, xxviii, 629-644; and Mallory, F. B., Parker, F. 
and Nye, N. N., Jour. Med. Res., 1920-21, xlii, 460-490 (bibl.). 832 
THE LIVER 
very frequently results from syphilitic infection, either congenitally or 
in the later stages of the acquired form. It may occur in a diffuse man- 
ner, new connective tissue being formed either between the lobules or 
within them between the rows of liver cells. The new tissue may be 
rich in cells, or dense and firm. This form is frequently seen in children 
and cannot be distinguished, either macroscopically or microscopically, 
from similar forms of interstitial hepatitis from other causes.1 
In other cases, particularly in children, there may be numerous small 
gummata (so-called miliary gummata) (Fig. 170, page 307) scattered 
through the liver, together with more or less new connective tissue. 
An extensive formation of giant cells in the liver has been described 
in connection with congenital syphilis.2 In adults, gummata are 
usually larger, varying in size from that of a pea to a hen's egg, and 
may be surrounded by larger and smaller irregular zones of ordinary 
connective tissue. In still other cases in adults there are larger and 
smaller dense, irregular bands or masses of connective tissue running 
through the liver, drawing in the capsule and often causing great deform- 
ity of the organ (Fig. 529). These bands and masses of new tissue 
may or may not inclose gummata, either large or small. These deform- 
ing cicatrices, either with or without gummata, are very characteristic 
of syphilitic inflammation of the liver. 
This, like the simple interstitial inflammation of the liver, may be 
associated with fatty and waxy degeneration, and with atrophy of the 
parenchyma from pressure. 
Tuberculous Hepatitis.-This lesion, which is usually secondary to 
tuberculous inflammation in some other part of the body or to acute 
general miliary tuberculosis, is most frequently characterized by the 
formation of larger and smaller miliary tubercles, which may be either 
within or between the liver lobules or in the walls of the bile-ducts. 
Many of the tubercles are too small to be seen with the naked eye; 
others may be just visible as grayish points; still others may be from 1 
to 3 mm. in diameter, with distinct yellowish-white centers. Micro- 
scopical examination shows considerable variation in the structure of 
the tubercles in different cases, as well as in the same liver. Some of 
them, usually the smaller ones, consist simply of more or less circum- 
scribed collections of small spheroidal cells, which are not morphologically 
distinguishable, so far as the form and arrangement of the cells are 
concerned, from simple inflammatory foci, or from the diffuse masses 
of lymphatic tissue which occur normally in the liver. 
In other forms we find a -well-marked reticulum -with larger and 
smaller spheroidal and polyhedral cells, with or without giant cells. In 
still other forms there is more or less extensive cheesy degeneration 
1 Summers, D., Internal. Clinics, Ser. 27. vol. i, Philadelphia, 1017. 
2 For a description of congenital liver cirrhosis with giant cells, see Binder, A., Virchows Arch., 1904, 
clxxvii, 44; also Lonicer, M., Zieglers Beitr., 1906, xxxix, 539 (bibl.). THE LIVER 
833 
(Fig, 530). The larger forms are conglomerate, being composed of several 
tubercle granula joined together to form a single nodular mass. The liver 
cells at the seat of the tubercle are destroyed, and the interstitial tissue 
and blood-vessels are either destroyed or merged into the tubercle tissue. 
In the periphery of the tubercles the liver cells may be in a condition 
of coagulation necrosis, and the tissue round about may be infiltrated 
with small spheroidal cells. There is in some cases a new formation of 
Fig. 529.-Syphilitic Hepatitis. 
The liver is greatly deformed by the contraction of new-formed connective tissue. The ragged surface 
is due to the tearing away of adhesions to surrounding parts. 
gall-ducts or of structures which resemble these and which in transverse 
sections resemble giant cells. Tubercle bacilli, frequently in small 
numbers, but often in great abundance, may be found within the tubercles. 
Tuberculosis of the liver may be associated with cirrhosis or with 
waxy or fatty degeneration. 
Much more rarely than the above form there are found in the liver 
more or less numerous scattered tuberculous masses from the size of a pea 
to that of a walnut or larger, with cheesy centers and usually a new 
growth of connective tissue in the periphery. These so-called solitary 834 
THE LIVER 
tubercles of the liver may be softened at the centers. Tuberculous inflam- 
mation of the gall-ducts may give rise to numerous scattered, cheesy 
nodules, as large as a pea or larger, which may be softened at the center 
and stained yellow with bile. Small cavities may thus be formed. 
This lesion is rare and seems to be more frequent in children than in 
adults. 
Perihepatitis.-Acute exudative inflammation of the serous covering of 
the liver, with the formation of fibrin, may occur as a part of acute gen- 
eral or localized peritonitis, or over the surface of abscesses, tumors, 
hydatids, etc., of the organ, when these lie near or approach the surface; 
or it may be secondary to acute pleurisy. 
Fig. 530.-A Miliary Tubercle of the Liver. 
Showing a cheesy center and giant cells. 
Chronic perihepatitis, resulting in the thickening of the capsule of the 
liver, and the formation of new connective tissue in and beneath it may 
be secondary to an acute inflammation of the capsule, or it may be 
chronic from the beginning and associated with chronic pleurisy, chronic 
peritonitis, and cirrhosis.2 In this way more or less extensive adhesions 
of the liver to adjacent structures may be formed; or, by contraction of 
the new-formed connective tissue, considerable deformity of the liver may 
be produced. The capsule is sometimes uniformly thickened, sometimes 
the new tissue occurs in more or less sharply circumscribed patches. The 
surface is sometimes roughened from little, irregular, projecting masses 
of connective tissue. Microscopically the new-formed tissue is usually 
dense and firm, but it may be loose in texture and contain many cells. 
1 See for a study of tuberculous cavities in the liver, Fletcher, H. M., Jour. Path, and Bacteriol, 
1900. vi, 147 (bibl.). 
2 Multiple serositis, Kelly, A. O. J., Am. Jour. Med. Sci., 1903, cxxv, 116 (bibl.). THE LIVER 
835 
Chronic obliterative pericarditis is often associated with the perihepatitis 
in which case the cardiac symptoms may dominate the clinical picture. 
HYPERPLASIA OF LYMPHATIC TISSUE IN THE LIVER. 
In leukemia and in Hodgkin's disease the liver is not infrequently 
enlarged and soft and sprinkled with small white spots or streaked with 
narrow whitish irregular bands; or it may be of a diffuse grayish color. 
Microscopical examination shows that this change is due to an accumu- 
lation of lymphocytes, leucocytes, and bone-marrow cells, either along 
the portal vein, diffusely through the liver tissue, or in small circum- 
scribed masses. The amount of accumulation of these cells varies, but is 
sometimes so great as seriously to compromise the liver cells. The origin 
of these cells is not yet definitely known. They may be, and doubtless 
in part are, brought to the organ through the portal vein; but they may, 
in part at least, be formed in the liver itself,1 possibly from the capillary 
endothelium (Fig. 298, page 541, and Fig. 307, page 558). In pernicious 
anemia the extensive formation of red cells takes place in the liver, as in 
embryonic life. In Hodgkin's disease the whitish areas show micro- 
scopically the characteristic connective-tissue hyperplasia with large 
multinucleated cells and often abundant eosinophile leucocytes. 
In typhoid fever, smallpox, scarlatina, diphtheria, and measles, small 
circumscribed masses of spheroidal cells are sometimes found in the 
liver. These nodules differ in character; some are due to focal necroses, 
such as occur in various toxemias with a later multiplication of cells or 
invasion of leucocytes. In some, as in typhoid fever, there is necrosis 
with proliferation of endothelium (page 271). Finally, some of the 
small masses of spheroidal cells encountered in the liver in infectious 
diseases are doubtless hyperplastic lymph-nodules. 
TUMORS. 
Tumors of the liver may be primary or secondary, the latter being 
the more common. 
Cavernous angioma (cavernoma, ncevus cavernosus).-These are usually 
but a few centimeters in diameter, either single or multiple, found most 
commonly in elderly persons accidentally at autopsy, and are of no prac- 
tical significance. They may be situated at the surface (Fig. 531) or 
embedded in the organ, and are of a dark red color; they may be sharply 
circumscribed by a connective-tissue capsule or merge imperceptibly into 
the adjacent liver tissue. They are sometimes found in combination 
with similar growths in other parts of the body, often in the skin.2 
Under the microscope they are found to consist of a congeries of irregular 
cavities (Fig. 228) filled with blood and frequently communicating freely 
with one another. The walls of the cavities consist of connective tissue 
1 See, for experimental investigation of this subject and bibl., Sternberg, C., Zieglers Beitr., 1909 
xlvi, 586; and Morris, R. S., Bull. Johns Hopkins Hosp., 1907, xviii, 200. 
1 x. Fahcowsici, Zieglers Beitr., 1914, Ivii. 385 (bibl.). 836 
THE LIVER 
often containing small blood-vessels. These growths are believed to be 
formed by dilatation of the liver sinusoids, perhaps on account of some 
congenital weakness, with subsequent thickening of their walls and 
atrophy of the adjacent liver cells. By the organization of clots within 
the blood cavities these tumors may be partially or entirely converted 
into masses of dense fibrous tissue.1 
The cavernoma is regarded by many observers as a hamartoma or 
developmental error rather than as a true tumor, since there is usually 
no evidence of actual proliferation in the vessels involved. Yet they 
may in rare cases invade the surrounding liver, produce symptoms, and 
actually be the cause of death; so that an occasional example may properly 
be regarded as a true tumor.2 
Fig. 531.-Cavernous Angioma of the Liver. 
Small fibromata and lipomata have been described, as also fibroneuro- 
mata of the sympathetic. Misplaced adrenal remnants are sometimes 
discovered in the liver,3 where they may be mistaken for adenomata. 
Benign and malignant hypernephromata may develop from them.4 
Adenomata5 of the liver are of not infrequent occurrence. They are 
sometimes small and circumscribed, sometimes large and multiple. 
They present two tolerably distinct types of structure. In one, they 
are of essentially the same structure as normal liver tissue except that 
the cells are apt to be larger and less uniform in arrangement (Fig. 532). 
These growths look like little islets of liver tissue, sometimes encapsulated 
1 Merkel, Zieglers Beitr., 1904, xxxvi, 574; Moise, T. 8., Bull. Johns Hopkins Hosp., 1920, xxxi, 369. 
2 Roggenbau, Zieglers Beitr., 1910, xlix, 313 (bibl.). 
3 Beer, Ztschr. f. Heilk., Abt. f. path. Anat., 1904, xxv, 381; Noyes, Proc. New YorkPath. Soc., 1899- 
1900, p. 4. 
4 Hirschler, Frankfurt. Ztschr. f. Path., 1812, ix, 343 (bibl.); White and Mair, Jour. Path, and 
Bacteriol., 1908, xii, 107 (bibl.); de Vecchi, Virchows Arch., 1904, clxxvii, 133 (bibl.). 
6 W&tzold, Zieglers Beitr., 1906, xxxix, 456 (bibl.). THE LIVER 
837 
and sometimes not, lying in the parenchyma. In the second variety,the 
cells are less like liver cells, being frequently cylindrical, and are arranged 
in irregular masses of tubular structure with more or less well defined 
lumina; metastases may be found in the lungs. These tubular adenomata 
are in some cases so closely similar to carcinoma as to be scarcely dis- 
tinguishable from them and seem, indeed, to merge into them.1 
Carcinoma, which is the most common and important of the hepatic 
tumors, may be either primary2 or secondary. Primary carcinomata are 
derived either from the epithelium of the parenchyma or from that of the 
gall-ducts, and in some cases are arranged along the larger trunks. The 
cells are usually polyhedral, sometimes cylindrical, and may be grouped 
Fig. 532.-Adenoma of Liver. 
Showing close resemblance of tumor cells to those of the normal liver 
irregularly in alveoli or may form more or less well-defined tubular 
structures (Fig. 533). Metastasis is relatively uncommon. 
Carcinoma of the liver is frequently found in association with cirrho- 
sis,3 and it should be remembered that it is not a really uncommon growth 
in children.4 
Secondary carcinoma, which is by far the more common, is usually 
due to dissemination of cells from carcinomata of the stomach,5 intestine, 
pancreas, or gall-bladder, though it may be the result of metastases from 
the mamma, esophagus, uterus, or other parts of the body. 
1 For a discussion of adenocarcinoma of the liver, see Herxheimer, Centralbl. f. allg. Path., 1902, 
xiii, 705. For adenocarcinoma with ciliated cells, see Sokoloff, Virchows Arch., 1900, clxii, 1 (bibl.). 
For a discussion of malignant adenoma, see Blumberg, Frankfurt. Ztschr. f. Path., 1912, x, 186 (bibl.); 
v. Hansemann, Virchows Arch., 1900, clxi, 453. 
2 Goldzieher and v. Bokay, Virchows Arch., 1911, cciii, 75 (bibl.); Herxheimer, Centralbl. f. allg. Path., 
1906, xvii, 724. 
3 Eggel, Zieglers Beitr., 1901, xxx, 506 (bibl.); Winternitz, Virchows Arch., 1912, ccix, 239 (bibl.). 
4 Griffith, Am. Jour. Med. Sc., 1918, civ, 79 (bibl.); Castle, Surg., Gynec., and Obst., 1914, xviii, 
477 (bibl.). 
6 For a study of retrograde metastasis from the stomach, see Jacob, Arb. d path. anat. Inst. z. 
Tubingen, 1904-05, p. 121. 838 
THE LIVER 
The form in which carcinoma of the liver occurs varies greatly. 
Sometimes the tumors are single, but more often they are multiple (Fig. 
534); they may be very large or so small as to be scarcely visible to the 
naked eye; numerous small nodules are frequently grouped about a 
larger one. They are sometimes deeply embedded in the liver, at others 
they project from the surface; and the liver is frequently, and sometimes 
enormously, enlarged. The nodules are usually whitish or yellowish or 
pink in color, or bile-stained; they are often the seat of hemorrhages, and 
may become softened at the center forming cysts. They are sometimes 
hard, sometimes soft and almost diffluent. Fatty degeneration is fre- 
quent and may be recognized by yellowish streaks or patches. 
Fig. 533.-Primary Carcinoma of Liver-Tubular Type. 
Owing to the degeneration and partial absorption of the central por- 
tions of the tumors, nodules on the surface of the liver frequently present 
a shallow depression at the center. The tumors may be sharply outlined 
against the adjacent liver tissue or may merge imperceptibly into it. 
They may be so large or numerous as to occupy the greater part of the 
enlarged organ and neighboring liver cells may become flattened or 
atrophic, while pressure upon the portal vein or its branches, or upon 
the gall-ducts, may seriously interfere with the functions of the organ. 
On the other hand, large and numerous tumors may be present with no 
apparent interference with hepatic function. 
In some cases, instead of forming separate distinct nodules, the can- 
cerous growth develops in the form of a diffuse infiltration so that the 
liver is irregularly mottled with white or reddish brown masses and may 
then somewhat resemble certain forms of chronic interstitial hepatitis; 
in this type the liver is often greatly enlarged. THE LIVER 
839 
A rather atypical diffuse carcinoma has been described under the 
name atypical hemorrhagic malignant hepatoma.1 
Melanotic carcinomata sometimes occur in the liver, most frequently 
as secondary tumors. A unique case of primary chorionepithelioma of 
the liver has been described,2 and referred either to one-sided develop- 
ment of a teratoma3 (page 1023/.) or to metastatic chorionic villi, the 
latter being regarded as more probable. 
Sarcoma.-Spindle-cell and round-cell sarcoma as well as angiosar- 
coma are among the more frequent types of the rare primary sarcoma 
of the liver.4 Melanosarcoma has been described.5 
Spindle-cell, melanotic, and telangiectatic sarcoma may occur in the 
liver as secondary tumors.6 Secondary myxomata and chondromata 
The section is through the entire organ, showing carcinomatous tumors of various sizes and forms; 
some are white, some are dark red from hemorrhage. The larger tumor at the left is softening at the 
center. 
Fig. 534.-Secondary Carcinoma of the Liver. 
have also been recorded, but they are very rare. Cavernous lymph- 
angiomata have been discovered in a few cases. 
Cysts.-Cysts,7 usually of small size, may be formed by dilatation of 
the bile-ducts. They may be multiple, and contain serum, mucus, and 
degenerated epithelium. Single cysts, apparently unconnected with the 
gall-ducts, are occasionally found in the connective tissue of the liver. 
They may be lined with ciliated epithelium. 
The liver is sometimes the seat of multiple cysts, varying from micro- 
scopic size to that of a pea or larger. They are sometimes combined 
with multiple cysts of the kidney and with congenital anomalies in other 
parts of the body. They may be associated with aberrant bile-ducts, in 
which they probably originate.8 
i L' Esperance, Jour. Med. Research, 1915, N. S. xxvii, 225 (bibl.). 
2 Fischer, Frankfurt. Ztschr. f. Path., 1913, xii, 462. 
3 Albrecht, Verhandl. d. deutsch. path. Gesellsch., 1902, v, 462. 
4 Arnold, J., Zieglers Beitr., 1890, viii, 123; Marx, Centralbl. f. allg. Path., 1904, xv, 433 (bibl.); 
Knott, Surg., Gynec., and Obst., 1908, vii, 328 (bibl.). 
5 Hetzel, Ein Fall von Melanosarkom d. Leber, Inaug.-Diss., Erlangen, 1895 (abstr. in Centralbl. f. 
allg. Path., 1896, vii, 917). 
6 Hektoen and Herricn, Tr. Assn. Am. Phys., 1898, xiii, 385. 
2 Dmochowski and JanowsKi, Zieglers Beitr., 1894, xvi, 102. 
s Moschcowitz, E., Am. Jour. Med. Sc., 1906, cxxxi, 674. 840 
THE LIVER 
Teratoma of the liver has been described.1 
Foamy Liver.-Occasionally the liver is found at the autopsy, even 
if this be made but a few hours after death, more or less completely rid- 
dled with small, irregular-shaped cavities, from the size of a pin's head to 
that of a pea. These holes are due to the accumulation of gases in the 
liver, formed by the Bacillus aerogenes capsulatus. This is the so-called 
"foamy liver" (Fig. 535) and is entirely a post-mortem process. 
Fig. 535.-"Foamy Liver." 
The liver is riddled with small holes formed by the accumulation of gas developed by B. aerogenes 
capsulatus-"gas bacillus." 
PARASITES. 
Echinococcus.-This parasite is the most common and important of 
those which occur in the human liver, forming the so-called hydatids of 
the liver which represent one of the developmental stages of the small 
tapeworm of the dog, Taenia echinococcus (page 147). The cysts in 
the liver may be very small and multiple, but they may be as large as 
a man's head or larger. The liver may be greatly increased in size, and 
the tissue about the cysts atrophied. The liver itself furnishes a connect- 
ive-tissue capsule, within which is the translucent, lamellated membrane 
furnished by the parasite. On the inside of this we may find a layer of 
cells, granular matter, and a vascular and muscular system belonging to 
the parasite. Projecting from this inner capsule are the brood capsules 
and heads or scolices of the immature tapeworm. The scolices may 
become detached from the wall and lie free in the cavity, which is filled 
with a transparent or turbid fluid. Not infrequently the cysts are 
sterile, and are then simply filled with clear or turbid fluid; or the embryes 
may have died and disintegrated, and their detritus, including the hook- 
lets, may be intermingled with the fluid contents of the cysts. The 
contents of the cysts may be mixed with fat, cholesterin crystals, pus, 
bile, or blood; or form a grumous mass, in which we may or may not 
be able to find the booklets of the scolices or fragments of the lamellated 
wall. The connective tissue of the walls of the cysts may be greatly 
thickened, or it may be calcified. 
In other countries the lesion is much more common and frequently 
1 Mi sick, Jour. Path, and Bacteriol., 1896. v. 128. THE LIVER 
841 
more formidable than in the United States. The cysts reach an enor- 
mous size, the veins of the liver may be compressed and filled with 
thrombi, the bile-ducts compressed and ulcerated. So much of the liver 
tissue may be replaced by the hydatids that the patient may die from this 
cause alone. Very frequently there is local peritonitis, and adhesions are 
formed between the liver and the surrounding parts. In some cases the 
cysts rupture, and their contents are emptied into the peritoneal cavity, 
the stomach, the intestines, the pleural cavity, or the lung tissue. Some- 
times the cysts perforate the bile-ducts, the vena cava, or some of the 
branches of the portal or hepatic veins; or the abdominal wall is per- 
forated and a fistula formed between the cavity in the liver and the 
surface. 
Echinococcus multilocularis (page 148), which is apparently an abor- 
tive form of the above species, is rare in the United States (Fig. 536).1 
Fasciola hepatica, Opisthorchis felineus, and Clonorchis sinensis may 
occur in the gall-ducts and gall-bladder. The last-named is found espe- 
A section of a small portion of the cystic and fibrous growth in the liver. There were no booklets 
within the cysts in this case, but the delicately lamellated character of the lining membrane sufficed 
for a diagnosis. 
Fig. 536.-Echinococcus Multilocularis of the Liver. 
cially in the East, and has been observed in great numbers in the bodies 
of Chinamen. Schistosoma haematobium is very common in Egypt and 
Abyssinia, occurring in the blood-vessels of the liver. Schistosoma 
japonicum also is found in the liver giving rise to a cirrhotic process 
(Fig. 86, page 145). 
Pentastoma denticulatum is the larval stage of Linguatula rhinaria, a 
parasite which inhabits the nasal cavity of dogs and some other animals. 
In the liver of man it usually occurs in the form of small, rounded, calci- 
fied cysts. The cysts may contain fat, calcareous matter, and the re- 
mains of the dead parasite, among which the booklets may be found. 
Ascaris lumbricoides sometimes finds its way from the intestines into 
the bile-ducts. It may cause no disturbance here, but in some cases the 
worms have been present in large numbers and caused occlusion, dilata- 
1 See Oertel, Yale Med. J'our., 1899, v, 233; consult also Posselt, A., Munchen, med. Wchnschr., 
1906, liii, 537, 605 (bibl.) 842 
THE LIVER 
tion, and ulceration of the biliary passages, and have led to the formation 
of abscess of the liver. 
Coccidium oviforme, a very common parasite in the rabbit's liver, 
has been found a few times in the liver of man. 
LESIONS OF THE BILIARY PASSAGES AND THE GALL-BLADDER. 
Perforation and rupture of the gall-bladder may occur under various 
conditions and is usually followed by peritonitis.1 
Catarrhal inflammation of the 
gall-ducts (cholangitis) most fre- 
quently involves the lower por- 
tion of the common duct and 
the gall-bladder. In the acute 
form it usually leaves but few 
changes appreciable after death. 
An abnormal coating of mucus, 
and sometimes congestion of the 
blood-vessels, are almost the only 
post-mortem lesions. Owing to 
the swelling of the mucous mem- 
brane and the accumulation of 
mucus in the lumen, the ducts 
may be temporarily occluded, 
but this occlusion may not be 
evident after death. If, how- 
ever, the inflammation becomes 
chronic, the walls of the bile- 
ducts may become thickened and 
their lumina more or less perma- 
nently obstructed (Fig. 537). In 
consequence of this, dilatation 
or ulceration of the bile ducts 
may ensue. Temporary obstruc- 
tion of the bile ducts may pro- 
duce marked pigmentation of the 
liver, owing to the accumulation 
of pigment granules in the liver 
cells, particularly in the vicinity 
of the capsule of Glisson, and 
jaundice of the entire body. 
The gall-bladder may be in- 
flamed by itself-cholecystitis-or 
in connection with inflammation 
of the biliary passages. If the 
disease is chronic the wall of the bladder may be thickened and bound 
to adjacent parts by fibrous tissue; polypoid growths may occur in the 
mucosa; the duct may be occluded; dilatation, ulceration, the forma- 
Fig. 537.-Suppurative Inflammation in the Gall-ducts-Cholangitis. 
1 See Machard, Arch. g6n. de m6d., 1900, iv, 159 (bibl.). THE LIVER 
843 
tion of gall-stones, calcification, and atrophy may ensue. In inflamed 
gall-bladders the penetration of the fibrous and muscular coats by deep 
processes of the lining epithelium, Luschka's ducts, may lead to an erro- 
neous diagnosis of carcinoma (Fig. 538). 
Inflammation of the stomach and duodenum, hyperemia and inflam- 
mation of the liver, concretions, and parasites frequently accompany 
catarrhal inflammation of the biliary passages, but it may occur without 
these. 
Suppurative and Membranous Inflammation of the Bile-Ducts (Chol- 
angitis) and Gall-Bladder (Cholecystitis).-The walls of the ducts may be 
Showing deep penetration down to the subserosa of a Luschka's duct. 
Fig. 538.-Chronic Inflammation of Gall-bladder. 
covered or infiltrated with a fibrinous or a purulent exudate; they may 
ulcerate. 
These lesions occur most frequently in connection with obstruction 
of the bile-ducts by gall-stones or otherwise, and in typhoid and typhus 
fever, pyemia, and cholera; or they may be due to the extension of 
inflammatory processes from without. They also occur under unknown 
conditions. 
In many cases of inflammation of the gall-ducts the Bacillus coli 
communis or Bacillus typhosus, in fewer the pyogenic streptococcus and 
staphylococcus, are apparently concerned. 844 
THE LIVER 
Suppurative inflammation may lead to perforations of the ducts or 
bladder, with escape of bile and peritonitis; or to fistulous openings be- 
tween the gall-bladder and the duodenum, colon, and stomach, or through 
the abdominal wall; or the inflammation may extend to the liver tissue 
and produce abscesses. Under the latter conditions there may be a series 
of small abscesses ranged along the walls of the suppurating gall-ducts 
(Fig. 539). In more advanced stages the abscesses may become large 
and communicate with one another, so that a considerable portion of 
the liver may be occupied by a series of communicating cavities with 
ragged walls, containing pus and detritus of liver tissue more or less 
tinged with bile. 
The suppurative foci are almost coalescent in the infected region. This lesion was secondary to 
suppurative inflammation in the larger gall-passages with the presence of gall-stones. 
Fig. 539.-Suppurative Inflammation of the Gall-ducts in the Liver-Cholangitis. 
Such abscesses may become more or less completely inclosed by con- 
nective-tissue walls. The portal vein may also become inflamed, and 
perforations may be formed between it and the bile-ducts. The excitants 
of these inflammatory processes in the gall-ducts and gall-bladder are 
probably usually bacteria. Those which have been most frequently 
found are the "pyogenic cocci,"1 the colon and typhoid bacilli, and the 
pneumococcus. It should be borne in mind that post-mortem invasion 
of the gall-bladder and passages by bacteria may take place early. 
Tuberculosis of the gall-bladder occurs in two forms: 1, In conjunc- 
tion with calculus cholecystitis as a secondary infection in an already 
diseased bladder; and, 2, as an active ulcerating lesion of the mucosa of 
1 For infections consult Cushing, Bull. Johns Hopkins Hosp., 1899, x, 166 (bibl.); and Posselt, A., 
Lubarsch-Ostertag, Ergobn. d. allg. Path., 1915, xvii2, 719 and 1919, xix1, 351. THE LIVER 
845 
the bladder without much thickening. In connection with this form 
there is usually an accompanying tuberculosis of the bile-ducts. Both 
forms are merely special localizations of a general tuberculosis existing 
in the body.1 
Constriction and Occlusion of the Bile-Ducts.-This may be produced 
by inflammation of the ducts themselves, by new growths in their walls, 
by calculi or parasites in their lumina, by changes in the hepatic tissue 
in chronic and acute hepatitis, by aneurysms, or by pressure on the duct 
from without, as by tumors in the head of the pancreas, etc. 
The obliteration of the smaller bile-ducts produces no marked lesions. 
When the ductus communis or the hepatic duct is obstructed, the ducts 
This section is from a small tumor growing within one of the gall-ducts in the liver. 
Fig. 540.-Adenoma of the Gall-Duct. 
throughout the liver are frequently dilated and the liver tissue is bile- 
stained. The liver may undergo atrophy and the whole body be intensely 
jaundiced. When the cystic duct is obstructed the gall-bladder is 
dilated.2 
Dilatation of the Bile-Ducts is usually produced by strictures in the 
ways just mentioned, or by calculi. When calculi have produced the 
dilatation this condition may sometimes continue after they have found 
their way into the intestines. Sometimes, however, there is very 
marked dilatation of the bile-ducts without evident present or past 
obstruction. The dilatation may affect only the common and hepatic 
ducts, or it may extend to the smaller ducts in the liver, which are then 
i Simmonds, M., Verhandl. d. deutsch. path. Gesellsch., 1910, xiv, 332. 
2 For a study of congenita) obliteration of bile-ducts, see Howard and Wolbach, Arch. Int. Med., 1911, 
viii, 557. 846 
THE LIVER 
dilated uniformly or in sacculated forms. They may contain bile, mucus, 
or calculi. The liver is at first enlarged, but may afterward atrophy. 
The gall-bladder may be dilated in consequence of obstruction of the 
common or the cystic duct. In the latter case it may reach an immense 
size and form a large tumor in the abdominal cavity. The dilatation 
is generally uniform, the bladder retaining its normal shape; sometimes, 
however, there are diverticula, which are usually produced by calculi. If 
the obstruction to the hepatic duct is incomplete or movable the gall- 
bladder may contain bile, and often calculi. If the obstruction is 
complete the contained fluid may gradually lose its biliary character and 
become a serous or mucous fluid of a light yellow color-hydrops cystidis 
fellece. The walls of the bladder may be of normal thickness, or thinned, 
or thickened, or calcified. If the obstruction is due to a calculus, this 
may pass into the intestine and the gall-bladder be suddenly emptied. 
Usually the bladder fills again, owing to its loss of contractile power. 
TUMORS OF THE GALL-BLADDER AND LARGER GALL-DUCTS. 
Small fibromata have been described in the gall-bladder and in the 
common duct, but they are very rare. Adenoma (Fig. 540) and papil- 
loma1 of the gall-ducts are of occasional occurrence.2 
The most common tumor, however, is the carcinoma,3 which may be 
either primary or secondary, and presents the usual structural variations. 
The cells may be cylindrical or polyhedral or present the characteristics 
of gelatinous cancer,4 while keratinizing carcinomata and epitheliomata 
have been described,5 though they are rare. 
Primary carcinomata are not infrequently combined with calculi.6 
This association is frequently advanced as an argument in favor of the 
importance of chronic irritation in the etiology of carcinoma, though there 
are not wanting authorities who regard the carcinoma as the primary 
lesion, the gall-stones being precipitated secondarily on account of the 
roughening of the epithelial surface or the presence of bits of debris, etc.7 
It has been pointed out that only in the case of cholesterin stones can 
it be assumed that the calculi antedate the cancer.8 Not infrequently 
the common duct and the pancreatic duct are both involved, and in such 
a case it is difficult to say whether the tumor arose primarily in the head 
of the pancreas or in the gall-ducts. The gall-bladder and its ducts may 
be secondarily involved in carcinoma of the stomach, liver, and duo- 
denum. Complex tumors of glandular and squamous-cell type9 have 
been observed, but are very rare. 
1 SchoenlanH, Frankfurt. Ztschr. f. Path., 1915, xvi, 293 (bibl.). 
2 For a discussion of diseases of the gall-bladder, including tumors, see Konjetzny, Lubarsch-Ostertag, 
Ergebn. d. allg. Path., 1910, xiv2, 712 (bibl.). 
3 Sherrill, Ann. Surg., 1906, xliv, 866 (bibl.). 
4 Treutlein, Centralbl. f. allg. Path., 1901, xii, 825 (bibl.). 
B Herxheimer, Zieglers Beitr., 1907, xli, 348 (bibl.); Lubarsch, Verhandl. d. deutsch. path. Gesellsch., 
1906, x, 198, 208; Nicholson, Jour. Path, and Bacteriol., 1909, xiii, 41 (bibl.); Simmonds, Centralbl. f. 
allg. Path., 1911, xxii, 577 (bibl.). 
6 Warthin, Philadelphia Med. Jour., 1900, vi, 38 (bibl.); Siegert, Virchows Arch., 1893, cxxxii. 353 
(bibl.). 
7 Konjetzny, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1910, xiv2, 712 (bibl.). 
8 Aschoff and Bacmeister, Die Cholelithiasis, Jena, 1909. 
9 Simmonds, M., Centralbl. f. allg. Path., 1911, xxii, 577. THE LIVER 
847 
Sarcoma of the gall-bladder, also, is rare.1 
BILIARY CALCULI. (Cholelithiasis.) 
These bodies are of common occurrence. They are found usually in 
the gall-bladder, sometimes in the hepatic, cystic, and common ducts; 
less frequently in the small ducts of the liver. In the gall-bladder from 
1 to 7,800 calculi have been counted. They vary in size from that of a 
pin's head to that of a hen's egg, or they may be larger. Single gall- 
stones are usually spheroidal or ovoidal; when multiple they are usually 
flattened at the sides or faceted (Fig. 541). 
They may be composed:2 
1. Principally of cholesterin, and may be of pure white color, or 
tinged with various shades of yellow or brown by bile pigment. The 
fractured surface shows a radiating crystalline structure. 
2. Of cholesterin, bile pigment, and salts of calcium and magnesium. 
These are usually dark colored, brown, reddish black, or green, and may 
Fig. 541.-Biliary Calculi. 
The smaller calculi show the faceted character; the larger, cut across, show the lamellation. 
be spheroidal or faceted, smooth or rough on the surface; the fractured 
surface is usually radiating crystalline. This is the most common form. 
3. Principally of calcium bilirubinate. Such calculi are rare, usually 
small, very dark colored, and not numerous. They occur not only in 
the gall-bladder but also in the smaller bile-ducts of the liver, where they 
incite a fatal form of obstructive jaundice. They may also lie in pockets 
formed of dilated ducts in the wall of the gall-bladder. 
4. Of calcium carbonate. These are rare, have a nodular surface, and 
a clear crystalline, not radiating fracture. 
Most calculi are formed around a central mass, sometimes called the 
nucleus, which may consist of cholesterin, bile pigment, mucus, epi- 
1 Landsteiner, Wien. klin. Wchnschr., 1904, xvii, 163 (bibl.); SchoenlanK, Frankfurt. Ztschr. f. Path., 
1914, xv, 307 (bibl.). 
2 For a study of the chemical composition of gall-stones, see Rosenbloom, J., Jour. Am. Med. Assn., 
1917, Ixix, 1765. 848 
THE LIVER 
thelium, or masses of bacteria, or more rarely of some foreign body. 
Thus a dead parasite, a needle, or fruit seeds may serve as nuclei. The 
body of the calculus may be homogeneous, or lamellated, or crystalline.1 
The cause of calculus formation is usually chronic inflammation of the 
bile passages with changes in the composition of the bile.2 Hypercholes- 
terinemia, such as is seen in pregnancy, may be a factor.3 The role of 
microorganisms in the formation of gall-stones has been the subject of 
significant studies.4 
Biliary calculi in the gall-bladder may produce no symptoms and be 
discovered only after death. In the hepatic and common ducts they may 
obstruct the flow of bile and lead to fatal jaundice; or they may pass 
from time to time into the intestine, producing biliary colic. If they 
are impacted in the cystic duct they may lead to dilatation of the gall- 
bladder. They may get into the duodenum by ulceration through the 
walls of the ducts or gall-bladder, or in the same way into the peritoneal 
cavity. Gall-stones which get into the intestinal cavity usually pass off 
without doing any further injury, but very large calculi may cause 
occlusion of the gut with fatal results. 
1 On formation of gall-stones, see Aschoff and Bacmeister, Die Cholelithiasis, Jena, 1909. 
2 Kretz, R., Krehl and Marchand, Handbuch d. allg. Path., Leipzig, 1913, ii, Abt. ii, 493; and Kelly, 
A. O. J., Am. Jour. Med. Sc., 1906, cxxxii, 446, 744. 
3 McNee, Deutsch med. Wchnschr., 1913, xxxix, 994. 
4 Consult Mignot, Arch. g6n. de m6d., 1898, ii, 129, 263; Cushing, H., Bull. Johns Hopkins Hosp., 
1899, x, 166; Mieczicowsiti, Mitt. a. d. Grenzgeb. d. Med. u. Chir., 1900, vi, 307; and Rosenow, E. C., 
Jour. Infect. Dis., 1917, xix, 527 (bibl.). CHAPTER IX. 
THE URINARY ORGANS. 
The Kidneys. 
Anatomy. 
The kidney is a paired organ of great anatomical complexity, correlated in its 
structure with the manifold activities of its component cells. The vascular supply 
Cortex 
Outer 
strip 
Outer zone 
Inner strip 
Inner zone 
Showing the localization of the maximal changes due to A, uranium salts, B, mercuric chloride, 0, 
chrome salts. (.After Suzuki.) 
Fig. 542.-Schema of the Urinari Tubules 
is so large that the whole of the blood in the body passes through the kidney every 
few minutes. 
849 850 
THE URINARY ORGANS 
The important unit structure is the kidney tubule. This begins as a cup-shaped 
cavity inclosing a tuft of arterioles covered with flattened cells. On leaving the 
Malpighian corpuscle the tubule narrows to a neck, then becomes convoluted, forming 
the proximal convoluted tube (Jiauptstuck), some 14 mm. in length. Differences in 
impregnation of the lining cells with carmine, and the results of poisoning with metallic 
salts suggest that there are four different segments of the convoluted tubule considered 
functionally (Fig. 542). The tubule gradually approaches the nearest medullary ray, 
still spiral or zigzag in shape, and turns toward the medulla as the descending portion 
of the loop of Henle, which is narrow, measuring only one third of the diameter of 
the convoluted tubule, though the lumen is as large as that of the convoluted portion. 
Near the papilla, while still of small diameter, it turns about, enlarging somewhat, 
and runs back toward the cortex as the distal or ascending loop of Henle, to touch 
the glomerulus from which the tubule originally sprang. The length of Henle's loop 
varies, but the average is about 9 mm. The tube again becomes convoluted on leav- 
ing the region of the Malpighian corpuscle to which it had returned. This part is 
called the second or distal convoluted tubule {Schaltstuck'). This has two portions: 
(a) the intermediary piece, about 0.8 mm. long, which forms the transition between 
the distal loop of Henle; and (6) the true distal convoluted tubule. Its lumen is 
wide and the lining epithelium is low. The distal convoluted tubule is about 4.5 
mm. long; its contour is irregular, the lumen is large and often pouched; and the epi- 
■A BCD 
A, Convoluted tubule. B, Descending loop of Henle. C, Ascending loop. D, Intermediary piece. 
E, Collecting tubule. 
Fig. 543. Sections, at Various Levels, of the Urinary Tubule. 
thelium is low. It once more narrows into the so-called junctional tubule, and taking 
a transverse course toward the medullary ray enters one of the straight or collecting 
tubules which lead to the papilla and the pelvis. The total length of a renal tubule 
is from 30 to 38 mm., depending upon the situation of the glomerulus. 
The epithelium lining the convoluted portion is high and cylindrical. The cell 
substance is granular and has a rod-like arrangement which terminates on the free 
surface in a thin layer of rods like short cilia. The descending loop of Henle is lined 
with very low epithelium which is not granular. The ascending loop, on the contrary, 
has granular cells and a rod-like structure, but no rod border. The intermediate 
piece has low epithelium which becomes thicker in the distal convoluted portion. The 
collecting tubules can be distinguished from the descending loop by their sharply 
outlined cells.1 
While the distinction between the cortical and the medullary substances of the 
kidney is usually made without difficulty in normal organs, there are several smaller 
divisions of some anatomical importance which are less easily differentiated. The 
cortical substance, which measures 4.8 mm. in thickness, is conventionally divided 
into a labyrinthine portion, in which lie the glomeruli surrounded by convoluted 
tubules, and the medullary rays, where the convoluted tubules pass downward to 
enter Henle s loop. Recently it has been shown that the medullary portion, which is 
18.3 mm. thick, is divided into an outer or boundary zone, measuring 8.2 mm., and 
an inner or papillary zone, measuring 10.1 mm. The outer zone is again divided by 
1 For further details and bibl., see Peter, Bau und Entwicklung der Niere, Jena 1909• Suzuki 
Morphologic der Nierensekretion, Jena, 1912; Schafer, E. A., Text Book of Microscopic Anatomy' 
Quain's Elements of Anatomy, vol. ii, part 1, London, 1912; Cushny, A.R., The Secretion of Urine New 
York, 1917. THE URINARY ORGANS 
851 
a narrow line into an outer and an inner strip. The outer strip is the point of termina- 
tion of the convoluted tubule, where it enters the descending loop of Henle; it also 
contains the collecting tubules which are joined by the horizontally running inter- 
mediary pieces. The inner strip contains only the descending and ascending loops 
of Henle and the collecting tubules. The inner zone contains only the clear 
thin portions of Henle's loop together with the collecting tubules. Transverse 
sections made at these different levels, therefore, will show different types of tubules 
(Fig. 543.) 
The blood after flowing through the glomerulus enters a dense meshwork of 
capillaries which surround the tubules. The exact relationships between the morpho- 
logical structures of the tubules and their functional activities is, despite an enormous 
amount of experimental and clinical research, by no means clear. It seems probable, 
from the study of dye elimination and the phenomena subsequent to injury of portions 
of the tubules by poisons, that the salts are filtered through the glomeruli, and many 
of the colloid materials also, such as albumin and hemoglobin, though only after 
slight injury. It seems likely that the tubular epithelium has relatively little ex- 
cretory power, except possibly for a portion of the uric acid and the phosphates; 
but that the highly diluted filtrate from the glomeruli has its composition altered in 
its passage down the tubule by selective absorption of certain substances by these 
cells. It is thought that there is thus removed from the glomerular filtrate 50 per 
cent, of the water and most of the glucose, while it has been calculated that 99.9 per 
cent, of the chlorides passing the tufts is turned back into the blood. Amino-acids, 
also, are returned, and more alkali than acid, the tubular epithelium rejecting the 
phosphoric acid in the phosphates. Hence, the urine is acid, while the blood from 
which it comes is faintly alkaline. The capacity of the tubular epithelium to absorb 
substances may be stimulated or depressed. Thus, phlorhizin interferes with the 
return of the sugar, hence, the urine after exhibition of this glucoside contains glucose. 
Uric acid probably is excreted in part through the tubular epithelium, and atophan 
increases the permeability for this substance without damaging the kidney, as do the 
salicylates. 
Malformations. 
Both kidneys may be absent in connection with extensive malformation in fetuses 
which are not viable. 
Absence of one kidney is not uncommon, the left kidney being missing more fre- 
quently than the right. The absence of the kidney may be complete, the ureter also 
being absent; there may be an irregular mass of much atrophied kidney tissue with 
connective tissue and fat; or there may be only a little mass of connective tissue and 
fat representing the kidney, and a ureter running down to the bladder. The single 
kidney which is present is usually much enlarged. It may be in its natural position or 
displaced downward. When both kidneys are present one of them may be much 
larger than the other. One kidney may have two pelves or two ureters. 
It is not impossible that some of the very much shrunken kidneys found in adult 
life may be due to prenatal interference with vascular supply or closure of the ureter 
including atrophy.1 
A frequent malformation is the so-called horseshoe kidney2 (Figs. 193 and 544). 
The lower ends of the kidneys are joined together by a commissure, which is composed 
usually of kidney tissue, but sometimes of connective tissue. The two kidneys may 
be normal, except for the commissure; or their shape, the arrangement of the vessels 
and ureters, and the position may be unnatural. The two kidneys may be united 
throughout so as to look like a single misshapen kidney with two or more pelves and 
irregular blood-vessels. The united kidneys may both be situated on one side of the 
vertebral column or in the pelvis. The adrenal glands remain in their normal position 
in the body even when the kidneys are greatly displaced. 
1 See Ballowitz, Virchows Arch., 1895, cxli, 309; Scheuer, Ztschr. f. Heilk., 1907, xxviii, 120. 
2 For a study of various types, see Eisendrath, D. N., Surg., Gynec., and Obst., 1912, xv, 467. 852 
THE URINARY ORGANS 
Double ureters may occur with normal kidneys.1 
The fetal lobulation of the kidney frequently persists during adult life (Fig. 545). 
Fig. 544.-Horseshoe Kidney. 
Fig. 545.-Fetal Lobulation of Kidneys in Adult. 
The kidneys were of normal size. 
The kidneys may be placed in an abnormal situation, in which they are either 
fixed or movable. 
Changes in Position. 
1 Meyer, R., Virchows Arch., 1907, clxxxvii, 408. For a general survey of the subject, see Hunting- 
ton, G. S., Variations of the genitourinary tract, Harvey lectures, 1906 -07, Philadelphia, 1908, p. 222. THE URINARY ORGANS 
853 
The change in position is either lateral or downward. When displaced downward 
the kidney may be over the sacrum or below this in the cavity of the pelvis. The 
vessels also have an irregular origin and distribution.1 The kidney is firmly attached 
in its abnormal position. . 
Movable or wandering kidneys are found in adult life, especially in those with 
general enteroptosis, but also as a result of tight lacing, of overexertion, and of un- 
known causes. They are very common in females, particularly those who have been 
pregnant; and the right kidney is most frequently involved. The blood-vessels be- 
come lengthened and the attachments of the kidneys longer and looser. Mobility 
in males is infrequent. 
COMPENSATORY HYPERTROPHY OF THE KIDNEY. 
In congenital absence of one kidney or in post-embryonal life when 
one kidney is involved in lesions which seriously interfere with its 
function, the other organ may increase in functional capacity through 
an hypertrophy and hyperplasia of its gland cells. A similar alteration 
may take place in the sound parts of an organ partially compromised by 
structural lesions.2 The marks of hypertrophy are not evident in the 
glomeruli and convoluted tubules. The epithelial cells are larger and 
increased in number; the tufts of the glomeruli also are enlarged. 
REPAIR OF THE KIDNEY. 
The tubular tissue of the kidney has but little regenerative power; 
the glomeruli none at all. A certain amount of regeneration of the tubu- 
lar epithelium occurs with moderate toxic destruction, especially subse- 
quent to sublimate poisoning, and also after experimental hydronephrosis 
when the obstruction is relieved. Regeneration of the tubules to a 
moderate degree may be seen after operative incision into the substance, 
but most of the reparative material is connective tissue.3 
ATROPHY. 
In old age, the kidney may atrophy, with increase of the fat of the 
capsule and hilus. The cellular elements and the glomeruli also shrink, 
and the latter show hyaline changes. The tubular epithelium may be 
pigmented, and minute calcified cysts may be apparent on section. 
When the flow of urine from the kidney is suddenly stopped, the kidney 
may atrophy, with replacement fibrosis, but the glomeruli survive for a 
long period. If the interruption is intermittent or slow, hydronephrosis 
results (page 885). Vascular changes leading to diminished blood supply 
cause atrophy of the kidney (page 851). 
DISTURBANCES OF CIRCULATION. 
Anemia of the kidney occurs in general anemia: it may be associated 
with various forms of diffuse nephritis. Local anemia may be due to 
thrombosis or embolism. 
1 Anitschkow, N. N., Virchows Arch., 1912, ccvii, 213. 
2 For a study of this condition see Sacerdotti, C., Virchows Arch., 1896, cxlvi, 267 (bibl.). Consult 
also for general consideration of hypertrophy, Thoma. Text-book of General Pathology, English 
translation, London, 1896, vol. i, 448. 
3 Wood, F. C., Process of Repair, Keen's Surgery, Philadelphia, 1906, i, 410. 854 
THE L'RINARY ORGANS 
Acute Hyperemia-Acute Congestion.-This may occur in early 
phases of an acute inflammatory process or after the ingestion of irritant 
poisons. The kidneys may be swollen, and the vessels distended, and 
bloody fluid may exude from the cut surfaces. There may be extravasa- 
tion of red blood-cells from diapedesis. 
Chronic Hyperemia-Chronic Congestion.-This may occur in con- 
nection with a similar condition in the other viscera when the circulation 
is impeded through uncompensated lesions of the heart and lungs, such as 
chronic endocarditis involving the aortic and mitral valves, cardiac dila- 
tation, aortic aneurysm, emphysema, or large accumulations of fluid in the 
pleural cavities; or it may be associated with obstruction of the renal 
vein or inferior vena cava by thrombosis or pressure from tumors, etc. 
The kidneys in this condition are, when typical, slightly or considerably 
enlarged, increased in weight, hard, and dark red in color with capsule 
not adherent and surface smooth. The congestion is most marked in the 
capillaries of the glomeruli, which are widely dilated, often with thickened 
walls, in the interlobular veins, the vasa recta, and the stellate veins of 
the cortical surface. 
The epithelium of the convoluted tubules may be swollen; or it may 
be much flattened so that the lumen of the tubule is enlarged. If the 
congestion persists, there is hyperplasia of the interstitial tissue of the 
kidney with degeneration of the epithelium, the formation of casts, 
atrophy of the tubules, etc. Chronic congestion may lead to chronic 
diffuse nephritis.1 
Embolism, Thrombosis, and Infarction.-If the renal artery or one of 
its branches be plugged by an embolus or thrombus, an anemic infarct 
of the region is the result. There may be one or several such infarcts 
which are usually more or less wedge-shaped, the apex directed inward, 
corresponding to the vascular territory compromised. They are pale or 
yellowish, and hard, and, as inflammatory reaction sets in, may be sur- 
rounded by a red hyperemic zone.2 
Within the limits of the infarct, necrosis of epithelium or of the 
entire mass of involved tissue may take place with such subsequent 
alterations as have been already described on page 36. 
The seat of old and healed infarcts may be indicated by small fibrous 
cicatrices.3 
Hemorrhagic infarcts in the kidney are rare. Infarcts may become 
the seat of gangrene when putrefactive bacteria gain access to them; 
or suppurative inflammation with the formation of abscesses may occur. 
Embolism of the renal artery may result in necrosis of the entire kidney. 
Thrombosis of the renal vein may be induced by the pressure of tumors, 
either on this vessel or on the vena cava; or it may occur in cachectic 
conditions. 
1 For a study of theories of renal secretion, see Lamy and Mayer, Jour, de phys. et path. g£n., 1906, 
viii, 660; and Cushny, A. R., The Secretion of Urine, New York, 1917. 
2 Studies in infarction: Experimental bland infarction of the kidney and the spleen. H. J. Karsner 
and J. .H. Austin, J. A. M. A., 1911, Ivii, 951. 
3 For a study of the regenerative capacity of the renal epithelium in infarcts, see Thorel, C., 
Virchows Arch., 1896, cxlvi, 297 (bibl.), and Deutsch. Arch. f. klin. Med., 1903, Ixxvii, 29. THE URINARY ORGANS 
855 
DISTURBANCES IN EXCRETION. 
Albuminuria.-Albuminous material or serum, with or without hemo- 
globin, not infrequently passes out of the blood-vessels of the kidneys 
through the glomerular tufts, and mingles with the excreted substances. 
It may also be set free by abnormal metabolism or disintegration of the 
renal epithelium. While this may occasionally occur under conditions 
which can not be shown to be abnormal, it is common in many diseases 
of the kidney, and is frequent, without marked kidney lesions, in fevers, 
infectious diseases, abnormal conditions of the blood, various forms of 
poisoning, disturbances of the circulation, ingestion of large amounts of 
native protein, especially egg albumin, etc. Even when kidney disease 
exists, the excretion of albumin may be very small in amount or may 
entirely cease so long as the patient is in a recumbent position, becoming 
large in amount, however, when the erect posture is assumed. 
An especial form of albuminuria without the accompaniment of casts 
or red blood-cells is seen in children, especially those of feeble or anemic 
constitution. It is perhaps best described as " postural" or " orthostatic 
albuminuria," and seems to be due to circulatory irregularities in the kid- 
neys of children who remain long in a strained position. A spinal lordosis 
is responsible for a certain number of instances, and the erect posture 
alone may at times bring on the phenomenon.1 
In albuminuria with pronounced kidney lesions there are usually well- 
defined alterations in the capillaries of the tufts and in their epithelial 
investment. There may be thrombi in the capillaries; their walls may 
be thickened; the flat epithelium covering them may be swollen or fatty; 
or it may peel off or proliferate. In the kidneys of persons with pro- 
nounced albuminuria, albuminous material may be seen as fine or coarse 
granules within Bowman's capsule or in the lumina of the tubules, after 
preservation in alcohol or other fixatives which coagulate albumin. 
Albuminous material in the tubules may form casts (see below), or when 
the conditions are favorable fibrillar fibrin may be formed. 
Hematuria.-The appearance in the urine of blood in considerable 
quantities may be due to hemophilia, to acute or chronic nephritis, to 
tumors of the kidney, to renal tuberculosis, or to stone in the pelvis. 
There is one type of hematuria, however, in which none of these causes 
can be demonstrated, and to this, because of the lack of a suitable name, 
the term "essential hematuria" has been applied. The disease occurs 
most frequently in males between the ages of forty and fifty years. The 
amount of blood passed may be large, and its appearance is usually inter- 
mittent, with considerable periods between the attacks. The phenom- 
enon may last for years, and in order to stop the hemorrhage it may be 
necessary to remove the kidney, though occasionally a cure has been 
observed after incision of the kidney or even after stripping of the capsule. 
The hemorrhage has been ascribed to a variety of lesions. Although 
1 Jeanneret, Arch, de med. d. enfants, 1915, xviii, 461; Hill, L. W., Am. Jour. Dis. Child., 1918, xv, 
146 (bibl.); Lanystein, Pfaundler and Schlossmann, Diseases of Children, English trans., 2d ed., Phila- 
delphia, 1912, iv, 1; and Die Albuminurien alterer Kinder, Leipzig, 1907; and Jehle, Ergebn. d. inn. 
Med. u. Kinderheilk., 1913, p. 808. 856 
THE URINARY ORGANS 
the kidneys are, as a rule, not especially movable, it has been thought 
that a slight kinking of the renal vein, with the incident chronic conges- 
tion, might cause the bleeding. Again, as there is often a fairly extensive 
arteriosclerosis of the kidney vessels, or erosions in the pelvic mucous 
membrane, or a papillitis or varicosity of the veins of the renal papillae, 
these lesions have been considered as explaining the hemorrhage; but 
none of them is constantly present and the most striking thing in the 
examination of such kidneys is the slight amount of disease which is 
often found.1 
Casts.-Albuminous material which under various abnormal condi- 
tions has escaped from the blood-vessels in solution may solidify or coagu- 
late, especially in the lumina of the tubules, owing to the abstraction of 
water and increased acidity, thus forming the more or less cylindrical or 
globular structures called casts. These may be homogeneous in structure 
-hyaline casts; or the albuminous material of which they are formed 
There are also degeneration and disintegration of the epithelium. 
Fig. 546.-Hyaline Globules in Uriniferous Tubule. 
may be mingled with the products of degeneration and disintegration of 
epithelial cells, either from the glomeruli or from the tubules or with red 
blood-cells, or leucocytes, or exfoliated epithelial cells. In this way 
granular casts, epithelial casts, blood-casts, etc., are formed. The epithe- 
lium of the tubules may peel off in masses, forming cast-like cell struc- 
tures. Homogeneous globules of various sizes may be formed in the 
epithelium of the convoluted tubules which is yet in place, and, as the 
cells degenerate and disintegrate, such homogeneous globules may collect 
in the lumina of the tubules (Fig. 546). The exact nature of these gran- 
ules is as yet a matter of discussion. They have been considered as 
secretory products allied to or derived from the Altmann granules, but 
1 For discussion and bibl. of the subject, see Braasch, IF F., Jour. Ain. Med. Assn , 1913, Ixi, 936; 
Spitzer, W. M, ibid., 1914, Ixiii, 2110; and Payne, R. L., Surg., Gynec., and Obst., 1916, xxiii, 76. For 
a discussion'of these cases from a surgical standpoint, see Payne, R. L., and MacNider, If7. B., Jour. 
Am. Med. Assn., 1916, Ixvii, 918 (bibl.). 857 
THE URINARY ORGANS 
the weight of opinion is that they are degenerative products.1 It is 
possible that they assist in the formation of hyaline casts after reaching 
the lumen of the tubule (Fig. 547). Homogeneous casts giving the micro- 
chemical characters of amyloid are of occasional occurrence in the tubules. 
Casts and cell detritus may form both in the cortical and medullary 
tubules and may pass out of the organ with the urine. 
NECROSIS. 
Necrosis of the epithelium of the kidney of varying extent may 
occur in disturbances of the circulation by thrombosis, degenerations, 
etc., in acute infectious diseases, in various nutritional disorders, such 
Fig. 547.-Hyaline Casts in Uriniferous Tubule. 
The epithelium is flattened in the tubules containing the casts. 
as gout, diabetes, etc., or autointoxications, as well as in poisoning by 
various substances, cantharidin, sublimate,2 chromates, chlorates, tar- 
trates, salicylates,3 uranium salts, arsenic (salvarsan), bismuth,4 etc. 
In sublimate and oxalic-acid poisoning, and after prolonged roentgeniza- 
tion,5 calcification (Figs. 33 and 35) may be associated with the necrotic 
process. 
The extent of the lesion varies greatly. In some instances a large 
part of the epithelium of the convoluted tubules may be necrotic without 
marks of inflammation. In other cases the lesion involves the tubules 
in limited regions (Fig. 542). It is suggested that certain forms of ex- 
tensive necrosis of renal epithelium are the analogues of some forms of 
acute yellow atrophy of the liver.6 In fact the kidney lesion may accom- 
pany acute yellow atrophy. 
1 See, for discussion of this question, Volhard and Fahr, Die Brightsche Nierenkrankheit, Berlin, 
1914. 
2 For studies on sublimate poisoning, see Neuberger, Zieglers Beitr., 1889, vi, 429; also Heineke, A., 
Zieglers Beitr., 1909, xlv, 197 and Elbe, Virchows Arch., 1905, clxxxii, 445. 
3 Hanzlik and Karsner, Arch. Int. Med., 1917, xvi, 1016. 
4 For cases of bismuth poisoning, see Mayer and Baehr, Surg., Gynec., and Obst., 1912, xv, 309 (bibl.). 
6 Warthin, A. S., Jour. Am. Med. Assn., 1907, cxxxiii, 736. 
6 For a resume of necrosis of renal epithelium,see Heivitt, Bull. Johns Hopkins Hosp., 1906, xvii, 272. 858 
THE URINARY ORGANS 
DEGENERATION. 
Albuminous Degeneration (Parenchymatous Degeneration-Acute 
Degeneration).-This form of degeneration is most common in the acute 
infectious diseases, such as diphtheria, scarlatina, measles, typhoid fever, 
yellow fever, and in many forms of septicemia, toxemia, or poisoning. It 
corresponds with the first stage of the simple nephroses according to 
Volhard and Fahr.1 It usually accompanies similar lesions in other vis- 
cera, as in eclampsia. In moderate degrees of the lesion, the epithelium, 
particularly of the convoluted tubules, is swollen and more coarsely gran- 
ular than normal (Fig. 548). In more pronounced lesions, in addition 
Fig. 548.-Albuminous Degeneration of the Kidney (Acute Parenchymatous Degeneration). 
From a case of yellow fever, a, The swollen and granular epithelium peeling off and disinte- 
grating; b, hyaline material in the lumen of the tubule. 
to simple albuminous degeneration, the epithelium may become more or 
less filled with minute fat droplets, or the cells may disintegrate and 
peel off, or they may become necrotic and the nuclei fail to stain. The 
cell body may then undergo coagulation or disintegrate. Similar pic- 
tures are produced by post-mortem autolysis, especially after severe in- 
fections involving the peritoneal cavity, so that unless the material is 
obtained immediately after death, a decision as to the significance of the 
lesion may be difficult. 
The gross appearance of the kidneys varies with the degree and 
extent of the degeneration. The kidney may be slightly or considerably 
enlarged. On section the cortex is usually thickened and pale with 
1 Volhard and Fahr, Die Brightsche Nierenkrankheit, Berlin, 1914. This valuable monograph con- 
tains a large number of observations, both clinical and pathological, on a number of nephritics studied 
by modern methods. THE URINARY ORGANS 
859 
obliteration of the normal cortical markings. The capsule of the kidney 
is not abnormally adherent. When there are other associated or ante- 
cedent lesions in the kidney, the gross appearance of the organ varies. 
Fig. 549.-Fatty Degeneration of the Epithelium in the Convoluted Tubules of the Kidney 
The fat droplets are stained black by osmic acid. 
If the lesion is not too extensive, complete restitution of the kidney may 
take place; but if the excretion of toxic substances is long continued, 
vascular and interstitial changes set in which are anatomically irreparable, 
though the kidney may functionate normally after the lesion has subsided. 
Fig. 550.-Amyloid Degeneration of Tuft Capillaries in the Kidney. 
a, The tuft is completely transformed into a waxy mass; b, portions of tuft waxy; c, tuft capillaries 
normal; d, convoluted tubule with disintegrating epithelium. 
Fatty Degeneration and Infiltration.-This may occur in those dis- 
eases of the blood or circulatory system in which general nutrition suffers; 
in infectious diseases often associated with or following albuminous degen- 860 
THE URINARY ORGANS 
eration; in various cachexiee; in acute and chronic forms of diffuse kidney 
disease, and in poisoning by phosphorus, arsenic, sublimate, etc. 
The degeneration may be diffuse and widespread or it may occur in 
patches; if it is diffuse, the cortex, in which it is most marked, is usually 
more or less thickened, opaque, and yellowish; if in patches there are 
opaque yellow streaks or spots in the cortex. But these appearances are 
often obscured by various other lesions. If the degeneration be moderate 
in degree, there are larger and smaller fat droplets, usually most abundant 
in the basal portion of the epithelium of the convoluted tubules (Fig. 549); 
but it must be remembered that a small amount of fat in the cells of 
Henle's loop and the distal convoluted tubules is physiological. In more 
marked degeneration, the cells of the convoluted tubules may be filled 
with fat droplets and may peel off; or they may disintegrate, setting the 
fat free in the lumen of the tubules. The degeneration may involve the 
tuft and capsule epithelium as well as that of the collecting tubes, and 
fat droplets may be found free or in cells in the interstitial tissue. It is 
not always possible in the slighter degrees of fatty change in the kidneys 
to distinguish between fatty degeneration and a mere fatty infiltration 
of the cells. It is usual to assume the latter condition unless there are 
other evidences of degeneration in the cells, such as alterations in the 
Fig. 551.-Glycogen Degeneration of the Epithelium of the Kidney in Diabetes 
nuclei, etc. The fat granules are often doubly refractile, indicating the 
presence of soaps or cholesterin compounds.1 
Amyloid Degeneration.-This is usually associated with amyloid de- 
generation elsewhere in the body, and commonly occurs in kidneys which 
are already the seat of various forms of acute or chronic lesions. The 
capillaries of the tufts (Fig. 550) and the vasa recta are most often 
involved. 
Glycogen Degeneration of the epithelium may take place in diabetes 
mellitus. It is usually most marked in the cells of the terminal portion 
of the convoluted tubules and the first part of Henle's loop (Fig. 551). 
Calcification may occur in chronic inflammatory lesions or in old 
infarctions, in the papillae, in the intertubular tissue of the medulla in 
the aged, and in casts in the collecting tubes, and is especially well marked 
in degenerated and necrotic epithelial cells in sublimate poisoning (Fig. 
33 and 35).2 
1 Kawamura, Die Cholesterinesterverfettung, Jena, 1911; also Adami, The Myelins, etc., Harvey 
Lectures, 1906-07, Philadelphia, 1908, p. 117. 
2 See Neuberyer, J., Zieglers Beitr. 1889. vi, 429: Heineice, A., ibid., 1909, xlv, 197; Elbe, Virchows 
Arch., 1905, clxxxii, 445. THE URINARY ORGANS 
861 
The formation of bone and bone-marrow in the kidney substance may 
be induced experimentally by temporary ligature of the renal artery. In 
the human kidney, bone and marrow have been found in old infarcts 
and in other conditions.1 
Pigmentation of the tubular epithelium from absorption occurs in old 
age, in jaundice as a deposit of bilirubin, in hemoglobinuria, and in per- 
nicious anemia when the hemosiderin may be demonstrable only by suit- 
able reagents. Granules of silver compounds may be found in the tube 
cells in argyria. 
Uric Acid Deposits or, more correctly, sodium urate deposits, are 
found as white chalky nodules in the medullary portion of the kidney in 
gouty adults. An area of necrosis and inflammatory reaction surrounds 
the deposit and foreign-body giant cells may be found. 
In infants, the so-called uric acid infarcts may be seen in the papillae. 
The crystals are spherical masses of radiating structure, doubly refracting, 
composed of ammonium urate. Such infarcts are frequent in the new- 
born and have been found occasionally in the kidneys of adults suffering 
from leukemia and pneumonia, both diseases in which large amounts of 
uric acid are formed from the destruction of leucocytes. In infants at 
birth the blood uric acid is normal, but it increases in a few days, probably 
from the destruction of the nucleated red cells and leucocytes of the 
blood as the child adapts its circulation to postnatal conditions.2 
DEGENERATIVE AND INFLAMMATORY DISEASES OF THE KIDNEY. 
General Considerations. 
In the classification which for the moment seems most practical, 
those lesions of the kidney in which the degenerative processes predomi- 
nate are collected under the heading "Nephroses;" these may be simple 
or complicated with other lesions. Those lesions in which inflammatory 
phenomena predominate are termed "Nephritides," with the usual sub- 
divisions of suppurative and acute diffuse. The latter may be conven- 
iently divided into the diffuse glomerular, the focal glomerular, the focal 
interstitial, and the focal embolic types. All of these may pass over into 
chronic forms of nephritis as the acute inflammatory process subsides. 
Finally, there is a class of kidney lesions, not primarily inflammatory, 
which may be called arteriosclerotic nephropathies. The kidney altera- 
tions may be the consequence purely of arterial change-the arterio- 
sclerotic kidney of Ziegler3-or the arterial degenerations may be com- 
bined with changes of an inflammatory origin producing the lesion long 
designated as the true contracted kidney. The nephritides due to tuber- 
culosis and syphilis are, as usual, considered separately. 
This classification by no means includes all types of kidney lesions 
which may be met with; it offers merely a series of roughly defined groups 
1 Pearce, R. M., Proc. New York Path. Soc., 1908, viii, 116; Tanaka, T., Zieglers Beit., 1912, liii, 338; 
Pirondini, Policlinico, 1917, xxiv, 339. 
2 See Sedgwick and Kingsbury, Am. Jour. Dis. Child., 1917, xiv, 98. 
3 Ziegler, Deutsch. Arch. f. klin. Med., 1879-80, xxv, 586. 862 
THE URINARY ORGANS 
in which the dominant lesions may be conveniently arranged and 
discussed.1 
The processes in the kidneys which may be properly considered in- 
flammatory are either exudative or productive, so that the apparently 
complex series of kidney changes which are grouped under the name 
nephritis or Bright's disease are really phases of exudative or productive 
inflammation, or of both, associated with degenerative processes. 
Whether the kidney be large or small, white or red or mottled, 
smooth or rough, whether the disease be acute or chronic, it is always 
these comparatively simple processes, varying in extent, in duration, in 
intensity, and in relative predominance, which are to be taken into 
account in the study of inflammation of this organ. 
The difficulties which are met with in the classification of renal disease 
are due to the fact that the various phases of inflammation and degenera- 
tion do not stand apart as independent processes or lesions, but are 
closely associated and often merge. It is difficult, perhaps impossible, 
to make a classification which shall meet the requirements of the clinic 
and the limitations of urinary tests, and at the same time accord with 
the revelations of the autopsy and the microscope. 
One of the chief obstacles in the framing of a detailed classification 
of kidney lesions is that there are many and serious abnormalities in the 
function of the kidney which do not find expression in such structural 
changes as we can at present recognize. Our knowledge of such of the 
minute structural lesions in the renal epithelium as are not manifested 
by alterations in the size and form and organic integrity of the cell is, in 
fact, very meager, so that the attempt to classify inflammatory lesions 
of the kidney upon both clinical and morphological data often leads to 
conjecture or confusion, frequently to both. Neither have the hopes 
based upon animal experiment been fulfilled, for it has as yet proved 
difficult or impossible exactly to reproduce in animals some of the im- 
portant renal lesions. 
Considering the scope of this book, it seems wiser, therefore, to set 
forth as concisely as possible the essential character of the lesions in acute 
and in chronic phases of inflammation and degeneration in the kidney, 
using the morphological data as a basis, and adding only such clinical 
findings as may assist in the comprehension of the disease as it affects 
not only the kidney but the body as a whole. 
The Nephroses. 
Poisons or bacterial toxins present in the blood are excreted through 
the glomeruli, and, acting upon the renal epithelium, give rise to degen- 
erative changes which are not strictly inflammatory in nature; hence, 
these lesions should not be classed as nephritis. Among the poisons 
which may so act are the chemical substances and bacterial products 
1 Those who are interested in the more complex phases of the question of nephritis will do well to 
consult Volhard and Fahr, Die Brightsche Nierenkrankheit, Berlin, 1914. For those to whom the 
German text is inaccessible, an excellent review and abstract with bibl., is given by Austin, J. H., 
Progr. Med., 1915, iv, 131. See, also, Aschoff, Pathologische Anatomie, 1913, 3d ed., vol. ii, 429-517, 
for further details and good bibl. THE URINARY ORGANS 
863 
mentioned in the previous paragraphs on necrosis and degeneration. The 
histological changes in the nephroses may be considered under four heads: 
1. The stage of cloudy swelling; 
2. The stage of extensive cellular changes; 
3. The stage of reaction in the vascular connective tissue; 
4. The stage of repair. 
The first phase is described in the paragraph on cloudy swelling; 
fatty degeneration may or may not be present in the convoluted tubule. 
The second phase is characterized by degenerative processes in the tubular 
epithelium, as hyaline-drop formation, disappearance of the nucleus, and 
often, but not always, extensive fatty degeneration; the glomeruli are 
not damaged. In the third stage, the fatty degeneration of the cells of 
the convoluted tubules becomes more prominent. There is desquamation 
and, in sublimate poisoning,calcification of the cells; casts and blood are 
present in the tubules. Inflammation is evident in the interstitial tissue, 
and a few glomeruli may show a capsular hyperplasia and ultimately 
atrophy of the tuft. In the last stage, the active process subsides, and 
the formation of scar tissue begins, with the atrophy of limited areas of 
tubules, the glomeruli in general not being affected. 
On gross examination, the kidney is seen to be congested and swollen 
in the first two phases; in the third it is a pale yellow with lost markings; 
and in the last stage it is small and mottled brown and yellow. The 
urine shows albumin and casts during the acute stage with retention of 
non-protein nitrogen. Even complete suppression is common in subli- 
mate poisoning. In the other forms, death is due, not to the kidney 
lesion, but to the progression of the infection. If the patient survive the 
acute lesion, the late effects of the poison on the kidney may be observed 
in the extensive growth of connective tissue between the tubules and 
about some of the glomeruli. Many of the latter, however, remain in- 
tact, so the blood-pressure is not elevated and cardiac hypertrophy is 
missing. Very good functional repair occurs in a large majority of 
properly treated cases of poisoning by corrosive sublimate,1 though even 
several years after restoration to apparent health traces of albumin and 
a few casts show that the kidney is not yet normal.2 
The nephrosis with amyloid degeneration of the vessels is due to long- 
continued bacterial infections, especially chronic osteomyelitis and tuber- 
culosis, and is, as a rule, accompanied by amyloid changes in the other 
organs of the body. The kidney shows the lesions just described; and, 
in addition, the vessels, especially the vasa recta, and tufts show extensive 
amyloid changes. In advanced lesions the degeneration may affect the 
interstitial tissue. Drop-like and fatty degenerations are often extensive. 
Large waxlike casts are present in the urine, but do not give the amyloid 
reactions (pp. 59 and 1213). The kidneys are large and pale, the cortex 
thick, the capsule free, and the substance firm and translucent. In the 
later stages there may be a diffuse growth of connective tissue with 
diminution in the size of the kidney. 
1 Lambert, S. W., and Patterson, H. S., Arch. Int. Med., 1915, xvi, 865. 
2 Goodwin, G. M., Jour. Am. Med. Assn., 1918, lii, 85. 864 
THE URINARY ORGANS 
Suppurative Nephritis. 
Suppurative inflammation of the kidney may follow injury with local 
infection. It is, however, most often due to the presence of bacteria, 
commonly the pyogenic cocci, which have been brought through the 
blood-vessels from a remote infective focus, as in ulcerative endocarditis, 
septic phlebitis, etc.-embolic infection. Or, on the other hand, the bac- 
terial excitant may be transmitted to the kidneys through the urinary 
passages or their lymphatics-ascending infection. 
Traumatic lesions of the kidney may lead to suppurative nephritis 
either through direct infection of the wound or by the establishment of 
local vulnerability to the action of bacteria which may later gain access 
to the injured tissue through the circulation.1 After infected wounds or 
injuries of the kidney, large abscesses may develop, or nearly the whole 
organ may be converted into a mass of pus, blood, and disintegrated 
tissue. 
In the embolic type of suppurative nephritis, small abscesses are formed 
most frequently in the cortex. Where bacteria lodge and grow in the 
tissue there is at first circumscribed hyperemia or hemorrhage and 
necrosis, with subsequent gathering of leucocytes and finally the disin- 
tegration of tissue and the formation of abscess. Such kidneys present 
to the naked eye on section small spots-or in the medulla, streaks- 
which are red or gray or yellow, depending upon the degree of advance- 
ment of the lesion. In such areas the bacteria may be readily demon- 
strated, sometimes in early stages in dense masses in the capillaries and 
other smaller vessels, or later scattered through the necrotic and disinte- 
grating tissue (Fig. 127, p. 236). Embolic abscesses are commonly 
developed in both kidneys and by extensive coalescence may give rise to 
large abscesses; but in a certain number of cases the infarcts may be 
unilateral. This condition may be due to mere mechanical distribution 
of the infectious material or to a local susceptibility, the lack of ability 
to resist the presence of small numbers of bacteria being produced by 
some previous lesions, by excessive mobility, or by direct trauma. There 
is reason to believe that in certain forms of septicemia bacteria may se- 
cure a foothold in the tubules, not as emboli, but through excretion.2 
In such cases the suppurative foci may be at first limited to the medulla. 
In late phases of either type, pus may collect beneath the capsule or even 
break through and extend into the perirenal fat. Under certain conditions, 
as yet but little understood, the presence of bacteria in the glomeruli 
may result, not in abscess formation, but in a glomerular nephritis.3 
Ascending Infection.-In suppurative nephritis associated with a 
similar process in the ureter, bladder, etc., the medullary portion of the 
1 Cheesman, T. M., and Meltzer, S. J., Jour. Exper. Med., 1898, iii, 533; Brewer, G. E., Surg., Gynec., 
and Obst., 1906, ii, 485; New York Med. Jour., 1915, ci, 556. 
2 For a study of excretion of bacteria by the kidney, see Asch, Centralbl. f. d. Krankh. d. Harn.-u. 
Sex.-Org., 1902, xiii, 249, 324. See also discussion of this subject on p. 176. For a study of elimination 
of pigment by the kidney, see Carter, Jour. Am. Med. Assn., 1903, xli, 1248; Suzuki, T., Zur Morphologic 
der Nierensekretion, Jena, 1912. 
s Baehr, G., Jour. Exper. Med., 1912, xv, 330. THE URINARY ORGANS 
865 
kidney is usually earliest involved, and then the elongated form of the 
suppurative areas (Fig. 552) corresponds to the grouping of the tubules 
in this region.1 
Whatever the form in which it may manifest itself, suppurative 
inflammation of the kidney is commonly induced by some one or combi- 
nation of the pyogenic microorganisms which may lodge within it under 
favorable conditions. Thus Streptococcus pyogenes, Staphylococcus 
pyogenes, Bacillus coli communis, Bacillus pyocyaneus, Bacillus proteus, 
the pneumococcus, the typhoid bacillus, and others, may be found in the 
Fig. 552.-Suppurative Nephritis. 
Developed from infection by way of the urinary passages (so-called "surgical kidney"). 
suppurative foci. Sometimes, however, especially in the more chronic 
processes, microorganisms are not demonstrable. 
Acute Diffuse Nephritis. 
This process may occur in acute infectious diseases; it is especially 
common in scarlatina and not infrequent in diphtheria, typhoid fever, the 
exanthemata, and malaria, and in septicemia due to various bacterial 
excitants. In a majority of instances the invasion of the infectious agent 
is through the tonsil. 
The lesions of acute diffuse nephritis vary greatly in extent, in degree, 
and in the relative involvement of one or other renal structure, as well as 
with the duration of the process. In this, as in other forms of inflamma- 
1 For further details concerning suppurative nephritis consecutive to similar processes in adjacent 
organs, see p. 883. 866 
THE URINARY ORGANS 
tion of the kidney, degeneration is an important and often predominant 
factor in the morphology of the lesions. 
We shall now consider those lesions which in varying degrees are 
characteristic of an early phase of acute diffuse nephritis, such as fre- 
quently occurs in the course of the acute infectious diseases. While 
changes in the different structural components of the kidney may occur 
simultaneously and are intimately related to each other, we shall study 
first the lesions of the glomeruli, second those of the tubules, third those 
of the interstitial tissue and its vessels. 
The Glomeruli.-One of the early alterations in the tufts of the glo- 
meruli is the swelling of the cells which cover the capillaries.1 These cells, 
which in normal conditions are thin and scarcely visible, save by their 
nuclei, now project from the capillary loops, sometimes remaining closely 
apposed to the capillary walls, sometimes assuming polypoid shapes 
(Fig. 553), sometimes forming a continuous thick covering of cuboidal 
Showing swelling of the cells covering the capillary tufts and lining Bowman's capsule. 
Fig. 553.-Acute Diffuse Nephritis. 
cells over the vessels. The nuclei are larger than normal and mitosis 
may be evident. Similar changes occur in the epithelium between the 
capillary loops. The capillaries are sometimes distended and plugged 
with cells; some of these are leucocytes; others are larger with large 
nuclei and may be swollen endothelium. Hyaline thrombi are often 
found in these tuft capillaries. The swollen and proliferating tuft 
epithelia often undergo fatty degeneration and may peel off into the 
glomerular space. 
In some cases the proliferation and exfoliation are extensive and 
the cells may collect in crescentic masses within Bowman's capsule, 
crowding the tuft toward its hilus. The cells in these crescentic masses 
may be flattened from pressure and in profile appear fusiform (Fig. 554). 
The capsular epithelium may be swollen or remain apparently intact 
while there is a large cell accumulation from the tuft; or it may proliferate 
or become fatty or peel off. Swelling, exfoliation, and proliferation 
of the glomerular epithelium in some degree are of frequent occurrence 
in acute nephritis. They are sometimes so pronounced, especially in 
acute nephritis following scarlatina, either with or without extensive 
1 For a study of the development of the glomeruli and their relation to pathological changes, see 
Herring, P. T., Jour. Path, and Bacteriol., 1900, vi, 459. THE URINARY ORGANS 
867 
associated lesions, as to have suggested a name for one phase of the lesion 
-glomerulonephritis. There is sometimes a considerable accumulation 
of albuminous exudate between the tuft and capsule. Such albuminous 
material in specimens fixed by alcohol is in the form of fine granules and 
may be mingled with exfoliated and often fatty epithelium or cell 
detritus. If large numbers of glomeruli are involved, the blood pressure 
is elevated; if the number is small, as in the focal type, the pressure re- 
mains normal. 
Fibrin, leucocytes, and red blood-cells may be present with other 
exudate within Bowman's capsule. When the fibrin and leucocytes are 
in excess, the lesion has been termed fibrinopurulent glomerulonephritis; 
when red cells form the predominant feature of the exudate, the term 
hemorrhagic glomerulonephritis is used. 
Swollen cells are seen upon the capillary tuft and lining Bowman's capsule. Polyhedral and 
flattened cells lie in masses between the capsule and the tuft; the latter has been pressed upon by the 
cells and other exudate within the capsule. 
Fig. 554.-Acute Diffuse Nephritis-Following Scarlatina. 
When the glomerular lesion is focal and consists in a fibrinous necrosis 
of the tufts apparently due to bacterial emboli, and the hemorrhagic 
glomeruli are sharply contrasted with the pale, edematous kidney tissue, 
the lesion has been called by Lohlein hemorrhagic focal glomerulonephritis.1 
A localized inflammatory reaction of the tubules and interstitial tissue 
usually occurs about the affected glomeruli. This type is seen with 
vegetative endocarditis due to Streptococcus viridans. When large num- 
bers of glomeruli are involved and abscesses are formed, the lesion be- 
comes identical with the acute suppurative nephritis type previously 
described. 
The Tubules.-The lesions of the tubules of the kidney in the early 
phases of acute nephritis are largely degenerative; the epithelium, 
especially of the convoluted tubules, is swollen and coarsely granular 
(Fig. 548), or it may contain few or many fat droplets (Fig. 549)-albu- 
minous and fatty degeneration. The epithelium may become necrotic 
1 Lohlein, Ergebn. d. inn. Med. u. Kinderh., 1910, v, 411; GasKell, J. F„ Jour. Path, and Bacterid., 
1911-12, xvi, 287. 868 
THE URINARY ORGANS 
and may disintegrate or peel off over larger or smaller areas. Thus the 
lumina of the tubules may contain fragments of epithelium or detritus 
mingled with albuminous fluid-serum-red blood-cells and leucocytes, 
or hyaline or other forms of casts (Fig. 547). Red blood-cells may be 
extravasated in considerable numbers and collect in the tubules or pass 
on with the exudates. The casts and other exudates may be present in 
the cortex or in the collecting tubes of the kidney. 
The Interstitial Tissue.-This in early phases of acute nephritis may 
be edematous or it may be more or less infiltrated with leucocytes or 
Fig. 555.-Acute Diffuse Nephritis. 
Showing proliferation of cells on the tuft and lining the capsule of the glomerulus and the formation 
of new interstitial tissue with large polyhedral cells-glomerular and interstitial type. 
fibrinous exudate. Patches of new-formed small spheroidal cells, or 
larger cells with conspicuous excentric nuclei may be present either in 
the vicinity of the glomeruli (Fig. 555) or near the interlobular veins, 
or a general thickening of the interstitial tissue may occur even very 
early in some forms of acute diffuse nephritis, particularly in those fol- 
lowing scarlatina and diphtheria. 
We have thus seen that in the early phases of an acute inflammation 
of the kidneys, such as may occur independently or in connection with 
acute infective processes elsewhere, there is an involvement of all the 
structural units of the organ, the glomeruli, the tubular epithelium, and 869 
THE URINARY ORGANS 
the interstitial tissue. Such a process involving the various kinds of 
tissue is called diffuse,1 and the process is therefore designated Acute 
Diffuse Nephritis. This is the acute diffuse glomerulonephritis of Volhard 
and Fahr, and the glomerulotubular or parenchymatous nephritis of Aschoff. 
While both kidneys are involved in acute diffuse nephritis, the lesions 
in each are by no means uniform either in extent or advancement and 
are often patchy or irregular in distribution. 
Variations in Type in Acute Diffuse Nephritis.-There are many 
variations in the type of the lesions in acute diffuse nephritis, some of 
which seem to be directly dependent upon the character of the excitant, 
while in others the variations cannot as yet be associated with known 
determining conditions. 
If one guard himself against the notion of distinct species in the 
lesions it is convenient to recognize certain structural variants or types. 
Thus the changes in the glomerular capillaries and epithelium may, 
as above indicated, be prominent-glomerular type-(so-called glomerulo- 
nephritis} (Fig. 554 and 555); the degenerative process in the tubular 
epithelium may be extreme-parenchymatous or degenerative type; there 
may with other lesions be considerable hemorrhage into the glomeruli, 
tubules, and interstitial tissue-hemorrhagic type. With or without 
marked structural involvement 
of the parenchyma and intersti- 
tial tissue there may be an exu- 
dative inflammation in which 
serum and leucocytes (Fig. 556) 
and more or less red blood-cells 
may gather in the glomeruli or 
tubules and with various forms of 
casts pass off in the urine. This, 
which is common, has been called 
by Delafield the exudative type 
of acute diffuse nephritis. The 
leucocytic exudate may collect 
largely about the tubules and 
glomeruli, giving rise to the acute 
focal interstitial type.2 As the 
lymphocytic or plasma cells are 
not in the lumina of the tubules this type may show little or no exudate 
in the urine, little albumin, and no casts. Finally, with any one or more 
of the above types of lesion there may be early and significant involve- 
ment of the interstitial tissue of the kidney, so that new and often very 
cellular tissue, either in small patches or through a large portion of the 
organ, may lead to tubular atrophy and to serious and permanent struc- 
tural alterations. This, which has been called by Delafield the productive 
Fig. 556.-Acute Diffuse Nephritis. 
Showing pus cells and granular exudate in the 
tubules, with flattening of the epithelium; also mod- 
erate edema of the interstitial tissue-exudative 
type. 
1 It should be understood that the word " diffuse " is not used in the sense of widespread or uniform, 
but as indicating involvement of the various structural units of the organ. 
2 See Councilman, W. T., Jour. Exper. Med., 1898, iii, 393, for interesting study of "acute interstitial 
nephritis." Councilman regards the new cells in the interstitial tissue as largely "plasma cells" 
derived from lymphoid cells of the blood. 870 
THE URINARY ORGANS 
type, by others the interstitial type, of acute diffuse nephritis (Fig. 555), is 
most frequent as a complication of scarlatina; but it may follow diphtheria 
or puerperal infections, and may occur as an apparently independent 
process. 
Between these types of lesion, largely based, as will be seen, upon the 
relative involvement of the structural units of the kidney, are many 
intermediate forms which the scope of this book does not permit us to 
consider. 
Kidneys which are the seat of acute diffuse nephritis sometimes 
appear almost normal on gross inspection. But in more typical forms 
they are slightly or considerably enlarged, the capsule is free, the cortex 
is thickened, and either reddened or pale or mottled red and gray. When 
the interstitial tissue is edematous the cortex may appear translucent. 
The glomeruli may be red or pale and conspicuous or normal in appear- 
ance. The pyramids may seem unusually red by contrast with the 
thickened pale cortex. In hemorrhagic forms of acute nephritis in 
Fig. 557.-Diffuse Nephritis. 
Showing an advancing lesion following an acute type. Note the formation of a patch of dense 
fibrous tissue, with thickening of the walls of the glomeruli and atrophy of the tubules. 
which blood may collect in the glomeruli, in the interstitial tissue, and in 
the tubules, the cortex may be mottled with red. 
In many forms of acute diffuse nephritis, particularly if the inter- 
stitial tissue be not considerably involved, resolution may take place. 
The Excitants of Acute Diffuse Nephritis.-In many cases of acute 
diffuse nephritis, the process seems to be due to toxic substances which 
are formed under the influence of microorganisms in other parts of the 
body and presumably excreted by the kidney with whose cells they come 
into intimate contact or in whose metabolism they may share. It may 
occur with extensive lesions of the skin and after exposure to cold. In 
the acute nephritis following extensive burns, exposure to cold, etc., it is THE URINARY ORGANS 
871 
probable that the poisonous products of abnormal body-cell metabolism 
are the direct excitants. 
Although bacteria may be eliminated from the body through the 
kidney sometimes without inducing lesions which are demonstrable with 
our present technique,1 they usually occur only when albumin also is 
present in the kidney. The following bacteria have been found by numer- 
ous observers in the kidney and in the urine in acute diffuse nephritis: 
the typhoid bacillus, pneumococcus, streptococcus and staphylococcus, 
the colon bacillus, and others. The Plasmodium malariae may be present 
in the kidney in large numbers.2 To what extent the kidney lesions are 
due to the presence of these organisms themselves and to what extent to 
eliminated toxins is not yet clear. 
Persistent and Advancing Lesions Following Acute Diffuse Nephritis. 
It we follow the alterations which the kidney in acute dinuse nephritis may un- 
dergo if resolution do not occur but the process continue, we find that in each of the 
three structural units of the kidney-the glomeruli, the tubules, and the interstitial 
tissue, with the blood-vessels-important changes take place which often lead to slight 
or to marked deformities of the organ, and to such minute changes as are in fact char- 
acteristic of what we are wont to call chronic diffuse nephritis. 
The capillaries of the tufts may become partly or wholly obliterated by a gradual 
thickening of their walls and an increase of the connective tissue between them, while 
at the same time Bowman's capsule is thickened and contracts upon the altered tuft 
(Fig. 557) with which it may unite so that the 
glomerulus may finally be represented by a small, 
dense spheroidal mass of fibrous tissue (Fig. 558). 
The interstitial tissue of the kidney may be in- 
creased in patches, most often at first near the 
glomeruli or along the interlobular veins. This 
tissue may at first be quite cellular, resembling a 
collection of small spheroidal cells or larger poly- 
hedral cells, among which new fibrillar stroma may 
develop; or there may be a more diffuse increase of 
connective-tissue cells and stroma. As this new- 
formed fibrous tissue grows less cellular it contracts, 
the tubules which it incloses are atrophied, the epi- 
thelium may undergo fatty degeneration and peel 
off or become flattened, casts may be present in the 
narrowed lumen, and the tubules may at last be 
represented by a small cluster of flattened cells with- 
out distinct tubular structure, or they may disap- 
pear altogether (Fig. 557). Such islets or masses 
of new-formed fibrous tissue inclosing variously 
altered and atrophied remnants of glomeruli and 
tubules vary greatly in size and usually merge 
gradually into less altered kidney tissue. When they are formed near the surface 
of the kidney, the shrinkage of the fibrous tissue, which is continuous with the 
inner layers of the capsule of the organ, may draw the surface inward, leaving between 
the irregular depressions the areas of less altered, or otherwise altered, kidney tissue 
somewhat projecting in irregular knobs or granules. Thus arise the granular surface 
and the adhesion of the capsule which are frequent in some forms of persistent diffuse 
nephritis. 
Fig. 558.-Atrophied Glomerulus 
in Chronic Nephritis. 
The tuft is converted into a dense 
mass of fibrous tissue. 
1 See Biedl and Kraus, Arch. f. exper. Path. u. Pharmakol., 1896, xxxvii, 1 (bibl.); ». Klee hi, ibid., 
1897, xxxix, 173; Sittmann, Deutsch. Arch. f. klin. Med., 1894, liii, 323. 
2 For a study of malarial nephritis, see Thayer, W. S., Am. Jour. Med. Sc., 1898, cxvi, 560; and 
Ewing, J., Tr. Assn. Am. Phys., 1901, xvi, 450. 872 
THE URINARY ORGANS 
In the parts of the kidney less involved, or not at all involved, in the production of 
new fibrous tissue, the tubules may undergo marked alterations. Thus, the epithelium 
may be swollen and coarsely granular or fatty; it may become necrotic so that the 
nucleus fails to stain; it may, when necrotic or degenerated, peel off or disintegrate so 
that the tubules may be extensively denuded. On the other hand, the epithelium may 
remain in position, but be much thinner than normal, while the lumen is largely 
dilated. This may take place by the blocking of the tubules below by desquamated 
cells or casts, or by compression of new-formed interstitial tissue. The whole tubule, 
not merely the lumen, may be dilated and irregular in shape, with well-preserved or 
fatty or otherwise altered epithelium. Casts of various forms may be present. 
Chronic Nephritis. 
General Considerations.-We have seen that when the inflammatory 
process in the kidneys, at first acute, is protracted, both the degenerative 
and the productive lesions may become more marked and extensive. 
Thus, with a preponderance now of the interstitial alterations and again 
of the degenerative or other changes in the parenchyma, the kidneys 
in a condition of chronic nephritis may present a considerable variety in 
gross as well as in microscopical appearance. They are sometimes larger 
than normal, as is often though not always the case when the parenchyma 
is more conspicuously involved; or smaller, as is usual when the interstitial 
lesions are widespread or advanced. 
Although there is no sharp line of separation, either clinical or mor- 
phological, to be drawn between acute and chronic nephritis, it is con- 
venient to group kidney lesions in this way with the understanding that 
many intermediate forms exist, as must be the case, since, as we have 
seen, acute nephritis may pass gradually into the chronic form. 
While acute diffuse nephritis may be followed by the alterations 
which have just been summarized, and w'hich are characteristic of certain 
phases of chronic nephritis, the latter process, it should be remembered, 
is by no means always or usually preceded by an acute form of inflam- 
mation. 
Anatomically, two rough groups of chronic nephritis can be distin- 
guished: 1, a group in which the vascular lesions predominate; and, 2, 
an inflammatory and degenerative group in which the tubular and inter- 
stitial lesions ^eem most important. These two groups can be differ- 
entiated clinically also. 
1. Vascular Type of Chronic Nephritis.-A form of kidney lesion fre- 
quently met with is one in which the process is chronic from the onset 
and seems based upon primary arteriosclerotic changes in the smaller 
renal vessels. Cases of this type are best classified as nephropathies oj 
vascular origin, and not according to current views, as of inflammatory 
origin. Two varieties may be distinguished: (a) the arteriosclerotic con- 
tracted kidney of the older authors; and (6) the true or primary contracted 
kidney or combined type. 
(a) Arteriosclerotic Contracted Kidney.-In this type, the primary 
lesion is an arteriosclerotic process of the finer capillaries supplying the 
kidney parenchyma, which occurs late in life.1 It results in a destruction 
1 For a discussion of the changes in the glomeruli and arteries, see Gasicell, J. F„ Jour. Path, and 
Bacteriol., 1911-12, xvi, 287. 873 
THE URINARY ORGANS 
of the glomerular tufts, which become first collapsed, and then hyaline, 
and, finally, lose all structure in a mass of hyaline connective tissue with 
occasional scattered nuclei. The tubules derived from such glomeruli 
atrophy and are replaced by connective tissue. Casts may be present 
in the tubules so long as their lumina are patent. The kidney tissue 
independent of the thickened vessels remains healthy. In this early 
state there is no contraction of the kidney, the markings of the cortex 
are preserved, and the capsule strips with ease, leaving a fairly smooth 
surface, the only gross lesion being a lobulation of the surface. The 
consistence of the organ is firm, the color a dark red. Later, when the 
changes are more extensive, the kidney contracts; the capsule is adherent; 
the surface is granular, because of the shrinking of the connective tissue 
from the still functionating tubules; the cortex is narrow (3 to 4 mm.); 
and the thickened vessel walls protrude from the cut section as empty 
rigid tubes. The markings of the cortex still remain fairly clear. The 
renal lesion is usually accompanied by extensive vascular sclerosis else- 
where. The blood pressure is regularly high; the heart is hypertrophied; 
and a moderate amount of polycythemia is not infrequent. The urine 
is normal, except occasionally, when a little albumin and a few hyaline 
casts may be present. Large quantities of albumin and edema point 
either to cardiac failure or to the onset of inflammatory changes in the 
kidney. The permeability of the kidney for chlorides, urea, and dyes is 
diminished only in the later stages, but not so markedly as in the next 
form described, for a certain number of kidneys of this type may give so 
few symptoms that the existence of the lesion can not be demonstrated 
except at autopsy. A terminal uremia is rare; death is usually due to 
cardiac decompensation, pneumonia, or apoplexy. 
Nevertheless while, as has been said, many persons with arterio- 
sclerotic kidneys may show no symptoms of the lesion, and, in fact, be 
capable of heavy manual labor, careful functional tests will usually reveal 
some alterations in the capacity of the organ. About one-half of the 
cases will from time to time show a slight retention of urea and have a 
systolic pressure over 160; at least a quarter of the cases have traces of 
albumin in the urine; and practically all show occasional hyaline casts. 
The phenolsulphonephthalein excretion also is slow. Persons with these 
lesions may remain in health for a long time, unless subject to an acute 
infection, in which case the symptoms are often almost entirely those of 
renal insufficiency with large amounts of albumin, casts, and edema.1 
(b) Combined Type or True Contracted Kidney.-In this form vascular 
changes are combined with inflammatory lesions of the glomeruli and 
tubules, and the disease is seen in younger people. As a result of the 
inflammatory changes, the markings of the cortex are lost, in contrast 
to the previous type; and the color of the cut surface is reddish with 
numerous yellowish stripes or spots. Cysts may be present on the sur- 
face. The capsule is moderately adherent, the surface finely granular, 
the granules being due in part to the projections of areas of regeneration 
of the surface tubules. The glomeruli are in part atrophied, as in the 
1 Rappleye, W. C., Boston Med. and Surg. Jour., 1918, clxxviii, 191; 1918, clxxix, 441. 874 
THE URINARY ORGANS 
pure vascular type; but, in addition, they may show inflammatory and 
degenerative lesions. Fatty degeneration of the tuft epithelium is fre- 
quent. Leucocytes, as well as red blood-cells, may be present in the 
capsular space. Crescentic capsular cell masses may be found as in 
acute glomerular nephritis. The cells of the convoluted tubules are 
often fatty and may show drop-like degeneration. The inflammatory 
process may also extend to the interstitial tissue. But all these acute 
or subacute lesions may, in some instances, be quite focal. Clinically, 
the disease runs a much more active course than the arteriosclerotic form. 
Very high blood pressure1 and cardiac hypertrophy are constant; anemia 
is the rule; and terminal uremia is frequent. Neuroretinitis albumin- 
urica is very often observed. In the early stages, albumin and casts 
may be small in amount, later they are regularly present in abundance. 
Epithelial casts and fatty tubular epithelium are occasionally seen. 
Nycturia and polyuria are the rule. As the chlorides are retained, edema 
is frequent. Creatinin, urea, and non-protein nitrogen are found in in- 
creased quantities in the blood after the disease becomes active. The 
permeability for dyes is much diminished. Death is due to cardiac de- 
compensation or uremia. This is the form of kidney lesion which in its 
terminal stages is often clinically called an acute nephritis. 
2. Inflammatory and Degenerative Type of Chronic Nephritis.- 
In addition to the forms of nephritis just described, in which the vascular 
lesions dominate the clinical picture and morphological findings, it 
is convenient to place in one group those kidneys in which, although 
there may be important changes in the glomeruli and the interstitial 
tissue, the most marked lesions are in the tubular epithelium. This may 
be conveniently called the parenchymatoihs or degenerative type of chronic 
diffuse nephritis. 
On the other hand, there is another large and important class of kid- 
neys which are characterized morphologically by a relatively prominent 
increase in the amount of interstitial fibrous tissue with associated destruc- 
tion by atrophy or otherwise of the tubular structures. This may be 
called the interstitial type of chronic diffuse nephritis. 
In considering this, in many respects artificial, grouping of persistent 
inflammatory kidney lesions, it should be remembered that while the 
parenchymatous and the interstitial types of lesion may originate as such 
and so persist, the lesion of the parenchymatous type may, as the disease 
progresses, assume the characters of the interstitial form.2 
(a) Parenchymatous Type of Chronic Nephritis.-This may originate 
in an acute diffuse nephritis, but more frequently develops independently 
of this or, at least, without any clinical history of previous renal disease. 
As in other forms of diffuse nephritis, the tubules, the glomeruli, and the 
interstitial tissue are more or less involved. The lesions are most marked 
in the cortex (Fig. 559), and here the epithelium may be swollen and 
1 For a study of nephritic hypertension, see Janeway, T. C., Am. Jour. Med. Sc., 1913, cxliv, 625. 
For experimental studies on the relationship between destruction of renal parenchyma and cardiac 
hypertrophy, see Passler and Heineke, Verhandl. d. deutsch. path. Gesellsch., 1905, ix, 99. 
For a study of subacute and chronic nephritis, see Ophuls, W„ Arch. Int. Med., 1912, ix, 156; for a 
study of classification, see Oertel, H., ibid, 1913, xi, 653. 875 
coarsely granular or often fatty. Droplets of clear fluid may form within 
the epithelium-so-called drop-like degeneration. The epithelium may 
be flattened or it may peel off or disintegrate, and the cells and cell detritus 
together with leucocytes, red blood-cells, and casts may collect in the 
irregular and often widened lumina. The casts may be hyaline or granu- 
lar or epithelial, or they may be covered with leucocytes or red blood- 
cells. In the glomeruli, the tuft and capsule cells may swell and pro- 
liferate and peel off (Fig. 560); albuminous fluid, which in specimens 
hardened in alcohol is represented by a granular precipitate, may be 
present in the intracapsular space and in the tubules. The interstitial 
tissue may be increased in amount, usually in circumscribed regions, and 
THE URINARY ORGANS 
Fig. 559.-Chronic Diffuse .Nephritis-Parenchymatous Type. 
At the left is a band of new-formed fibrous tissue with atrophy of tubules and swelling and pro- 
liferation of the capsule cells; in the central portions the tubular epithelium is disintegrating at the 
edges, while at the right the lumina of the tubules are dilated, with flattening of the epithelium. 
here the inclosed tubules are atrophied. Not infrequently more or less 
extensive hemorrhages occur. 
If the disease have been of long standing the new-formed interstitial 
tissue may be present in considerable amount with much destruction of 
the tubules. The glomeruli may be compromised by the thickening of 
Bowman's capsule and the obliteration of the capillaries, so that at length 
the tuft and capsule may fuse and the glomeruli may be represented by 
dense fibrous nodules (Fig. 558). The growth of interstitial tissue in 
patches may, when near the surface of the organ, bind the capsule to the 
kidney so that in its removal small masses of the parenchyma may be 
stripped off, leaving a rough surface on which grayish depressed areas, 
corresponding to the interstitial growth, are intermingled with more 
projecting light or yellowish portions, in which albuminous or fatty degen- 876 
THE URINARY ORGANS 
eration of the tubular epithelium may be marked and extensive. Very 
often the new fibrous tissue develops along the course of the interlobular 
vessels so that cylindrical or narrow wedge-shaped areas are affected, 
extending inward from the capsule (Fig. 561). Amyloid degeneration 
involving the capillary tufts, the vasa recta, and the larger arterial trunks 
is common. 
Such kidneys as have just been described present varying gross 
appearances which are dependent upon the character, extent, and dis- 
tribution of the lesions. In general, they are firm, and the capsule is 
smooth and lightly but widely adherent. The surface may be smooth 
or finely granular. Some are larger than normal with a thickened 
Showing swelling of tuft and capsule epithelium; flattening of the tubular epithelium and slight increase 
in the interstitial tissue. 
Fig. 560.-Chronic Diffuse Nephritis. 
whitish or yellowish cortex. These are often called large white kidneys. 
But kidneys with essentially similar lesions are not always large, and are 
often nearly normal in appearance; or they may be smaller and have a 
cortex thinner than normal. These include the chronic parenchymatous 
or secondary contracted kidneys of the older authors, or nephrocirrhosis 
glomerularis of Aschoff, which in their more advanced stages with exten- 
sive vascular changes can not be distinguished from the true contracted 
kidney, the lesions of which are primarily arterial and not inflammatory 
in character. If hemorrhage into the tubules or interstitial tissue be a 877 
THE URINARY ORGANS 
marked feature of the lesion, the cortex may be reddish or mottled red 
and yellow. Such are the so-called large red kidneys. 
Arteriosclerosis and cardiac hypertrophy may accompany this type 
of kidney lesion, especially in the later stages. With these changes the 
urine, which in the earlier phases is concentrated, highly albuminous, 
and full of casts, becomes more abundant and of low specific gravity, 
and contains but traces of albumin and only few casts. Edema, with 
salt, creatinin, urea, and non-protein nitrogen retentions, may appear in 
either phase, but is extensive only in the late stages when serious failure 
of the heart is added to the nephritic insufficiency. 
Showing a wedge-shaped mass of new-formed tissue extending inward from the capsule of the 
kidney, to which it is firmly attached. The tubules within the fibrous area are atrophied, while the 
tubules elsewhere show various degenerative epithelial changes. 
Fig. 561.-Chronic Diffuse Nephritis-Parenchymatous Type. 
(6) Interstitial Type of Chronic Nephritis.-The type of chronic 
nephritis in which the growth of interstitial tissue is conspicuous, the 
interstitial or indurative type, apparently sometimes represents a later 
phase of the parenchymatous type, but appears to be more frequently 
an independent process. As the new interstitial tissue which is formed 
in patches or streaks or large masses gradually becomes less cellular and 
more dense, and shrinks, the kidneys are usually smaller than normal 
and, owing to the uneven distribution of the lesion, are rough upon the 
surface when the thickened and adherent capsule is stripped off. The 
areas of the cortex in which the fibrous tissue is most abundant (Fig. 562) 
are grayish or translucent and depressed, while the parenchyma between, 878 
THE URINARY ORGANS 
often fatty, projects as yellowish rounded knobs or granules. This con- 
dition is therefore sometimes spoken of as "granular atrophy," and such 
kidneys are often called "granular kidneys" or "atrophied kidneys." 
The tissue is firm and resistant to the knife; and on section the cortex is 
seen to be in general thinned, often extremely so, some portions being 
much more atrophied than others. Small cysts of various sizes may be 
formed from dilatation and coalescence of tubules. The cortex is usu- 
ally more involved than the medulla. The fat with which the kidney is 
surrounded is often largely increased. 
On microscopical examination new-formed interstitial tissue is found 
sometimes in patches (Fig. 562) or streaks along the course of the inter- 
lobular vessels, with less affected regions between them. In these 
The capsule is thickened and adherent, especially to the dense mass of fibrous tissue at the left of 
the section, in which the tubules are greatly atrophied. At the right the parenchyma is less atrophied, 
but here the lumina of the tubules are dilated, the epithelium is degenerating and flattened. 
Fig. 562.-Chronic Nephritis-Atrophied Kidney-Vascular Type 
fibrous portions there may be flattening of the epithelium and various 
degrees of atrophy or complete destruction of the epithelium and the 
tubules. Between these fibrous regions, slightly altered tubules may be 
present, or others with granular and fatty degeneration, exfoliation, and 
disintegration of the epithelium. Various forms of casts may be present 
in the tubules; the epithelium maybe flattened, with enlargement of the 
lumen. The glomeruli are variously altered; thus there may be thicken- 
ing of the capillary walls and of Bowman's capsule (Fig. 564), increase 
and exfoliation of the tuft and capsular epithelium, or a more or less 
complete conversion of the glomerulus into a knob of dense fibrous tissue. 
Occasionally there is partial or complete atrophy of the tuft with more THE URINARY ORGANS 
879 
or less dilatation of the capsule. Thus small cysts are formed lined 
with flat cells and containing a homogeneous or granular fluid and 
sometimes small masses of calcium salts.1 
Fig. 563.-Chronic Nephritis. 
Showing interstitial tissue, dense and fibrous in type, between the tubules. The epithelium is in part 
flattened; in places shows albuminous degeneration. 
Fig. 564.-Chronic Nephritis. 
Showing fibrous thickening of the glomerular tuft with a mass of dense fibrous interstitial tissue at 
one side (below) of the glomerulus. From an atrophied kidney. 
In advanced phases of the lesion the kidney may be very small; then 
a large part of the tissue is involved; and while the atrophy is always 
1 For a study of atrophic glomerular cysts, see Beer, E., Am. Jour. Med. Sc., 1904, cxxvii, 611. 880 
THE URINARY ORGANS 
more marked in some places than in others, it is often difficult to find 
any normal structural elements.1 
Fibrous thickening of the walls of the arteries and veins of the kid- 
neys is usual in this type of chronic diffuse nephritis (Fig. 565). Amy- 
loid degeneration of the vessels is not infrequent. The heart is often 
greatly hypertrophied, and general arteriosclerosis is common. 
The Excitants of Chronic Nephritis.-The conditions under which 
chronic nephritis occurs are most diverse. Thus, judging from the 
clinical history, it may be a primary process; it may follow infectious 
diseases either with or without a previous acute nephritis; it is not infre- 
quently associated with gout and syphilis, with lead poisoning, with 
excessive use of alcohol, with general arteriosclerosis, with general chronic 
congestion of the viscera and with chronic suppurative and tuberculous 
processes, and appears in many cases to develop under the influence of 
dietetic excesses and protracted gastrointestinal disorders. The nature 
of the excitants under these various con- 
ditions is most obscure. Although in 
gout, lead poisoning, alcoholism, etc., a 
fairly definite inciting toxic agency may 
be assumed, the exact mode of action of 
such extrinsic or intrinsic poisons is 
almost wholly unknown. In regard to 
other excitants of chronic diffuse nephri- 
tis, the prevalent views as to the impor- 
tance of disturbed metabolism in the 
body which may lead to the excretion 
of abnormal harmful products favor the 
conjecture that in many cases at least 
both the degenerative and the pro- 
ductive processes may be the marks of 
a persistent autointoxication. 
It has not been possible experimentally to imitate the human lesions.2 
After poisoning with uranium salts3 or with diphtheria toxin4 a glomerular 
lesion is induced in animals, which, in uranium poisoning, is combined 
with lesions also in the convoluted tubules; the animals die, however, 
before the interstitial changes begin to be extensive. 
Fig. 565.-C h r o n i c Obliterating 
Endarteritis in an Atrophied Kidney 
with Chronic Nephritis. 
During the last twenty years the study of the function of the kidney 
has led to the accumulation of much information of value in the prognosis 
and treatment of kidney lesions, but the results so obtained do not as yet 
permit of an accurate correlation between the existing anatomical lesion 
and the clinical symptoms. Certain symptoms, such as edema, high 
FUNCTIONAL PATHOLOGY OF NEPHRITIS. 
1 For a r6sum£ of views on the nature and origin of the contracted kidney, see Aschoff, L., Cartwright 
Lectures, Arch. Int. Med., 1913, xii, 723. 
2 For studies bearing on experimental nephritis, see Emerson, H., Arch. Int. Med., 1908, i, 485; 
Pearce, Hill and Eisenbrey, Jour. Exper. Med., 1910, xii, 196; Christian and O'Hare, Jour. Med. Research, 
1913, N. S. xxiii, 227; and O'Hare, J. P., Arch. Int. Med., 1913, xii, 49 and 61; Ophuls, IT., Jour. Am. 
Med. Assn., 1917, Ixix, 1223. 
3 Baehr, G., Zieglers Beitr., 1913, Iv, 545. 
* Bailey, C. H., Jour. Exper. Med., 1917, xxv, 109; Faber, H. K., ibid., 1917, xxvi, 139. THE URINARY ORGANS 
881 
blood-pressure, etc., have been mentioned during the discussion of the 
lesions; but a short resume of some of the results of chemical and func- 
tional tests may be of interest here. 
The presence of albumin, casts, and blood-cells in the urine is still 
the most delicate indicator we have of a renal lesion, but offers little 
information as to the extent and nature of the changes in the kidneys. 
In general it may be said that the severe nephroses show large quantities 
of albumin and numerous casts, with a reduction in the quantity of urine, 
even to complete suppression, and the accumulation in the blood of large 
amounts of solid matter, especially urea and sodium chloride. The same 
is true of the acute nephritides. Edema is not infrequent in the nephro- 
ses, common in the nephritides. 
The history of poisoning or the demonstration of an existing or recent 
infection are important points in determining the nature of the lesion. 
For example, the appearance of the kidney in a case of poisoning by cor- 
rosive sublimate is quite as characteristic as the glomerular nephritides 
of scarlatina or bacterial endocarditis. 
The chronic forms of nephritis offer the greatest difficulties in inter- 
pretation. The purely arteriosclerotic kidney with the concomitant high 
blood-pressure and scanty albumin and casts, the excretory power being 
otherwise fairly good, can be recognized in many instances. The ana- 
tomical changes underlying the chronic secondary types and the com- 
bined arteriosclerotic-nephritic forms can not at present be determined 
with any accuracy. The tendency is, for clinical purposes, to separate 
chronic nephritis into three rough groups: (1) Cases with salt retention, 
usually accompanied by edema. (2) Cases with nitrogen retention, which 
are less apt to show edema if the cardiac function is good; and, (3) the 
combined forms.1 
These groups do not necessarily correspond to the anatomical forms 
of nephritis which have just been described. The complexity of the 
lesions and our lack of methods for testing the functional deficiencies of 
the various portions of the glomerulus and renal tubule as yet prevent 
such correlation. 
The methods for making the functional tests and the interpretation 
of the results can be referred to here only in brief. They include the 
determination by chemical means of the amount of urea, sodium chloride, 
and creatinin present in the blood, these substances, if present in excess, 
representing the summation of the kidney deficiencies on a normal diet. 
The momentary deficiency in excretory power is best estimated by the 
phenolsulphonephthalein test.2 The excretion of this substance may be 
normal when other substances are retained, showing an as yet unknown 
difference in the selective excretion of the kidney. Also, the urea, for 
example, may not be retained in excess and yet a slowing of its output 
may exist as shown by a comparison between the amount in the blood 
and the amount excreted in the urine. This ratio expressed numerically 
1 For a discussion of this classification, due largely to the French school, see Ambard, Phys. Normal 
et Pathologique des Reins, Paris, 1914. 
2 Rowntree and Geraghty, Jour. Pharmacol, and Exper. Therap., 1910, i, 579. 882 
THE URINARY ORGANS 
and taking into account the patient's weight, is the Ambard coefficient.1 
Finally, the urinary constants are determined with the patient on a 
standard diet2 with or without the addition of known amounts of urea 
or sodium chloride. Useful results may occasionally be obtained by the 
use of a diuretic. With the help of these methods, the existence of a 
mild functional disturbance of renal excretion can be detected as exempli- 
fied in a preceding paragraph on arteriosclerotic kidneys. 
A separation can often be made between cardiovascular disease in 
which the chronic congestion of the kidney incites the passage of traces 
of albumin and a few casts and thus simulates nephritis, and true renal 
disease with secondary cardiac failure. In the former, the kidney still 
performs its excretory functions well; in the latter, some one of the tests 
mentioned will usually reveal a renal insufficiency. 
These tests also permit of the demonstration, otherwise impossible, of 
an insidious progress of the kidney lesion to the final stage of utter refusal 
to excrete the toxic end results of protein decomposition, with the ulti- 
mate appearance of acidosis3 and a terminal uremia.4 
Tuberculous Nephritis. 
Miliary tubercles may be present in the kidney in general acute mili- 
ary tuberculosis or in a localized tuberculous inflammation which is most 
marked elsewhere. Renal tuberculosis is, however, most often associated 
with tuberculous processes in other parts of the genitourinary tract. It 
is not infrequently primary in the kidney and is then often unilateral. 
If only one kidney be involved the other may become the seat of chronic 
diffuse nephritis with waxy degeneration of the walls of the arteries. 
Tuberculous inflammation may occur in a kidney already the seat of 
chronic inflammatory changes. 
The process is apt to begin in the mucous membrane of the pelvis and 
calyces, and extend from thence first to the pyramidal and afterward to 
the cortical portion of the kidney.5 In the mucous membrane of the 
pelvis and calyces there is a growth of new cellular tissue studded with 
tubercle granula, while the epithelial cells proliferate, become deformed, 
and desquamate. This process is often soon followed by cheesy degen- 
eration of the inflammatory products. Similar changes occur in the 
kidney which may become extensively involved and largely destroyed. 
The portions of the organ which do not share directly in the tuberculous 
1 See Ambard, Phys. Normal et Pathologique des Reins, Paris, 1914; McLean, F. C., Jour. Am. Med. 
Assn., 1916, Ixvi, 415; Jour. Exper. Med., 1915, xxii, 212. 
2 For dietary methods, see Schlayer and Hedinger, Deutsch. Arch. f. klin. Med., 1914, cxiv, 120; 
Mosenthal, H. O., Arch. Int. Med., 1915, xvi, 733; and Christian, H. A., Jour. Urol., 1917, i, 319. 
3 Peabody, F. IF., Arch. Int. Med., 1914, xiv, 236; ibid., 1915, xvi, 955. 
• For further information on this subject, see Hinman, F., Internat. Abstracts Surg., 1914, xix, 465 
(bibl.); Kahn, M„ ibid., 1917, xxiv, 449 (bibl.); Christian, Frothingham, O'Hare, and Woods, Am. Jour. 
Med. Sc., 1915, cl, 657 (bibl.); Janeway, T. C., ibid., 1916, cli, 157; Christian, H. A., ibid., 1916, cli, 
625 (bibl.). For the surgical aspects of these tests, see Braasch, N. F., and Thomas, G. J., Jour. Am. 
Med. Assn., 1915, Ixiv, 104; Rowntree, L. G., Am. Jour. Med. Sc., 1914, cxlvii, 352. 
For a general review, with bibl., see Karsner, H. T., Jour. Lab. and Clin. Med., 1916, i, 910; and 
Thomas, B. A., and Birdsall, J. C., Jour. Am. Med. Assn., 1917, Ixix, 1747. For a study of prognostic 
relations of blood constituents to renal disease and surgery, see Squier, J. B., and Myers, V. C., Jour. 
Urol., 1918, ii, 1. 
6 For a study of ascending urogenital tuberculosis, see Baumgarten, Arb. Path. Anat. Inst. Tubingen, 
1906, v, 372; also Kappis, ibid., p. 379. 883 
THE URINARY ORGANS 
process often develop lesions of the interstitial type of chronic diffuse 
nephritis or of suppuration. Thus the kidney may become hollowed out 
into a series of ragged cavities with caseous and disintegrating walls 
(Fig. 566). Sometimes the process comes to a standstill, and then the 
caseous portions may be infiltrated with salts of lime.1 The ureters and 
bladder are frequently involved in the later stages of the disease. 
Fig. 566.-Tuberculous Nephritis, 
An acute nephritis may arise in the course of an active syphilitic 
infection.2 Gummata of the kidney are of occasional occurrence. A 
close relationship between syphilitic arteritis and atrophied forms of 
chronic diffuse nephritis seems probable.3 
Syphilitic Inflammation. 
SUPPURATIVE PYELITIS AND PYELONEPHRITIS. 
Suppurative pyelitis is often associated with suppuration of the kidney 
substance, more frequently with a similar process in the bladder or ureters. 
But it may occur by itself without bladder or ureteral involvement, espe- 
cially in female infants or young children.4 Cystitis is a usual complica- 
tion in the male. The lesion is frequently bilateral. It is incited by the 
same microorganisms as are concerned in the induction of the associated 
lesions in the kidney and bladder, in the latter case most often the 
Bacillus coli communis, the Streptococcus pyogenes, and the Staphylo- 
coccus pyogenes. The first mentioned organism is most frequent in the 
pyelitis of children and is probably introduced from the bowel through 
the blood or the lymph-channels, though the greater frequency of the 
disease in females suggests that the portal of entry is the urethra. 
The mucous membrane of the pelvis may be congested or hemorrhagic, 
1 For a study of renal tuberculosis, see Walker, Johns Hopkins Hosp. Rep., 1904, xii, 455. 
F., Berl. klin. Wchnschr., 1913, 1, 1416. 
3 For bibliography, see Delamare, Gaz. d. Hop., 1900, Ixxiii, 425. 
4 Smith, R. M., Amer. Jour. Dis. Child., 1916, xii, 235; Quinby, W. C., Jour. Am. Med. Assn., 1917, 
xviii. 591. 884 
THE URINARY ORGANS 
thicker and more opaque than normal, and coated with pus or with 
patches of fibrin. The presence of pelvic calculi is to be regarded as a 
predisposing rather than as a direct inciting agent in suppurative pyelitis. 
The path of invasion of the kidney substance from the pelvis is 
through the interstitial tissue of the pyramids. The bacteria then in- 
vade the veins or in the upper portion of the medulla pass from the 
invaded vessels to the Henle's loops.1 
Suppurative Ureteritis.-The conditions under which suppurative 
inflammation of the ureter occurs are similar, as is the general appearance 
of its mucous membrane, to those just indicated in the pelvis. 
Fig. 567.-Chronic Pyelonephritis. 
Showing dilatation of the pelvis and calyces 
Suppurative Pyelonephritis with Cystitis.-In this association of 
lesions of the bladder and kidneys, which is usually initiated by the 
inflammation of the bladder, the affection of the kidneys is commonly 
bilateral. The suppurative areas in the kidney may be in the form of 
small abscesses scattered through the kidneys, or in the form of elongated 
whitish streaks or wedges between the tubules (see Fig. 552). The 
purulent foci are often surrounded by a red zone of congestion. 
The kidney tissue in the vicinity of the abscesses may be necrotic, the 
outlines of the cells being preserved but their nuclei absent or not revealed 
by the usual staining agents. 
The infective agent often traverses the ureters in passing from the 
inflamed bladder to the kidneys, leaving the mucous membrane of the 
ureter intact. The path followed in such ascending infections seems to 
be most often lymphatic, an extensive network of lymphatic vessels ex- 
isting in the walls of the bladder, the ureter, and the substance of the 
kidney.2 If bacteria are introduced into the bladder, they may pass up 
the ureter and involve the pelvis, giving rise to an acute lesion; or they 
may enter the kidney and either involve that organ or pass to the perirenal 
fat.3 
1 Ribbert, H., Virchows Arch., 1916, ccxx, 294. 
! Kumita, Arch. f. Anat., 1909, Suppl.; Bauereisen, Ztschr. f. gynak. Urol., 1911, ii, 235. 
3 Sweet and Stewart, Surg., Gynec., and Obst., 1914, xviii, 460; Eisendrath and Schultz, Jour. Med. 
Research, 1917, N. S. xxx, 295; Jour. Am. Med. Assn., 1917, Ixviii, 540. 885 
THE URINARY ORGANS 
Chronic Pyelonephritis.-Chronic cystitis or calculi in the pelvis of 
the kidneys may set up a chronic inflammation which involves both the 
pelvis and calyces and the kidney tissue. The mucous membrane of the 
pelvis and calyces is thickened, the epithelial layer is changed in mor- 
phology by the inflammation, or may partially desquamate. There is a 
growth of granulation tissue beneath the epithelium, and there may be 
little polypoid outgrowths. Usually collections of lymphocytes are found 
in the mucous membrane and the papillae, and a general infiltration with 
these cells and pus cells may be noted. The surface of the mucous 
membrane is coated with pus or fibrin, or the cavity of the pelvis and 
calyces is dilated and distended with purulent serum (Fig. 567). 
The kidney itself is the seat of a chronic interstitial inflammation 
with the production of new connective tissue, and sometimes of pus, 
with obliteration of the renal tubules. 
HYDRONEPHROSIS. 
Hydronephrosis may occur congenitally in consequence either of ab- 
sence of the ureters or of obstruction of any portion of the genitourinary 
tract. When bilateral, it is, of course, incompatible with life. Acquired 
hydronephrosis may be due to a variety of causes which induce reverse 
hydrostatic pressure on the kidney. Among these causes may be men- 
tioned malformations, such as horseshoe kidney,1 spurs or valves in the 
pelvis of the kidney, kinking of the ureter from movable kidney, inflam- 
matory lesions of the mucous membrane of the pelvis, ureter, or urethra, 
compression of the ureters or pelvis by tumors in these organs or by 
tumors of other organs, such as the rectum, bladder, prostate, or uterus; 
even by enlargement of the pregnant uterus. Narrowings or strictures of 
the ureter or urethra, prostatic hypertrophy, phimosis, inflammatory 
lesions of the bladder, ureter, or urethra, or calculi may also act as causa- 
tive agents. Finally, hydronephrosis may be induced by accidental liga- 
ture of the ureter in the course of a surgical operation.2 The amount of 
hydronephrosis and the ultimate change in the kidney vary somewhat 
depending upon whether the stoppage of the urine is immediate and com- 
plete or whether it is intermittent or partial, as it is with valves in the 
pelvis, with movable kidney, and with calculi. It is obvious that ob- 
struction in the ureter leads to unilateral (Fig. 568), obstruction in the 
bladder or urethra to bilateral, hydronephrosis. 
Experiments on animals3 have shown that if the ureter is ligated 
there may be a very considerable hydronephrosis produced, with a pri- 
mary distention of the pelvis of the kidney followed by enlargement of 
the collecting tubules and a growth of connective tissue in the substance 
of the kidney. The hydronephrotic process develops to a stage depend- 
ing upon the back pressure on the glomeruli; when this reaches a certain 
point, the glomerulus ceases to secrete fluid and the kidney atrophies. 
This atrophy is probably also correlated with diminished blood supply 
to the kidney, for it may not occur if a good collateral circulation is estab- 
1 Eisendrath, D. NSurg., Gynec., and Obst., 1912, xv, 467. 
2 See, for a discussion of such cases, Barney, J. D., Surg., Gynec., and Obst., 1912, xv, 290. 
3 See, for example, Scott, G. D., Surg., Gynec., and Obst., 1912, xv, 296 (bibl.). 886 
THE URINARY ORGANS 
lished through the capsular vessels. Such sudden interruptions of urinary 
flow are not frequent in human beings, and when they do occur after 
operative ligature usually do not give rise to any extensive hydronephro- 
sis. There may be a small amount of dilatation at first, chiefly of the 
pelvis, but later the kidney atrophies without symptoms, unless infection 
takes place. If the obstruction is released the organ shows astonishingly 
rapid restoration of functional power, even when the closure of the ureter 
has existed for a number of days or even weeks, but in order to regain 
function this release must take place before any extensive connective 
tissue growth has occurred in the kidney substance. 
When, for any reason, the urinary flow is interfered with only partially 
or intermittently, the hydronephrosis is very much greater in extent 
than in complete closure, and the kidney substance may atrophy almost 
completely, so that the organ is turned into a large lobulated sac which 
may contain many liters of clear, bloody, brownish, or opalescent fluid. 
The thinned-out kidney is pale and firm on account of the new foi mation 
of connective tissue. The walls of the blood-vessels are thickened, the 
lining membrane may be smooth or covered with warty thickenings of 
epithelium or masses of fibrin and debris. Usually a few remnants of 
glomeruli and tubules can be found microscopically in the thin sac wall. 
The reason for the more extensive hydronephrosis following partial 
or intermittent closure is that the pressure does not lead to early inter- 
ference with the secreting power of the kidney, so that the glomeruli 
continue to furnish urine and the kidney tissue regenerates when the 
pressure is relieved; then when the flow is again interfered with fresh 
dilatation takes place; this long-continued repetition of the alternate 
process of regeneration and compression accounts for the large sacs which 
may form. 
PERINEPHRITIC SUPPURATION. 
The loose connective tissue about the kidney may become the seat of 
suppurative inflammation. This may follow mechanical injury or may 
be secondary to suppurative or other inflammatory processes, such as 
caries of the spine, empyema, pelvic cellulitis, puerperal parametritis, 
perityphlitis, and suppurative nephritis. It may be associated with 
acute infectious diseases in children. The suppuration may extend back- 
ward through the muscles; downward into the iliac fossa, the perineum, 
the bladder, the scrotum, or the vagina; forward into the peritoneal 
cavity or the colon; or upward through the diaphragm. 
The kidney itself may be simply compressed by the abscess or may 
become involved in the suppurative process. 
CYSTS IN THE KIDNEYS. 
Cysts are formed in the kidneys during either intrauterine or extra- 
uterine life.1 
Congenital Cystic Kidneys are often striking objects. Either one or, 
more frequently, both kidneys may be greatly enlarged and converted 
into a mass of cysts (Fig. 569). The cysts are of various sizes and are 
1 For bibl., see Berner, Die Cystenniere, Jena, 1913. THE URINARY ORGANS 
887 
separated from each other by fibrous septa or compressed kidney tissue. 
They contain a fluid which may be clear, yellow, and acid, holding in 
solution the urinary salts, or may be turbid and brown, and contain 
blood, uric-acid crystals, and cholesterin. The cysts are often lined 
with a single layer of flat, polygonal cells. Some of them seem to be 
formed by a dilatation of the tubules and of the capsules of the Malpighian 
bodies. As causes for such dilatations there may be found obliteration 
of the tubes in the papillse, and stenosis of the pelvis, ureters, bladder, 
Fig. 568.-Hydronephrosis. 
From obstruction of ureter. 
or urethra. Other congenital malformations, such as cortical adeno- 
mata, islands of cartilage, and pearly or squamous epithelium, are not 
infrequent in cystic kidneys, a fact which strengthens the view that the 
lesions have a developmental origin, as does the occurrence of even 
grosser defects in the genitourinary system and other organs. The most 
widely accepted attitude is that the whole lesion is due in many cases to 
lack of junction of the urinary tubules with the budding canals from the 
pelvis. As this failure of union may occur at different stages of develop- 
ment, various types and locations may be observed. 
The surgical removal of a cystic kidney is usually followed by the 
death of the patient, for the amount of functional kidney tissue in the 888 
THE URINARY ORGANS 
other organ is apt to be too small to allow proper elimination of waste 
products, even though previous functional tests may have suggested 
good permeability. 
Cysts of the Kidney in the Adult may be single and occur in otherwise 
normal organs. There may be one or more cysts filled with clear or 
colored serum or gelatinous material (Fig. 570). These cysts do not 
appear to interfere with the function of the kidneys. 
In chronic diffuse nephritis, especially in the atrophic form, groups 
of tubes may be dilated. Apparently one or more of the larger tubes 
in the pyramids are obstructed, and this causes dilatation of a correspond- 
ing group of tubes. Such a dilatation may be moderate in size, or it 
Only very small portions of the kidney tissue remain, crowded between the cysts. 
Fig. 569.-Congenital Cystic Kidney. 
may form cysts visible to the naked eye. Very small cysts of Bowman's 
capsule may form, with atrophy of the vascular tuft. 
Occasionally both kidneys are very much enlarged and converted 
into a mass of cysts containing clear or colored serum or gelatinous mate- 
rial. The nature of these cysts is uncertain; they may be congenital; 
and they are sometimes associated with similar cysts in the liver.1 
Some six cases of dermoids of the kidney have been reported.2 
1 For a study of cystic kidney with extensive bibl., see Ritchie, Laboratory Reports, Royal Coll, of 
Phys., Edinburgh, vol. iv; also Braunwarth, C., Virchows Arch., 1906, clxxxvi, 341 (bibl.). 
2 Baldwin, J. F., Surg., Gynec. and Obst., 1915, xx, 219. THE URINARY ORGANS 
889 
Fig. 570.-Single Cyst of the Kidney. 
Fig. 571.-Calculus in the Pelvis of the Kidney 890 
THE URINARY ORGANS 
Small multiple cysts of the ureter, lined with flattened or cuboidal 
epithelium, are of occasional occurrence, and may be associated with 
similar cysts in the pelvis of the kidney. Such cysts in the ureter may be 
pedunculated.1 
RENAL CALCULI. 
In the kidneys of new-born children, from the first to the fourteenth 
day after birth, the large tubes of the pyramids often contain small 
brownish, rounded bodies composed of the urates of ammonium and 
sodium. Similar masses may also be present in the calyces and pelves. 
In still-born children these masses are usually absent. The carbonate 
and phosphate of lime, in the form of white linear masses, may be depos- 
ited in the tubes of the pyramids, in the kidneys of old persons and of 
those who have suffered from destructive diseases of the bones. 
Urate of soda in the form of acicular crystals is deposited both in the 
tubes and in the stroma of the kidneys of gouty persons. 
Concretions of the urinary salts are often formed in the pelves of the 
kidneys. They may remain there as rounded masses (Fig. 571), or they 
may attain a large size and be moulded into the shape of the pelvis and 
calyces. Smaller calculi may pass into the ureter and either become 
impacted there or pass through it into the bladder. The most common 
form of calculus is that composed of uric acid. But they may also be 
formed of uric acid with a shell of 
oxalate of lime, or of oxalate of 
lime alone, or of the phosphates, or 
of cystin.2 
The most serious result of the 
presence of these calculi is the oc- 
clusion of the ureters or the incite- 
ment of pyelonephritis. 
TUMORS.3 
Small fibromata, lipomata, myo- 
mata, and angiomata may occur in 
the kidney and, with the exception 
of the fibromata, are most common 
in the cortical portion. Papilloma 
may form in the mucous membrane 
of the pelvis. Sarcoma and myxo- 
sarcoma, often of large size, may 
develop in the kidney; these are 
frequently soft and vascular and are prone to hemorrhage. Primary 
sarcoma of the kidney is common in children. Secondary carcinoma 
and sarcoma are not rare. 
Fig. 572.-Small Adenoma of Kidney. 
Situated in the cortex. 
1 For a r6sum6 of cysts of the ureter with bibl., see Harris, Am. Med., 1902, iii, 731. 
2 For a study of the composition of renal calculi, see Ultzmann, R., Die Harnconcretionen des 
Menschen, Wien, 1882; Fowler, H. A., Johns Hopkins Hosp. Rep., 1908, xiii, 507; Kleinschmidt, O., 
Die Harnsteine, Berlin, 1911; Kahn, M„ Arch. Int. Med., 1913, xi, 92; Rosenbloom, J., Jour. Am. Med. 
Assn., 1915, Ixv, 161. 
3 For a general discussion of tumors of the kidney, see Nuernberg, F., Frankfurt Zt«chr f Path. 
1907, i, 433 (bibl ). THE URINARY ORGANS 
891 
There often occur in childhood mixed tumors of the kidney which 
have a sarcomatous and adenomatous character or may contain mucous 
or elastic or striated muscle tissue, cartilage, and bone, with structures 
suggesting glomeruli.1 In all probability these tumors are teratoid in 
nature and arise by the simultaneous segregation of nephrogenous and 
muscle tissue at a very early embryonic stage. A few much more com- 
plex tumors, with ectodermal and 
other structures, have been de- 
scribed, suggesting segregation at a 
still earlier stage. 
Adenoma is of frequent occur- 
rence in the kidneys. It usually 
originates in the cortex and may 
be invisible to the naked eye (Fig. 
572), or, in the form of a well-de- 
fined, circumscribed nodule (Fig. 
573 and 574), it may invade the 
medulla or largely replace the kid- 
ney. The adenomata are usually 
light in color save when very vas- 
cular with hemorrhage, and may 
be separated from the kidney struc- 
ture by a fibrous capsule. It is 
probable that many of these 
tumors are due to arrested de- 
velopment of the kidney paren- 
chyma. Such tumors are not rare 
in children.2 
There are two principal varie- 
ties of these tumors, the papillary 
and the alveolar, which are, how- 
ever, closely related. 
1. Papillary Adenoma.-There 
are cavities of different sizes, from 
the walls of which spring branching 
tufts covered with cylindrical or 
cuboidal epithelium (Fig. 575). 
These tufts nearly fill the cavities. 
Occasionally neoplasms of the type of adenoma form metastases at a 
distance, and hence they must be considered, despite their morphology, 
as carcinomata.3 
2. Alveolar Adenoma.-There is a connective-tissue framework in- 
closing small round, oval, or tubular alveoli, lined or filled with cells 
(Fig. 576). The cells are usually large, either cylindrical, cuboidal, or 
Fig. 573.-Adenoma of the Kidney. 
(Hypernephroma.) 
A tumor of the kidney formed from 
aberrant adrenal tissue. 
1 For a study of the mixed tumors of the kidney, see Wilms, Die Mischgeschwulste der Niere, 
Leipzig, 1899; Hedren, G., Zieglers Beitr., 1907, xl, 1 (bibl.); Buerger and Lautman, Am. Jour. Surg., 
1914, xxviii, 453. 
2 Engel/cen, H., Zieglers Beitr., 1899, xxvi, 320 (bibl.); Dunn, J. S., Jour. Path, and Bacteriol., 1913, 
xvii, 515. 
3 Kretschmer, H. L., and Moody, A. M., Surg., Gynec., and Obst., 1914, xix, 766. 892 
THE URINARY ORGANS 
Fig. 574.-Adenoma of the Kidney. 
Showing encapsulation of the nodules. 
Fig. 575.-Adenoma of the Kidney. 
Papillary variety. 893 
THE URINARY ORGANS 
polyhedral, and may be pigmented or fatty in a manner similar to the 
cells of the adrenals. 
Hypernephroma.--The most frequent type of kidney tumor is 
that long considered as arising from remnants of adrenal tissue. These 
tumors vary from those a few millimeters in diameter to large neo- 
plasms occupying a considerable portion of the abdomen. The cut 
surface has the dull yellow color of the adrenal cortex. The micro- 
scopic appearance resembles that of the adrenal (Fig. 573 and 577). The 
cells are filled with fat globules and contain a large amount of glycogen. 
The interstitial tissue is small in amount and through it runs a fine 
capillary network. In the more malignant type, giant cells (Fig. 578) 
may be found, or the stroma may take on active growth and the tumor 
simulate a spindle-cell sarcoma. Recently1 the view has been gaining 
ground that these growths are renal and not adrenal in origin, and it has 
been pointed out that in the undoubted adenomata cells may be found 
which resemble those of supposed adrenal origin. The problem needs 
further study for its solution. Owing to the high vascularity of the 
tumors, hemorrhages are very apt to occur in their substance, often 
leading to the formation of large hemorrhagic cysts. Intravascular 
growth is frequent and the tumor may invade the vena cava or even the 
heart,2 or proceed to the pelvis of the kidney, in the latter instance calling 
early attention to its presence by the profuse hematuria which accom- 
panies such extension. Metastasis is frequent, especially in the lungs 
and bone-marrow,3 but the liver, intestine, retroperitoneal and other 
lymph-nodes, and even the skin may be the seat of numerous deposits. 
A retrogression or quiescence of the primary tumor has been observed, 
lasting for years after operative removal of a bone-marrow metastasis 
in the tibia. 
Primary carcinoma of the kidney is rare, adenoma being frequently 
mistaken for it.4 The morphology may be adenocarcinomatous or 
medullary in type. Early invasion of the whole organ is usual and 
metastases in the opposite kidney are frequent. Squamous-cell tumors 
are derived from the mucous membrane of the pelvis. 
Primary tumors of the renal pelvis are very rare; from this site they 
may metastasize and involve the ureter and bladder.5 
PARASITES. 
Echinococcus, in its ordinary form of mother and daughter cysts, is 
sometimes found in the kidney. The cysts may open into the pelvis of 
the kidney, into the pleura, or through the wall of the abdomen. 
Cysticercus cellulosae is of very rare occurrence. Filaria bancrofti 
is found in the arteries, veins, lymphatics, and stroma, and may pass 
i Grawitz, P., Virchows Arch., 1883, xciii, 39; Stoertc, O., Zieglers Beitr., 1908, xliii, 393; Sisson, W. R., 
Zieglers Beitr., 1910, xlix, 476; Wilson and Willis, Jour. Med. Research, 1911, N. S. xix, 73; Ipsen, J., 
Zieglers Beitr., 1912, liv, 233; Fraser, A., Surg., Gynec., and Obst., 1916, xxii, 645; Glynn, E. E., Quart. 
Jour. Med., 1912, v, 157; Dunn, J. S., Jour. Path, and Bacteriol., 1913, xvii, 515. 
2 Jacobson, V. C., and Goodpasture, E. W., Arch. Int. Med., 1918, xxii, 86 (bibl.). 
3 Scudder, Ann. Surg., 1906, xliv, 851. 
* For a careful study of tumors and other growths in the kidney, see Kelynack, Renal Growths,1898 
(bibl.); also bibl. by Busse, 0., Virchows Arch., 1898, clvii, 346, 377. For a statistical study of malig- 
nant tumors of the kidney in children, see Oshima, T., Wien. klin. Wchnschr., 1907, xx, 93. 
6Lower, W. E., Surg., Gynec., and Obst., 1914, xviii, 151 (bibl.). 894 
THE URINARY ORGANS 
Fig. 570.-Adenoma of the Kidney. 
Alveolar variety. 
The cells filling the alveoli are in part transparent, resembling those of the adrenal. 
Fig. 577.-Hypernephroma. THE URINARY ORGANS 
895 
Metastasis in lymph-node of arm. Atypical form with multinucleated cells. 
Fig. 578.-Hypernephroma. 
Fig. 579.-Diverticula of the Bladder. 896 
THE URINARY ORGANS 
into the urine. Eustrongylus gigas has been found several times in the 
pelvis of the kidney. 
The Urinary Bladder. 
Malformations. 
Absence of the bladder is of rare occurrence. The bladder may be very small, 
the urine passing almost directly into the urethra. The bladder may be separated 
into an upper and a lower portion by a circular constriction. It may be completely 
divided by a vertical septum into two lateral portions. Diverticula of the wall of the 
bladder are sometimes found in new- 
born children. Partial or complete 
closure of the neck of the bladder may 
occur. This may lead to hydronephro- 
sis, or the urine may be discharged 
through the open urachus. 
Extroversion of the bladder is 
one of the most frequent malforma- 
tions, and may occur in either sex. 
It presents several varieties I1 
1. The umbilicus may be lower 
down than usual, the pubic bones not 
united at the symphysis, and the pel- 
vis wider and shallower than it should 
be. Between the umbilicus and pubes 
the abdominal wall may be wanting. 
In its place may be a projecting, ovoid 
mass of mucous membrane, in which 
may be seen the openings of the 
ureters. The penis is usually rudi- 
mentary; the urethra an open fissure 
(epispadias); the clitoris may be sepa- 
rated into two parts. The ureters 
usually open normally; sometimes 
their openings are displaced or are 
multiple. They may be dilated. 
2. There may be a fissure in the 
abdominal wall, filled up by the per- 
fectly formed bladder. 
3. The umbilicus may be well 
formed, and there may be a portion of 
abdominal wall between it and the 
extropbied bladder. 
4. The external genitals and ure- 
thra may be well formed, and the symphysis pubis united, while only the bladder is 
fissured. 
5. The genitals, urethra, and symphysis may be well formed, the bladder closed 
except at the upper part of its anterior wall. The bladder may be entirely or in part 
inverted and pushed through the opening in the abdominal wall. 
The urachus normally remains as a small fibrous cord, 12 cm. long, and 1.5 mm. 
in diameter, extending under the peritoneum from the apex of the bladder to the 
umbilicus. It is not patent after birth, except that occasionally a very small canal 
lined with epithelium and from 5 to 7 cm. long remains. This may or may not open 
into the bladder. Fluid may collect in such a patent urachus and give rise to single 
or multiple cysts, which occasionally reach a very large size. The cysts are lined 
with epithelium; they may suppurate or calculi may form in their lumina. In rare 
Fig. 580.-Hypertrophy of the Wall of 
the Bladder. 
1 Mayo, C. H., Jour. Am. Med. Assn., 1917, Ixix, 2079; Enderlen, Sammi, kiln. Vortr. (Volkmann), 
1908, No. 472.) THE URINARY ORGANS 
897 
instances the urachus may remain patent throughout its entire length, and the patient 
may pass urine simultaneously from the urethra and the umbilicus. If the normal 
exit of urine is obstructed, the remnant of the urachal tube may dilate and an acquired 
urinary fistula develop at the umbilicus. 
Carcinomata and sarcomata have been described as originating in the urachus, 
and two cases of tuberculosis are on record.1 
Changes in Size and Position. 
Dilatation.-This may be general or partial, leading to the formation of 
diverticula. 
General dilatation of the bladder is produced by the accumulation of urine in 
consequence of some mechanical obstacle to its escape, or of paralysis of the muscular 
walls of the organ. The dilatation is usually uniform and may be very great, so that 
the bladder may reach to the umbilicus. If the walls of the bladder are paralyzed, or 
the obstruction occurs suddenly or is complete, the wall of the bladder is thinned. 
When an incomplete obstruction exists for some time the walls of the bladder are apt 
to hypertrophy, so that, although the bladder is larger than normal, the walls may not 
only be of the usual thickness, but even very much thicker. In the fetus dilatation 
of the bladder may reach such a size as to interfere with delivery. 
The retained urine in dilated bladders is liable to decomposition, from the presence 
of bacteria, and this may lead to inflammation or gangrene of the mucous membrane. 
Diverticula of the bladder may be produced by the pouching out of circumscribed 
portions of the wall of the organ, the wall of the pouch containing all the layers of 
the bladder wall. More frequently, however, they are produced by a protrusion of the 
mucous membrane between hypertrophied bundles of muscle fiber. They may be 
very small (Fig. 579), or they may be as large as a child's head. They may communi- 
cate with the bladder by a large or small opening. The decomposition of stagnant 
urine in diverticula is apt to induce inflammation with ultimate formation of adhesions. 
Calculi may be formed in them or may slip into them from the bladder. Mechanical 
obstruction to the outflow of urine is the usual cause, urethral stricture, phimosis, 
and prostatic hypertrophy being the most frequent exciting agents; but simple trauma 
of the bladder region may be followed by diverticula.2 
Hypertrophy of the muscular coat of the bladder is usually due to mechanical 
obstructions to the outflow of urine, such as stricture of the urethra, enlarged prostate, 
calculi, new growths, etc. The muscular coat is thickened uniformly or assumes a 
trabeculated appearance (Fig. 580). The organ retains its normal capacity, or is 
dilated, or becomes smaller. The mucous membrane is frequently the seat of chronic 
or acute inflammation. Dilatation of the ureters and hydronephrosis frequently 
accompany this condition. 
Hernias of a portion of the bladder wall sometimes accompany intestinal herniae 
through the inguinal and crural canals and the foramen ovale. The changes in posi- 
tion of the bladder produced by displacements of the vagina and uterus will be men- 
tioned with the lesions of those organs. 
In the female, after injury of the perineal floor following delivery, the base of the 
bladder may press downward, causing protrusion of the vaginal wall {vaginal cystocele) ; 
or there may be inversion and prolapse of the bladder through the dilated urethra. 
WOUNDS-RUPTURE-PERFORATION. 
Penetrating wounds of the bladder may permit escape of urine into 
the abdominal cavity, or infiltration into the surrounding connective 
tissue, or permanent fistulae. Such wounds are always serious and fre- 
quently fatal, owing chiefly to the severe and often gangrenous inflam- 
mation which decomposing urine sets up in the connective tissue, or to 
the peritonitis induced by the same cause. 
1 For further details and bibl., see Cullen, The Umbilicus and Its Diseases, Philadelphia, 1916. 
2 Thomas, G. J., Surg., Gynec., and Obst., 1916, xxiii, 378. 898 
THE URINARY ORGANS 
Rupture of the bladder may be produced by severe blows and falls 
when the bladder contains urine. More rarely rupture takes place from 
overdistention, especially in tabes or transverse lesions of the spinal cord. 
Death may occur from rupture of the bladder with escape of urine into 
the peritoneal cavity, without evidences of peritonitis. 
Perforations of the bladder may be due to ulceration, either simple or 
cancerous, to gangrene, to abscesses from without, and to cancerous 
ulceration from the adjoining organs. Fractures of the pelv c bones 
may be accompanied by laceration of the bladder. Perforations of the 
bladder may lead to the establishment of fistulae, communicating with 
the rectum, vagina, or uterus, or opening externally. 
DISTURBANCES OF CIRCULATION. 
Hyperemia.-Aside from active hyperemia of the mucous membrane 
in acute inflammation, the bladder is not infrequently the seat of chronic 
congestion from obstruction to the venous circulation. Under these 
conditions there may be chronic catarrhal inflammation, or a marked 
dilatation of the veins (vesical hemorrhoids), which may give rise to 
hemorrhage or to obstruction of the opening of the ureters. 
There are exfoliation of epithelium and emigration of leucocytes from the submucosa. 
Fig. 581.-Acute Catarrhal Cystitis. 
Hemorrhage.-Extensive hemorrhages into the bladder are com- 
monly due to injury or to the presence of calculi, tumors, or filariasis. 
In this condition the urine is usually also clouded with finely divided 
fat-chyluria. Small hemorrhages into the substance of the mucous 
membrane may accompany inflammation, the hemorrhagic diathesis, 
scurvy, purpura, smallpox, etc. Small amounts of blood are not infre- 
quently passed in the urine in tuberculosis or syphilis of the bladder. 
If the hemorrhage is considerable and occurs rapidly in an empty blad- 
der, a clot is apt to form; but when the blood mixes with urine as it 
is extravasated, it more commonly remains liquid and is discharged as a 
reddish brown fluid. 
INFLAMMATION. (Cystitis.) 
Acute Catarrhal and Exudative Cystitis.-This may be incited by the 
presence of urine which has decomposed under the influence of bacteria; 
by cantharides or other drugs; by the presence of foreign bodies and 
calculi; it may be due to an extension of gonorrheal urethritis or vaginitis; 899 
THE URINARY ORGANS 
or it may occur with acute general infectious diseases. The mucous 
membrane is swollen and congested, although these alterations may not 
be very evident after death. There may be ecchymosis; the epithelium 
is granular, and may proliferate and peel off. Leucocytes may infiltrate 
the submucosa and pass out between the epithelial cells (Fig. 581). 
Mixed with the urine there may be shreds of mucus, pus cells, epithelial 
cells of various shapes, usually more or less swollen and granular, or 
fragments of such cells; red blood-cells, bacteria, and various urinary 
crystals; abscesses may form in the mucous membrane; or there may 
be phlegmonous inflammation in the submucosa and muscularis of the 
bladder with formation of abscesses. Thus perforations and fistulae may 
occur. Resolution may take place after acute catarrhal and exudative 
cystitis, but the inflammation very frequently assumes a chronic character. 
Chronic Cystitis.-In this form the mucous membrane may be swollen, 
Fig. 582.-Hyperplasia of the Bladder Epithelium. 
The hyperplastic epithelium is transparent and, dipping into the submucosa, forms gland-like structures. 
succulent, grayish., or mottled with spots of congestion or extravasation, 
and covered with a layer of mucus and pus. Microscopically the mem- 
brane may be more or less infiltrated with pus cells, and pus may be 
constantly produced and thrown off into the urine. Later the mucous 
membrane may become thickened either diffusely or in the form of tufts 
or polypi. In some cases it becomes atrophied. Owing to decomposi- 
tion of hemoglobin in the extravasated blood the mucosa may become 
pigmented, brown, or slate-colored. The mucous membrane frequently 
becomes eroded, especially on the most elevated portions, or deep ulcer- 
ations may occur. The muscular coats may become paralyzed and the 
bladder dilated; or the submucosa or the muscularis, or both, may be- 
come hypertrophied. The mucous membrane may become encrusted 
with urinary salts. 
In another class of cases the inflammation assumes a necrotic charac- 900 
THE URINARY ORGANS 
fer. Larger and smaller patches of the mucosa die, become brown 
or gray in color, loosen or peel off and become mixed with the urine 
and exudations. The gangrenous process may extend to all the coats 
of the bladder, so that perforation and fatal peritonitis may occur. The 
gangrenous form of cystitis is more apt to occur in paralytics. 
In still another class of cases the inflammation is suppurative. The 
submucosa, the intermuscular connective tissue, and the adjacent parts 
become infiltrated with pus, either diffusely or in the form of larger and 
smaller abscesses, which may open externally or internally, forming deep 
ulcers. In all these cases the inflammation may extend to the ureters 
and kidneys; it may skip the ureters and involve the kidneys. 
The small nodules of lymphoid tissue in the mucous membrane of 
the bladder, especially near the neck, may become enlarged and promi- 
nent in cystitis, and may then be mistaken for miliary tubercles (nodular 
cystitis). 
Hyperplasia of the epithelium of the bladder sometimes occurs in 
chronic cystitis and under other conditions. This may be diffuse or 
circumscribed and the epithelium may assume a squamous character. 
Thus masses of transparent epidermis-like cells may lie between papillary 
projections of the submucosa, forming structures which resemble glands 
The epithelium has assumed the squamous type and is exfoliating. 
Fig. 583.-Hyperplasia of the Bladder Epithelium. 
(see Fig. 582), or layers of flattened epithelium may cover or peel from 
the surface (see Fig. 583).1 
The hyperplasia and subsequent softening of the epithelium in the 
deep crypts (Fig. 582) may lead to the formation on the surface of minute 
cysts filled with clear yellow or brownish fluid {cystitis cystica).2 The 
lesion in the bladder is most usually about the trigone; it may involve the 
rest of the urinary tract. 
A few cases have been described in which scattered over the mucous 
membrane of the bladder are small thickened areas, from two to fifteen 
millimeters in diameter, usually surrounded by a hyperemic zone, and 
frequently ulcerated. These areas of chronic inflammatory thickening 
are formed by hyperplasia of the connective tissue with small-cell infil- 
tration and by peculiar large cells which appear to be phagocytes con- 
1 For a study of regeneration in the mucous membrane of the bladder, see Lasio, G., Virchows Arch,, 
1904, clxxviii, 65. 
2 For bibl. of cystitis cystica, see StoerK, O., Zieglers Beitr., 1911, 1, 361. THE URINARY ORGANS 
901 
taining red blood-cells, fragments of other cells, bacteria, etc. The 
nature of this lesion is not yet clear. It has been called malakoplakia and 
cystite en plaque.1 
Membranous Cystitis.-In connection with any of the above lesions 
the mucous membrane of the bladder may be covered, in patches or some- 
times over a considerable portion of its surface, with a layer of fibrin, 
either granular or fibrillar, inclosing pus and epithelial cells and bacteria. 
The mucosa may be infiltrated with fibrin. 
This form of inflammation may occur in connection with severe 
infectious diseases-measles, diphtheria, scarlatina, typhoid fever; in 
connection with similar inflammation of the external genitals; in puer- 
peral fever and noma; and sometimes in the presence of foreign bodies. 
It rarely occurs independently. In severe types, a more or less complete 
cast of the bladder wall may be passed from the urethra. 
In the so-called emphysematous cystitis, due to the presence of Bacil- 
lus aerogenes capsulatus, larger and smaller gas blebs may be present in 
the mucosa and underlying tissue.2 
The most common microorganisms which act as excitants of acute 
catarrhal and exudative cystitis are Bacillus coli communis, Streptococ- 
cus pyogenes, and Staphylococcus pyogenes, the gonococcus and typhoid 
bacillus,3 Bacillus proteus, and Bacillus aerogenes capsulatus. Many 
other forms are of occasional occurrence.4 
Tuberculous Cystitis.-There may at first be miliary tubercles formed 
in the submucosa. These are often about the ureteral openings if the 
kidney is the source of the infection. By the coalescence of these and 
the degeneration of tissue about them, ulcers are formed, and it is most 
frequently in the ulcerative stage that the lesion is seen. The ulcers, 
which may be large or small, are usually most abundant at the base of 
the organ. Their edges may be cheesy, and miliary tubercles in greater 
or smaller numbers are usually found in the mucosa about them. Not 
infrequently large shreds of tissue are loosened and cast off. The mucosa 
about the ulcers is apt to be infiltrated with small spheroidal cells. Tu- 
bercle bacilli are present in many of the tubercles and in the edges and 
base of the ulcers, and may be found in the urine. Catarrhal inflamma- 
tion is a very constant accompaniment of this lesion. Tuberculous 
cystitis may occur in connection with tuberculous inflammation of the 
lungs and intestines, or of the kidney, uterus, prostate, etc. In the early 
stages, the urine remains clear and acid; later secondary infections are 
usual, and the urine then contains much pus and mucus. 
Syphilis.-In secondary syphilis, lesions of the same type as those 
occurring on the skin may exist in the bladder, giving rise to symptoms 
of cystitis, but without marked changes in the urine. A little pus or 
blood may be found in severe lesions. In tertiary syphilis, gummatous 
1 For a description and discussion of this lesion, see von Hansemann, Virchows Arch., 1903, clxxiii, 
302; and Landsteiner and Stoerk, Zieglers Beitr., 1904, xxxvi, 131. 
2 See, for bibl., Kedrowstcy, W. J., Centralbl. f. allg. Path., 1898, ix, 817; Ruppaner, E., Frankfurt. 
Ztschr. f. Path., 1908, ii, 343. 
3 See Curschmann, H., Munchen, med. Wchnschr., 1900, xlvii, 1449. 
4 For a study of bacteria of the urinary passages, see Faltin, Centralbl. f. d. Krankh. d. Harn- u. 
Sex.-Org., 1902, xiii, 130. 902 
THE URINARY ORGANS 
Fig. 584.-Papilloma of the Bladder. 
Fig. 585.-Cabcinoma of the Bladder. 903 
THE URINARY ORGANS 
or papillomatous lesions may develop in the bladder wall. Pain and 
hematuria are the most frequent symptoms.1 
TUMORS. 
Small nodular fibromata and adenomata may form in the submucosa. 
Fibromyxomata, myxosarcomata, angiomata, and complex tumors have 
been described. The last, which may contain bone, cartilage, striated 
muscle, and glandular structures must be due to congenital displacements 
of multipotent tissues.2 
Aside from the polypoid thickenings of the mucosa occurring in 
chronic cystitis, soft vascular papillomata are of frequent occurrence. 
These tumors vary in size from that of a pea to that of a pigeon's egg or 
larger. They consist of a fibrous, often very vascular stroma, and are 
covered on the surface with numerous small, closely set, villous projec- 
tions, over which are irregular layers of elongated or cylindrical cells 
(Fig. 584). These tumors are very liable to bleed, are often accompanied 
by vesical catarrh, and may be covered by a precipitate of urinary salts. 
The epithelium is liable to peel off from the surface of the villi and 
appear in the urine. A number of examples have been reported in 
workers with aniline products.3 
Sarcoma of the bladder has been described, but is rare.4 
Fig. 586.-Papillary Carcinoma of the Bladder. 
1 For details and bibl., see Fowler, H. A., Jour. Am. Med. Assn., 1917, Ixix, 1399. 
2 Fischer, Arb. a. d. Path. Inst. z. Tubingen, 1908, i, 6; Stumpf, R., Zieglers Beitr., 1911, 1, 171. 
3 Nassauer, M., Frankfurter Ztschr. f. Path., 1919-20, xxii, 353; see, also, review in Medical Science, 
1921, iii, 316. 
4 Wilder, J. A., Am. Jour. Med. Sc., 1905, cxxix, 63. 904 
THE URINARY ORGANS 
Carcinoma.-Carcinoma of the bladder is often secondary, and is then 
due, not to metastasis, but to an extension of the growth from neighboring 
parts, as the uterus, vagina, prostate or rectum. Invasion by neoplasms 
of the kidney occurs either through the ureteral lymph-channels or by 
direct implantation of particles passing into the bladder in the urinary 
stream. Melanosarcomata involve the mucous membrane through the 
blood-stream. Vesical fistulae not infrequently follow sloughing of the 
tumor. 
Primary carcinoma of the bladder may occur: 
1. As a diffuse scirrhous infiltration of the entire wall of the bladder, 
usually with ulcerations of its inner surface. 
2. As a circumscribed nodule (Fig. 585) which grows inward and out- 
Fig. 587.-Vesical Calculus. 
Showing lamellations indicating successive depositions of different texture and composition 
ward, ulcerating on its inner surface, and sometimes producing perfora- 
tions. 
3. As a villous or papillomatous growth. The tumor grows from one or 
more points of the inner surface of the bladder. It is formed of tubular 
follicles lined with epithelium (Fig. 586), while on its surface are tufts 
covered with cylindrical epithelium The new growth may involve 
the entire thickness of the wall of the bladder. 
4. A few cases of carcinoma have been described in which the stroma 
contained a varying quantity of smooth muscle tissue.1 
Cysts.-Dermoid cysts of the wall of the bladder have been described, 
but are rare.2 Small cysts with serous contents sometimes occur in the 
1For study of carcinoma of the ureter, see Metcalf and Safford, Am. Jour. Med. Sc., 1905, cxxix, 50. 
aSee case by Block and Hall, Am. Jour. Med. Sc., 1905, cxxix, 651. 905 
THE URINARY ORGANS 
mucous membrane; a part of them, at least, are believed to be due to 
faulty embryonal development. Echinococcus cysts may form in the 
bladder wall or rupture into the lumen with the discharge of their con- 
tents through the urethra. 
PARASITES, FOREIGN BODIES, AND CALCULI. 
Among the animal parasites occasionally found in the bladder may 
be mentioned Echinococcus, Schistosoma haematobium, Filaria bancrofti, 
Ascaris, and Oxyuris. 
A great variety of foreign bodies may be found in the bladder, par- 
ticularly in the female. If their stay is long they are apt to become 
encrusted with urinary salts. 
Calculi. 
Vesical calculi may occur singly or in great numbers, and vary greatly in size, 
ranging from small, sand-like particles up to masses four or five inches in diameter; 
but the usual range is from the size of a pea to that of a hen's egg. They are usually 
oval, spheroidal, or elongated; or, when several are present, they are apt to be faceted. 
The surface may be smooth or rough. They are usually more or less distinctly lamel- 
lated, and are frequently formed around a central body called a nucleus, which may 
be formed either of urinary salts or of some foreign body. They are rarely composed of 
a single substance. Their most common constituents are phosphates, uric acid and 
urates, and calcium oxalate, or various combinations of these. 
Uric-acid Calculi.-These are a frequent type of vesical calculi. In the form of 
small brownish red, crystalline aggregations they may be passed as "gravel." The 
larger uric-acid calculi are not commonly of very great size, are frequently finely 
nodulated on the surface, but may be smooth. The color varies from light yellow to 
dark reddish brown; they are usually dense and lamella ted. 
Calculi Formed of Urates.-Calculi composed of pure urates are rare, these 
salts being more commonly combined with uric acid and the phosphates to form the 
complex calculi. Sodium urate, in the form of small spined, more or less globular 
crystalline masses, forms one of the varieties of "gravel." Ammonium urate is the 
chief component of the larger stones. 
Phosphatic Calculi.-Pure calcium-phosphate calculi, though rare, are found as 
whitish, usually smooth, and small lamellated concretions. 
Mixed or Triple Phosphate calculi are common, and frequently attain large 
size. These calculi are sometimes pure, but the deposit is more frequently associated 
with other salts, either as encrusting or intercalated lamellae. Triple-phosphate 
calculi are usually rough on the surface, of grayish white color, lamellated, and fre- 
quently very friable (Fig. 587). 
Calcium-carbonate Calculi.-Small gray or white, hard, and usually smooth 
calculi of pure calcium carbonate occur rarely. Calcium carbonate is sometimes passed 
as gravel in the form of minute spheroidal bodies, either singly or in clusters. 
Calcium-oxalate Calculi (mulberry calculi) are comparatively common, either 
pure or in combination with uric acid or the phosphates. Calcium oxalate may occur 
in the form of very small, hard, smooth concretions, or as larger, heavy, hard, finely or 
coarsely nodulated brown or blackish lamellated masses. The nucleus or some of the 
lamellae, or both, are often composed of uric acid. 
Cystin Calculi are usually ovoidal in shape, of waxy consistence, of clear or 
brownish or greenish yellow color, with mammillated surface and crystalline fracture. 
Cystin may be associated in a variety of ways with other calculi. 
Xanthin Calculi, which are very rare, are usually of moderate size, smooth, of a 
cinnamon or cinnabar-red color, lamellated, and oval or flattened in shape. 
Solid masses of fibrin and blood1 or bacteria2 sometimes occur in the kidney pelvis 
1 Schmidt, M. B., Centralbl. f. allg. Path., 1912, xxiii, 865. 
2 For description of bacterial calculi in kidney, see Neumann, A., Deutsch, med. Wchnschr., 1911, 
xxxvii, 1473. 906 
THE URINARY ORGANS 
or in the bladder, and may exist as independent structures, or form nuclei for the 
deposit of urinary salts. 
For a detailed account of calculi, the conditions under which they form, modes of 
analysis, etc., we refer to special works on this subject. 
The Urethra. 
Some of the malformations of the urethra are described with those of the penis. 
The urethra may be impervious or may open at the root of the penis. More com- 
monly there is partial obliteration or stricture of some part of the canal. The entire 
urethra may be dilated into a sac. 
There may be a canal on the dorsum of the penis, formed by the fusion of the sper- 
matic cords, and opening in the glans above the urethra. 
There may be two or more openings of the urethra. The canal may be misplaced 
so as to open in the inguinal region. 
A number of cases have been reported in which a valve in the urethra has led to 
hypertrophy of the bladder, dilatation of the ureters, and hydronephrosis. Diver- 
ticula may occur in any portion of the urethra. They have been supposed to be due 
either to action of the valves just described, or to the congenital lack of closure of 
the genital furrow.1 
Owing to its narrowness, greater length, and peculiar connections with the internal 
generative organs, the male urethra is much more liable to disease than the female. 
Malformations. 
Fig. 588.-Stricture of the Male Urethra. 
Changes in Size and Position. 
Dilatation of the urethra may be produced by strictures, or by calculi or other 
bodies fixed in its lumen. The dilatations are fusiform or sacculated in shape, and 
may reach the size of an orange or be even larger. 
Strictures of the urethra are usually due to inflammation of its walls. 
The stricture may be temporary, and due to a diffuse inflammatory swelling of the 
mucous membrane, or to the raising of the relaxed membrane into a fold or pocket. 
Permanent strictures are produced by structural changes in the walls of the urethra. 
1. The mucous membrane and submucous tissue become thickened in inflamma- 
tion or as the result of injury and the new-formed fibrous tissue which contracts and 
narrows the canal. 
2. Ulceration of the mucous membrane leaves cicatricial tissue, which contracts, 
and also produces adhesions and bands of fibrous tissue (Fig. 588). 
3. There is fibrous induration of the corpus spongiosum and consequent constric- 
tion of the urethra. 
The most frequent position of strictures is at the junction of the mambranous and 
1 For further details and bibl., see Englander, S., Jour. Am. Med. Assn., 1917, Ixviii, 351. THE URINARY ORGANS 
907 
spongy portions of the urethra, or close to this point. They also occur at the fossa 
navicularis and meatus, but more frequently in the prostatic portion. There may be 
one stricture or several. The consequences of stricture are dilatation of the urethra, 
the bladder, and the ureters, and hydronephrosis; inflammation and ulceration of the 
urethra behind the stricture, with perforation, infiltration of urine, or the formation of 
fistulae. 
The urethra may also be obstructed by folds of the mucous membrane; by muscular 
valves at the neck of the bladder; by wounds; by polypi and swollen glands; by new 
growths; by changes in the prostate and perineum; by calculi, mucus, blood, and 
echinococci coming from the bladder; by foreign bodies introduced from without. 
Prolapse and inversion of the mucous membrane occur occasionally in young 
girls and women. There is a bluish-red swelling (urethral caruncle), from the size of 
a pea to that of a walnut, at the meatus. In the male, invagination of the mucous 
membrane of the urethra has been seen after injuries of the perineum. 
INJURIES-PERFORATION-HEMORRHAGES. 
Wounds of the urethra are produced in many ways, but most com- 
monly by catheters and bougies. The wounds may cicatrize, or there 
may be infiltration of urine or the formation of fistulae or false passages. 
Ruptures of the urethra are produced by severe contusions and by 
fracture of the pelvic bones. Extravasations of blood and urine, and 
gangrenous inflammation of the surrounding soft parts, are the ordinary 
results. Urethral varices in the female may lead to hemorrhage. 
Ulceration and perforation of the urethra may lead to the formation 
of fistulae, which open in various directions through the skin. 
INFLAMMATION. (Urethritis.) 
Catarrhal Urethritis may be due to the action of chemical irritants, and 
to the extension to the urethra of inflammation from other parts; but its 
most frequent excitant is the gonococcus. In its acute form it involves 
either a portion or the whole of the urethra. The mucous membrane 
is red, swollen, and covered with mucopus. The epithelium may be 
loosened or exfoliated; pus cells are present in the submucosa between 
the epithelial cells. The gonococcus is present usually in considerable 
numbers in the exudate, both free and in the pus cells. It may pene- 
trate between the epithelial cells. 
Resolution may follow acute gonorrheal urethritis. But the condi- 
tion may become chronic and then is often confined to the posterior por- 
tions of the urethra. Here the gonococcus may persist for a long time 
and may be mingled with the exudate, which is now less purulent and 
consists very largely of mucus which in thread-like forms may be passed 
with the urine. 
Chronic Inflammation of the urethra may exist for a long time with 
the production of a mucopurulent exudation, but without the occur- 
rence of marked structural lesions. In other cases it leads to ulceration, 
to fibrous induration of the wall of the canal (see Fig. 588), to indura- 
tion and swelling of the mucous follicles, to polypoid thickenings of the 
mucous membrane. 
The inflammation may extend to the fibrous wall of the urethra, the 908 
THE URINARY ORGANS 
corpora spongiosa and cavernosa. This may result in the formation of 
new connective tissue or of abscesses, especially near the fossa navicu- 
laris. There may be involvement of the bladder, the glands of Cowper, 
the prostate, the spermatic cord, and the testicles. The inguinal nodes 
also may be swollen and inflamed, and the lymphatic vessels on the 
dorsum of the penis may be involved in the same process. 
Membranous Inflammation is sometimes seen, especially in children. 
Fibrinous casts of a small or large portion of the canal may be formed. 
Tuberculous Inflammation occurs in the mucous membrane of the 
urethra in connection with tuberculous inflammation of the bladder, 
prostate, or testicles, but is rare. 
Syphilitic Ulcers may be situated at the meatus or as far back as the 
fossa navicularis. They are apt to produce strictures. 
TUMORS. 
Aside from the polypoid outgrowths from the mucous membrane of 
the urethra as the result of chronic inflammation or of stricture, fibrous 
polyps may occur congenitally; polyps containing glandular structures or 
cysts are rarely seen.1 Carcinoma may occur as a result of local exten- 
sion from adjacent organs or metastasis from the bladder and with 
extreme rarity as a primary growth.2 
Cysts may occur in the membrane as a result of the dilatation of the 
mucous glands. Circumscribed masses of dilated veins occasionally 
occur in the urethra, forming the so-called urethral hemorrhoids. 
The sinus pocularis may be dilated in children by the retention of its 
secretion, so as to form a mass which may obstruct the exit of urine and 
lead to hypertrophy of the bladder and dilatation of the ureters. 
1 Fluss, K., Wien. klin. Wchnschr., 1907, xx, 1225. 
2 Kaufmann, C., Deutsch. Chir., 1886, Lief. 50 A (very complete bibl.); and Preiswerk, Ztschr.'f. 
Urol., 1907, i, 273. CHAPTER X. 
THE REPRODUCTIVE ORGANS OF THE FEMALE.1 
The Vulva. 
Malformations.2 
The external genitals may be entirely absent or imperfectly developed; this occurs 
chiefly in fetuses otherwise so deformed that they are not viable. The fissure between 
the labia may be unformed, or the labia may have grown together, with or without 
obstruction of the urethra. The clitoris and nymphae may be abnormally large, or 
the nymphae may be increased in number. The clitoris may be abnormally long; at 
the same time the vagina may be narrow; the uterus small and undeveloped or mal- 
formed, the ovaries small and sometimes situated in the labia; the mammae small; 
and the body of a masculine character. These are the characteristics of infantilism. 
The clitoris may be perforated by the urethra or may be cleft and apparently double. 
The hymen is subject to various anomalies: it may be entirely absent; the opening 
may be very large or in an unusual place; there may be several openings; the free edge 
may be beset with papillary projections; or there may be no opening at all (imperforate 
hymen). 
HEMORRHAGE, HYPEREMIA, ETC. 
Hemorrhage may take place from wounds or ulcers of the vulva, but 
the most important form is that which takes place in the connective tis- 
sue of the labia majora; this may occur during labor or may result from 
external injury. One of the labia may be much swollen and distended 
by the extravasated blood. The accumulation of blood may produce 
sufficient pressure to rupture the overlying parts so that profuse external 
hemorrhage results; or the blood may be gradually absorbed, or may 
decompose with suppuration or gangrene of the surrounding tissue. 
Varicose Veins in the labia are not infrequent, but are most common 
during pregnancy. Edema of the labia majora may occur in pregnancy 
or in labor. It frequently accompanies disturbances of the venous cir- 
culation, as in certain heart and lung diseases; or it may result from 
systemic conditions, as chronic diffuse nephritis or wasting diseases, or 
from local causes, as a result of thrombosis3 or other disturbances of cir- 
1 The most important source of information on the pathology of the female generative organs is the 
Handbuch d. Gynakologie, edited by J. Veit, 2d ed., Wiesbaden, 1908. Much recent knowledge is 
given in the well illustrated Handbuch d. gesamten Frauenheilkunde, edited by W. Liepmann, Leipzig, 
1914. Of the recent works in English the most valuable is the three volume System of Gynaecology, 
edited by Eden and Lockyer, London, 1917. Useful information on the diagnosis of gynecological lesions, 
though somewhat out of date, is contained in Gebhard, C., Pathologische Anatomie d. weiblichen Sexual- 
organe, Leipzig, 1899. A recent and most valuable text is Frank, R. T., Gynecological and Obstetrical 
Pathology, New York, 1922. 
2 For full details of the embryology and malformations of the female generative organs, see Felix, 
W., Keibel and Mall, Human Embryology, Philadelphia, 1912, ii, 752: Kermauner, F., Schwalbe, Die 
Morphologie der Missbildungen des Menschen u. der Tiere, Jena, 1909, iii, 253: Nagel, Veit, Handbuch 
d. Gynakologie, 1st edition, Wiesbaden, 1897, i, 519: Aschoff, Pathologische Anatomie, 3d edition, 
Jena, 1913, ii, 569: Keith, A., Human Embryology and Morphology, 3d edition, London, 1913: and 
Ballantyne, in Eden and Lockyer, System of Gynaecology, London, 1917, i, 215. 
3 Stolz, M., Gynak. Rundschau, 1908, ii, 213. 
909 910 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
culation in the uterine or perivaginal venous plexuses. In the latter 
case the edema may be excessive, leading to the transudation of fluid 
through the skin, to the formation of vesicles, to superficial erosion, or 
even to gangrene. 
INFLAMMATION. (Vulvitis.) 
The skin, mucous membrane, connective tissue, and glands of the 
vulva may be the seat of inflammation. 
Acute Catarrhal Inflammation of the mucous membrane may be in- 
duced by a variety of agents; in infancy it is most frequently due to 
gonorrheal infection. Bacteriological examination will reveal the pres- 
ence of gonococci in the pus from the urethra and Skene's glands. The 
adult vulva is very resistant to the local invasion of the gonococcus, but 
irritating discharges from above, usually cervical, whether due to gono- 
coccal or other forms of cervicitis or to the breaking down of cervical or 
corporal carcinoma, etc., may by their chemical action set up a severe 
vulvar irritation. The mucous membrane may be swollen and red, and 
covered with a mucopurulent exudate. The labia may be swollen, the 
glands of Bartholin may be involved, and abscesses of the labia may 
develop. Superficial ulcers usually accompany an acute vulvitis, espe- 
cially in childhood. 
Chronic Catarrhal Inflammation may lead to superficial or deep ulcer- 
ation of the mucous membrane, to papillary outgrowths, or to thickening 
of the labia. Suppurative inflammation of the tissue of the labia may 
occur with a similar process in neighboring parts. 
Chronic Gonorrheal Infections in adults usually manifest themselves 
by the so-called maculae gonorrhoicoe, deep-red indurated areas around 
the openings of Skene's and Bartholin's ducts. Erysipelatous inflam- 
mation of the skin of the vulva is frequent in young children; in adults 
it is less common. Inflammation of the vulvovaginal glands, usually 
gonorrheal, may be acute and lead to abscesses, or may be chronic and 
produce induration or cyst formation of the gland or of its duct. 
Gangrene may follow erysipelatous inflammation or may occur after 
parturition; it may accompany severe exhausting and infectious diseases; 
or it may follow bruises or other injuries. In some forms, such as those 
known as noma and hospital gangrene, the destruction of tissue proceeds 
with extreme rapidity, and in weak children usually proves fatal.1 
Membranous Inflammation may occur, with or without diphtheria 
and a similar lesion of the fauces or elsewhere, and is frequently associ- 
ated with gangrene. 
Tuberculous Inflammation, usually with ulceration, occasionally 
occurs in the vulva. Sometimes nodular elevations, which later may 
break down and ulcerate, are seen. The ulcerations are serpiginous, 
with undermined edges. 
Syphilitic Inflammation and ulceration are of frequent occurrence on 
the vulva, particularly on the mucous surfaces, and may lead to con- 
siderable destruction of tissue and cicatricial contractions. The primary 
1 For a study of noma, see Blumer, G., and MacFarlane, A., Am. Jour. Med. Sc., 1901, cxxii, 527. THE REPRODUCTIVE ORGANS OF THE FEMALE 
911 
lesion of syphilis, the hard chancre, is often located at the vulva. It be- 
gins as a hard nodule with indurated base, and eventually breaks down, 
producing a superficial ulcer. Treponema pallidum can be found in the 
lesion. Of the secondary manifestations, the most common are mucous 
patches, which are superficial lesions of the skin or mucous membrane. 
Flat condylomata {condylomata lata) are a late secondary lesion, while 
gummata are more rare tertiary manifestations. Soft chancre is less 
frequent than the hard form, but often occurs. 
Venereal Warts {pointed condylomata, condylomata acuminata) are ex- 
crescences found at the vulvar or anal margin, and are most commonly 
due to the irritation produced by gonorrheal pus, but are not infrequently 
the result of innocent discharges. These growths may assume enormous 
dimensions, reaching the size of two fists, especially during pregnancy. 
They are soft, finely fissured, elevated excrescences, with a moist surface 
Fig. 589.-Kraurosis Vulv^e. 
producing an acrid discharge. Histologically they show a branching 
connective-tissue framework covered with a thick but otherwise normal 
layer of epithelium. 
Kraurosis is a disease peculiar to the vulva, which is characterized by 
a progressive atrophy of the adjacent skin and mucosa with secondary 
shrinkage of the parts.1 Its etiology is obscure. It usually begins in 
middle life and in many cases is preceded by intractable pruritus. The 
labia majora atrophy, the skin losing its pigment, hair, and glands; the 
labia minora disappear; the urethra is tense, but gaping; and the vulvar 
orifice may contract so as not to permit the introduction of the tip of a 
finger. The parts look dry, tense, cracked, and shiny. In many cases, 
carcinoma (epithelioma) ultimately develops. The subcutaneous con- 
1 Darger, W., Arch. f. Gynec., 1902, Ixvi, 637: Jung. P., Ztschr. f. Geburtsh. u. Gynak., 1904, lii, 
13: Baldy, J. M., and Williams, H. L., kia. Jour. Med. Sc., 1899, cxviii, 528. 912 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
nective tissue (especially the elastic fibers) atrophies, the papillary pro- 
jections flatten out, and the Malpighian layer atrophies. In the lower 
layers of the epidermis, there are often found areas of large clear cells, 
the significance of which is unknown (Fig. 589). 
Closely related to kraurosis, is leukoplakia vulvaris, which is a 
chronic inflammatory thickening and downgrowth of the vulva re- 
sembling leukoplakia elsewhere. The disease is rare and often leads to 
carcinoma.1 
Esthiomene is another disease peculiar to the vulva.2 Its etiology 
is likewise obscure, although it may eventually prove to be a late mani- 
festation of syphilis. A rodent ulcer develops somewhere along the 
vulvar circumference, and is always accompanied by much edema and 
infiltration. Finally, a large number of communicating fistulae, together 
with the superficial ulceration, produce great distortion and destruction. 
The diseased tissue shows no specific characters, resembling that of any 
indifferent ulcer, though there is often excessive thickening of the vascular 
walls. 
Elephantiasis of the vulva is due to lymphangiectasis and secondary 
hypertrophy. Rarely, the etiological factor is filariasis; more commonly 
some other interference with the inguinal lymphatic channels (such 
as extirpation for bubo) may be the cause. Firm, nodular masses of 
variable size and consistency develop; instances of tumors weighing over 
twenty pounds have been reported. The surface may be smooth or 
papillary or even cauliflower-like; secondary ulceration is common. The 
tissue is edematous, contains dilated lymph-channels, and frequently 
shows evidences of inflammation (round and plasma cells). The skin 
is not affected except by secondary changes. 
TUMORS. 
Fibromata.-Circumscribed fibrous tumors are found in the connect- 
ive tissue of the labia, mons veneris, perineum, and clitoris, and at the 
entrance to the vagina.3 They may attain large size, and, attached only 
by a pedicle, may hang far down between the legs. The skin is usually 
movable over the surface of these tumors. They may consist of soft 
edematous fibrous tissue (fibroma mollo) or of hard well-marked strands 
(fibroma durum). Fibromyomata and adenomy omata occur at the inser- 
tion of the round ligament. 
Papillomata consist of hypertrophied papillae covered with thick 
layers of epithelium. They vary in size from that of a pea to that of an 
apple, and have a cauliflower appearance. Lipoma, myoma, fibro- 
sarcoma, and angioma are of occasional occurrence in the vulva. A few 
cases of melanosarcoma4have been recorded, but later investigations have 
1 Berkeley, C., and Bonney, V., Proc. Roy. Soc. Med., 1909, iii®, 29: Bonney, V., Lancet, 1908, i, 1465. 
2 For study of esthiomene and secondary elephantiasis vulvse, see Stein, A., and Heimann, W. J. 
Surg., Gynec., and Obst., 1912, xiv, 345. See also Kurz, L., Jour. Obst. and Gynec. Brit. Emp., 1913, 
xxiii, 353. 
3 Leonard, Bull. Johns Hopkins Hosp., 1917, xxviii, 373 (bibl.). 
4 Wiener, G., Arch. f. Gynak., 1907, Ixxxii, 521; Meyer, P., ibid., 1908, Ixxxv, 512, 540; and Hinsel- 
mann, H., Ztschr. f. Geburtsh. u. Gynak., 1908, Ixii, 34. THE REPRODUCTIVE ORGANS OF THE FEMALE 
913 
shown that these growths are usually melanocarcinoma. Chondroma of 
the clitoris has been described. 
Carcinoma of the vulva may be primary, usually in the form of epi- 
thelioma of the clitoris or labia, or may be a metastasis of cancer of the 
uterus, vagina, etc. The disease usually occurs late in life. The com- 
monest form is the squamous-cell type (epithelioma) with pearl forma- 
tion. Large, hard tumors which ulcerate early in their course, or flat, 
superficial rodent ulcers are encountered. The inner side of the labia 
majora and the clitoris or urethral opening are the commonest sites. 
Very early involvement of the inguinal and deep lymphatic glands is 
the rule.1 Contact cancers, i.e., cancers on apposing surfaces, are not 
infrequent. 
Urethral caruncle, an innocent growth at the mouth of the urethra, should not be 
confused with carcinoma. Its bright red color (unless changed by trauma or strangu- 
lation) and tenderness to touch distinguish it from cancer. Histologically, caruncles 
are either angiomatous in nature or resemble granulation tissue. They are covered 
by the transitional urethral epithelium. 
Adenoma and carcinoma of Bartholin's glands is noted,2 also the rare 
adenoma hydradenoides,3 a small growth developing from the sweat- 
glands and composed of acini containing epithelium in double layers. 
Metastatic hypernephroma and chorionepithelioma of the vulva have 
been reported.4 Histologically these growths resemble the primary 
tumor. The latter variety is especially prone to hemorrhage and break- 
ing down of the tissue. 
CYSTS. 
Cysts are found in the connective tissue of the labia majora and 
minora. They range from the size of a pea to that of a child's head. 
They may contain serum, colloid material, or purulent or blood fluid, or 
may have the characters of epidermoid or atheromatous cysts, depending 
on their origin, which is in many cases obscure. In some cases they 
are doubtless due to dilatation of lymph-vessels. Cysts may be formed 
by a stoppage and filling with fluid of the canal of Nuck, or by a dilata- 
tion of the ducts or acini of the vulvovaginal glands.5 
The Vagina. 
The vagina may be entirely absent, and the internal organs of generation also 
absent or imperfectly developed. Either the upper or the lower portion of the canal 
may be absent, while the remaining portion is present. 
The vagina may be closed by an imperforate hymen or by transverse septa at 
any part of its canal. The canal may be abnormally small without being occluded. 
Malformations. 
1 KUstner, O., Arch. f. Gynak., 1881, xviii, 253; Teller, R., Ztschr. f. Geburtsh. u. Gynak., 1907, 
Ixi, 309. 
2 Pape, Deutsch, med. Wchnschr., 1907, xxxiii, 1620; Graham, Edinburgh Med. Jour., 1908, N. S. 
xxiii, 149; Spencer, H., Proc. Royal Soc. Med., 1913-14, vii2, 102. 
3 Rupe, H., Ztschr. f. Geburtsh. u. Gynak., 1905, Ivi, 307; Schroder, R., Centralbl. f. allg. Path., 
1911, xxii, 529; Pica, L., Virchows Arch., 1904, clxxv, 312. 
4 Grafenberg, E., Virchows Arch., 1908, cxciv, 17 (bibl.); Vassmer, Festschrift f. Orth., Berlin, 1903, 
p. 237. 
6 For a study of cysts of Bartholin's glands, see Cullen, T. S., Jour. Am. Med. Assn., 1905, xliv, 204. 914 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The vagina may be double, in connection with a double uterus; or, while the uterus 
is normal, the vagina may be incompletely divided by a longitudinal septum. 
Changes in Size and Position 
Dilatation of the vagina is produced by tumors, by injury to its supporting 
structures (birth trauma), and by the accumulation of blood and mucus behind con- 
strictions or obliterations of the canal. 
Lengthening of the vagina is produced by any cause which draws the uterus 
upward. Narrowing may occur as a senile change, may be produced by the pressure 
of tumors, or may follow ulceration of the wall of the canal through cicatricial con- 
traction (caustics, trauma of labor, infection). 
Prolapse of the vagina occurs independently, usually from injury during child- 
birth, or in connection with prolapse of the uterus. A larger or smaller portion of 
the canal is inverted and projects through the vulva. The entire circumference of 
the canal may be inverted and prolapsed, or only the anterior or posterior wall. The 
prolapse, at first small, may afterward gradually increase in size. In other cases, 
prolapse of the uterus is primary, and the vagina is inverted by the descent of that 
organ; or the body of the uterus retains its normal position, while an hypertrophy and 
lengthening of the cervix alone drags down the vagina. 
Cystocele is due to injury of the supports of the bladder, especially of the pubo- 
cervical fascial layers. The anterior vaginal wall increasingly protrudes until the 
entire bladder base, between fixed trigone and cervix, bulges through the vulva, 
covered merely by the vaginal mucosa. 
Rectocele is a similar bulging of the rectum through the torn rectal fascia, the 
rectum, covered by posterior vaginal wall, protruding first into the vagina, and later 
pushing its way into the vulva over the perineal body, if' this barrier is still intact. 
The everted vaginal walls in prolapse, cystocele, and rectocele, show distinct 
changes due to trauma, the drying effect of exposure to the air, and vascular stasis. 
Superficial erosions, ulceration, keratinization of the epithelium (epidermization), and 
edema of the subepithelial tissues develop. 
Hernia Intestinovaginalis is commonly a congenital defect, though the lesion 
may not manifest itself until adult life. The primary condition is a deep position of 
the bottom of Douglas's cul-de-sac. The peritoneal reflection may extend down to or 
into the perineal body; when filled with intestine a mass similar in appearance to a 
rectocele may bulge into the vagina through its posterior wall. The condition is 
often complicated by prolapse of the rectum. 
WOUNDS-PERFORATIONS. 
Wounds of the vagina are made by penetrating bodies, by forceps 
and other obstetrical instruments, by the fetus during delivery, or by 
coitus. Such wounds may heal; or they may give rise to large hemor- 
rhages, or may suppurate and lead to abscesses in the surrounding tissue 
or leave fistulous openings into the vagina; or they may, by cicatricial 
contraction in healing, lead to constriction or obliteration of the vaginal 
canal; or, finally, they may communicate with the peritoneal cavity, pro- 
ducing peritonitis. 
Vesicovaginal Fistulas are usually produced by injuries from instru- 
ments or from the fetus during delivery, less frequently by operative 
injuries arising during hysterectomy, by ulceration of the vagina, blad- 
der, or adjacent connective tissue, or by abscess in the surrounding parts. 
The sloughing of neoplasms involving the walls of the vagina and 
bladder may also give rise to fistulae, especially if the tumors have been THE REPRODUCTIVE ORGANS OF THE FEMALE 
915 
too vigorously treated with radium. The fistulse form an opening be- 
tween either the bladder or the urethra and the vagina, allowing the 
urine to pass into the vagina. Spontaneous cure takes place in a small 
number of instances. In some cases, the fistula leads into the cervical 
canal, which allows the urine to empty into the vagina by way of the 
external os. 
Rectovaginal Fistulae are formed in the same way as the last men- 
tioned, and allow the passage of gas or feces into the vagina. They, also, 
sometimes heal spontaneously. 
INFLAMMATION. (Vaginitis.) 
The vaginal canal is the habitat of many bacteria. Saprophytic 
streptococci and staphylococci, which under favorable conditions, as 
after injuries, during the puerperium, etc., may develop virulence, are 
regularly present. Doederlein's acid-forming bacillus is always present 
and accounts for the acid reaction of the vaginal secretion. From the 
anus near by, the colon and related groups of bacilli readily gain entrance. 
It is only because of the impervious character of the squamous epithelium 
that vaginitis is a rare disease.1 
Catarrhal Inflammation of the vaginal mucous membrane may be acute 
or chronic. It is most frequently induced by the gonococcus, but may 
be due to local irritation or may accompany acute infectious processes. 
It not infrequently occurs in the new-born. The adult vagina, like the 
adult vulva, is resistant to the gonococcus; and although a few cases of 
chronic gonorrheal vaginitis have been reported in adults, they are the 
exception. In the acute form of inflammation the mucous membrane 
is swollen and frequently covered with a mucopurulent or a purulent 
exudation. In the chronic form it may be swollen and covered with a 
purulent exudation; there may be an exfoliation of epithelium, shallow 
or deep erosions, or ulcers. Usually the vagina is irritated by discharges 
flowing down from the cervix or uterine cavity. 
Sometimes large shreds or membranes are cast off from the vagina, 
consisting wholly of exfoliated, flat epithelium.2 This may be seen after 
the use of very strong irrigations of mercuric chloride. In other cases, 
the mucous membrane is thickened, dense, and sometimes pigmented, 
or it may be roughened, covered with papillae, or relaxed and prolapsed. 
Membranous Inflammation of the vagina may occur after parturition, 
and in dysentery, typhus and typhoid fevers, diphtheria, scarlatina, 
measles, and other infectious diseases. The mucous membrane is swollen 
and covered with a grayish layer of fibrin and pus; and the mucosa and 
submucosa may be infiltrated with fibrin and pus. The infiltrated por- 
tions of the mucosa and submucosa may die and become gangrenous, 
and thus deep and extensive ulcers may be formed. 
Suppurative Inflammation of the fibromuscular coat of the vagina may 
occur after injuries or in pregnant or puerperal women. Abscesses which 
1 For a study of the flora of the vagina, see Shaw, E. HEden and Lockyer, System of Gynaecology, 
London, 1917, i, 97 (bibi.). 
2 See McFarland, J., Proc. Path. Soc., Philadelphia, 1899, ii, 115. 916 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
penetrate into the labia or into the pelvic connective tissue may be 
formed. In other cases the intense phlegmonous inflammation may lead 
to the death and casting-off of portions or even of the entire vaginal wall. 
Granular Vaginitis manifests itself by numerous, slightly elevated, red, 
and easily bleeding spots in the vagina. Small nodules composed of 
round or plasma cells lie beneath the epithelium which is thinned out or 
deficient over these prominences. 
Senile Vaginitis is a concomitant of senile involution. The surface 
epithelium becomes attenuated and in spots deficient; and consequent 
agglutination of apposing surfaces occurs, with resultant bands and scars. 
Emphysematous Vaginitis.-Anaerobic bacilli developing in the 
vaginal wall may give rise to small cysts or blebs. 
Gangrene of the vagina may occur as a result of membranous or 
intense suppurative or syphilitic inflammation or from unknown causes. 
In the form of noma it may be very extensive and rapidly destructive. 
Bichloride of mercury poisoning, resulting either from the ingestion of 
large doses or from absorption, after vaginal douching with strong solu- 
tions, may produce gangrene and ulceration of the vagina, quite similar 
to mercurial stomatitis. 
Tuberculous and Syphilitic Inflammation, usually leading to more or 
less extensive ulceration, may occur in any part of the vagina. Tuber- 
culous inflammation is usually secondary to tuberculosis of other parts, 
particularly of the vulva, uterus, or rectum. The usual form is an ulcer 
with undermined edges and miliary tubercles in its margins. Syphilitic 
ulcers may heal, sometimes leaving marked cicatrices and sometimes not. 
TUMORS. 
Fibroma,1 fibromyoma2 and adenomyoma3 are of occasional occurrence 
in the vagina. Sarcoma of the vagina may be pedunculated, nodular, 
or diffusely infiltrating. All varieties of sarcomata are observed, includ- 
ing the melanotic form,4 though the spindle- and round-cell type are 
most common. Early necrosis and ulceration are the rule. Sarcoma 
botryoides,5 or grapelike sarcoma, occurs most often in early childhood, 
but is occasionally seen in old persons.6 Soft, grapelike bodies of reddish 
to grayish color, arising from the cervix, fornix, and vaginal wall, project 
from the vagina. Penetration of adjacent structures occurs and recur- 
rence after removal is the rule. On section, the growths are found to 
be composed of myxomatous tissue with smooth or even striated muscle 
cells, covered by normal vaginal surface epithelium. These growths are 
mixed tumors, often rhabdomyosarcomata (Fig. 590). A teratoma has 
1 Lewers, H. N., Am. Jour. Obst., 1895, xxxi, 277. 
2 Ries, E., Am. Jour. Obst., 1902, xlv, 265; Smith, R. B., ibid., p. 145. 
3 Kleinhaus, F., Ztschr. f. Geburtsh. u. Gynak., 1904, lii, 266. 
4 Boldt, H. J., Am. Jour. Obst., 1906, liv, 550. 
6 Pick, L., Arch. f. Gynak., 1894, xlvi, 191; WiZms, Die Mischgeschwiilste, Leipzig, 1900; Thomas, T. 
G., Am. Jour. Obst., 1874-75, vii, 51; Schuchardt, K., Virchows Arch., 1889, cxvii, 262; Kolisko, A., Wien, 
klin. Wchnschr., 1889, ii, 119; MbncKeberg, J. G., Virchows Arch., 1907, clxxxvii, 47; Amann, J. A., 
Arch. f. Gynak., 1907, Ixxxii, 746; Meyer, R„ Lubarsch-Ostertag, Ergebn. d. allg. Path., 1905, ix2, 518 
6 Puech and Massabuau, Ann. de gynec. et d'obst., 1908, 2d ser., v, 306. THE REPRODUCTIVE ORGANS OF THE FEMALE 
917 
been described and a few cases of endothelioma,1 the latter being, in all 
probability, carcinomata of unusual morphology. The only demonstrable 
metastases from a hypernephroma may appear in the vagina.2 
Papillomata are of infrequent occurrence, resulting from chronic in- 
flammation. They are usually of gonorrheal origin and most frequent 
in pregnancy. Histologically, they are identical with papilloma of the 
vulva. 
Carcinoma of the vagina is usually secondary to cancer of the cervix. 
The rare primary carcinomata3 usually develop on the posterior surface 
Small insert in corner of cut shows more highly magnified striated muscle fibers. 
Fig. 590.-Sarcoma Botryoides. 
of the upper third of the vagina in women past the menopause. The 
tumors may be slightly elevated and papillary, or cauliflower-like, or, 
most rarely, diffusely infiltrating. Early involvement of the paravaginal 
tissues, the parametria, and the cervix occurs. The most frequent form 
is medullary or squamous-cell carcinoma, though adenocarcinoma aris- 
ing from Gartner's duct or other gland remnants has been reported. 
Leukoplakia occurs just as in the oral cavity. White, "asbestos-like" plaques, 
with glistening surfaces, are noted. The condition is regarded as a " precancerous " 
1 Raschkes, H., Centralbl. f. allg. Path., 1903, xiv, 657; and Jellett, H., Jour. Obst. and Gynec. Brit. 
Emp., 1907, xii, 285. 
2 Gellhorn, G., Amer. Jour. Med. Sc., 1918, clvi, 94. 
3 Broun, L., Am. Jour. Obst., 1902, xlv, 706; Taylor, H. C., ibid., 1906, liv, 860; Menge, Munchen, 
med. Wchnschr., 1906, liii, 30. 918 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
manifestation. Great increase in the superficial layers of the epithelium produces the 
appearance as in the vulva. 
CYSTS. 
These are not very common and may be small or as large as a hen's 
egg. They may be lined with flattened epithelium and contain serous 
or viscid, dark-colored or transparent fluid.1 Most vaginal cysts occur 
in the anterior wall, resulting from remnants of Gartner's ducts. They 
may extend upward in the subperitoneal tissues alongside the cervix. 
They usually have thin walls, and project as bluish prominences into 
the vagina. They are lined with epithelium of very varied character.2 
PARASITES. 
Among the animal parasites Oxyuris and Trichomonas vaginalis are 
of occasional occurrence. Among the vegetable forms Oidium albicans, 
particularly in diabetes, and Leptothrix are occasionally seen, while 
various forms of bacteria are regular inhabitants, especially Doederlein's 
bacillus. Staphylococcus and Streptococcus pyogenes have been found 
many times in the normal vagina, and while these and other bacteria 
may be harmless in the normal vagina, should conditions favoring their 
growth or an increase in their virulence occur, as, for example, after 
delivery, serious infectious processes might follow.3 The role of the 
gonococcus as an excitant of catarrhal inflammation is well established. 
The Uterus. 
Malformations. 
The uterus, tubes, and vagina may be entirely absent, with or without absence 
of the external genitals; or the uterus, alone or with the upper part of the vagina, 
may be absent. 
The uterus may be only rudimentary while the vagina is normal; it then appears 
as a flattened solid body with solid cornua. Or there may be two cornua joined at 
their lower extremities so as to form a small double uterus (Fig. 591); the uterus may 
be represented by a small sac, which may or may not communicate with the vagina; 
or there may be a very small uterus, with thin muscular walls and two large cornua. 
Only one of the cornua which should form the uterus may be developed, while the 
other is arrested in its growth. The uterus is then a long, cylindrical body, termi- 
nating above in one tube. On the side where the horn should have been developed 
there is no tube, or only a rudiment. Both ovaries are usually present. 
The two cornua may be fully developed, but their lower ends may remain separated 
and form a double uterus. An entire separation into two distinct uteri and vaginae is 
rare. More frequently the uterus consists of one body, divided by a septum into two 
cavities. There are then two cervical portions of the uterus projecting into a single 
vagina, or each into a separate vagina; or there is only a single cervix. The septum 
in the uterus may be complete or only partial 
* StoKes, J. E., Johns Hopkins Hosp. Rep., 1899, vii, 109 (bibl.); and Cullen, T. S., Bull. Johns Hop- 
kins Hosp., 1905, xvi, 207. 
s Pierce, F. E., Am. Jour. Obst., 1904, 1, 507, 534; PollaK, E., Ztschr. f. Geburtsh. u. Gynak., 1904, 
lii, 428. 
3 See Shaw, E. H., Eden and Lockyer, System of Gynaecology, London, 1917, i, 97 (bibl.). THE REPRODUCTIVE ORGANS OF THE FEMALE 
919 
The uterus may be abnormal in size or be variously flexed; the cervix may be 
solid or may be closed by the vaginal mucous membrane; or the cervix may have an 
abnormal form with a small opening or canal. 
Changes in Size. 
In the new-born infant the uterus is small, the body flattened, the cervix dispro- 
portionately large and the cervical canal dilated with mucus. During childhood the 
organ increases in size, but the body remains small in proportion to the cervix. At 
puberty the shape changes and the body becomes larger. 
At every menstruation the uterus is somewhat swollen and congested. After 
pregnancy it does not return to its virgin size, but remains somewhat larger. In old 
Fig. 591.-Uterus Bicornis. 
age it gradually becomes smaller; its walls are harder and more fibrous; and the cervix 
atrophies. 
Abnormal Smallness of the uterus is sometimes found as an arrest of develop- 
ment. It may result, however, from lactation atrophy, from old age, or from chronic 
exhausting diseases. Its cavity may be smaller than normal, or distended with 
mucus. Large myomata sometimes induce atrophy of the uterine wall. Atrophy 
of the vaginal portion of the uterus is sometimes observed after repeated pregnancies. 
Narrowing and obliteration of the cavity of the uterus and of the cervix are usually 
produced by chronic inflammation. 
Enlargement of the Uterus may be due to premature sexual development. It 
is accompanied by abnormally early development of all the sexual organs and func- 920 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
tions. The uterus may be enlarged in connection with heart disease, prolapse, and 
abnormal flexions, chronic inflammations, repeated pregnancies, myomata, and 
accumulations of blood or mucus in the uterine cavity. Enlargement of the vaginal 
portion alone may occur. One or both lips of the cervix may be uniformly increased 
in size, or they may be lobulated. 
Dilatation of the uterus is produced by accumulations of blood, mucus, or pus in 
consequence of narrowing or obliteration of the cervix or vagina. The uterine walls 
may retain their normal thickness, or be thickened or thinned. The most frequent 
site of the stneosis is the os internum. The retained contents after a time change in 
character, forming a thin, serous fluid-hydrometra; or they may be mixed with blood. 
The dilated uterus may be of enormous size. If both os internum and os externum 
are closed, the cervical cavity also may be dilated and the uterus have an hour-glass 
shape (Fig. 592); or the dilatation may be limited to the cervix. If the obstruction is 
Fig. 592.-Hour-glass Uterus. 
Showing a small uterus with distention of the cavities of the body and cervix from fibrous-tissue con- 
traction at the os externum and the os internum. 
not complete, the retained fluid may escape into the vagina and be followed by a fresh 
accumulation. If the obstruction be in the vagina, the uterus and vagina may form 
a large, flask-shaped body, and the line of demarcation between cervix and vagina 
be lost. 
Accumulation of menstrual blood in the cavity of the uterus-hematometra-is 
usually due to imperforate hymen, in which case hematocolpos precedes the hema- 
tometra. Rarely, it may be due to congenital stenosis of the cervix or vagina, and 
then may be very great. If the fluid is not evacuated by surgical interference there 
may be either rupture or ulcerative perforation of the uterus. The blood may escape 
into the abdominal cavity, or be shut in by adhesions, or perforate into the bladder 
or intestines. Sometimes the blood passes into the Fallopian tubes, dilates them, 
and escapes through their abdominal ends. 
The body of the uterus may become fixed in an abnormal position, while the situa- 
tion of the cervix is unchanged. 
Flexion.-The body may be bent forward-anteflexion, generally regarded as the 
normal position; backward-retroflexion (Fig. 593); or sideways-lateral flexion. The 
Changes in Position. THE REPRODUCTIVE ORGANS OF THE FEMALE 
921 
flexion may be slight, or so great that the neck and body form an acute angle. Ante- 
flexion is the most common variety, and that in which the flexion is greatest. Peri- 
toneal adhesions, flaccidity of the uterine walls, particularly after delivery, atrophy 
of the walls, ovarian and other tumors, etc., are the usual causes of abnormal flexion. 
Version of the uterus consists in an abnormal inclination of the long axis of the 
organ to that of the vagina. The uterus may be inclined backward, forward, or to 
one side. 
Retroversion is the most common displacement. The fundus uteri is directed 
backward and downward, the cervix forward and upward. This condition is found 
Small cysts may be seen in the mucous membrane of the body. 
Fig. 593.-Retroflexion of Uterus. 
in various degrees; in the highest the fundus lies in Douglas's cul-de-sac with the cervix 
upward, so that the axis of the uterus is parallel to that of the vagina, but in a direction 
nearly opposite to the normal. Abnormal looseness of the uterine ligaments, abnor- 
mally large capacity of the pelvis, enlargement or tumors of the uterus, and early 
pregnancy, are some of the more common conditions under which this lesion occurs. 
Anteversion, an inclination of the fundus forward and downward, and of the cervix 
backward and upward, is not common and seldom reaches a high degree. 
Lateroversion is not very common as a simple lesion, but is not infrequently com- 
bined with other displacements. It may be produced by congenital or inflammatory 
shortening of one of the broad ligaments, by adhesions, or by the pressure of tumors. 
Uncomplicated versions produce few symptoms. The lesion producing the ver- 
sion, as adhesions or impactions of a growing pregnant uterus, may cause serious or 922 
fatal disturbances; exfoliative cystitis, perforation of bladder, dilatation of the ureters, 
hydronephrosis, and fatal obstruction of the bowels may follow. If pregnancy exist, 
abortion may take place, or the inverted uterus may be forced through the peritoneum 
and posterior wall of the vagina and project through the vulva. In the non-pregnant 
uterus, pressure on the veins results, and chronic stasis of the organ may follow. 
Prolapsus uteri consists of a descent of the uterus into the vagina. The uterus 
may be only slightly lowered or it may project at or beyond the vulva (Fig. 594). In 
complete prolapse we find a tumor projecting through the vulva, covered by the dis- 
tended vagina, and presenting the opening of the os externum near its center. The 
bladder and rectum may be drawn 
down with the vagina, or may re- 
main in place. The exposed cervix 
and vagina usually become inflamed 
and sometimes ulcerated, or the 
mucous membrane may become 
thickened. The lesion is frequently 
complicated by hypertrophy of the 
cervix. 
Gradual prolapse, which is most 
frequent, may be due to an increased 
weight of the uterus, as in preg- 
nancy, in the presence of tumors, 
etc., or, most generally, to injury of 
the uterine supports, especially tear- 
ing and stretching of the pericervical 
connective tissue during labor. 
Sudden prolapse is most apt to oc- 
cur following a severe and sudden 
lifting effort by a person whose 
uterine supports have been weak- 
ened by parturition or long wasting 
illness. In nulliparae prolapse is a 
great rarity; it is occasionally noted, 
however, in subjects afflicted with 
spina bifida, of either the occult or 
the overt variety. 
Elevation of the uterus is pro- 
duced by mechanical causes crowd- 
ing or dragging it upward, as ad- 
hesions, tumors, etc. The vagina is 
drawn up and lengthened, and the 
vaginal portion of the cervix may 
be obliterated. The commonest 
causes are large fibroid tumors and 
ovarian cysts with short thick 
pedicles.1 
Inversion of the uterus consists of an invagination of the fundus. The fundus 
may be invaginated into the body, the fundus and body into the cervix, or the entire 
organ into the vagina. It usually occurs when the uterine walls are relaxed, and may 
be due to traction on the placenta during parturition. It may take place spon- 
taneously after parturition. Acute intrapartum cases are often fatal from shock, 
hemorrhage, or sepsis. In rare instances, the onset is survived, and the condition 
becomes chronic. Inversion may be produced by intrauterine tumors, such as a 
pedunculated fibroid arising from the fundus The mucous membrane of the inverted 
organ is frequently inflamed, particularly when the inversion is complete. The epi- 
thelium may become squamous and lamellated in type. 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The cervix projects from the vulva and there are 
small ulcerations about the os externum. 
Fig. 594.-Prolapse of Uterus. 
1 For details concerning the various types of displacements, see Eden and Lockyer, System of Gynae- 
cology, London, 1917, ii, 595, 627, 687. THE REPRODUCTIVE ORGANS OF THE FEMALE 
923 
Hernia of the uterus are rare. Ventral hernia? may occur during the latter months 
of pregnancy, the peritoneum, aponeurosis, and skin being forced outward to form 
a sac in which the uterus lies. Crural hernias are produced by the drawing down of 
the uterus and ovaries into the sac of a femoral hernia. Inguinal hernia may be 
produced in the same way or may be congenital. Ischiatic hernia have been seen. 
Pregnancy may occur in the uterus while it is within a crural or inguinal hernia. 
RUPTURE AND PERFORATION. 
Rupture of the unimpregnated uterus is rare. It may occur, however, 
when the uterine cavity is distended with blood or serum, or in connec- 
tion with large myomata of the uterine walls. It occurs during operative 
dilatation of the cervix. 
In the gravid uterus ruptures have been seen in nearly every month 
of pregnancy, but most frequently toward the end. The rupture may 
be due to a thinning of the uterine wall by tumors, by deep penetration 
of placental villi, or by violent contusions, or as the result of cicatricial 
contraction of the os. It most frequently takes place during parturition. 
Malpositions of the fetus, narrowing of the pelvis, protracted labor, thin- 
ning of the uterine wall from tumors, forcible use of the forceps and 
other instruments, and attempts at version are the ordinary causes. 
The rupture may be in the body of the uterus or in the cervix or in both; 
it may be large or small; it may extend completely or only partly through 
the uterine wall; it may extend into the peritoneal cavity or be extra- 
peritoneal. The consequences of partial rupture are hemorrhage, gan- 
grenous inflammation of the edges of the rupture, peritonitis, and, usu- 
ally, death. In some cases, the rupture cicatrizes, and the patient 
recovers. Complete rupture usually leads to death in a short time. The 
fetus may escape partly or completely into the abdominal cavity. If the 
patient survive the immediate shock, fatal peritonitis usually soon ensues. 
In rare cases the fetus is shut in by adhesions, and the patient survives. 
Perforations of the uterus may be produced by carcinoma, by ab- 
scesses in its neighborhood, by ovarian cysts, and by instrumentation. 
HYPEREMIA-UTERINE HEMORRHAGE. 
Hyperemia.-Aside from the active menstrual hyperemia, the uterus 
may be hyperemic in acute and chronic inflammation, as a result of 
displacement of the organ, and in certain forms of heart disease. The 
organ is usually enlarged, the mucous membrane is swollen, and the 
veins are more or less evidently dilated. Edema may be associated with 
hyperemia. 
Hemorrhage.-Effusion of blood into the cavity of the uterus occurs 
normally at the menstrual periods. For the abnormalities to which this 
function is subject we refer to works on gynecology. Effusions of blood 
at other than the menstrual periods may be associated with numerous 
causes: local intrauterine (such as tumors, polypi, fibroids, and preg- 
nancy) ; local neighboring (pressure from intraligamentous cyst, cyst with 
twisted pedicle, ectopic gestation); acute systemic (infectious diseases, as 924 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
typhoid fever, typhus fever, and scurvy); and chronic systemic, with 
resulting general circulatory disturbances, as decompensated heart lesions. 
A large number of hemorrhages are due to functional ovarian disturbances. 
ATROPHY, DEGENERATION, ETC. 
Atrophy of the uterus occurs as a physiological process in old age. 
The glands of the endometrium are few, the interstitial tissue is relatively 
Fig. 595.-Senile Atbophy of Endometrium. 
increased (Fig. 595). It may be associated with severe general or infec- 
tious diseases or may follow removal of the ovaries. It may follow preg- 
nancy apparently as an excessive involution process (lactation atrophy). 
Advanced degrees of atrophy are noted in the later stages of many dis- 
eases of the glands of internal secretion, especially in hypopituitarism.1 
1 Goetsch, E., Surg., Gynec., and Obstet., 1917, xxv, 229. 925 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Fatty Degeneration may occur in connection with inflammatory 
changes, in acute infectious diseases, and in phosphorus poisoning. 
Amyloid Degeneration in the uterus is of rare occurrence. It may 
affect the muscle fibers or the walls of the blood-vessels. 
Hyaline Degeneration of the walls of the blood-vessels and the con- 
nective tissue is occasionally seen, but is much more frequent in myo- 
matous uteri. 
INFLAMMATION. (Metritis and Endometritis.) 
I. Inflammation of the Unimpregnated Uterus. 
A. Of the Corpus Uteri. 
Acute Catarrhal Endometritis.-In this disease, which in its lighter 
grades may leave but little alteration after death, the mucous membrane 
Fig. 596.-Interval Phase of Endometrium. 
is swollen and hyperemic, and is sometimes the seat of punctate hemor- 
rhages. The epithelium may be degenerated and may desquamate, and 
the mucosa may contain an undue quantity of polynuclear leucocytes. 
The surface is more or less thickly covered with mucopurulent exudate. 
In severe cases shreds of mucous membrane may be exfoliated. The 926 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
lesion is usually most marked in the mucous membrane of the body, but 
it may involve the cervix at the same time, or the cervix alone. The 
body of the uterus may be soft, swollen, and hyperemic. The condition 
is most frequently of gonorrheal origin, though the introduction of un- 
clean instruments may also be the cause. On the whole, the non-preg- 
nant uterus rapidly rids itself of most bacteria except the gonococcus. 
In membranous dysmenorrhea there may be an expulsion, with more 
or less blood, of membranous masses consisting of fibrin mingled with 
blood and leucocytes, or of exfoliated superficial layers of endometrium. 
The exfoliated epithelium is frequently much flattened so as to resemble 
the vaginal epithelium.1 The decidual reaction in interstitial tissue is 
occasionally very considerable, so that pregnancy may be suspected; but 
the cells never reach the size of those seen in pregnancy. Membranous 
dysmenorrhea appears to be a purely functional condition, possibly due 
Fig. 597.-Premenstrual Endometrium. 
to an excess production of the menstrual decidual reaction. It is a 
common sequel of infantile habitus. 
Chronic Endometritis.-What was formerly classed as chronic endo- 
metritis, is to-day recognized to be due mainly to various functional and 
normal cyclical changes of the mucosa. The symptoms usually assigned 
to endometritis--hemorrhage and leucorrhea-are due to other causes. 
Hemorrhage results from ovarian stimuli; leucorrhea from cervical in- 
flammation. The ovarian overfunction, in rare instances, is due to 
ovarian or tubo-ovarian inflammations, but most commonly it is a dis- 
turbance of internal secretion (primarily or secondarily of ovarian origin). 
Normal Cyclical Uterine Changes.-Subject to ovarian influences, 
the uterus, after the onset of puberty, undergoes a "monthly" cycle. 
(Actually, the cycle varies from twenty-one to thirty-five days, the 
average being twenty-eight days.) According to the histological changes, 
1 See DeWitt, L. M., Am. Jour. Obst., 1900, xlii, 308 (bibl.); Ascheim, S., Arch. f. Gynak., 1906, 
Ixxx, 320. THE REPRODUCTIVE ORGANS OF THE FEMALE 
927 
the phenomena are best divided into three stages, though some writers 
describe a fourth stage {postmenstruum). 
1. The Interval is the period following menstruation, during which 
the mucosa is thin and pale, its glands are circular and far apart, and 
their epithelium is low columnar, inactive, and regular. The stroma is 
dense; the cell bodies are not distinguishable; and the nuclei are closely 
packed (Fig. 596). This picture corresponds to the "normal endo- 
metrium" of older authors, and also to "chronic interstitial endometritis." 
Fig. 598.-Premenstbual Phase of Endometrium. 
2. The Premenstruum is characterized by thickening of the mucosa 
(Fig. 597). The mucous membrane, on section, shows three distinct 
layers, a superficial layer, in which the stroma is edematous and decidual 
in character, a spongy layer, in which the tortuous corkscrew glands lie 
closely packed, in some areas even in actual contact, and a thin basal 
layer, close to the uterine musculature, harboring the gland fundi, in 
which very little glandular or stroma change has occurred (Fig. 598 and 
599). 
The key-note to the premenstruum is secretory activity. In the early 
part of this change, mitoses in the epithelium abound. In consequence 
of an increased number of cells and the distention of the old and new 928 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
cells with secretion, the glands become tortuous and corkscrew in shape; 
the cells are crowded out into the gland lumina, and their superficial 
boundary is irregular and feathery, forming so-called "pseudopapillae," 
and the gland lumen contains secretion. The caoillaries, especially those 
Fig. 599.-Premenstrual Phase of Endometrium. 
in the outer layers of the mucosa, distend; and first the circumpapillary, 
and later the entire stroma becomes decidual in character. This im- 
plies that the round cells acquire epithelioid characteristics. Their cell 
bodies enlarge; the cell boundaries grow distinguishable; and the nucleus 
stains less deeply. This phase was formerly classified as "glandular 
endometritis.'' 
Highly magnified glands. 
Fig. 600.-Glandular and Cystic Hyperplasia of the Mucous Membrane. 
The stroma of the mucosa is increased in amount and is dense and fibrous in texture. 
3. Menstruation is ushered in by an increase of the capillary engorge- 
ment. Red blood-cells permeate between the stroma cells, and finally 
obscure them. The glands rapidly empty themselves of their secretion, 
and the glandular epithelium, a few hours after menstruation has begun, 
reassumes a resting columnar appearance. Blood-cells in increasing 
numbers accumulate in the uterine cavity, mixed with secretion, and THE REPRODUCTIVE ORGANS OE THE FEMALE 
929 
produce the phenomenon known as menstruation. Occasional small 
areas of the surface epithelium are raised up by the blood-cells, until the 
pressure produces a minute epithelial rupture, but large areas of denuda- 
tion do not occur. The picture in normal menstruation is identical with 
that in irregular hemorrhages, because in both instances the bleeding is due 
to ovarian influences. 
As the onset of the cyclical changes is not abrupt and as different 
parts of the endometrium do not respond at exactly the same rate, one 
part of the cavity may show a picture of the late interval, for example; 
another, one of the beginning or even of the advanced premenstrual 
change. 
Bleeding Due to Ovarian Hyperfunction {Menorrhagia or Metror- 
rhagia).-The histological picture during the hemorrhagic period does 
Fig. 601.-Polypoid Endometrium. 
not differ from that seen in normal menstruation. During the interval 
and premenstruum, the cyclical changes may be exaggerated; the three 
distinct layers described above, under the premenstruum, may not be 
clearly marked; and, especially in the hemorrhages of puberty and the 
preclimacterium, cystic dilatation of the glands is common. Consider- 
able familiarity with the normal conditions is required to distinguish 
these slight and, after all, mainly quantitative changes. 
Polypoid Endometrium is a condition in which the excessive and 
continued ovarian hyperfunction has produced a diffuse hyperplasia of 
the mucosa which throws it into projecting folds; later, polypi may 
develop, so that finally the uterine cavity may be filled with soft knobby 
masses (endometritis fungosa of Ohlshausen, Fig. 601). The mucosa is 
edematous and many dilated glands are seen. Hemorrhage is the usual 
symptom. 930 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Subacute and Chronic Endometritis are probably of not very frequent 
occurrence, are of very little clinical significance, and can be recognized 
only when plasma cells are found.1 Even when such lesions are present, 
the usual cyclical changes are unaffected. 
Membranous Endometritis {Endometritis dissecans).-This form of 
inflammation is not very common. It occasionally occurs in the puer- 
peral uterus and in acute infectious diseases. It sometimes involves the 
vulva, vagina, and Fallopian tubes. It may coexist with membranous 
inflammation of the colon. 
Tuberculous Endometritis.-This is not uncommon, and usually 
occurs as part of tuberculous inflammation of the genitourinary tract, 
especially of the Fallopian tubes. The disease occurs in two forms, the 
diffuse caseous and the discrete nodular, although both varieties may be 
encountered in the same uterus. Tuberculous pyometra may be pro- 
duced if the cervix becomes obstructed. A part or the whole of the 
cavity of the uterus may be lined with a rough, yellowish or gray, caseous 
mass, which may deeply involve the muscular walls of the organ. At the 
edges of the ulcerating caseous areas there may be typical miliary tuber- 
cles, or these may be scattered through the otherwise intact mucosa.2 
The peritoneal surface of the uterus may be studded with tubercles, usu- 
ally as part of a tuberculous peritonitis {tuberculous perimetritis). 
Pyometra.-If the cervix becomes stenosed from trauma, cauteriza- 
tion, or tumor formation (chiefly carcinoma), and a severe bacterial in- 
vasion develops in the uterus, the corporal cavity is distended by pus. 
The mucosa first loses its surface epithelium, and later changes into a 
pyogenic membrane (Fig. 602). Occasionally, the surface epithelium 
persists and changes into squamous epithelium. 
Syphilitic Endometritis.-This condition is rare and but few authentic 
cases are on record. It is characterized by a diffuse thickening of the 
mucosa and gummatous infiltrations. 
Acute Metritis is usually associated with acute catarrhal endometritis. 
The organ is swollen, succulent, and congested; the mucous membrane 
is covered with mucopus; and the peritoneal coat is congested. There 
may be small extravasations of blood in the wall or cavity of the uterus. 
The inflammation, in rare cases, becomes suppurative, and abscesses are 
formed in the uterine wall; these may perforate into the peritoneal cavity 
or into the rectum. Residua of the process leave connective-tissue scars 
in the musculature. 
Perimetritis.-The peritoneal coat of the uterus may be inflamed, with 
the production of membranous adhesions or of pus. The adhesions may 
be small or very extensive, and, owing to their contractions, may cause 
various distortions and displacements of the pelvic organs. The inflam- 
mation is usually an accompaniment of chronic salpingitis and is due to 
1 This is the view expressed by Hitschmann and Adler in their original monograph; in a later paper, 
however, they modified this opinion (Arch. f. Gynak., 1913, c, 233). Others think that the presence 
of plasma cells is not necessary for a diagnosis of endometritis, though they indicate an inflammatory 
process. See Fothergill, W. E., Brit. Med. Jour., 1911, i, 559; SchicKele, G., and Keller, R., Arch. f. 
Gyn.k., 1911-12, xcv, 586: Buttner, O., ibid., 1910, xcii, 781: and Albrecht, H., and Logothetopulos, K., 
Frankf. Ztschr., 1911, vii, 150. 
5 Cullen, T. S., Johns Hopkins Hosp. Rep., 1895, iv, 441. THE REPRODUCTIVE ORGANS OF THE FEMALE 
931 
repeated attacks of pelvic peritonitis, arising from the discharge of infec- 
tive material from a partially closed tube. In prostitutes, such adhesions 
are of very common occurrence. 
Parametritis-The connective tissue about the uterus, between that 
organ and the reflexions of the peritoneum, may be the seat of suppura- 
tive inflammation. This most frequently ends in recovery, usually with 
the formation about the uterus of dense connective-tissue scars which 
draw that organ into the hollow of the sacrum or toward one of the pelvic 
walls. 
The subperitoneal tissues surrounding the uterus are of broad extent 
and may be divided into anterior, posterior, and lateral parametria, 
although they are directly continuous with each other and with the pre- 
a, Uterine muscle tissue; b, mucous membrane of uterus; c, new-formed vascular tissue. 
Fig. 602.-Pyometra. 
vesical, retroperitoneal, and iliac connective-tissue strata. These ana- 
tomical relations and the course of the lymphatic channels account for 
the direction of extension taken by phlegmons. Infections far down in 
the base of the broad ligaments spread into the rectovaginal septum and 
the posterior parametrium, and along the lateral pelvic wall; those of 
the upper broad ligament extend upward upon the flare of the ilium and 
above Poupart's ligament; prevesical infections progress alongside the 
bladder toward the space of Retzius, etc. 
The vast majority of phlegmons are due to the streptococcus. En- 
trance is afforded to the germ by unclean cervical instrumentation, by 
birth trauma followed by infecl ion, and by acute endometritis. An acute 932 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
lymphangitis and cellulitis is set up, rapid exudation producing more or 
less voluminous tumor-like masses. Depending upon the virulence of 
the process, absorption or abscess formation takes place. The affected 
tissues are doughy, yellowish-white, and succulent. 
Pus exudes from the lumen of cut lymphatics; the veins may be filled 
with dark red or purulent thrombi. If abscesses form, they may per- 
forate into the vagina, cervix, or rectum. The process may produce a 
general systemic thrombophlebitis (pyemia). In milder cases, abscesses 
do not form, and resolution with resultant scar formation (strands in the 
base of the broad ligament) occurs. 
Chronic Metritis may follow acute metritis or may accompany acute 
or chronic endometritis, and is dependent upon similar conditions: sub- 
involution, displacements, the presence of tumors, active irritants, etc. 
The uterus is enlarged, the wall congested, thickened, and soft, or, owing 
to the new formation of connective tissue, hard and dense. The lesion 
is usually accompanied by chronic perimetritis and parametritis; in fact, 
a separation of the three conditions is somewhat artificial. 
B. Of the Cervix Uteri. 
Inflammations of the cervix uteri produce hypersecretion (leucorrhea), 
erosions of the vaginal portion, and cystic hyperplasia (ovuli Nabothi). 
Specific inflammations-syphilitic and tuberculous-are also found. 
Acute Endocervicitis manifests itself by profuse mucopurulent dis- 
charge. The cervical glands are found distended with secretion, the 
surface epithelium of the vaginal portion is succulent, and the stroma is 
infiltrated with leucocytes and round cells. Gonorrhea is the most 
frequent cause. 
Chronic Endocervicitis.-In this condition the mucopurulent dis- 
charge persists, and glands whose openings have been closed off distend, 
their high columnar epithelium gradually becoming cuboidal and flat- 
tened as the intracystic pressure increases. The stroma is fibrous, with 
round-cell infiltration. 
Erosions are the result of cervical inflammation. Normally, the 
cylindrical epithelium lining the cervical canal ends at the margin of the 
external os, where an abrupt transition to stratified squamous epithelium 
takes place (Fig. 603). Under the influence of the irritating cervical 
discharge (to which the cylindrical cervical epithelium is most resistant), 
the squamous covering of the vaginal portion is cast off and the unpro- 
tected cervical stroma is exposed. The cervical columnar epithelium 
rapidly covers the epithelial defect. The resultant bright red, granular, 
easily bleeding areas around the external os are called erosions. 
Healing of erosions takes place by resubstitution of squamous epithe- 
lium, which may creep under the persistent cylindrical epithelium or may 
crowd it out. The squamous epithelium often grows over cervical gland 
openings, or grows downward into wide open gland lumina (Fig. 604). 
This struggle for supremacy frequently imparts an appearance of great THE REPRODUCTIVE ORGANS OF THE FEMALE 
933 
activity to the epithelium, which may assume bizarre shapes and con- 
figurations causing the inexpert to make a diagnosis of carcinoma. 
Syphilis of the cervix takes the form of chancre, of maculopapular 
lesions, and, rarely, of gummata, depending upon the stage of the disease. 
Tuberculosis produces undermined ulcers and papillary excrescences. 
Fig. 603.-Fibrous and Glandular Hyperplasia of Cervix Uteri. 
The figure shows one side of the cervix in longitudinal section. The fibrous tissue of the cervix 
is very dense and the walls of the blood-vessels are thickened. There is hyperplasia of the glands of 
the cervical canal. The Nabothian glands are distended with clear, glairy fluid (ovula Nabothi). 
There is erosion of the epithelium at the os externum, and this, with the congestion of the small super- 
ficial vessels here, gave a rough red appearance to the os, suggestive of a malignant growth. 
II. Inflammation of the Pregnant Uterus. 
The forms of inflammation which have just been described may also 
occur in the pregnant uterus. Metritis may lead to softening of the 
uterine wall, so that rupture takes place during labor. Perimetritis and 
parametritis produce adhesions and abscesses about the uterus. 
Infectious Inflammation (Puerperal Fever).-Under normal condi- 
tions, for a week or more after delivery the inner surface of the still en- 934 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Showing downgrowth of epithelium into the mouths of the cervical glands during the repair of an 
endocervicitis glandularis. 
Fig. 604.-Repair in Cervix. 
Fig. 605.-Unaltered Decidua from Early Pregnancy. THE REPRODUCTIVE ORGANS OF THE FEMALE 
935 
larged uterus is rough, especially at the insertion of the placenta, and 
covered with dark shreds of blood, remains of mucous membrane, and 
placenta. This condition should not be mistaken, as it sometimes is, 
for inflammation or gangrene. 
As a result of injury to the uterus or vagina during or after delivery, 
and the action of bacteria which gain access to the tissues in this vulner- 
able state, the puerperal uterus is liable to become the seat of a series of 
severe and often destructive inflammatory and necrotic changes. These 
may be confined to the uterus; they may induce serious alterations in 
surrounding parts; or they may lead to an involvement of the peritoneum 
or to bacteriemia or pyemia and its accompanying lesions in the most 
Fig. 6U6.-Uterine Phlebitis following Delivery; with Retained Placenta. 
Death nine days after delivery. Micrococci in the walls of the inflamed veins stained violet. 
distant parts of the body. In some cases a more or less extensive gan- 
grenous inflammation of the mucous membrane and the underlying parts 
may lead to the casting-off of larger and smaller shreds of necrotic tissue 
and the formation of deep and spreading ulcers, which may be accom- 
panied by severe parametritis and fatal peritonitis. In other cases, the 
inflammation may be membranous and may affect the vagina, leading 
to necrosis, gangrene, ulceration, or peritonitis. 
In connection with any of the above forms of inflammation, or with- 
out them, there may be thrombosis of the uterine sinuses, purulent in- 
flammation of the veins, suppuration and abscess in the uterine wall, 
suppurative inflammation of the ovaries and tubes, and, owing to the 
generalization of the infectious material, metastatic abscesses in the 
lungs, spleen, kidneys, etc. Or acute pleurisy, ulcerative endocarditis, 
erysipelas, purulent inflammation of the joints, hyperplastic swelling of 
the spleen and lymph-nodes, thrombosis or thrombophlebitis of the saphe- 936 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
nous veins, etc., may follow. In some cases which rapidly pass to a 
fatal termination, the local lesions may be but slightly marked, and gen- 
eral alterations characteristic of pyemia, such as metastatic abscesses, 
etc., be entirely wanting. Death, in such cases, is due apparently to 
toxemia produced by the bacteria circulating in the blood (blood cultures). 
Bacteria are usually present in the exudate, and in the lymph-vessels, 
veins, and inflamed tissue of the uterus (Fig. 606), and often in enormous 
quantities in the peritoneal exudation and in the metastatic inflammatory 
foci. Streptococcus pyogenes, the gonococcus, B. aerogenes capsulatus, 
and the colon bacillus are the most frequent excitants of the lesion.1 
In general, it may be stated that puerperal infections begin as local 
processes. If the uterine reaction is sufficient and the virulence not ex- 
cessive, the process remains localized as an endometritis or metritis. If 
the local resistance is overcome and invasion proceeds through the lym- 
phatics and veins, more or less diffuse thrombophlebitic processes are 
set up, producing parametritic exudates (rarely fatal), progressive throm- 
bophlebitis (pyemia, grave prognosis), and occasionally puerperal peri- 
tonitis by pure lymphatic extension (almost invariably fatal). Still more 
acute invasions rapidly overcome the local resistance, leave no evidence 
of infection in the periuterine connective tissues, lymph and venous chan- 
nels, but flood the entire systemic vascular system with bacteria which 
rapidly multiply in the blood stream. Only a small number of patients 
with such infections recover. 
TUMORS. 
Simple fibromata of the uterus are almost unknown, the so-called 
fibromata being, in most cases, myomata or fibromyomata. 
Lipomata have been described.2 
Uterine Polypi are a common form of growth from the mucous mem- 
brane. Apparently they are intermediate between "polypoid endo- 
metrium," a simple endometrial hyperplasia, and true submucous fibro- 
myomata which have become pedunculated. The presence of unstriped 
muscle fibers will decide the nature in favor of myoma. The polypi 
consist of more or less vascular connective-tissue stroma covered with 
epithelium. The surface may be smooth or villous. It may contain 
very numerous gland follicles, and then approaches the type of adenoma, 
or even of carcinoma (Fig. 607). The stroma may be loose and succulent 
and resemble mucous tissue, forming the so-called mucous polypi. The 
stroma may give rise to sarcoma or to myosarcoma. In any of these 
forms the blood-vessels may be abundant and dilated, forming telan- 
giectatic or cavernous polypi. The adenomatous polypi may become 
cystic from dilatation of the gland follicles. 
Polypi of the uterus may be multiple or single, small or large. In 
addition, numerous smaller and larger papillary outgrowths from the 
mucous membrane may occur from chronic stimulation of the uterine 
1 See Wadsworth, A. B., Am. Jour. Obst., 1901, xliii, 439, for study of puerperal infection. 
2 Ellis, A. G., Surg., Gynec., and Obst., 1906, iii, 658. THE REPRODUCTIVE ORGANS OF THE FEMALE 
937 
mucosa, probably ovarian in origin. Single polypi may grow from the 
mucosa of the body of the uterus or from the cervix, and hang by a long 
pedicle down into the vagina. The place of insertion of the pedicle is 
not the sole determining factor, but the character of the surface or glan- 
dular epithelium-in corporal polypi, low columnar in type; in cervical 
polypi, high columnar with clear protoplasm-must also be taken into 
consideration. 
The large number of glandular structures in many of these chronically 
inflamed papillary and polypoid outgrowths often justifies the name of 
adenomatous hyperplasia of the mucous membrane or of adenomatous 
papillomata or polyps. 
Polyps when projecting from the external os are subjected to trauma 
and to the irritating secretions of the vagina. Transformation of the 
Showing great abundance of glandular structures. 
Fig. 607.-Polyp of Uterus. 
surface epithelium from the columnar to the squamous type,1 invasion 
of gland lumina by the latter, as in erosion, and great proliferation of the 
epithelium are common. These changes do not signify malignancy. 
Myomata.2-These tumors, whose characteristic structural elements 
are smooth muscle cells (Fig. 225), are the most common of uterine tumors 
and, while frequently of little practical importance, sometimes have 
serious consequences. They are especially common in negresses. They 
are most frequently composed of both muscular and fibrous tissue- 
fibromyomata-but the relative amount of the two kinds of tissue is 
1 Oerie, R., Ztschr. f. Geburtsh. u. Gynak., 1906, Ivii, 384; Hunziker, HFrankfurt. Ztschr. f. Path., 
1911, viii, 1; v. Franque, O., Ztschr. f. Geburtsh. u. Gynak., 1911, Ixix, 409. 
2 Frankl, O., Arch. f. Gynak., 1911, xcv, 269; Kelly and Cullen, Myomata of the Uterus, Philadelphia, 
1909; and Lockyer, C., Fibroids and Allied Tumors, London, 1918. 938 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
subject to great variation. Myomata are most apt to occur after pu- 
berty, during the period of sexual maturity. They may be single or 
multiple, small or of enormous size; they are usually sharply circum- 
scribed, whitish or pink, dense and hard, or sometimes soft, and on section 
present interlacing bands or irregular masses of glistening tissue. Their 
usual situation is in connection with the body of the uterus, but they 
may occur in the cervix1 or in the folds of the broad ligaments. Accord- 
ing to their position, subserous, submucous, and intramural (interstitial) 
forms may be distinguished. 
The subserous myomata, often multiple, grow from the outer layers 
of the uterus in the form of little nodules. As they increase in size they 
Shows the uninvolved interior of the uterus containing a well-formed fetus. 
Fig. 608.-Extramural Myomata. 
may become separated from the uterine wall and remain attached only 
by a narrow pedicle or by a little connective tissue; or they may be 
entirely free from uterine connections, having formed new attachments 
to the adjacent or even more distant organs ("wandering" fibroids). 
They may work their way between the folds of the broad ligament until 
they are at some distance from their point of origin. The tumors may 
become very large, but still remain firmly attached to the uterus; this 
organ may then be drawn upward, the cervix and vagina being elongated 
and narrowed. The traction may be so great that the body of the uterus 
is entirely separated from the cervix. The bladder may also be drawn 
1 Kolb, K., Ztschr. f. Geburtsh. u. Gynak., 1910, Ixvii, 399. THE REPRODUCTIVE ORGANS OF THE FEMALE 
939 
upward. Subserous myomata of considerable size may interfere but 
slightly with the function of the uterus (Fig. 608). 
The submucous myomata grow from the inner muscular layers of the 
uterine wall, most frequently in the fundus. They may project into the 
uterine cavity and remain sessile or become pedunculated; the uterus 
dilates with the growth of the tumor, and its wall may become thickened. 
The submucous myomata are usually single, although there may exist 
at the same time subserous and intraparietal tumors. They are fre- 
quently soft, and if of large size and polypoid in form, may be extruded 
through the cervix and, in rare instances, drag down the fundus of the 
Fig. 609.-Intramural Myomata of Uterus. 
uterus, producing inversion. The mucous membrane covering them may 
be atrophied or hyperemic, with dilated blood-vessels, and may thus give 
rise to severe and repeated hemorrhages. In some cases the pedicle of a 
tumor is destroyed and the growth is spontaneously expelled. Submu- 
cous polypi are especially vulnerable to changes in circulation producing 
hemorrhage, necrosis, and subsequent infection of the growth. 
The intramural myomata grow in the substance of the uterine wall, 
but, if they attain large size, usually project beneath the serous or the 
mucous coat (Fig. 609). They are found in every part of the uterus, 
but are most frequent in the posterior wall. 
The uterine musculature about a myoma is circumferentially arranged 
and lamellated. Except where the nutrient vessels enter' the growth, 940 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
only a tenuous connection exists; hence, fibroids readily shell out of their 
"capsule." 
The shape of the uterus is altered in a great variety of ways by the 
presence of these tumors; its cavity is narrowed, dilated, or misshapen; 
it undergoes flexion or version. The tumors may sink downward and 
become fixed in Douglas's cul-de-sac. 
Myomata may undergo a variety of secondary alterations. A vary- 
ing amount of interstitial edema may alter the size and consistence of the 
growth. The muscle fibers may undergo fatty degeneration, and the 
tumor may then diminish in size, or may even, it is said, be entirely 
destroyed. Degeneration of fibromyomata occurs most commonly in the 
puerperium as a result of the sudden cutting off of the blood supply. 
The most common degeneration is hyaline, which primarily affects the 
connective tissue of the growth, converting it into a structureless, faintly 
staining, glassy matrix (red, if stained with Van Gieson), between which 
the widely separated muscle 
bundles and fibers appear. Later, 
from lack of nutrition, the muscle 
also disappears. Calcification or 
ossification may occur, converting 
a part or the whole of the tumor 
into a stony mass. The intra- 
mural and submucous myomata 
may give rise to profuse hemor- 
rhages; they may suppurate and 
become gangrenous. 
Aseptic necrosis of myomata 
produces the so-called corneous 
fibroid, which on cross-section ap- 
pears beefy, soft to semifluid, and 
in color from bright pink to deep 
red or violaceous. The histological details gradually disappear, a granu- 
lar, diffusely staining debris marking the final stage. 
Sometimes the tumors or circumscribed portions of them are very 
vascular, constituting the telangiectatic or cavernous variety. These 
tumors, which possess some of the characters of erectile tissue, may show 
sudden change in size from variation in the amount of blood which they 
contain. Larger and smaller cysts may develop within these tumors- 
fibrocystic tumors. These may be multiple and may communicate; they 
may be filled with a clear or bloody fluid. These cystic myomata some- 
times reach an immense size and fill the abdominal cavity. The cysts 
may be lined with ciliated epithelium,1 although this is the great excep- 
tion. The majority of cystic cavities develop from aseptic necrosis of the 
tumor tissue, due to lack of blood supply, and, therefore, possess, no 
epithelial lining. 
Myomata of the cervix2 are moderately rare. They may grow as 
Fig. 610.-Adenomatous or Glandular Myoma 
of Uterus 
1 Breus, Ueber wahre Epithet fiihrende Cystenbildung d. Uterusmyomen, Leipzig, 1894. 
2 Kolb, K., Ztschr. f. Geburtsh. u. Gynak., 1910, Ixvii, 399. 941 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
polypi beneath the mucous coat, produce enlargement of the anterior 
or posterior lips, develop subperitoneally, elevating the uterus completely 
out of the pelvis, or grow outward into the abdominal cavity. 
Myomata of the uterus, either subserous, intraparietal, or submucous, 
containing glandular structures of the type of those in the uterine mucosa, 
are of occasional occurrence (Fig. 610). These glandular myomata or 
adenomyomata are occasionally directly connected with the uterine 
mucous membrane, but are sometimes so distant and so entirely sepa- 
rated from it as to justify the conjecture that they are derived from some 
embryonal abnormality associated with the development of the Wolffian 
body.1 Similar tumors have been described in the round ligament,2 in the 
rectovaginal septum,3 or at the umbilicus.4 These embryonal rests are 
most commonly located at the tubal angles (v. Recklinghausen). Adeno- 
myomata rarely have a well-defined capsule and, therefore, can not be 
"shelled out" as can fibromyomata. 
Myomata evidence themselves mainly by an increase in size of the 
uterus and by producing hemorrhage (meno- and metrorrhagia). Pres- 
sure effects occur more often from small tumors in the pelvis or from 
impacted or subperitoneal growths than from large growths which rise 
into the peritoneal cavity. The mucous membrane overlying submucous 
tumors is usually thin and atrophic, but the neighboring mucosa, where 
not pressed upon, is usually hypertrophic. There is some evidence that 
myomata are due to excessive ovarian stimulation, which likewise pro- 
duces the uterine hemorrhage commonly ascribed to the influence of the 
fibroid. Although fibroids may seriously complicate pregnancy, their 
influence in causing sterility is greatly overestimated. During the early 
months of pregnancy, the growth of fibroid tumors is usually rapid; but 
after the fifth month the rate generally diminishes. Sometimes the huge 
size attained by the tumor produces abortion before term is reached, or 
necessitates operation. Fibroids may produce dystocia. If the placenta 
is inserted upon a submucous fibroid, the afterbirth may remain adher- 
ent, as the thinned-out mucosa does not undergo a complete decidual 
reaction and the spongy layer of the endometrium is poorly developed. 
During the puerperium, fibroids are vulnerable to infection and often 
undergo degeneration. 
Malignant Myomata.-Certain very cellular myomata have been 
known to produce metastases and evince an infiltrating growth. They 
may show no histological evidence of malignancy. Fortunately these 
tumors are rare.5 
Sarcomata of the uterus occur most commonly in circumscribed intra- 
mural growths, usually developing in a myoma.6 Next in frequency are 
the intramural sarcomata; while endometrial sarcomata are the most 
1 Cullen, T. 8., Johns Hopkins Hosp. Rep., 1897, vi, 133 (bibl.); also monograph in Festschrift fiir 
Orth, Berlin, 1903. 
2 Cullen, T. 8., Bull. Johns Hopkins Hosp., 1898, ix, 142 (bibl.); Blumer, G., Am. Jour Obst., 1898, 
xxxvii, 37. 
3 Jessup, D. 8. D., Proc. New York Path. Soc., 1912, xii, 3. 
4 Cullen, T. 8., The Umbilicus and Its Diseases, Philadelphia, 1916. 
6 Hoevels, K., Frankfurt. Ztschr. f. Path., 1911, viii, 477. 
6 For references on the occurrence of sarcomatous changes in myomata, see Cullen, T. S., Jour. Am. 
Med. Assn., 1906, xlvi, 695. 942 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
rare. The latter are primarily polypoid; the former often show an early 
tendency to project at various points into the uterine cavity. Sarcoma- 
tous fibroids may appear well encapsulated, though on histological ex- 
amination invasion of the musculature may be apparent. On gross sec- 
tion, sarcomata are often softer, more friable, less glistening, more waxy, 
and more yellowish than myomata. Hemorrhagic, gangrenous, and 
necrotic areas are usually found. 
Sarcomata of the uterus, if within the center of fibroids, may remain 
latent for a time; sarcomata of the endometrium, or those that penetrate 
into the uterine cavity, slough and bleed. Invasion of the parametrium 
takes place; recurrence after operation is frequent; and metastases in 
the liver, lungs, lymph-nodes, etc., are common. 
Fig. 611.-Myosarcoma of Uterus. 
Histologically, transitions from the so-called "malignant myoma" to 
the most atypical giant-cell growths are reported. Myosarcomata (Fig. 
611) or sarcomatous "degeneration" of fibroids are not common. 
Great cellularity and variation in size of nucleus and cell body are charac- 
teristic. Small round, large round, and spindle-cell sarcomata are formed 
in various combinations. Polymorphous-cell sarcomata are readily rec- 
ognized. Giant cells may be found. 
Sarcoma of the cervix may appear as a cauliflower-like grow'th, indis- 
tinguishable from carcinoma (Fig. 612), or as a diffuse enlargement of 
the cervix. 
Sarcoma botryoides has been previously described. Carcinosarcoma,1 
angiosarcoma,2 chondrosarcoma,3 and ganglioma4 occur rarely. 
1 Forssner, H., Arch. f. Gynak., 1909, Ixxxvii, 445. 
2 Polano, 0., Ztschr. f. Geburtsh. u. Gynak., 1910, Ixvii, 413. 
3 Gebhard, C., Ztschr. f. Geburtsh. u. Gynak., 1902, xlviii, 111; and Penkert, M., Beitr. z. Geburtsh. 
u. Gynak., 1905, ix, 488. 
Picic, L., Berl. klin. Wchnschr., 1912, xlix, 16. THE REPRODUCTIVE ORGANS OF THE FEMALE 
943 
Carcinomata.1-From the descriptive aspect, carcinoma of the uterus 
is advantageously divided into tumors of the vaginal portion of the 
cervix, tumors of the cervical canal, and tumors of the uterine cavity 
(corpus carcinoma). This division also corresponds most closely to clin- 
ical considerations. 
1. Carcinoma of the vaginal portion of the cervix most probably always 
originates in the immediate vicinity of the external os, in most cases from 
erosions or from lacerations. Multiparae are more subject to this form 
of cancer than nulliparae. The tumor may assume cauliflower or papil- 
lary form, appear as an indurated invasive ulcer, or begin as a subepi- 
thelial diffuse thickening of part of the cervix. Necrosis, subsequent 
Fig. 612.-Epithelioma of Cervix Resembling Sabcoma. 
infection, bleeding, and foul-smelling discharge are early symptoms. 
Extension to the vaginal vault, vagina, and parametria, and involvement 
of the bladder and rectum regularly occur. The cervical canal is even- 
tually invaded, and nodules, apparently independent, may be found in 
the vagina and uterine musculature, though serial section proves them 
to be direct lymphatic extensions. 
2. Carcinoma of the cervical canal may be diffuse or nodular. The 
vaginal portion may appear normal although the entire cervical canal is 
involved. Hemorrhage and foul discharge are early symptoms. This 
form of tumor is very malignant because the thin shell of cervix permits 
early extension into the parametria. 
3. Carcinoma of the corpus uteri begins most frequently as a polypoid 
growth in one of the tubal angles; a diffuse involvement of the uterine 
cavity is less common. Clinically, this is the least malignant variety of 
uterine carcinomata,2 because it remains localized for a long period. 
1 Cullen, T. S., Cancer of the Uterus, New York, 1900. 
2 LadinsKi, L. JSurg., Gynec., and Obst., 1915, xx, 325; Boldt, H. J., ibid., p. 313. 944 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Gross Appearance.-Uterine carcinomata are whitish to pinkish, friable 
growths, which on gross section show infiltration and substitution of 
surrounding structures and a soft granular surface from which 11 cancer 
juice" can be wiped away with the knife edge. 
Fig. 613.-Adenocarcinoma of Uterus. 
Extension.-Uterine cancer is of frequent occurrence and, although a 
disease of early middle life, has been reported in young women (eighteen 
years). Early stages are rarely recognized. In the operable cases the 
parametria are found involved in more than 50 per cent. Involvement 
Fig. 614.-Adenocarcinoma, of Uterus. 
of the lymphatic nodes is also of frequent occurrence, even in operable 
cases (more than 20 per cent.), the parametrial, iliac, hypogastric, and 
aortic nodes being affected. 
Invasion.-As previously mentioned, neighboring structures are in- 
vaded by continuous or discontinuous growth. The vagina, bladder, 
Showing a small portion of a glandular and papillary growth. THE REPRODUCTIVE ORGANS OF THE FEMALE 
945 
and rectum may be converted into a single cancerous cloaca. The para- 
metrial outgrowths often surround the ureters, causing stenosis, hydro- 
ureter, hydronephrosis, and pyonephrosis. 
The ureteral wall is highly resistant to the 
tumor. 
Metastases to other organs are of late oc- 
currence. In order of frequency, the lung, 
liver, kidney, and ovary are involved. 
Histology.-An almost unbroken series 
can be traced from apparently adenomatous 
growths (all of which are malignant) to squa- 
mous-cell carcinoma. In many growths 
different areas show a different morphology. 
"Malignant Adenoma" and Adenocarci- 
noma.-This variety is most characteristic of 
corpus carcinoma, although very malignant 
tumors of this type are frequently found 
within the cervical canal. Parts of the sec- 
tion may consist of an inextricable network 
of irregular, closely crowded glands lined with 
a single layer of epithelium (Fig. 613); while in other parts the gland 
Fig. 615.-Adenocarcinoma of 
the Uterus. 
Showing a small portion of the 
epithelium in Fig. 614 more highly 
magnified. Mitotic figures are 
seen in the deeper layers. 
Showing the gross appearance of the interior of the uterus with an adenocarcinomatous involvement 
of the entire mucosa. 
Fig. 616.-Adenocabcinoma of Uterus. 
epithelium will be found arranged in several layers, and will show 
great diversity in size, shape, and nuclear dimensions (Fig. 614 and 946 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Fig. 617.-Carcinoma of Uterus. Medullary type. 
Fig. 618.-Carcinoma of Cervix Uteri. 
The infiltrating and ulcerating type. THE REPRODUCTIVE ORGANS OF THE FEMALE 
947 
615). Invasion and destruction of the uterine wall, also, may be ap- 
parent (Fig. 616). Toward the surface a gradual transition into the 
squamous type is occasionally found. 
Medullary carcinoma appears in an alveolar distribution (Fig. 617), 
forming "solid" carcinoma if the alveoli are large, "scirrhous" carcinoma 
if the connective tissue predominates. Pseudoglandular forms are pro- 
duced by central necrosis in the alveoli, though intermingling of areas of 
true glandular (adenomatous) configuration may be noted. The cells 
are closely crowded; the cell bodies are small and not plainly outlined. 
At the periphery, extension into the lymph-channels, or between the 
muscle or connective-tissue bundles, shows the invasive properties of the 
growth. 
Fig. 619.-Epithelioma of Cervix. Syncytial Type. 
Squamous-cell carcinoma may be highly differentiated, resembling the 
normal squamous epithelium of the vaginal portion of the cervix, but 
distinguished by the absence of regular arrangement into three layers, 
by invasion downward of finger-like processes projecting into the con- 
nective tissue and glands (Fig. 618), and by the marked round-cell zone 
of reaction which surrounds its margins. In other areas, the cells show 
marked deviations from the normal, nuclear irregularity, polymorphism, 
giant-cell or even syncytial complexes appearing (Fig. 619). Prickle 
cells and pearl formations are of common occurrence (Fig. 620); necrosis, 
hemorrhages, or hyaline degeneration of some areas may be noted. 
Types of growth resembling basal-cell carcinoma have been described. 
Multiple carcinomata, for example, appearing simultaneously in the 
corpus and on the vaginal portion, have been noted. Unless the possi- 
bility of lymphatic extension is excluded by serial sections between the 
sites of the tumors, such cases should not be classed as authentic, even 
if the tumors are dissimilar in type. 948 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Carcinoma and fibroid or carcinoma invading a fibroid have been 
reported. The coincidence may be accidental. 
Carcinoma and tuberculosis are occasionally found in the same uterus. 
Carcinoma and Pregnancy.-The carcinoma is always of the cervix, 
usually of the vaginal portion. Gestation appears to favor the rapid 
extension of the growth. Infection, hemorrhage, and, during labor, 
dystocia, may develop. 
Metastatic carcinoma of the uterus is rare. It is noted most frequently 
as a sequel to ovarian cancer. Next in order of frequency are those 
Fig. 620.-Carcinoma (Epithelioma) of Uterus. 
Showing ramifying epithelial cell masses. 
secondary to gastric, gall-bladder, breast, and rectal cancers. The 
metastatic nodules are found most often in the uterine musculature and 
when small are often situated in the lymph-channels. 
Chorionepithelioma of Pregnancy. (Chorioma.) 
Malignant tumors derived from chorionic villi or from some abnormal 
form of these, as hydatid moles (page 956), and composed of cells more 949 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
or less closely resembling the various types of chorionic epithelium, are 
known as chorionepitheliomata of pregnancy.1 
Characters of the Chorionic Villi.-The chorionic villi consist of a 
vascular mucoid connective-tissue framework which is covered with two 
layers of epithelial cells of fetal origin. The inner layer is formed in 
general of a single layer of sharply defined, polyhedral, transparent cells 
with oval nuclei. These cells contain glycogen, and are called Langhans1 
cells. The outer layer is composed of a cell mass with many nuclei of 
Fig. 621.-Chorionic Villus from Ectopic Pregnancy. 
various shapes embedded in a deeply staining vacuolated protoplasm, 
the whole resembling masses of giant cells, as no cell boundaries exist. 
This outer layer of cells is called the syncytium, and from it small proto- 
plasmic, bud-like processes- syncytial buds-project (Fig. 621). The 
outer surface, in appropriately fixed specimens, shows a margin covered 
with rods resembling cilia. In the later periods of pregnancy the cell 
layers are, as a rule, less distinct than at an earlier time, the Langhans' 
type disappearing. The cells covering chorionic villi, by virtue of a 
proteolytic ferment, penetrate the maternal decidua, mingling with its 
1 This specific designation is necessary because tumors of similar morphological characters, but 
differently derived, occur in non-pregnant women, in the testicle, and elsewhere as parts of teratomata. 
For a summary of these tumors, with a study of new cases and bibl., see Franic, Jour. Am. Med. Assn., 
1906, xlvi, 248: Risel, W., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1907, xi;, 928: and Woglom, W. H., 
St. Luke's Hospital Medical and Surgical Rep., iv, 1917, p. 188. 950 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
cells, and may invade the structures of the uterine wall. Certain of the 
covering cells of the chorionic villi have remarkable powers of penetrating 
the maternal tissues, their invasion being secured, apparently, through 
this lytic action. These are called chorionic wandering cells. They may 
erode blood-vessels, causing hemorrhage and thrombosis, and may enter 
the maternal circulation and be carried as emboli into the viscera1- 
liver, lungs, etc.-usually without the production of disturbing symptoms. 
It is cells of these three types-Langhans' cells, syncytium, and 
chorionic wandering cells--invading the tissues of the uterus, from which 
A mediastinal tumor showing the syncytial cells and the Langhans' cells in characteristic relationship 
to each other. 
Fig. 622.-Chorionepithelioma. 
they directly derive their nourishment, without the development of a 
special stroma, as is the case of most tumors, that give a malignant 
character to chorionepitheliomata when they have become freed from 
the restraints of normal growth. 
Chorionepitheliomata of the uterus form polypoid or nodular tumors, 
most commonly at the placental site, usually appearing a short time after 
the expulsion of a mole or after an abortion. Cases are on record where 
a long period of latency (five years) intervened between the pregnancy 
and tumor formation. The tumors are red to purplish, friable, and in- 
1 For a study of embolism of chorionic cells, see Schmorl, Verhandl. d. deutsch. path. Gesellsch 
1904, viii, 39; Zentralbl f. Gynak., 1905, xxix, 129; and Scholten, B., and Veit, J., Ztschr. f. Geburtsh. 
u. Gynak., 1903, xlix, 210. THE REPRODUCTIVE ORGANS OF THE FEMALE 
951 
filtrating. They are often multiple. On section, blood clots are noted 
as integral parts of the tumors. 
Ectopic chorionepithelioma is a rare variety, in which the tumor first 
occurs at a distance from a possible pregnancy site (i.e., uterus or tube), 
and is evidently due to the transportation of fetal elements by the blood 
stream, the embolus proliferating, the placental originator being expelled 
from the uterus. 
Regression of chorionepithelioma has been observed.1 Both primary 
tumors and metastases may regress; and cures have resulted after in- 
complete removal. On the whole, while chorionepithelioma is one of the 
most malignant varieties of tumors known, no histological distinctions 
between malignant and less malignant varieties have been discovered. 
Fig. 623.-Large Cells from Chorionepithelioma of Lterus. 
Vaginal curettings. 
In typical chorionepithelioma of pregnancy (Fig. 622) two character- 
istic types of cells are distinguishable: the first, large polynuclear cells 
or cell masses-syncytial masses-appearing in irregular multinuclear 
strands or branching protoplasmic structures, and the second, more 
transparent, sharply circumscribed, polyhedral cells with single oval 
nuclei, with glycogen-containing protoplasm. These tumors regularly 
contain free blood and fibrin, and the stroma is largely made up of the 
tissue which they invade. 
In many instances these tumors are less typical in structure, depart- 
ing more from the character of the chorionepithelium. The delicately 
outlined transparent cells may be absent; the syncytial masses may fail; 
the whole growth may be made up of irregularly shaped cells of various 
sizes with nuclei varying in size but often very large (Fig. 623). The 
cells are sometimes multinuclear. Chorionepithelioma, therefore, may 
be divided into typical and atypical, the latter including those tumors in 
which syncytium or chorionic wandering cells predominate almost to the 
exclusion of the other types. 
1 Teacher, J. H., Jour. Path, and Bacteriol., 1908, xii, 487. 952 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Chorionepitheliomata were at first regarded as sarcomata, but are 
now known to be derived from cells of the chorionic villi which are derived 
from fetal ectoderm. 
The development of these tumors most often follows hydatid mole. 
In the malignant types there may be invasion of the wall of the uterus 
and the pelvis (Fig. 624). Vaginal metastases are common and develop 
early, and there may be general metastasis with secondary tumors, most 
often in the lungs and liver. They may develop as a sequel to ectopic 
gestation (tubal chorionepitheliomata), but this is rare.1 
Chorionepithelioma of the uterus produces severe hemorrhages, fever, 
and cachexia. On curettage, suspicious material may be obtained. 
Fig. 624.-Invasion of Uterine Sinus by Chorionepithelioma. 
Quite characteristic is the fact that if the first curettage is inconclusive, 
another curettage, practised within a few weeks, will evacuate even more 
placenta-like material. 
Chorionepithelioma with Teratoma. 
Several cases are recorded in which females whose age or condition 
precluded the possibility of pregnancy have developed tumors of the 
ovary having the characters of the chorionepitheliomata. These, it is 
believed, are all instances in which teratomata furnished the embryonal 
ectodermal tissues in which the tumors originated. Similarly, the so- 
called chorionepitheliomata of the testicle (Fig. 702), of which several 
cases have been described, are derived from teratomata. (See pages 393 
and 1024.) 
1 For a study of clinical and microscopical variations of these tumors, with suggestions for diagnosis, 
see Franlc, R. T., N. Y. Med. Jour., 1906, Ixxxiii, 793. 953 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
PARASITES. 
Echinococcus has been found in the body and neck of the uterus, and 
may rupture into the peritoneal cavity or into the vagina. 
The Placenta. 
Aside from the variations from the normal in size, shape, and position, 
for a description of which we refer to the works on obstetrics, we may 
mention here briefly some of the more important structural changes 
which the placenta may undergo. 
DEGENERATION. 
Fatty Degeneration and calcification of the placental tissue are of not 
infrequent occurrence. A certain degree of fatty degeneration and calci- 
fication is physiological as the end of pregnancy is approached. 
HEMORRHAGE. 
This may occur either on the maternal surface in the decidua, or 
between the fetal surface and the membranes, or in the substance of the 
placenta. The latter form of hemorrhage constitutes the true placental 
apoplexy. This may occur as the result of rupture of a placental sinus. 
The placental tissue is crowded apart, and a blood-clot, often infiltrating 
the parenchyma, is formed. This may lead to abortion, or the blood may 
undergo disintegration and absorption and its place be occupied by a 
cicatrix. The placental tissue in its vicinity may undergo fatty degen- 
eration. Under other conditions, without evidence of rupture of the 
vessels, the placental tissue may become infiltrated with blood in the 
form of an infarction. In this, degenerative changes similar to the above 
may occur, leading to fibrous induration of the placenta. 
Placental hemorrhage varies in dignity depending upon its effect on 
the embryo. If the embryo is destroyed in the early months and expul- 
sion of the chorion does not take place, a 11 placental mole " may develop. 
If hemorrhage occurs in the later months of pregnancy, maternal death 
may result from loss of blood. Hemorrhage occurs most commonly in 
patients with a high degree of albuminuria and is almost invariably ac- 
companied by diffuse disintegration of the uterine musculature. 
The so-called "infarctions" of the placenta vary in size, appearance, 
structure, and origin. They are most frequently due to an endarteritis 
of the vessels of the chorionic villi. They appear to be of little signifi- 
cance when of moderate size. Microscopically they consist of necrotic, 
poorly staining villi surrounded by fibrin. 
INFLAMMATION. (Placentitis.) 
Suppurative Inflammation of the placenta, with the formation of 
abscesses, is of rare occurrence as the result of injury. 
1 For a study of the placenta, normal and pathological, see Eden, T. W., Jour. Path, and Bacteriol., 
1896, iii, 449; 1897, iv. 265 (bibl.). 954 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Chronic Indurative Inflammation of the placenta may result in the 
formation of circumscribed masses of cellular and loose, or dense and 
cicatricial, connective tissue, or in a diffuse formation of connective tissue 
which may interfere with the nutrition of the fetus and cause abortion. 
The new-formed connective tissue may undergo fatty degeneration or 
calcification. 
In another class of cases, the new connective tissue is formed mainly 
in the walls of the vessels, particularly the arteries. This may occur in 
circumscribed portions of the vessels, leading to nodular growths around 
the arteries, or it may occur extensively along the various ramifications 
of the vessels, converting them into thick fibrous cords. The change is 
primarily in the adventitia, but all the coats of the vessel may become 
involved, leading to more or less complete obliteration of the lumen. 
Various proliferative and indurative changes in the placenta must be 
ascribed to syphilitic inflammation. On the other hand, the placenta 
may show no alteration in this condition. Suspicion of syphilis is 
aroused by a disproportionately large placenta. The villi may be over- 
plump and closely packed, and the intervillous space obliterated. Spiro- 
chetes have been found in the placenta, but are more readily discovered 
in the fetal lungs, liver, etc. Endarteritis of the vessels of the villi is 
not characteristic, though it may be suggestive, of lues. 
Tuberculous Inflammation of the placenta may occur in connection 
with other tuberculous processes in the mother. 
TUMORS. 
Moles.-Under various conditions interfering with its nutrition the 
fetus may die and be cast off. The placenta and membranes, if retained, 
Fig. 625.-Fragment of Macerated and Edematous Decidua in Curettings from the Uterus. 
may then dry, forming a fibrous or fleshy or bloody mass-fibrous mole; 
fleshy mole; bloody mole. These are not genuine tumors. 
Placental Polyps.-Not infrequently, especially after abortions, por- 
tions of the placenta (Fig. 625) remain attached in the uterus and may 
undergo various phases of hyperplasia forming polypoid outgrowths THE REPRODUCTIVE ORGANS OF THE FEMALE 
955 
Fig. 626.-Curettings from Uterine Cavity showing Portion of Retained Placenta, and of 
the Mucous Membrane showing Glandular Hyperplasia. 
Fig. 627.-Hydatid Mole. 
Showing a small portion of the mass. 956 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
or diffuse thickening of the mucous membrane, resembling some of the 
forms of moles in character. This condition is often associated with 
persistence of the decidual reaction, and curettings of the uterus may 
then show both placental structures and glandular hyperplasia of the 
mucous membrane with marked decidual characters (Fig. 626). 
Sometimes, however, the placenta, or some part of it, is transformed 
into an irregular mass of rounded pink or colorless transparent or trans- 
lucent bodies, from two to ten millimeters in diameter-hydatid moles 
(Fig. 627 and 628). These bodies, macroscopically resembling bunches of 
grapes in which the individual grapes are attached to one another directly 
or by tenuous stalks, consist of loose vascular connective tissue resem- 
bling mucous tissue, and are covered with very actively proliferating 
Fig. 628.-Hydatid Mole. 
Section of a small portion showing mucous and slightly fibrous tissue covered with a layer of 
epithelial cells. 
chorionic epithelium. The cause of this transformation of the placenta 
is unknown. It may be cast off with the fetus or there may be no trace 
of the embryo. The hydatid mole may remain after the fetus is dis- 
charged, and through the growth of the chorionic epithelium may give 
rise to chorionepithelioma1 (page 948), or to chorionepithelial emboli in 
various parts of the body,2 with metastatic growths having the characters 
of hydatid moles.3 An hydatid may destroy the fetus; a live fetus and 
a partly hydatid placenta may occur; in twin pregnancy one twin may 
be represented by the hydatid. Clinically, the uterus increases far 
beyond the corresponding size for the same month of pregnancy. A 
peculiar, often transient enlargement of the ovaries, lutein cystic degen- 
eration, is not infrequently noted in connection with hydatid mole and 
chorionepithelioma. 
1 See Pick, L., Berl. klin. Wchnschr., 1897, xxxiv, 1069, 1097. 
2 See Schmorl, Verhandl. d. deutsch. Naturf. u. Aerzte, 1897, ii, part 2, 21, 111; also ibid., Verhandl. 
d. deutsch. path. Gesellsch., 1904, viii, 94. 
3 For pathology of hydatid mole and chorionepithelioma, see Frank, R. T., Am. Jour. Obst., 1911, 
Ixiv, 435. THE REPRODUCTIVE ORGANS OF THE FEMALE 
957 
Cysts of the placenta are of occasional occurrence; their origin is in 
many cases obscure.1 
The Ovaries. 
Malformations. 
One or both ovaries may be absent, the other organs of generation also being absent 
or undeveloped; or they may be only partially developed. There may be accessory 
ovaries or even a third ovary. Absence or arrest of development of one ovary occa- 
sionally occurs in otherwise well-formed individuals, and is sometimes accompanied 
by a low position of the kidney on the same side. The ovaries may pass into the 
inguinal canal or into the labia majora, and may remain fixed there through life. 
Less frequently they are found in the crural canal or in the foramen ovale. 
The ovaries may become larger than normal through chronic inflammation or 
through the formation of cysts and tumors. In old age they become atrophied, the 
Graafian follicles disappearing and the organ shrivelling into a small, irregular, fibrous 
body. Atrophy may be produced by chronic inflammation or by unknown causes. 
As the result of the maturing and rupture of the Graafian follicles, with or without 
pregnancy, the surface of the ovary, which before puberty is smooth, may become 
roughened by irregular cicatricial depressions; in extreme cases, so-called "gyrate" 
ovaries result with incisures resembling the convolutions of the brain. 
In adult life the ovaries may pass as herniae into the inguinal or crural canal, the 
foramen ovale, or the umbilicus. Their position in the abdomen may be changed 
by the pressure of tumors, the traction of false membranes, etc. This may occur in 
enlarged ovaries or in those of normal size, and by the compression of the veins may 
lead to congestion and chronic inflammation of the organs. 
Changes in Size and Position. 
HYPEREMIA AND HEMORRHAGE. 
Aside from the normal hyperemia of the ovaries during various sexual 
functions, the vessels may be congested in inflammation, in displacements 
with interference with the venous circulation, in certain diseases of the 
heart, etc., and this congestion may be followed by interstitial changes. 
Such changes are usually accidental findings and are of no importance. 
The menstrual periods are followed by the effusion of blood into a 
ruptured Graafian follicle. Normally, the amount of blood is small; it be- 
comes solid, is decolorized, and then gradually is absorbed. Sometimes, 
the effusion of blood is much greater, so that the follicle filled with blood 
is as large as a pigeon's egg. The blood remains in the follicle and is 
absorbed, or, rather, replaced by fibrous connective tissue which wanders 
into the fibrin network of the clot from the periphery. More rarely, it 
is replaced by a serous fluid, and in exceptional instances, it may, through 
rupture, escape into the peritoneal cavity. Death has been known to 
ensue from the hemorrhage; sometimes the blood collects in Douglas's 
cul-de-sac and becomes encapsulated. Hemorrhages also occur in folli- 
cles which have become cystic. Interstitial hemorrhage in the ovary 
sometimes occurs without known cause. 
1 Biland, J., Zieglers Beitr., 1907, xl, 195 (bibl.). 958 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
INFLAMMATION. (Oophoritis.) 
Acute Exudative Inflammation of the ovaries occurs most frequently 
in the puerperal condition, either as part of a general peritonitis or as a 
primary affection, through direct extension by the lymphatics or, more 
rarely, metastatically through transportation of bacteria by the blood 
current. 
In puerperal peritonitis, both ovaries are usually inflamed; they are 
swollen, congested, soft, infiltrated with serum or pus, and gangrenous. 
The lesion may involve principally the capsule, the stroma, or the follicles. 
Inflammation of the capsule results in adhesions and collections of pus, 
shut in by faise membranes; inflammation of the stroma, in abscesses 
and fibrous induration; inflammation of the follicles, in their dilatation 
with purulent serum 
1, Dense connective-tissue stroma; b, dilated veins; c, cysts; d, cyst with granular contents; e, cortical 
zone of immature Graafian follicles. 
Fig. 629.-Chronic Oophoritis with Dilated Blood-vessels and Cysts. 
If the inflammation of the ovary be the primary lesion, and this must 
be considered the utmost rarity, it is usually confined to one organ. The 
stroma of the ovary is infiltrated with serum and pus, and may contain 
abscesses of large size. In other cases, the ovary itself is but little 
changed, but it is surrounded by a mass of fibrinous and purulent exuda- 
tion. Such independent forms of ovarian inflammation may terminate 
in recovery; or the abscesses may perforate into the free peritoneal cavity, 
causing peritonitis, or into the rectum and vagina; or the ovary may be 
left indurated and bound down by adhesions. 
Acute exudative inflammation of the ovaries unconnected with the 
puerperal condition is not common, but it may occur in connection with 
acute or chronic peritonitis or perimetritis, with various infectious dis- 
eases (mumps, diphtheria, typhus fever, pyemia, etc.). THE REPRODUCTIVE ORGANS OF THE FEMALE 
959 
Chronic Oophoritis, though described by many authors, must, per se, 
be a great rarity (Fig. 629). Usually the condition is the residuum 
from an acute puerperal or postabortive infection, or it is the final stage 
of a gonorrheal process. In the latter case, characteristic tubal changes 
will be found which show the mode of origin long after live gonococci 
have disappeared. 
As the result of repeated attacks of salpingo-oophoritis, the organ may 
finally be smaller than normal, because of the formation of dense new 
interstitial connective tissue, and its surface may be greatly roughened 
and distorted. The atrophied ovary may be made up largely of thick- 
walled arteries and of fibrous masses which are the result of incomplete 
resolution of the corpora lutea (Fig. 630). 
From a case of valvular disease of the heart with chronic metritis and endometritis, a, Thickened 
and dense interstitial tissue; &, old corpora lutea; c, arteries with greatly thickened walls; d, dilated veins. 
Fig. 630.-Chronic Oophoritis with Atrophy. 
The so-called microcystic ovary is sometimes classified as chronically 
inflamed. This peculiar change, by which the ovary is converted into 
a honeycomb mass of thin-walled, closely contiguous, small cysts, is prob- 
ably functional and not inflammatory. For some unknown reason, the 
follicles develop to a certain stage, usually attaining the size of a small 
pea, fail to rupture, but are not absorbed, as is usual. In consequence 
of successive crops, the ovary becomes honeycombed and moderately 
enlarged. Its albuginea grows thicker. This condition is noticed 
especially in sterile women; it may be permanent, but in some cases is 
of transitory duration. A somewhat similar appearance is almost in- 
variably found accompanying, perhaps causing, fibroids of the uterus. 
Tuberculous Inflammation of the ovaries is moderately rare, and may 
accompany tuberculous inflammation of other organs, particularly of the 
peritoneum or Fallopian tubes. It usually results in the production of 
dense caseous nodules of considerable size. Tuberculous infection of 
recently ruptured Graafian follicles may occur, probably through the 
blood-stream. 960 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Syphilitic Inflammation, in the form of gummata, is uncommon. 
Actinomycosis of the ovary is occasionally encountered, usually in 
connection with actinomycosis elsewhere in the body. The organisms 
are found in the pus. 
TUMORS. 
Classification of tumors of the ovaries is more difficult than that of 
tumors of any other part of the genital tract. The simplest method is 
to divide the tumors into two main classes: connective tissue and epi- 
thelial. 
The ovary being only partly covered by peritoneum (at the hilus), 
tumors of this organ may be free or may be covered by the peritoneal 
layer, depending upon the direction of their development. The pedicle 
will always consist of the mesovarium, and, as growth progresses, may 
include also the ovarian, infundibulopelvic, and broad ligaments. Tu- 
mors which grow into the broad ligament and become intraligamentous 
have the Fallopian tube running over their surface. 
Fig. 631.-Papilloma of Ovary. 
Torsion of the pedicle occurs in a certain number of cases. The twist 
of the pedicle may produce complete shutting-off of the circulation, hem- 
orrhage, necrosis, and rupture of the growth with the formation of adhe- 
sions or the development of peritonitis. 
Connective Tissue Growths. 
Fibroma is not common,1 forming only about two per cent of all 
tumors occurring in the ovary, nor, when it occurs, is it usually of great 
importance. The tumors may be small or large; they are usually dense 
in texture, and seem often to originate in the tissue formed in the closure 
of the ruptured Graafian follicle. They may contain cysts or be accom- 
1 Hellman, A. M., Surg., Gynec., and Obst., 1915, xx, 692 (bibl.). 961 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
panied by cysts of the surrounding stroma. Fibromata of the ovary usu- 
ally produce massive ascites (in about 75 per cent, of the cases). Papil- 
lary fibromata of the surface of the ovary are not infrequent (Fig. 631). 
They may contain cysts (Fig. 632) and the growth may be transplanted 
from this situation to the general peritoneal surfaces. Angioma has been 
described. 
Chondroma of the ovaries has been described, but is rare; cartilage 
occurs not infrequently, however, in dermoid cysts and in teratomata 
(Fig. 650, page 974). 
Fig. 632.-Papilloma of Ovary. 
Shows cyst with papillary growth within. 
Osteoma is probably always secondary to ossification of a calcified 
focus,1 except where the bone represents the overgrowth of one tissue in 
a dermoid cyst. 
Leiomyoma, containing more or less fibrous tissue, is of occasional 
occurrence. 
Sarcoma of the ovaries is not common, making up only about 5 per 
cent, of all ovarian tumors. It is usually primary, but may be meta- 
static. Fifty per cent, of the ovarian tumors occurring in children are 
sarcomata, small round-cell tumors predominating at this period. In 
adults, spindle-cell sarcomata are more often found. Polymorphous-cell 
tumors and even giant-cell sarcomata of the ovary have been reported 
1 Moschcowitz, E., Proc. New York Path. Soc., 1913, xiii, 19. 962 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
(Fig. 633). Sarcomata of the ovary are very malignant, especially the 
softer forms; recurrence with metastatic involvement of the retroperi- 
toneal lymph-nodes is almost the rule. The tumors may be hard or soft, 
and in about 10 per cent, of the cases involve both ovaries.1 
Fig. 633.-Sarcoma of Ovary.-Giant-cell Type. 
Endotheliomata have been described in the ovaries, though tumors 
of this morphology are now more usually classed as carcinomata. 
Fig. 634.-Follicular Cysts of Ovary. 
At the right an old corpus luteum is visible. 
Epithelial Growths. 
Retention Cysts.-Follicular Cysts of the Ovary.-The Graafian folli- 
cles may be dilated so as to form cysts. The condition may occur in one 
1 Smith and Motley, Surg., Gynec., and Obst., 1915, xx, 419 (sarcoma of both ovaries in child of 
three years). THE REPRODUCTIVE ORGANS OF THE FEMALE 
963 
or both ovaries, and the cysts may be small or large, single or multiple 
(Fig. 634). They are usually found after middle life, but may occur 
during youth or childhood, or even in the fetus. The follicles dilate from 
the accumulation of fluid within them; the ovum is destroyed, and the 
epithelium flattened. The contents are usually serous and colorless, but 
may be viscid, purulent, or variously colored, red, yellow, or brown. The 
ovary may be crowded with numerous cysts of moderate size, whose adja- 
cent walls may coalesce and atrophy, forming communications between 
them.1 
Corpus Luteum Cysts.-A variety of this type of cyst is formed by 
the dilatation of a corpus luteum, either with or without the hyperplasia 
of the wall. 
Lutein Cysts of Ovary.-Hydatid mole of the uterus in a large per- 
centage of cases, and chorionepithelioma occasionally, cause multiple 
Fig. 635.-Cystadenoma of Ovary-(Mttltilocular Ovarian Cyst-Cystadenoma). 
About four-fifths natural size. 
cystic dilatations of atresic follicles. The ovaries may attain the size of 
an adult fist. The cysts have thin walls and are often denuded of epi- 
thelium, but contain many lutein cells in the stroma. After expulsion 
or removal of the mole, the ovaries may resume a natural size, though 
this does not always occur. 
Adenomatous Cysts.-Cystadenomata.-The best classification of 
these tumors is based upon the nature of the cyst contents, and is supple- 
mented by the characteristics of the lining epithelium. The older classi- 
fication of "glandular" and "papillary" types can not be maintained, 
because the so-called cystadenoma "glandulare" or "pseudomucinosum" 
may contain papillary outgrowths. 
Cystadenoma pseudomucinosum contains a fluid varying from watery 
to jelly-like consistency, which is not precipitated by acetic acid. 
1 v. Kahlden, C., Zieglers Beitr., 1900, xxvii, 1 (bibl.). 964 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Cystadenoma serosum contains a fluid with high albumin content. 
Cystadenoma {pseudomucinous, glandular, simple, or multiple).-There 
is a marked tendency in this form of adenoma to the formation of cysts. 
There may be a number of cavities equally dilated so as to form a number 
of cysts of moderate size (Fig. 635); or a few follicles may be greatly 
dilated to form a large multilocular cyst with but few compartments (Fig. 
Showing large cysts, with a glandular mass within one of the cysts. 
Fig. 636.-Pseudomucinous Cystadenoma of Ovary. 
636). The walls of the cysts may fuse together and be absorbed, so as 
to form one large cyst divided by incomplete septa-unilocular cysts. 
The stroma in which the follicles and cysts are embedded may be largely 
developed or very scanty. 
The walls of the larger cysts are composed of fibrous tissue which is 965 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
dense in the outer layers, more cellular in the inner, upon which the epi- 
thelium is placed. They may be thin and membranous, or there may be 
upon their internal surfaces an intracystic growth composed of a fibrous 
stroma and tubular follicles. These secondary follicles may also be 
filled with fluid and form larger and smaller cysts. The intracystic 
growths may be so large as to fill up the original cysts. Sometimes the 
Fig. 638.-Cystadenoma of Ovary-Glandular Type. 
intracystic growth presents very little dilatation of its follicles, so that 
the entire tumor has the character more of a solid growth than of a cyst. 
Flat papillae are not infrequently found on the inner surface of the 
cyst walls. They rarely attain the height of the papillary growths com- 
monly occurring in cystadenoma serosum (Fig. 637). 966 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The cylindrical epithelium lining the cysts usually forms a single 
layer (Fig. 638), but several layers, often irregular in thickness, may form, 
and, owing to the accumulation of fluid, the cells may become flattened 
and atrophied, or they may be fatty or desquamated. The lining cells 
are usually columnar, with a clear protoplasm and with a deeply staining 
rod-like nucleus at the basal periphery. Goblet cells are noted between 
the more columnar structures, representing cells ready to discharge their 
secretion. The contents of the cysts differ considerably in different cases, 
and even in different cysts in the same case. They may be tough and 
ropy, or gelatinous, or serous; transparent and colorless, or yellow, red- 
dish, or reddish-brown; or they may be turbid and colorless, or variously 
colored-red, brown, or chocolate-depending upon the amount of blood 
effusion that has taken place into the cyst fluid. 
Fig. 639.-Pseudomyxoma of Peritoneum. 
Chemically, the cyst contents include pseudomucin or paralbumin, 
and perhaps other less well-known compounds belonging to the same 
class. It is probable that the contents of these cysts are, so far as the 
pseudomucin and paralbumin are concerned, produced by a metamorpho- 
sis of the protoplasm of the lining cells, similar to that by which the mucin 
is produced in the mucous glands and in mucous membranes. Numerous 
degenerating cells from the cyst lining and white and red blood-corpuscles 
are found in the cyst fluid. In addition to the above structural elements, 
there may be found free fat droplets, cholesterin crystals, pigment gran- 
ules, hematin, and more or less granular detritus. The gelatinous mate- 
rial filling these cysts is sometimes called colloid, and the cysts are fre- 
quently called colloid cysts. THE REPRODUCTIVE ORGANS OF THE FEMALE 
967 
Numerous secondary changes are likely to occur in these cysts. The 
cells may peel off, the walls of the cysts may atrophy or become calcified. 
Suppurative inflammation (infection with pyogenic bacteria, gonococcus, 
or typhoid or colon bacilli), perforation into the peritoneum, bladder, 
vagina, or rectum, hemorrhage, gangrene, etc., may occur. As a result 
of chronic productive processes, the cyst walls may become thickened 
and extensive adhesions may form. Carcinoma may develop from these 
tumors. 
Cystadenoma pseudomucinosum is one of the most frequent of ovarian 
tumors (forming about 50 per cent.); it is of bilateral occurrence in less 
than 20 per cent., and is rarely malignant. Nevertheless, peritoneal 
implantations are noted, though these usually disappear after the cyst is 
removed. Occasionally, after spontaneous or traumatic rupture of a 
cyst, "pseudomyxoma of the peritoneum" develops (Fig. 639). This is a 
Fig. 640.-Multiple Papillary Cysts of Omentum, Secondary to a Similar Growth in 
the Ovary. 
The papillary outgrowths are themselves becoming softened at their centers, forming 
accessory cysts. 
diffuse, sluggish growth, between the coils of intestine and other abdom- 
inal viscera, of a jelly-like material, containing columnar cells and pseudo- 
mucin (see page 797). Eventually, the abdomen distends to huge dimen- 
sions and death results from malnutrition or intestinal obstruction. 
Pseudomyxoma of the peritoneum may also result from the rupture of 
a pseudomyxoma of the appendix. Very rarely, during an operation, 
particles from ovarian cyst contents become implanted in the abdominal 
or vaginal scar and later lead to local recurrence at these sites. 
Usually, ovarian cysts of this type produce symptoms merely because 
of their size, through the formation of adhesions, or because of torsion 
of their pedicle. 
Cystadenoma Serosum (papillary').-This type of cystadenoma was 
formerly regarded as but a variety of the form described above-a variety 
characterized by papillary outgrowths in cauliflower-like tufts from the 
walls of the cysts, which often in large degree fill the cyst spaces. 968 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The papillary cystadenomata are not, as a rule, so large as the glandu- 
lar form. The cysts are usually fewer and contain, not colloid material, 
Fig. 641.-Papillary Cystadenoma of Ovary-Ciliated Cells. 
Fig. 642.-Carcinoma of Ovary-Medullary Type. 
but a thin watery fluid. One rare variety is composed of grape-like 
clusters of cysts attached to one another, in gross appearance much like 
a hydatid mole of the uterus. The papillary outgrowths often break THE REPRODUCTIVE ORGANS OF THE FEMALE 
969 
through the cyst walls, and may be transplanted to the peritoneal or 
other surfaces in the form of multiple cystic or papillary tumors (Fig. 
640). The papillse and cyst walls are lined with ciliated, cubical or 
columnar cells, containing a granular protoplasm and large nucleus 
(Fig. 641). The cells are, as a rule, in a single layer. 
Malignant changes occur*more frequently in serous than in pseudo- 
mucinous cystadenomata. The epithelium then becomes irregular, 
assumes multiple layers, and penetrates the stroma. 
Fig. 643.-Alveolar Carcinoma of Ovary. 
Clinically, serous cystadenoma is malignant. Recurrences appear in 
75 per cent, of the cases; ascites is the rule; secondary peritoneal im- 
plantations are frequent and are less apt to disappear after removal of 
the ovarian tumor. On the other hand, in some instances even after 
incomplete removal of the growth permanent cure results. 
Carcinoma, usually of the medullary variety, may occur as a primary 
tumor of the ovary (Fig. 642). It may be due to a continuous extension 
from neighboring organs or, more rarely, may be of metastatic origin. 
Although the medullary carcinomata are the most common, adenocar- 
cinoma and scirrhous, melanotic, and gelatinous forms sometimes occur. 
Macroscopically, carcinoma of the ovary may be either solid, partly 970 
solid with cystic portions, or colloid. It may originate from carcinoma- 
tous changes in a cystadenoma or in a dermoid. In nearly 50 per cent, 
of the cases it is bilateral. The tumors may reach a large size, are friable 
when soft, and form adhesions early. They produce not only multiple 
peritoneal implantations, but also metastases in the lymphatics. After 
operative removal, recurrence is the rule (in about 90 per cent.). 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Fig. 644.-Krukenberg Tumor. 
The primary growth was in the stomach. 
Histologically, alveolar carcinoma is most common (Fig. 643). Pure 
adenocarcinoma is rarely found, alveolar distribution occasionally being 
apparent in small areas. Combinations of carcinoma and sarcoma (car- 
cinosarcoma) are found most frequently in children. Such tumors prob- 
ably are teratomata. 
Fig. 645.-Ganglion Cells fbom Teratoma of Ovary. 
Metastatic carcinoma, secondary to carcinoma of the intestinal tract, 
breast, and uterine fundus, occurs in the given order of frequency; the 
tumors are almost always bilateral. The cells of these tumors often 
produce a mucoid material which more or less fills the cell body and THE REPRODUCTIVE ORGANS OF THE FEMALE 
971 
pushes the nucleus to one side, giving a characteristic signet-ring appear- 
ance to the cells involved. The stroma may be unusually cellular so 
that the tumor is with difficulty distinguishable from a sarcoma (Fig. 
644). It was for this reason called fibrosarcoma ovarii mucocellulare 
(carcinomatodes) by Krukenberg1 who first described it, and by whose 
name also it is known. The secondary nature of this growth has been 
only recently determined.2 
Teratomata (Dermoids and Solid Teratomata). 
Both dermoid cysts and teratomata probably develop from embryonal 
cells which remain latent in the ovary for a variable number of years 
after birth. In dermoids, the tissues found resemble the adult type and 
show a tendency to form rudimentary organs. Representatives of all 
the embryonal layers (ectoderm-skin, hair, sweat and sebaceous glands, 
Fig. 646.-Glia Tissue from Teratoma of Ovary. 
teeth, retina, nerve tissue (Fig. 645 and 646), etc.; entoderm-intestine, 
bronchi, etc.; and mesoderm-cartilage, bone, muscle) may be present, or 
only two or even a single layer may be represented (see also page 1023). 
In teratomata, with few exceptions, the tissues are in the fetal stage 
of development, and elaborate organ formation is not seen. Teratomata 
likewise fail to develop large cysts with sebaceous contents, forming more 
solid tumors riddled with small cysts. 
Dermoid Cysts (Embryomata).-These cysts may be uni- or multi- 
locular, and are usually of moderate size, though they sometimes become 
as large as a man's head or larger. Multiple dermoids in one ovary are 
not uncommon, and bilateral occurrence is also not infrequent. The 
fibrous walls of the cysts may be thick or thin, and portions of the internal 
surface may present more or less completely developed cuticular struc- 
1 Krukenberg, Arch. f. Gynak., 1895-96, 1, 287. 
2 For discussion and bibl., see Metzger, M., Les metastases ovariques des cancers digestifs, Paris, 
1911; Hall, M. E., Proc. New York Path. Soc., 1912, xii, 57; and Stone, W. S., Surg., Gynec., and Obst., 
1916, xxii, 407: Major, R H , Surg., Gynec., and Obst., 1918, xxvii, 195 (bibl.). 972 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Fig. 647.-Teratoma of Ovary. 
Showing skin and rudimentary hair follicles. 
Fig. 648.-Dermoid Cyst of Ovary. 
One of the cysts contains a mass of hair and sebaceous material. 973 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
tures, such as corium, papillae, epidermis, hairs and hair follicles, sebaceous 
glands, etc. (Fig. 647). The cavity may contain a thick, whitish, greasy 
material composed of flattened epithelium, fat, or cholesterin crystals. 
Or the cavity or walls may contain masses of irregularly formed hair 
(Fig. 648), teeth, bone, cartilage, pharyngeal ciliated epithelium, striated 
muscle, thyroid gland (Fig. 649),1 and nerve fibers and cells.2 
Dermoids are divided into tumors containing all three embryonal 
layers, those containing two layers, and those rare tumors which contain 
Fig. 649.-Thyroid Tissue in Dermoid of Ovary. 
only one. It is possible to trace an unbroken series, from cases of so- 
called fetus in fetu, in which a more or less complete individual has been 
found in a dermoid cyst, through the less regular dermoids with only 
part of an individual, such as the upper jaw with full set of teeth and 
other organs only rudimentary in development, to a single layer dermoid, 
as, for example, the thyroid tumors of the ovary {struma ovarii), in which 
1 For a resume with case of thyroid tissue in the ovary (struma ovarii), see Frank, R. T., Am. Jour. 
Obst., 1909, lx, 433; see, also, Fiebach, Zieglers Beitr., 1911, li, 648. 
2 For a study of the origin of dermoid cysts of the ovary, see Arnsperger, Virchows Arch., 1899, clvi, 
1; and Askanazy, Die Dermoidcysten des Eierstocks, Bibliotheca Medica, Abth. C.,Heft 19, Stuttgart, 
1905. 974 
THE REPRODUCTIVE ORGANS CF THE FEMALE 
only thyroid tissue is found. Saxer reports having found a tooth em- 
bedded in an otherwise healthy ovary; R. Meyer has found the lens of 
the eye. 
The commonest form of dermoid has a projection on the inner wall 
of the cyst, the so-called dermoid "papilla," which may be regarded as 
the embryonal anlage. From this region the hair arises, and on section- 
ing the papilla, the various structures above enumerated may be found. 
A number of cases in which cancer has developed in the skin layer 
of the dermoid are recorded. The carcinoma is of the squamous-cell 
type (epithelioma). It may be accidentally found on sectioning the 
Fig. 650.-Teratoma of Ovary. 
A, Cartilage. B, Ganglion Cells. 
growth, or it may produce clinical symptoms by extending to neighboring 
organs or by causing metastases. 
Such embryonal growths may exist for many years without causing 
inconvenience; but inflammatory changes may occur in them, leading 
to adhesions and perforations into adjacent organs. They may form 
the nidus for the development of carcinoma, chorionepithelioma (page 
952), and other tumors, or they may calcify. 
Teratomata,1 as previously mentioned, are more irregularly developed, 
and are structurally of an earlier stage than dermoids. The tissues are 
of the early fetal period. Hence, myxomatous connective tissue, sar- 
1 Wilms, M., Zieglers Beitr., 1896, xix, 367; Sjovall, E., Frankfort. Ztschr. f. Path., 1911, vii, 10. THE REPRODUCTIVE ORGANS OF THE FEMALE 
975 
coma-like and carcinoma-like stretches are inextricably intermingled, 
riddled with cysts lined by varying epithelium. Cartilage, bone, undif- 
ferentiated striated muscle, neuroglia cells, etc. (Fig. 650), occur. These 
Fig. 651.-Small Pedunculated Cyst Growing from Broad Ligament. 
Fig. 652.-Parovarian Cyst or Intraligamentous Cyst. 
The tumor measured about 10 cm. in its longest diameter. 
solid tumors are usually malignant and may metastasize. The metas- 
tases are usually sarcomatous, but, at times, "organoid" metastases, 
similar to the primary growth, are encountered. 976 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
In addition to the above described dermoid cysts, there are a number 
of composite forms of not infrequent occurrence. Thus, in connection 
with dermoid cysts or separately, there may be simple ciliated cysts or 
combinations of both pseudomucinous and dermoid cysts. These may 
be multilocular and be lined with flattened, cylindrical, or ciliated epi- 
thelium, and may contain epidermal cells, cholesterin or mucin, etc. 
Small cysts, sometimes pedunculated, sometimes not, of doubtful 
origin and usually of no special significance, are frequently found growing 
from the broad ligament near the ovary (Fig. 651). The walls are 
usually very thin, and lined with flattened epithelial cells, and the con- 
tents are serous. 
Cysts of the Parovarium lie between the peritoneal layers of the broad 
ligament, and hence have a double vascular network on their surfaces 
(Fig. 652). They are usually small, but may be as large as a man's head 
They are lined usually with ciliated epithelium, but sometimes with non- 
ciliated cells. The contents may be serous, or may be thick and contain 
mucin and paralbumin. 
The Fallopian Tubes. 
Malformations. 
Absence of both tubes occurs with absence of the uterus. One tube may be absent, 
with arrested development of the corresponding side of the uterus. Both tubes may 
be imperfectly developed; either of their ends may be closed; they may be inserted 
into the uterus at an abnormal place; they may terminate in two or three abdominal 
ostia. Diverticula in the tube are common. Accessory tubes have been found. 
Changes in Size and Position. 
The Fallopian tubes may participate in the various malpositions of the uterus and 
ovaries; but they are most frequently displaced by the contraction of adhesions 
formed in perimetric and periovarial inflammations. 
The lumen of the tube may be partially or completely closed as the result of in- 
flammation of the mucous membrane; of peritonitis about the fimbriated extremity; 
of tumors or inflammation of the uterus; or by pressure from without, or by adhesions, 
tumors, etc. It may become stopped by plugs of mucus or pus. In inflammatory 
processes, the tube is closed either by false membranes which obliterate the opening 
without greatly affecting the fimbriae, or, more commonly, by retraction of the fim- 
briae (which are merely prolongations of the tubal mucosal folds over the peritoneal 
ring at the ostium). When inflammation occurs the fimbriae are drawn inward as 
the tubal lumen distends through swelling or accumulation of fluid. The retracted 
fimbriae are then agglutinated. 
Dilatation of the tubes may be produced by an accumulation of catarrhal or other 
exudation, when there is partial or complete stenosis at some portion of the tube. 
The dilatation may be moderate, converting the tube into a tortuous, sacculated 
canal containing mucous or serous fluid; or, more rarely, large cysts may form contain- 
ing several pounds of serous fluid-hydrosalpinx1 (Fig. 653). In the mild grades of 
infection which produce hydrosalpinx, the tubal wall does not hypertrophy, but may 
become as thin as paper and translucent. It must not be forgotten that sometimes 
the final outcome of a pyosalpinx is a hydrosalpinx. Then, however, the sac wall 
usually is thicker. 
1 For a study of hydrosalpinx with full bibliography, see Cullen, T. S., Bull. Johns Hopkins Hosp., 
1895, v, 351. 977 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Tubo-ovarian cysts are formed by coalescence of a hydrosalpinx and a follicular 
ovarian cyst or an ovary which has become cystic from inflammatory adhesions. 
Large complex masses are thus formed. 
As the fluid collects, the epithelium may become flattened or fatty, or may des- 
quamate. Inflammation may occur in the walls of the dilated tube, and the contents 
may be mixed with pus or blood. Rupture of the dilated tube sometimes takes place; 
or there may be severe and even fatal hemorrhage into its cavity. Papillary growths 
are sometimes found springing from the inner wall of the cyst. 
Salpingitis Nodosa.1-The inflammation may be localized in the isthmic or inter- 
stitial part of the tube. The lesions appear as firm nodules, usually multiple, reaching 
the size of a pea or cherry, in the wall of the tube. On section, a labyrinth of small 
lumina, lined with normal tubal mucosa is found. The lumina all communicate with 
the main tubal cavity, as is shown by serial sections. With few exceptions, this dis- 
ease is due to chronic inflammation. A small minority of cases may be due to adeno- 
myomata of mesonephric origin (v. Recklinghausen). 
The tube at the left is much distended, but still tubular. The tube at the right is dilated to cystic 
form. Between the distended tubes is the fundus of the uterus. 
Fig. 653.-Hydrosalpinx. 
Hemorrhage2 into the tube may occur in hematometra and tubal 
pregnancy, in acute infectious diseases, and in diseased tubes during 
menstruation. The blood may undergo degenerative changes and be 
largely absorbed, or it may escape into the peritoneal cavity and incite 
peritonitis. 
HEMORRHAGE. 
INFLAMMATION. (Salpingitis.) 
Inflammation of the mucous membrane of the Fallopian tubes com- 
monly occurs in connection with endometritis, most frequently in an 
1 Wallart, J., Ztschr. f. Geburtsh. u. Gynak., 1910, Ixvi, 130; 1913, Ixxiii, 1. 
2 Bazy, L., Rev. de gynSc., 1910, xv, 1. 978 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
ascending gonorrhea, which usually, though not invariably, progresses 
by a surface growth of the gonococci extending upward from the endome- 
trium. In the puerperal infections, which, as a rule, are strepto- or 
staphylococcic in origin, the organisms more commonly propagate along 
the lymph-channels and, therefore, reach the tubal wall before they infect 
the mucosa. In the acute stage, the mucous membrane is hyperemic and 
swollen, and is covered with a mucous or mucopurulent, often bloody, 
exudate. Pus exudes from the tubal ostium and infects the neighboring 
peritoneum. In gonorrheal processes, the resulting peritonitis tends to 
remain localized, causing repeated attacks of pelvic peritonitis and ad- 
hesions; in strepto- or staphylococcic infections a more diffuse peritonitis, 
often with fatal outcome, is more common. During the acute stage, 
the tubal lumen contains fluid, leucocytes, plasma cells, and microorgan- 
isms. The mucous membrane is overvascular and infiltrated with plasma 
cells and leucocytes. Superficial erosions of the epithelial layer and 
coalescence with opposite folds are frequent. 
The inflammation may subside, leaving no lesions, but it more fre- 
quently becomes chronic, and may then result in peritoneal adhesions, 
thickening of the walls, obliteration of the tubes, dilatations, etc.; or the 
mucous membrane may undergo hyperplasia with papillary outgrowth. 
Such papillary masses may partially coalesce, forming, on the accumula- 
tion of fluid, cyst-like cavities lined with epithelium. Hyperplasia of the 
muscle wall of the tube may be associated with these conditions.1 
Suppurative Salpingitis.-Catarrhal inflammation of the mucous 
membrane may assume a suppurative character, sometimes in connection 
with puerperal metritis and peritonitis, and often as a result of gonorrheal 
infection.2 Under these conditions the wall of the tube is involved. It 
is difficult in many cases of suppurative salpingitis associated with peri- 
tonitis, unless the clinical history makes the origin clear, to say which is 
the primary lesion. 
If the abdominal end of the tube be closed3 by adhesions or otherwise, 
there may be a considerable collection of pus in the tubes, causing dilata- 
tion-pyosalpinx (Fig. 654 and 655). Such a collection may rupture 
into the peritoneal cavity, or the pus may escape into a cavity shut in by 
adhesions, or may perforate into the intestine or bladder; or it may ab- 
sorb and finally become calcified. In pyosalpinx, the tubal wall may be 
greatly thickened. In the acute stage, this is primarily due to exudation 
and invasion of leucocytes. Not only the tube, but its mesosalpinx also, 
then presents an edematous, tense, and glistening appearance. Later, 
when the condition has become more chronic, the tubal wall becomes 
fibrous, hard, and sometimes almost cartilaginous in consistence. In 
nearly two-thirds of all the chronic cases, the pus proves to be sterile on 
culture. Pus tubes may reach enormous dimensions, and usually sink 
down into the pelvic cavity and form dense adhesions with all neighboring 
viscera. 
1 Ries, E., Jour. Exper. Med., 1897, ii, 347 (bibl.J. 
2 For a study of gonorrheal salpingitis, see Gurd, F. B., Jour. Med. Research, 1910, N. S. xviii, 151: 
Miller, J. W., Monatschr. f. Geburtsh. u. Gyn.k., 1912, xxxvi, 211: and Schridde, H., Die Eitrige 
Entzundiingen des Eileiters, Jena, 1910. 
8 Ovitz, E., Ztschr. f. Geburtsh. u. Gynak., 1904, lii, 485. THE REPRODUCTIVE ORGANS OF THE FEMALE 
979 
The walls of a chronic pyosalpinx show an increase of fibrous tissue, 
an infiltrated thickened mucosa containing plasma cells, thickened tubal 
Fig. 654.-Pyosalpinx. 
folds, and, often, adhesions between adjacent rugae. At times, innum- 
erable coalescences of folds on cross-section give the appearance of many 
The distended tube containing pus is attached to the ovary. 
Showing a cyst-like distention of the occluded tube. 
Fig. 655.-Pyosalpinx. 
small cystic cavities. Although plasma cells are more commonly found 
in pyosalpinges of gonorrheal origin, their presence is not so absolute a 
criterion as was asserted by Schridde.1 
1 Schridde, H., Die eitrigen Entziindungen des Eileiters, Jena, 1910. 980 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Tuberculous Salpingitis.'-The lesions are most frequently seen in 
the later stages of the process, when the mucous membrane is partially 
or entirely converted into a thick caseous, often ulcerating layer (Fig. 
656). The lumen of the tube may be dilated, and the wall thickened 
from chronic inflammation. This lesion may occur by itself, or may be 
associated with tuberculous inflammation of the lungs, of the other 
genitourinary organs, or of the peritoneum. It usually commences at 
the abdominal ends of the tubes, and both tubes are apt to be involved. 
Fig. 656.-Tuberculous Salpingitis. 
The wall of a portion of the tube is converted into a dense mass of fibrous and necrotic tissue which 
is disintegrating. 
At times, the peritoneal surface of an otherwise normal appearing 
tube is covered with miliary tubercles. This is usually due to widespread 
infection of the peritoneal serosa. The writer has seen three cases of 
hemorrhage from an apparently normal tube-hemorrhages into the free 
peritoneal cavity sufficient to produce symptoms of ruptured ectopic 
pregnancy-due to tuberculosis of the tubal mucous membrane. In the 
earlier stage of tuberculosis the mucosa shows large accumulations of 
epithelioid cells which greatly thicken the rugae (Fig. 657). As the process 
advances, many tubercles, with giant cells, form, coalesce, caseate, and 
invade and destroy the musculature. The entire mucosa may be de- 
stroyed, a large sac lined with tuberculous granulation tissue resulting 
1 Simmonds, M„ Arch. f. Gynak., 1909, Ixxxviii, 29; Jung, P„ ibid., 1910, xcii, 764; and Engelhom, 
E., ibid., 775. 981 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Calcification may take place and most of the cases of so-called teratomata 
with bone formation which have been reported, have proved to be end 
processes of tuberculosis. 
Syphilitic Inflammation, manifested by a gummatous thickening of 
the wall, has been described. 
Actinomycosis of the tube, usually in connection with actinomycosis 
of the other pelvic organs, leading to abscesses and fistulse, has been 
described. 
PARASITES. 
Echinococcus may occur in the tube. Oxyuris, also, has been found, 
the ova as well as the worms. 
Fig. 657.-Tuberculous Salpingitis. 
Small fibromata and fibromyomata sometimes occur in the wall of 
the tubes or in the fimbrise. Small lipomata and bits of adrenal tissue 
have been seen between the folds of the broad ligament in close connec- 
tion with the tubes. Papillomata of a benign nature probably do not 
occur. Myxoma is recorded Sarcoma is rare. 
Carcinoma of the tubes may be primary or secondary. Primary 
carcinoma,1 which is the most common tumor of the tube, begins as a 
papillomatous outgrowth, spreading in the tubal lumen. The tube is 
usually retort-shaped, its ostium closed. The growth may break through 
the tubal wall, extending to the peritoneum, or may, by metastasis, 
involve the uterus, ovary, or regional lymph-nodes. 
Histologically, a connective-tissue framework covered with a single, 
TUMORS. 
1 Doran, A., Jour. Obst. and Gynec., Brit. Emp., 1904, vi, 285; 1910, xvii, 1; Orthmann, E. G., Ztschr. 
f. Geburtsh. u. Gynak., 1906, Iviii, 376. 982 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
or more often, multiple layers of epithelium is encountered. The cells 
are of varying size and show irregular nuclei. In other areas, adenoma- 
tous configurations are assumed; in still other portions, solid cell masses 
invade the musculature. 
Secondary carcinoma of the tube originates from carcinoma of the 
uterus, ovary, or gastrointestinal tract (colloid cancer). 
Chorionepithelioma of the tube occurs, originating from an ectopic 
tubal pregnancy. The growth in its histological features is similar to 
chorionepithelioma elsewhere. 
Cysts, usually of small size, sometimes pedunculated and with thin 
walls, are frequently seen in the peritoneal covering of the tubes or in 
the fimbriae. They are believed to be of embryonal origin. Small col- 
lections of clear cells are occasionally found on the tubal surface. They 
may be adrenal in origin, but more frequently are derived from hyper- 
plasia of the peritoneal mesothelium (Fig. 658). 
Fig. 658.-Small, Cellular Masses of Mesothelial Origin on Peritoneal Surface of Fallopian 
Tube. 
Extrauterine Pregnancy. 
Tubal Pregnancy.1-The impregnated ovum, in some way hindered 
from passing into the uterus, may become fixed in the tube, and there 
develop (Fig. 659). The arrest of the ovum may be due to injury of 
the ciliated tubal epithelium from preceding inflammatory disease, to 
arrest in preformed diverticula,2 to distortion of the tube by external 
adhesions, tumors, etc. A few instances probably due to internal migra- 
tion (i.e., cases in which the ovum from the left ovary, for example, 
wanders through the right tube) have been reported. The extra time 
consumed permits the ovum to acquire the erosive properties which, 
under normal circumstances, it attains only after it has reached the uterus. 
The villi of the chorion grow into the mucous membrane of the tube, 
forming an incomplete placenta. 
1 For a very full discussion of the older literature on the subject of ectopic pregnancy, see Werth, R. 
Winckel, Handbuch d. Geburtshilfe, Wiesbaden, 1904, ii, Part 2, p. 1. 
2 Huffman, O. V., Surg., Gynec., and Obst., 1913, xvi, 548. THE REPRODUCTIVE ORGANS OF THE FEMALE 
983 
The placenta is incomplete because the tubal mucosa has neither the 
glandular elements nor the thickness of the uterine mucous membrane. 
Decidual reaction in the tube, when it does occur (and decidua can be 
detected in only a small number of cases) is incomplete. As the decidua 
is one of the strongest barriers against the invasion of the fetal elements, 
erosion of the musculature of the tubal wall is the common sequel of 
tubal nidation. For a similar reason, the fetal trophoblastic elements 
invade the maternal blood-vessels more freely than in intrauterine im- 
plantation (Fig. 660). 
The tubal pregnancy may develop in the interstitial, isthmic, or ampul- 
lary portion of the tube. As the ovum and its chorion enlarge, the 
Fig. 659.-Cross-section of Unruptured Ectopic Pregnancy. 
Masses of chorionic villi can be seen in the clot in the center of the tube. 
affected portion of the tube distends and forms a tumor of variable size. 
From lack of nutrition, the ovum may die at an early stage, and may 
form a blood mole. This is a rare outcome. 
More commonly, due to abundant erosion of blood-vessels, hemor- 
rhage into the tubal lumen takes place. The partly clotted blood flows 
or is expelled through the peritoneal ostium and collects around the tube. 
If the ovum also is expelled the condition is called a tubal abortion. If the 
bleeding continues, a hematocele, usually situated in Douglas's cul-de-sac, 
arises. The peritoneal irritation causes the formation of adhesions and 
shuts off the blood in a closed cavity, its walls formed by fibrin which 
may organize and produce a firm structure. The blood-clot may become 
infected, producing a secondary abscess. 
In about one-fourth of all cases, erosion of the tubal wall produces 984 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
tubal rupture. The large, torn blood-vessels of the placental site occasion 
severe intraperitoneal hemorrhage, which may prove rapidly fatal, or 
repeated smaller hemorrhages may lead to the same outcome. Inter- 
stitial pregnancies are especially prone to rupture. If the rupture takes 
place into the mesosalpinx an intraligamentary accumulation of blood 
results. 
Both tubal abortion and tubal rupture are most frequent between 
the fifth and seventh weeks of gestation. 
Exceptionally, the tube is not eroded and the placental circulation 
proves sufficient for the fetus. Under these circumstances, gestation 
continues to term within a dilated but unruptured tube. More com- 
monly, though still very rarely, the ovum is gradually extruded, either 
Fig. 660.-Ectopic Pregnancy. 
Trophoblastic elements in vessel in wall of tube. 
through the abdominal ostium or through a hole in the tubal wall, so 
slowly that it has the opportunity to form connections with neighboring 
organs. A secondary abdominal pregnancy, which may reach term, then 
ensues. The fetal membranes and placenta are agglutinated with the 
intestine, pelvic wall, uterine fundus, etc. When term is reached, the 
fetus dies, the amniotic fluid is absorbed, and the fetus may mummify and 
be impregnated with lime salts. This is termed a lithopedion. Such 
remains have been retained for long periods of years. At times they 
become infected and ulcerate through, and may be expelled per vaginam 
or rectum,. 
In tuboabdominal pregnancy the development of the ovum is in the THE REPRODUCTIVE ORGANS OF THE FEMALE 
985 
fimbriated extremity of the Fallopian tube. Adhesions are formed, so 
that the fetus is partly in the end of the tube and partly in the abdomen. 
Fig. 661.-Endometrium in Ectopic Pregnancy. 
Fig. 662.-Endometrium in Ectopic Pregnancy. 
Primary Abdominal Pregnancy.-The ovum, after escaping from 
the ovary, may not enter the Fallopian tube, but may become fixed to 
the peritoneum, usually near the ovary, and develop in that position. 
Ovarian Pregnancy.-The existence of this form of pregnancy is no 
longer doubtful. There are some cases in which the ovum develops in 
its Graafian follicle. In others, it develops extrafollicularly. 
(High power.) 986 
Simultaneous intra- and extrauterine pregnancies have been reported. 
Twin tubal pregnancies, either of the same or of both tubes, are 
on record. 
Hydatid mole and chorionepithelioma developing from tubal gesta- 
tion are known. 
The decidual reaction produced by tubal pregnancy is of interest. 
Quite regularly, though not invariably, a massive decidual change takes 
place in the uterine mucous membrane beginning about the second 
month of gestation (Fig. 661 and 662). The change may include the 
cervix. The accompanying hyperemia produces the irregular bleeding 
and "spotting" usually seen in ectopic pregnancy. Not infrequently, 
the 11 uterine cast" is expelled per vaginam, and is a fleshy, triangular sac, 
resembling that seen in dysmenorrhea membranes, formed by the super- 
ficial layers of the mucosa, and showing glandular changes of pregnancy 
and well-marked decidual reaction of the stroma. Islets of decidual 
cells may also be found in the ovary, peritoneum, appendix, etc., even 
more frequently than in intrauterine gestation. 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The Mamina. 
Embryology and Anatomy. 
At about the second month in the mammalian embryo there is a thickening of 
the ectoderm extending as a ridge on either side from the axillae to the groins. Soon 
this line, which is the anlage of the future mammary glands, is broken up into wart-like 
buds. Between the fourth and fifth months, the epidermis grows down into the con- 
nective tissue of the mammary area; these solid processes send off a number of sprouts 
which form the milk ducts and, finally by further growth and branching, the glandular 
tissue of the mamma. 
The acini are lined with a layer of cylindrical and an outer layer of cubical or 
flattened epithelium, and possess a membrana propria of connective tissue. The 
ducts have a flattened cell lining and a wall of connective and elastic tissue. The 
presence of muscle fibers in the walls of the ducts and acini is both affirmed1 and 
denied. 
The lacteal structures in the adult form only a small portion of the mamma in the 
resting phase, but during lactation there is a great increase in the size and number of 
the glands. The milk fat is brought to the breast in soluble form, and is secreted by 
the glandular epithelium in the form of granules which occupy all of the cell except 
the nucleus. The granules are extruded into the lumen of the alveolus, after which 
the cell regenerates.2 After lactation is completed, these glands largely regress. In 
the breast in which lactation is beginning or which is the seat of chronic cystic mastitis, 
the acini contain colostrum corpuscles, which are large cells filled with fat granules. 
They are either desquamated epithelium from the walls or phagocytic cells which 
have wandered into the ducts from without3 and collected the fat. The interstitial 
tissue is composed of coarse collagen fibers and but few nuclei. Fat tissue forms 
most of the bulk of the remaining structures of the lactating mamma. Numerous 
sweat and sebaceous glands are present about the nipple. 
At the menopause, there commences the process of senile involution, in which there 
is a gradual disappearance of the glandular structure, often with an increase of the 
adipose tissue in the breast.4 
1 Kuru, H., Deutsch. Ztschr. f. Chir., 1909, xcviii, 415. 
2 Arnold, J., Zieglers Beitr., 1905, xxxviii, 421. 
• Thomas, E., Ztschr. f. Kinderheilk., 1913, viii, 291. 
4 For normal histology, see Berka, Frankfurt. Ztschr. f. Path., 1911, viii, 203. THE REPRODUCTIVE ORGANS OF THE FEMALE 
987 
The mammary gland is inclosed in a capsule formed by two layers of fascia. It 
receives its blood supply from branches of the axillary, internal mammary, and 
intercostal arteries. The lymph-nodes receiving vessels directly from the breast are 
the axillary, retrosternal, retropectoral, supraclavicular, deep cervical, and paramam- 
mary. The axillary groups are most often invaded by carcinoma from the breast, 
the retrosternal chiefly in tumors of the inner quadrant; the retropectoral nodes are 
few in number and are not often invaded; the deep cervical are invaded in only a 
small percentage of carcinomata. The adjacent lymph-nodes which may become 
involved late in carcinoma of the breast are the axillary of the opposite side, diaphrag- 
matic, hepatic, supraxiphoid, upper brachial, intercostal, and inguinal. 
Physiology and Pathology of Function. 
The first sign of any activity in the mammary gland is frequently shown in both 
sexes within a few days after birth; at this time a few drops of a milk-like substance 
can often be expressed from the nipples, and this is frequently accompanied by a 
slight swelling and tenderness of the breasts. This "witch-milk" is composed largely 
of desquamated cells and degenerated products, and is not a true lacteal secretion.1 
From this time until puberty, the mammary glands are quiescent except in those 
occasional cases in very young girls where the breasts enlarge until they attain their 
full size and are even seen to functionate. Such conditions of infantile hypertrophy, 
however, are uncommon 
From puberty until the menopause, the glands functionate with the advent of each 
pregnancy, whether it proceed to term or not. There is often a slight premenstrual 
hyperemic increase in the size of the breasts, and rarely the appearance of small 
quantities of blood at the nipple (vicarious menstruation). At the termination of each 
pregnancy or lactation, the glands return to their normal non-functionating state. 
Arrest of develpoment of the mammae may occur alone or, more frequently, as a 
sequela to arrest of development of the other reproductive organs. This has 
repeatedly been shown when the ovaries have been removed before puberty. 
Failure of proper function of the thyroid or pituitary gland is often accompanied 
by imperfect sexual or mammary development. Excessive or perverted function 
of the pituitary or adrenal gland may cause premature enlargement of the breasts. 
Enlargement of the breasts and the secretion of milk has been observed to coincide 
with the occurrence of tumors of the ovary, especially of the malignant type. Con- 
versely, the removal of the ovaries may check for a few months or a year the growth 
of a carcinoma of the breast or the development of metastases. 
Malformations. 
Absence of one or both mammary glands is known as amastia and is noted in both 
sexes; together with undeveloped mammary glands, micromastia, it is an nucommon 
condition due to some developmental detect. Absence of one or both nipples, athelia, 
is a rare condition also. Supernumerary mammary glands, polymastia, at one time 
considered comparatively rare, are now known to be frequent; and the literature 
abounds with references to their occurrence in both sexes and on almost every portion 
of the body.2 In many cases these supernumerary glands are inactive, but in iemales 
they may become functionally active at each pregnancy and differ in no way from 
the normally situated glands; in the male also these glands may secrete milk. Ade- 
noma or carcinoma may develop in them. In the axilla the sweat and sebaceous 
glands may undergo hyperplasia during pregnancy and may closely simulate mam- 
mary tissue.3 The same condition may appear with acute infections of the axillary 
skin glands. When the glands assume an excessive size in the male, the condition is 
known as gynecomastia. 
Occasionally an extra nipple is found on a normal breast or elsewhere; this condi- 
tion is known as polythelia and is of great rarity, for supernumerary nipples are 
usually associated with polymastia. 
1 Raubitschek, H., Ztschr. f. Heilk, 1904, N. S. v, 16. 
2 Kayser, FArch. f. Gynak., 1908, Ixxxv, 459. 
3 Seitz, L., Arch. f. Gynak., 1906, Ixxx, 517; 1909, Ixxxviii, 94. 988 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
HYPERTROPHY. 
A few cases are reported in which hypertrophy of the breasts was 
present at birth. Hypertrophy of the adult mammary gland is not very 
rare, and is due to enlargement of the mammary tissue itself (Fig. 663). 
In some cases the breasts are of enormous size, and of very rapid growth. 
The condition is more often found in both breasts, though it has appeared 
as a unilateral hypertrophy in many instances. The hypertrophy may 
begin at puberty, but usually the change occurs during pregnancy or may 
follow it. Occasionally the hypertrophy disappears spontaneously. 
Nothing so far is known as to the cause of the condition.1 
Fig. 663.-Hypertrophy of the Mamma. 
Histologically the glandular parenchyma is increased as well as the 
stroma between the glands (Fig. 664 and 665). In size the breasts may 
vary from three or foui' times the normal to those reaching down to the 
knees; breasts extending to the umbilicus are not uncommon. Tumors 
within the breast causing enlargement must not be overlooked, and ele- 
phantiasis of the organ must be considered, especially in tropical countries. 
A few instances of extensive hypertrophy of the breast in the male, 
gynecomastia, have been reported. The condition develops about pu- 
1 For a study of hypertrophy of the breast, see Kirchheim, L., Arch. f. klin. Chir. (Langenbeck), 
1902, Ixviii, 582 (bibl.). THE REPRODUCTIVE ORGANS OF THE FEMALE 
989 
berty, and both sides are usually affected; it is occasionally accompanied 
by secretory activity. In some cases there has been an accompanying 
genital malformation which may have been the cause of the condition, 
From case shown in Fig. 663. Low power, showing topography. 
Fig. 664.-Hypertrophy of Mamma. 
Fig. 665.-Hypertrophy of Mamma. 
Showing structure of the enlarged breasts of Fig. 663. 
or a disease of the endocrine glands, which affects all of the generative 
organs.1 
1 For a very extensive study of these and other lesions of the breast, see Deaver, J. B., and McFarland, 
J., The Breast: Its Anomalies, Its Diseases, and Their Treatment, Philadelphia, 1917. The book 
contains an extensive bibliography, but unfortunately many of the references are incorrectly given. 990 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
HEMORRHAGE. 
In young women who suffer from amenorrhea or dysmenorrhea, small 
hemorrhages sometimes occur in the mammae at the time of menstrua- 
tion. The blood may find its way into the milk ducts and exude in 
small quantities at the nipple. 
Contusions of the breast may produce extravasations of blood in the 
mammary gland or the surrounding connective tissue. The blood may 
be absorbed, or may remain and be surrounded by fibrous tissue, or may 
be converted into cysts. 
In some cases of papillary cystadenoma of the breast, especially 
where the tumor has undergone a malignant change, there may be a 
hemorrhagic or serohemorrhagic discharge from the nipple.1 Hemor- 
rhage from the nipple is occasionally associated also with chronic mas- 
titis or cystadenoma when there has been extravasation of blood into a 
dilated duct. 
During lactation the nipple is liable to become inflamed, and ulcers 
and fissures may form. 
INFLAMMATION. (Mastitis.) 
Fig. 666 -Suppurative Mastitis in Non-functionating Gland. 
a, Milk duct; b, interstitial tissue; c, dense collections of pus; d, diffuse infiltration of lobule with pus. 
There is a form of eczematous inflammation of the nipple and areola 
which tends to ulcerate and in which carcinoma may occur. This is 
known as Paget's disease (see page 1009). 
Acute Exudative Inflammation. (Mastitis).-This occurs most fre- 
quently during lactation, being seen in about 4 per cent, of all parturient 
women. Occasionally this condition occurs during pregnancy, also, and 
1 Greenough and Simmons, Ann. Surg., 1907, xlv, 188; Lewis, D., Surg., Gynec., and Obst., 1916, 
xxii, 666. THE REPRODUCTIVE ORGANS OF THE FEMALE 
991 
even in women who are neither pregnant nor nursing. The portal of 
infection is the nipple. 
The process may involve the subcutaneous connective tissue, the 
gland itself, or the connective tissue between the gland and the wall of 
the thorax. The inflamed tissues are at first congested, swollen, hard, 
and painful. The inflammation often stops at this point, and resolution 
takes place if the retention of the milk be relieved and natural drainage 
of the gland tissue inaugurated; but occasionally it progresses to sup- 
puration. If the inflammation involve the subcutaneous connective 
tissue the abscess may be superficial and may soon open through the 
skin. If the gland be involved one lobule after another may become 
affected (Fig. 666), so that successive abscesses are formed. If the con- 
nective tissue beneath the gland be inflamed, a deep abscess of large size 
may be formed which usually perforates through the skin, but sometimes 
into the pleural cavity. In both these latter forms of abscess there is 
Showing dilatation of glands and cellular reaction in the connective tissue. 
Fig. 667.-Chronic Inflammation of Mammary Gland. 
apt to be necrosis of large portions of tissue. These abscesses may cica- 
trize, or they may pass into a chronic condition and remain for a long 
time as suppurating, fistulous tracts. Suppurative mastitis when in- 
volving the glandular tissue is usually due to the presence of the Staphy- 
lococcus aureus or albus, less often to the presence of a streptococcus; 
when the interstitial connective tissue is affected the streptococcus is 
usually responsible. 
In new-born children an acute mastitis may occur with painful swell- 
ing of the breasts, which usually subsides in a few days, but may go on 
to suppuration. 
Acute exudative inflammation may occur in a gland which is already 
the seat of chronic inflammation, and chronic mammary abscesses may 
be formed. 
Epidemic parotitis is sometimes complicated by mastitis. 
Chronic inflammation of the interstitial connective tissue of the mam- 
mary gland (Fig. 667) may follow acute processes or be chronic from the 992 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
onset. It leads to the formation of dense connective tissue, which re- 
places the destroyed parenchyma of the gland, and may or may not be 
Fig. 668.-Plasma Cells and Lymphocytes in Breast in Chronic Mastitis. 
Fig. 669.-Giant Cells Formed about Fatty Acids and Cholbsterin Crystals in Chronic 
Mastitis. 
Extensive lymphocytic infiltration surrounds the giant cells. 
associated with cystic dilatation of the milk ducts and extensive atrophy 
of the glandular elements. THE REPRODUCTIVE ORGANS OF THE FEMALE 
993 
If the fibrous hyperplasia is excessive, cystic dilatation of the smaller 
ducts may extend throughout the organ owing to obliteration of the 
lumen by pressure.1 Plasma and connective-tissue mast cells are often 
abundant in the interstitial tissue (Fig. 668). The collection of milk in 
the ducts or acini sets up irritative reactions (Fig. 669) and the separation 
of cholesterin in the contents of the broken down gland structures abets 
the process (Fig. 670). The epithelium may become atrophied or it may 
proliferate, and it frequently forms papillary projections into the dilated 
ducts. If this epithelial hyperplasia reaches any great extent it may be 
impossible to differentiate the lesions from a cystadenoma with secondary 
inflammation. This is the explanation of the confusion which long ex- 
isted in regard to the nomenclature of the lesion. Konig,2 considering 
the inflammation the most important, applied the name chronic mastitis, 
while Reclus3 and others4 thought that the glandular proliferative activi- 
Fig. 670.-Giant Cells about Cholesterin Crystals in Chronic Mastitis. 
ties were vital, and hence termed the disease maladie cystique or cyst- 
adenoma (page 997). 
Tuberculous inflammation of the mammary gland and its excretory 
ducts is of occasional occurrence. A primary infection of the breast, 
except in those rare cases in which the tubercle bacilli have gained en- 
trance through abrasion of the nipple, is denied by most authorities. 
The majority of cases of infection are secondary to a lesion situated else- 
where in the body, reaching the breast through the blood-vessels or 
lymphatics. The infection may be manifested in the form of miliary 
tubercles, larger and smaller caseous masses of new-formed tissue, a dif- 
fuse tuberculous fibrosis resembling carcinoma, a direct inflammation,5 
1 Ingier, A., Virchows Arch., 1909, cxcviii, 338. 
2 Konig, Centralbl. f. Chir., 1893, xx, 49. See, also, Lichtenhahn, F., Deutsch. Ztschr. f. Chir., 1907, 
xc, 507. 
3 Reclus, P., Rev. de chir., 1883, iii, 761; Gaz. d. hop., 1887, lx, 673, 769. 
4 Brissaud, Arch, de physiol, norm, et path., 1884, iii, 99; Schimmelbusch, C., Arch. f. klin. Chir. 
(Langenbeck), 1892, xliv, 117; v. Saar, G., ibid., 1907, Ixxxiv, 223; Theile, P., ibid., 1908, Ixxxviii, 261. 
For a study of this lesion with bibl., see Greenough, R. B., and Hartwell, H. F., Jour. Med. Research, 
1903, N. S. iv, 416; and Bloodgood, J. C., Surg., Gynec., and Obst., 1906, iii, 721. 
6 Halstead, A. E., and Le Count, E. R., Ann. Surg., 1898, xxviii, 685. 994 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
or cold abscesses.1 Fistulous connections with the breast or axillary 
node lesions occur in the late stages. Microscopically the lesions show 
no important differences from tuberculosis elsewhere in the body. 
A few cases of tuberculosis with adenoma or carcinoma of the breast 
have been reported, but the association is rare (Fig. 671).2 The possi- 
bility of a retrograde transport of the bacilli from the axillary lymph- 
nodes has been suggested.3 
Fig. 671.-Carcinoma and Tuberculosis of Mamma. 
The occurrence of these lesions together is unusual. 
Syphilis of the breast4 may occur as chancres, mucous patches, or 
gummata In very rare instances, the syphilitic process may consist only 
of a diffuse lymphocytic exudate with perivascular condensations, with 
accompanying endarteritis and swelling of the capillary endothelium. 
Such areas may be very hard, and the writer (Wood) has seen two 
specimens which had been excised for carcinoma. 
Actinomycosis5 may occur as a primary lesion of the breast, the in- 
fection gaining entrance probably through abrasions. It is seen also 
1 Scudder, C. L., Am. Jour. Med. Sc., 1898, cxvi, 75. 
2 Warthin, A. 8., Am. Jour. Med. Sc., 1899, cxviii, 25 (bibl.). 
3 Bundschuh, E., Zieglers Beitr., 1914, Ivii, 65. 
4 Deutsch, K., Wien. klin. Wchnschr., 1909, xxii, 127. 
6 Sehrt, E., Beitr. z. klin. Chir. (Bruns), 1907, Iv, 589: Risel, Verhandl. d. deutsch. path. Gesellsch., 
1909, xiii, 322. THE REPRODUCTIVE ORGANS OF THE FEMALE 
995 
following actinomycosis in other situations, in the pleura, for example, 
and probably reaches the breast through the lymphatics. The charac- 
teristic sulphur yellow granules may be found in pus from the lesions. 
A few cases of sporotrichosis have been reported.1 The disease is 
caused by a spore-bearing mycelium which reaches the breast through 
the nipple by metastasis. An inflammatory area is found at the portal 
of entrance, and an abscess which contains polymorphonuclear leucocytes 
and large phagocytes forms in the center; surrounding this there is an 
area composed of inflammatory tissue with tubercle-like formation. In 
the pus from the abscess the mycelium may be demonstrated by suitable 
stains. 
Sprue.-This fungus may develop in the tissue of the nipple in nursing 
women. 
Fibroma.-Circumscribed tumors composed solely of dense connec- 
tive tissue are very rarely found in the breast. In the nipple they occur, 
TUMORS. 
Fig. 672.-Intracanalicular Fibroma of Mamma. 
but very infrequently.2 In the usual type of fibroma the gland ducts 
and acini form a portion of the tumor. 
Intracanalicular Fibroma.--These tumors are formed by a diffuse pro- 
liferation of loose connective tissue, and a growth of polypoid fibrous 
tumors from the walls of the milk ducts into their cavities, leading to 
dilatation. The glandular acini may be atrophied, or enlarged, or cystic. 
A section of such a tumor looks like a solid mass of fibrous tissue, divided 
by clefts and fissures lined with cylindrical or cuboidal epithelium (Fig. 
672), or fibrous tissue containing cysts into which project polypoid fibrous 
i Quenu, Rev. de chir., 1914, xli, 585. 
2 Creite, Deutsch. Ztschr. f. Chir., 1911, cix, 199. 996 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
outgrowths from the walls. Sometimes the new-formed fibrous growths 
into the dilated ducts are adenomatous in character, containing many 
new-formed irregular acini (Fig. 673). Such tumors may be called 
Fig. 673.-Intracanalicular Fibroadenoma of Mamma. 
Showing new-formed gland acini in the fibrous-tissue mass growing into a duet. 
Fig. 674.-Pericanalicular Fibroma of Mamma. 
intracanalicular fibroadenomata. These tumors grow slowly, but if left 
to themselves may reach an enormous size. The skin over them may 
ulcerate and the tumor project through the opening in fungous masses. 997 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
They may be associated with interstitial fibrous hyperplasia of the gland, 
and sarcoma occasionally develops in them.1 Wandering cells of various 
types are formed in the connective tissues, especially plasma cells and 
connective-tissue mast cells. There may be much mucoid material be- 
tween the collagen fibers. The fat cells also may join in the hyperplasia, 
forming large multinucleated cells which have lead to an erroneous diag- 
nosis of sarcoma or tuberculosis. 
Pericanalicular Fibroma.-Sometimes the new connective tissue forms 
a more or less thick cylindrical investment of the duct without growing 
into its lumen. This formation (Fig. 674) is sometimes called peri- 
canalicular fibroma. 
Cystadenoma.2-This form of breast tumor is of great clinical impor- 
tance as not infrequently it forms the starting point for carcinoma. It 
has been variously called chronic cirrhosing mastitis (Billroth), chronic 
Fig. 675.-Papillary Cystadenoma of Mamma. 
interstitial mastitis (Bryant), cystadenoma (Schimmelbusch), cystic dis- 
ease of the breast (Reclus), and chronic cystic mastitis (Konig). This 
complexity of nomenclature has been previously mentioned (page 993) 
as due to the fact that the lesion varies greatly from case to case. 
These tumors are most frequent about the time of the menopause, 
but they may occur before the age of twenty. Grossly, the breasts are 
usually not greatly increased in size, but one or often both may be more 
or less filled with a flat cake-like hard mass, on the surface of which are 
often palpable small elastic masses which are thin-walled cysts. These 
cysts may occupy a large part of the breast, or the breast may be ex- 
tremely firm and hard with or without very minute cysts. Large or 
small papillary outgrowths may more or less fill the cysts. When the 
papillary growths form a large part of the tumor mass, the name papillary 
1 Speese, Ann. Surg., 1910, li, 212; Prym, Frankfurt. Ztschr. f. Path., 1912, x, 60. 
2 Tietze, Deutsch. Ztschr. f. Chir., 1904, Ixxv, 117; Berka, Zieglers Beitr., 1912, liii, 284; v. Saar, 
Arch. f. klin. Chir. (Langenbeck), 1907, Ixxxiv, 223 (bibl.). 998 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
cystadenoma is employed (Fig. 675). The tumor may be solid through- 
out or may be composed of discrete nodules. 
Fig. 676.-Cystadenoma of Mamma. 
Showing masses of epithelium in the alveoli, and small cysts. 
Fig. 677.-Giant Cells and Connective-tissue Reaction in Cystadenoma of Breast. 
The connective tissue may be dense and fibrous with very few nuclei; 
it may be infiltrated with cells of lymphoid type (Fig. 676); rarely it may THE REPRODUCTIVE ORGANS OF THE FEMALE 
999 
Fig. 678.-Adenomatous Type of Gland with a Few Small Cysts. 
Senile type of cystadenoma. 
Fig. 679.-Cystadenoma of Mamma. 
Papillary outgrowths of epithelium in dilated glands. 1000 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
show mucoid degeneration. When the inflammatory phase of the growth 
is predominant, the free fat and fatty acids from the retained milk give 
rise to extensive cellular reactions of either spindle-cell or lymphoid-cell 
type with giant-cell formation. Such lesions are often erroneously con- 
sidered as tuberculous (Fig. 669 and 677). The morphology of the epi- 
Fig. 680.-Cystadenoma of Mamma. 
Wall of acinus lined with duct epithelium. 
thelium is most variable, covering all varieties between the adenomatous 
type with glands not far from normal, some of which properly belong to 
senile involution changes (Fig. 678); glands having a number of layers 
of epithelium such as are frequently found in senile breasts; glands 
dilated with papillary projections of epithelial cells from the walls (Fig. 
Extensive hyperplasia of the lining epithelium of the glands, but without breakdown of the basement 
membrane. 
Fig. 681.-Cystadenoma of Mamma. 
679 and 680); and, finally, glands which are entirely filled with solid 
masses of epithelium (Fig. 676). While these masses are very suggestive 
of carcinoma, they can usually be distinguished by the fact that the 
nuclei are not hyperchromatic and show no mitoses, and that the cells do 
not pass beyond the basement membrane into the surrounding tissues THE REPRODUCTIVE ORGANS OF THE FEMALE 
1001 
Proliferation of the epithelium lining the ducts, with slight inflammatory reaction surrounding the 
altered glands. 
Fig. 682.-Cystadenoma of Mamma. 
Fig. 683.-Fibroadenoma of Mamma, very Cellular, Resembling Carcinoma. 1002 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
(Fig. 681 and 682). When there is much inflammation, however, the 
sharp outline of the membrane is often obliterated and the cells look as 
though they were invading the surrounding tissues; but even this picture 
may be seen in tumors which are still benign. The only certain evidence 
Wall of acinus lined with irregular epithelial cell masses. 
Fig. 684.-Cystadenoma of Mamma. 
of malignancy is the presence of cells as individuals or groups in the con- 
nective tissue at a considerable distance from the gland in question. 
Occasionally one will meet with a tumor of this type in which cells 
greatly resembling cancer cells are found distributed throughout the 
connective tissue (Fig. 683). On careful inspection, however, these are 
Fig. 685.-Colostrum Cells Filling Duct in Cystadenoma of Mamma. 
found to resemble more closely the connective-tissue cells or endothelial 
cells. The writer (Wood) has seen a number of such suspicious cases in 
which no axillary involvement was found, and no recurrence followed 
simple operative removal of the tumor, which is some evidence, though 
not final proof, that the growth was not carcinomatous. THE REPRODUCTIVE ORGANS OF THE FEMALE 
1003 
Another type of cyst has been considered either as lined with duct 
epithelium or as derived from sweat glands1 (Fig. 684). 
These new-formed acini, while maintaining the gland character, are still quite atypical in form and 
grouping and in the irregularity of the epithelium. 
Fig. 686.-Adenoma of Mamma. 
Fig. 687.-Adenoma of Mamma. 
1 Krompecher, E., Zieglers Beitr., 1908, xliv, 51, 88; Verhandl. d. deutsch. path. Gesellsch., 1913, 
xvi, 365; v. Saar, Ergebn. d. Chir. u. Orthoped., 1910, i, 413, also believes that they have their origin 
in the sweat glands. 1004 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
In this type of cyst also there may be budding of the lining epithelium 
(Fig. 685). The wall is lined with high cylindrical epithelium which 
takes a deep stain with eosin and has a small nucleus, rather poor in 
chromatin. The cells are entirely different in appearance from those of 
the glands of the breast. There may be papillary projections into the 
lumina, also. 
A third form is occasionally seen, in which the gland is entirely filled 
with large foam or colostrum cells (Fig. 685), evidently derived from the 
wall of the gland and corresponding to the milk cells of the secreting 
breast; in some instances they may be cells in which lipoid material has 
developed during the course of degeneration. 
A case of cystic adenoma with ciliated epithelium has been described.1 
Adenoma and fibroadenoma are composed of glandular acini and 
ducts surrounded by connective tissue, and are the most frequently occur- 
Fig. 688.-Calcification of Inflammatory Exudate in the Breast with Foreign Body Giant 
Cells. 
ring growths of the mamma (Fig. 686 and 687). These tumors are usu- 
ally referred to as fibroadenoma,2 for a pure adenoma composed only of 
glandular tissue is of rare occurrence.3 They are either single or multiple, 
or several may be developed successively in the same breast. They 
grow, as a rule, at first slowly, afterward more rapidly. Their structure 
may be further complicated by the dilatation of one or more of the ducts 
which compose the tumor into cysts, and the ingrowth of connective 
tissue from the walls of these cysts. 
Myxoma.-This may be a circumscribed growth replacing part of the 
mamma, or it may form in the same way as the intracanalicular fibro- 
mata. It is composed of a fibrous connective tissue filled with mucin. 
True myxomata of the breast are uncommon, but in the intracanalicular 
tumors there may be found a combination of fibrous, mucous, and sar- 
comatous tissue (adenomyxosarcoma). 
i Buday, K., Virchows Arch., 1899, clvi, 395. 
2 Berka, Zieglers Beitr., 1912, liii, 284. 
3 Kuru, H.. Deutsch. Ztschr. f. Chir., 1909, xcviii, 415. THE REPRODUCTIVE ORGANS OF THE FEMALE 
1005 
Osteoma and chondroma are rare forms of tumors in the mamma. 
The osteomata may consist of osseous tissue alone or may contain bone- 
marrow. Chondromata may consist solely of cartilaginous tissue, or of 
both bone and cartilage, osteochondroma.1 The origin of such heter- 
ologous masses is generally assumed to be due to metaplasia of the con- 
nective tissue, but may be explained also as a congenital dislocation of 
embryonic structures from the ribs. Calcification of inflammatory tis- 
sue must be distinguished from true bone formation (Fig. 688). 
Lipoma consists of adipose tissue, and may be intraglandular or ex- 
traglandular. Unusually large tumors of the breast have been reported, 
weighing up to twenty-five pounds. The tumors may be bilateral; and 
Fig. 689.-Fat Tumor of Breast Following Blow. 
The tumor is largely composed of newly formed fat cells, cholesterin crystal and fatty acid giant cells. 
they may also be multiple, and are, as a rule, encapsulated. They are 
often mistaken for cysts owing to the fluctuation noticeable on palpation. 
After a blow an inflammatory reaction may be set up in the fat tissue 
of the breast with active regeneration of fat, and the formation of a 
considerable mass of firm tissue which has been mistaken, even micro- 
scopically, for carcinoma (Fig. 689). 
Myoma2 may arise from the unstriated muscle cells found in the 
nipple. 
Angioma of the mammary gland may be composed of blood-vessels 
or lymph-vessels, though the latter type is very rare. 
1 Cornil, Les Tumeurs du Sein, Paris, 1908. 
2 Lindfloss, Monatschr. f. Geburtsh. u. Gynak., 1900, xi, 763. 1006 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Sarcoma of the breast1 is rare, being estimated to form only 2 to 3 
per cent, of all breast tumors. The neoplasms are sometimes limited, 
tending to displace the gland rather than to infiltrate it; or they may 
develop in a nodular or diffuse form, so that the entire gland may be 
replaced by the growth; in other cases the sarcoma may arise in intra- 
canalicular growths. The tumors are composed most frequently of 
round or spindle cells; the giant-cell types are rare (Fig. 690). When 
the growths become large they often ulcerate. Metastasis in the axillary 
lymph-nodes, while it does occur, is very infrequent, the usual path being 
through the blood-vessels, as with sarcoma in general. 
Among the rarer types of sarcoma are the melano sarcomata, the richly 
vascular angiosarcomata, chondrosarcomata,2 and osteoid sarcomata,3 as 
Fig. 690.-Sarcoma of Mamma, giant-cell, Type. 
well as complex tumors containing muscle fibers, and carcinosarcomata, 
either as separate tumors4 or mixed.5 
Cholesteatomata have been occasionally found;6 and chloromata and 
leukemic tumors7 of the breast have been reported as secondary deposits. 
Carcinoma of the mamma is most common in women between the 
ages of thirty-five and fifty-five, as is sarcoma, though it has been reported 
as early as the eleventh year and also in very elderly persons. It is more 
1 Finsterer, J., Deutsch. Ztschr. f. Chir., 1907, Ixxxvi, 352; Rohdenburg, G. L., Proc. New York Path. 
Soc., 1917, xvii, 112. 
2 St. Arnold, Virchows Arch., 1897, cxlviii, 449 (bibl.). 
3 Stilling, Deutsch. Ztschr. f. Chir., 1881, xv, 247; Hueter and Karrenstein, Virchows Arch., 1906, 
clxxxiii, 495; Sehrt, Beitr. z. klin. Chir. (Bruns), 1907, Iv, 574. 
4 Schlagenhaufer, Centralbl. f. allg. Path., 1906, xvii, 385. 
3 Orth, J., Charit6-Ann., 1910, xxxiv, 357; Krompecher, E., Zieglers Beitr., 1908, xliv, 88 (bibl.). 
• Konjetzny, G. E., Beitr. z. klin. Chir. (Bruns), 1912, Ixxviii, 504; Stoerlc and Erdheim, Wien. klin. 
Wchnschr., 1901, xvii, 358. 
7 McWilliams, C. A., and Hanes, F. M., Am. Jour. Med. Sc., 1912, cxliii, 518. THE REPRODUCTIVE ORGANS OF THE FEMALE 
1007 
frequent in the unmarried. While it occurs in either breast, though in 
the right rather more frequently than in the left, it is rare that both 
Fig. 691.-Gelatinous Cabcinoma of Mamma with Laminated Calcified Masses Scattered 
THROUGH THE TUMOR. 
Fig. 692.-Lymphoid Infiltration about Alveoli of a Slow Growing Keratinizing Carcinoma 
of Mamma. 
breasts are involved. Carcinoma of the male breast forms about 2 per 
cent, of all mammary carcinomata. 
Carcinoma generally begins as a small circumscribed nodule, situated 1008 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
most frequently in the upper outer quadrant of the gland. The cells 
may remain confined to the alveoli for a time and invasion of the sur- 
rounding connective tissue, lymphatics, and veins may occur late. Such 
outgrowths may, however, occur very early when the tumor is small, 
occasionally not more than a centimeter in diameter, and extensive in- 
vasion of the nodes may be an early occurrence also. The cells of the 
tumor may be small or large; they may keratinize. The adenomatous 
type is not frequent, but may metastasize into the nodes and preserve 
its morphology. The squamous-cell type arises most often in the nipple 
or from the ducts. Its metastases also are of squamous keratinizing 
cells. The gelatinous form may calcify (Fig. 691). 
Fig. 693.-Gelatinous Carcinoma of Mamma (Carcinoma Myxomatodes). 
Of ten years' duration without metastasis. 
Lymphoid infiltration of the fibrous tissue of the breast is most fre- 
quent and extensive in the slow growing types (Fig. 692), and may be 
absent in the medullary forms. Mucoid degeneration of the connective 
tissue is often seen. 
The tumor enlarges and involves more and more of the breast. Some- 
times it is diffuse from the first, and sometimes it begins in the nipple. 
All the adjacent tissue may become infiltrated including the axillary and 
cervical nodes. The axillary nodes may be involved very early and by 
the end of a year are almost invariably the seat of disease, and from here 
metastatic tumors are formed in different parts of the body.1 The ex- 
1 For a study of dissemination of carcinoma of the breast, see Stiles, H. J., Brit. Med. Jour., 1899, 
i, 1452; and Handley, W. S., Cancer of the Breast, London, 1906. tension of carcinoma may take place by transference of the cells through 
the main lymph-channels, by growth or ameboid wandering of cells 
along the smaller lymphatic vessels, and by way of the blood-stream. 
The medullary form of carcinoma is the most malignant, next in 
order of malignancy being carcinoma simplex, scirrhus, adenocarcinoma, 
and squamous-cell and colloid or gelatinous carcinoma. Unfortunately, 
the colloid or gelatinous type, the least malignant (Fig. 693), is also the 
most rare, occurring in about 1 per cent, of all cases, while the medullary 
and the carcinoma'simplex forms are the most common. The relative 
rate of metastasis formation seems to be dependent somewhat upon the 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
1009 
The nipple is retracted by the shrinkage of the fibrous tissue. The growth is extending along the 
fibrous bands of the mammary fat and at the left has reached the plane of excision. The darker portions 
in the figure are lobules of fat. 
Fig. 694.-Cabcinoma of Mamma-Fibrous Type-Scirbhus. 
size of the cells, a small-cell scirrhus (Fig. 694) metastasizing much 
earlier and more extensively than a large-cell medullary carcinoma. 
Cancer en cuirasse is a condition in which there is extensive superficial 
involvement of the chest, shoulder, and arm with carcinoma. 
Paget's disease1 is an eczema around and involving the nipple, which 
it eventually destroys. When it has existed for a long period, it is com- 
monly followed by squamous or glandular carcinoma in the neighboring 
breast tissue. Many of the cases clinically diagnosticated as Paget's 
disease and treated disastrously with salves or radiation, are actually 
from the beginning either carcinomata of the ducts leading to the nipple 
1 Jopson, J. H., and Speese, J., Ann. Surg., 1915, Ixii, 212. 1010 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
with secondary invasion of the skin, or primary epitheliomata of the 
areola; in fact, the opinion is gaining ground that the eczema is in 
many instances secondary to a slow growing carcinoma arising from 
the ducts.1 Microscopically the tumor cells are often found to have 
invaded the lymph-channels at the base of the epidermis and there 
given rise to pictures which have been mistaken for parasites. 
All cases of chronic eczema of the nipple which do not heal after a 
few weeks' treatment should be considered carcinomata. 
Cysts of the mamma seem to be for the most part retention cysts, 
formed by the dilatation of the gland ducts or acini. During lacta- 
tion such retention cysts are sometimes formed, and then contain milk.2 
If retained for a long period the milk becomes inspissated to form a 
yellowish greasy mass, the so-called butter cysts of the breast.3 They 
may reach an enormous size. At other times retention cysts are formed 
containing serous or viscid, brownish fluid, which often exudes through 
the nipple. These cysts may be large or small, single or multiple. There 
are usually at the same time some growth and induration of the con- 
nective tissue of the gland. In some cases there are polypoid outgrowths 
of connective tissue from the wall of the cyst. These cysts are not to be 
confounded with the cysts which are developed with the intracanahcular 
tumors, described above. 
Sebaceous cysts, dermoid cysts, and hydatid cysts of the breast have 
been described.4 
1 Handley, W. S., Lancet, 1917, i, 519. 
2 Nordmann, A., Virchows Arch., 1897, cxlvii, 475. 
3 Rogowitsch., N., Zieglers Beitr., 1895, xviii, 487: and Samelson-KliwansKy, L., Virchows Arch., 
1905, clxxix, 76. For an analysis of the fat content of these cysts, see Wells, H. G., Chemical Pathology, 
Philadelphia, 1918, p. 515. 
4 For a study of cysts of the breast, see Bloodgood, J. C., Bull. Johns Hopkins Hosp., 1907, xviii, 139. CHAPTER XI. 
REPRODUCTIVE ORGANS OF THE MALE. 
The Penis. 
The penis may be absent with great defects of development of the rest of the body. 
The urethra then usually opens into the rectum. In rare instances a double penis 
is present. 
An abnormally small penis may be associated with absence or arrested develop- 
ment of the testicles. The prepuce may be rudimentary or absent. 
Congenital phimosis is not uncommon. 
Hypospadias is an arrest of development of the penis and scrotum. In its high- 
est degree the penis is short, the glans penis small. On the lower side of the penis is a 
deep cleft lined with mucous membrane, into which the urethra opens at the root 
of the penis. The scrotum remains separated into two parts, resembling labia 
majora. The testes may descend into their proper position on each side or remain in 
the abdomen. If the testicles continue to develop normally the individual has the 
appearance and capacities of a man; if their development is arrested the individual 
is apt to be of feminine type. 
In lesser grades of hypospadias the two parts of the scrotum are joined and the 
penis is larger, but a part of the urethra remains open as a cleft at some point of the 
penis. 
Epispadias is an opening of the urethra on the upper side of the penis. It pre- 
sents various grades and forms.2 
Hermaphroditism.-This is a union of two sexes in the same person, the test of 
which is the presence of the secreting organs, the ovaries and testicles. True her- 
maphroditism may perhaps occur, although most of the conditions called hermaphro- 
ditism are in reality due to varying malformations of the external generative organs. 
Pseudohermaphroditism.-In the male, normally, the greater part of Muller's 
canal disappears and its lower end forms the vesicula prostatica. In this malforma- 
tion Muller's canal is changed, as it is in the female, into Fallopian tubes, uterus, and 
vagina, while at the same times the testes, epididymides, vesiculae seminales, and 
spermatic cord are formed as usual. In the lesser degrees of this malformation we 
find, in the place of the vesicula prostatica, a pear-shaped sac as large as a pigeon's egg, 
with muscular walls and an epithelial lining. This sac may be incompletely divided 
into a uterus and vagina, and open into the urethra. In the higher grades we find 
a well-formed vagina and uterus. The uterus may or may not have Fallopian tubes. 
The testicles are usually retained in the abdomen or inguinal canals, and are small. 
The spermatic ducts run on the sides of the uterus and open into the urethra or are 
closed. The penis and scrotum appear as in hypospadias, or are well formed. The 
appearance of the individual varies with the development of the testicles. 
True Hermaphroditism.-There is considerable doubt as to the existence of true 
hermaphroditism, that is, in the sense that a person possesses separate and normally 
functionating male and female glands.3 
Malformations.1 
i Foi* a detailed consideration of the malformations of the male generative organs, consult Klebs, 
Handbuch d. pathologischen Anatomie, Berlin, 1873; v. Neugebauer, Hermaphroditismus beim Men- 
schen, Leipzig, 1908; Kermauner, Schwalbe, Die Morphologic der Missbildungen des Menschen und 
der Tiere, Jena, 1909, iii, 41; and Sauerbeck, Frankfurt. Ztschr. f. Path., 1909, iii, 339, 661, 829. 
2 For details of these malformations, see Kaufmann, Lehrbuch d. pathologischen Anatomie, 6th ed., 
Berlin, 1911, p. 900. 
3 For a discussion of the older classification, see Kaufmann, Lehrbuch d .spez. path. Anatomie, 
Berlin, 1911, ii, 904. 
1011 1012 
REPRODUCTIVE ORGANS OF THE MALE 
Enlargement of the penis is sometimes caused by venous congestion from 
heart disease; by long-continued masturbation, as a result of which the corpus caver- 
nosum may lose its contractility; and in rare cases by hyperplasia of the stroma of the 
corpus cavernosum. Continuous erection is seen occasionally in myelogenous leu- 
kemia, and is probably due to thrombosis of the veins or of the sinuses. The phe- 
nomenon is met with, also, in infectious diseases and in metastatic tumors of the penis.1 
INJURY AND HEMORRHAGE. 
Injuries to the penis are liable to give rise to severe hemorrhage on 
account of its peculiar vascular character; suppurative inflammation, 
gangrene, infiltration with urine and its consequences, are also liable to 
occur. The contractions of the cicatricial tissue by which wounds are 
healed frequently give rise to various distortions of the organ. 
INFLAMMATION. 
Balanitis-inflammation of the glans penis and the prepuce-is 
usually due to gonococcal or syphilitic infection, or it may be incited 
by foul accumulations of smegma. The parts are red and swollen and 
may ulcerate. Condylomata may be formed, and adhesions between 
the prepuce and glans. The glans may ulcerate and the prepuce may 
be much thickened. If the prepuce be long, phimosis may occur with 
the accumulation of exudate beneath. The prepuce may become 
gangrenous. 
Paraphimosis is produced by the retraction of a narrow prepuce be- 
hind the glans, with consequent stricture, inflammation, and sometimes 
gangrene. 
Inflammation of the Corpora Cavernosa may be the result of injury, 
may follow fistulse, may occur in connection with inflammation of the 
connective tissue of the penis, and may accompany the acute infectious 
diseases. It may result in fibrous induration of portions of the corpora 
cavernosa; rarely in abscess or diffuse purulent infiltration; sometimes 
in gangrene Larger and smaller masses or plates of very dense fibrous 
tissue sometimes form in the sheath of the corpora cavernosa without 
history of antecedent lesion.2 
Tuberculous Inflammation of the penis has repeatedly followed 
ritualistic circumcision performed by persons suffering from pulmonary 
tuberculosis. The presence of acid-fast bacilli (smegma bacilli) in the 
sebaceous secretion of the preputial glands and in the urethra is a reason 
for great caution in diagnosing tuberculosis from the presence of bacilli 
alone. 
Syphilitic Ulcers frequently occur in the glans penis and prepuce. 
The indurated chancre is derived either from an excoriation in which 
a pustule is formed or from a little nodule. The pustule breaks and 
its walls are infiltrated with small round cells. The nodule softens, 
breaks down, and forms an ulcer whose walls are infiltrated with cells, 
1 Blum, V., Wien. klin. Wchnschr., 1906, xix, 1133; Rosenthal, F., Berl. klin. Wchnschr., 1910, xlvii, 
147. 
2 For a study, with bibl., of indurations in the corpora cavernosa penis, see Sachs, M., Wien. klin. 
Wchnschr., 1901, xiv, 999. REPRODUCTIVE ORGANS OF THE MALE 
1013 
and whose vessels have the characteristic perivascular lymphatic infil- 
trations. Syphilitic condylomata occur frequently on the glans. 
Soft chancre may occur on the prepuce or glans, and is often accom- 
panied by suppurative inflammation of the inguinal nodes (bubo). The 
streptobacillus of Ducrey may be demonstrated in the pus. 
Herpes of the prepuce occurs in the form of small vesicles, which may 
later become ulcers. Erysipelatous and furuncular inflammation some- 
times involves the skin of the penis. 
TUMORS. 
Papilloma is found on the prepuce and glans penis. It occurs in the 
form of little warty growths (condylomata acuminata), or of composite, 
cauliflower masses, even as large as a fist. In either case the structure 
is the same-hypertrophied papillae covered with epithelium. Some- 
times the epithelial layers become thick and horny, forming large, dense 
projections. Papillomata may become malignant and invade the glans 
and the inguinal nodes. 
Fibroma diffusum, or elephantiasis of the prepuce, may occur, leading 
to great thickening. It is due to a diffuse growth of fibrous tissue in the 
cutis. Lipoma, angioma, circumscribed fibroma, and sebaceous cysts may 
occur in the penis. Carcinoma, which is most frequent in the prepuce 
and glans penis, is usually of the epitheliomatous type, and may have 
the form of a flat ulcer, or of infiltrating, ulcerating nodules, or may be 
papillary. Such growths may attain great size, ulcerate, or undergo a 
variety of inflammatory changes. Carcinoma may involve the entire 
skin of the penis or may invade deeper parts; the inguinal glands may be 
involved. Distant metastases are not frequent Medullary or gland- 
ular carcinoma of the penis is not common. It may be secondary to 
carcinoma in some other part of the body.1 
Sarcoma of the vascular2 and melanotic types3 occurs in the penis. 
Dermoid tumors of the penis are of occasional occurrence.4 
Calcification and ossification of the connective tissue of the corpora 
cavernosa sometimes occur.5 Large and small preputial calculi are occa- 
sionally found between the prepuce and the glans. These may be formed 
in situ, may come from the bladder or from without, and may later 
increase in size. 
The Scrotum. 
The skin of the scrotum is subject to the various types of lesions 
which may occur in any part of the integument. 
Elephantiasis of the scrotum consists in the main of a development of 
new connective tissue in the cutis, which is sometimes accompanied by 
dilatation of the lymph-vessels; thus the thickened scrotum may form a 
1 Kiittner, Beitr. z. klin. Chir. (Bruns), 1900, xxvi, 1. 
2 C aimers, F., Zieglers Beitr., 1903, xxxiv, 295; Borrmann, R., Lubarsch-Ostertag, Ergebn. d. allg. 
Path., 1900, vii, 833. 
3 Payr, Deutsch. Ztschr. f. Chir., 1899, liii, 221. 
1 Gerulanos, Deutsch. Ztschr. f. Chir., 1900, Iv, 326. 
6 zur Werth, M., and Scheele, K., Deutsch. Ztschr. f. Chir., 1913, cxxi, 298. 1014 
REPRODUCTIVE ORGANS OF THE MALE 
large tumor, often rough upon the surface, which may entirely cover in 
the penis. 
TUMORS. 
Lipoma and fibroma occur. Epitheliomata, in the form of flat or 
papillary ulcerating tumors, are of frequent occurrence among chimney 
sweepers1 and coal tar workers, and may lead to extensive ulcerations of 
the adjacent parts and involvement of neighboring lymph-nodes. 
Dermoid Cysts and Teratomata of the scrotum are not uncommon. In 
very rare cases tumors containing a considerable portion of a fetal skele- 
Fig. 695.-Undescended Testicle in an Hermaphrodite of Female Type. 
Showing atrophy of the tubules and retention of the interstitial cells. 
ton have been found in the scrotum. Occasionally the skin of the scro- 
tum is beset with numerous larger and smaller sebaceous cysts, which 
raise the surface into little globular or wart-like projections. 
The Testicles. 
Malformations. 
Absence of both testicles, either with or without absence of the epididymides, 
spermatic cords, and vesiculse seminales, occurs in rare cases. The scrotum is only 
indicated or may contain the epididymides. The penis is small, and the individuals 
are small and poorly developed. 
1 Butlin, H. T., Brit. Med. Jour., 1892, i, 1341; ii, 1; Morley, J., Lancet, 1911, ii, 1545. REPRODUCTIVE ORGANS OF THE MALE 
1015 
The testes may be imperfectly developed. The individuals are effeminate 
Absence of one testicle with healthy development of the other, is more frequent 
The corresponding epididymis and cord may be absent or present. 
The spermatic cords and vesiculse seminales may be absent or imperfectly devel- 
oped on one or both sides, while the testes are normal. 
Cryptorchismus.-Either one or both testicles may remain permanently in their 
fetal position, or may not descend into the scrotum for several years after birth 
{cryptorchismus), or not at all. This condition, which occurs in about two per thou- 
sand of healthy males, may be due to an arrest of development in the testes or the 
gubernaculum testis; adhesions produced by 
antenatal peritonitis; narrowing of the in- 
guinal canal; narrowing or shortening of the 
vaginal process of the peritoneum; or to ab- 
normal size or position of the testicle. Usu- 
ally the malformation is confined to one tes- 
ticle, and then is more frequent on the left 
side. The testicle is usually found in the 
abdomen close to the mouth of the inguinal 
canal, or in the inguinal canal just below the 
external ring; but it may be beneath the skin 
in the perineum, or in the crural canal with 
the femoral vessels, or elsewhere. Hernia is 
present in half the cases. The retained 
testis is usually not fully developed, or un- 
dergoes fatty degeneration or fibrous hyper- 
plasia. The interstitial cells are often in- 
creased, and may even form macroscopic 
nodules (Fig. 695).1 The retention of one 
or even of both testicles does not preclude 
the possibility of procreation. Retained 
testicles are prone to inflammatory changes; 
they early lose the capacity to furnish sper- 
matozoa, and are liable to become the seat of 
malignant tumors.2 
Sometimes, while the testis is retained, the 
epididymis and spermatic cord descend into 
the scrotum. In rare cases the position of 
the testis may be changed so that the epi- 
didymis and cord are in front. The occur- 
rence of supernumerary testicles is described. 
In varicocele the veins of the spermatic 
cord are dilated, often forming tortuous 
masses of considerable size (Fig. 696). 
Varicocele. 
Hydrocele. 
The distended and tortuous vessels have 
been filled with wax. 
Fig. 696.-Varicocele. 
In hydrocele of the tunica vaginalis there 
is an accumulation of fluid in the cavity of the sac. It is usually unilateral and is 
commonly associated with acute or chronic inflammation of the tunica vaginalis, 
varicocele, or general dropsy. The serum is present in small or in large quantity; 
it is usually transparent, may contain cholesterin, or be purulent or mixed with 
blood. The tunica vaginalis remains unchanged, or is thickened, or contains plates 
of bone, or is covered with polypoid fibrous bodies which may fall off and be found 
1 Odiorne and Simmons, Ann. Surg., 1904, xi, 962. 
2 For histology of undescended testicle, see Vffreduzzi, Arch. f. klin. Chir. (Langenbeck), 1913, c, 
1151; and ci, 150. For a study of malignant tumors of the undescended testicle, see Bulkley, Surg., 
Gynec., and Obst., 1913, xvii, 703 (bibl.); see also, Butt, ibid., 1914, xix, 419. 1016 
REPRODUCTIVE ORGANS OF THE MALE 
free in the cavity of the sac. There may be adhesions between the layers of the tunica 
vaginalis, and in this way the fluid becomes sacculated. The testis is pushed down- 
ward and backward; it remains unchanged or is atrophied. 
In hydrocele of the processus vaginalis there is an accumulation of serum in the 
cavity of the vaginal process of the peritoneum, which remains open after the descent 
of the testicle. There are several varieties. 
(a) The vaginal process is entirely open and there is a free communication with 
the peritoneal cavity. The serum may originate in the cavity of the peritoneum or 
of the vaginal process, and passes freely from one to the other. 
(6) The processus vaginalis is closed in the inguinal canal, while its lower portion 
is filled with serum. 
(c) The processus vaginalis is closed about the testis and the visceral layer of the 
tunica vaginalis is formed. The serum accumulates in the upper part of the vaginal 
process which communicates with the peritoneal cavity. 
(d) The vaginal process is closed in the inguinal canal and over the testis; the 
serum accumulates so as to form one or more sacs between these two points. Inguinal 
hernia may complicate this form of hydrocele. 
In hydrocele of the spermatic cord there is general edema or the development of 
circumscribed cysts in the connective tissue of the cord. 
A peculiar type of hydrocele is formed by the accumulation of serum in the sac of 
an inguinal hernia from which the intestine has become retracted. 
Hematocele. 
In hematocele of the tunica vaginalis there is an effusion of blood into the cavity 
of this sac. It may occur in injury, in scurvy, or with the hemorrhagic diathesis, or 
it may complicate a pre-existing hydrocele. The effused blood usually soon degen- 
erates, and the sac is filled with a brownish fluid or a thick, grumous mass. The 
tunica vaginalis may be thickened. The testis may remain normal or be atrophied. 
Effusion of blood into the loose connective tissue of the scrotum is often called 
extravaginal hematocele. 
Hematocele of the spermatic cord occurs in rare cases as a diffuse infiltration of 
blood in the connective tissue of the cord; or blood maybe effused into a hydrocele of 
the cord. 
Cysts containing spermatic fluid not infrequently arise from the epididymis or 
from the rete testis. These sometimes acquire a large size and crowd the tunica vag- 
inalis before them, so that they simulate a collection of fluid in the cavity of the latter. 
The wall of the cyst may be lined with ciliated or with flattened epithelium. The 
contents are sometimes simply serous, but more frequently opalescent, and may con- 
tain spermatozoa.1 
Spermatocele. 
Atrophy of the testicle may occur in old age or in persons who are in 
a condition of premature senility; or as the result of injury or of pressure 
from hernise, hydrocele, or inflammatory products. Fatty degeneration 
and the accumulation of various degeneration products in the lumen of 
the tubules may accompany atrophy. 
ATROPHY. 
INFLAMMATION. (Orchitis.) 
Inflammation of the testicles may follow injuries, exposure to cold, 
and gonorrheal inflammation of the urethra; it may occur in parotitis or 
1 Hanusa, Beitr. z. klin. Chir. (Bruns), 1910, Ixix, 255; Whitney, C. M., Am. Jour. Urol., 1907, iii, 
175 (bibl.). / 1017 
with syphilis and various other infectious diseases, among which may be 
mentioned scarlet fever, typhoid fever, cerebrospinal fever, pneumonia, 
and variola. The testes, epididymis, or tunica albuginea may be prin- 
cipally involved. Usually only one testicle is inflamed, sometimes both. 
The inflammation may extend to the vas deferens. 
Acute Exudative Orchitis is most frequent in the epididymis and tunica 
albuginea. When the testis is involved the organ is congested and infil- 
trated with serum or pus. From this condition it may return to the 
normal state; or small abscesses may form which may be absorbed, or 
increase in size so as to involve nearly the entire organ. They may 
perforate externally, and then healing may occur by means of granula- 
tion tissue; or extensive gangrenous destruction of the scrotum may 
occur. Abscesses may become inclosed in a fibrous capsule, when the 
REPRODUCTIVE ORGANS OF THE MALE 
a. Thickened interstitial tissue; c, thickened membrana propria of the tubules; d, separated epithelial 
cell mass in the lumina of the tubules. 
Fig. 697.-Chronic Interstitial Orchitis with Atrophy of the Seminiferous Tubules. 
contents may dry and become caseous or calcified, and so persist for a 
long time. The acute inflammation may become chronic. 
Acute epididymitis is frequently the result of gonorrheal infection, 
and may or may not be associated with inflammation of the testis. The 
products of inflammation may collect in varying quantity in the lumina 
of the seminiferous tubules and in the ducts of the epididymis, and the 
epithelium of these structures may degenerate. As the inflammation 
subsides, the contraction of the connective tissue may obliterate the 
canals, which then become cystic. This type of epididymitis is, there- 
fore, a frequent cause of sterility. 
Chronic Orchitis, in some grade, is a frequent disease, being found in 
about 30 per cent, of adult males. The condition is due usually to an 
infectious process, and either is a consequence of an acute lesion or is 
chronic from the outset. Syphilis is responsible for about half of the 
cases, gonorrhea for a tenth; the proportion due to epidemic parotitis is 1018 
REPRODUCTIVE ORGANS OF THE MALE 
difficult to estimate. The other most frequent causes of the lesion are: 
tuberculosis, variola, leprosy, arteriosclerosis, indirect injury from the 
pressure of herniae or hydrocele, and trauma. Undescended testicles, 
also, show a compensatory interstitial fibrosis due to the tubular atrophy. 
The most striking feature of the lesion is the presence of more or less 
connective tissue in the organ; hence, the designation of the condition as 
fibrosis testis, a term to be preferred to chronic orchitis as the presence 
of inflammatory processes can not always be demonstrated.1 The de- 
gree of the fibrosis found is very variable. In the less extensive lesions 
the only thing noticeable may be that the tubules do not well up from 
the cut surface of the organ as they do normally under these circum- 
stances. After chronic inflammation the cut surface remains smooth, 
the tubules being held in their position by the new fibrous tissue. In 
the more extensive cases, there may be radiating bands of connective 
tissue extending throughout the organ, or the fibrosis may be limited to 
a particular portion. This is the usual form in arteriosclerosis, the fibro- 
sis being limited to the periphery of the organ, and the atrophy of the 
tubules being evident from scattered pale transparent areas distributed 
irregularly, while the rest of the parenchyma is normal. In the most 
severe grades the whole organ is converted into a dense fibrous tissue 
mass, in which little or no glandular tissue can be recognized. The 
microscopic picture is equally variable. The increase in the connective 
tissue may be slight, and the disease may affect simply the seminal 
tubules, which are atrophic with thickened hyaline walls (Fig. 697). The 
epithelium is desquamated, and the lumen is filled with granular and 
hyaline masses of debris. The elastic tissue of the tubules remains 
fairly intact for a long period when there is no formation of granulation 
tissue.2 The specific interstitial cells of the testicle are occasionally more 
abundant than normal. 
In another type, the intercanalicular tissue may be greatly increased 
so that the seminiferous tubules are separated from each other by wide 
spaces. A considerable number of lymphocytes and plasma cells lie in 
the connective tissue, especially in the luetic cases; the lumina of the 
ducts are obliterated; the walls are thickened; the epithelium is desquam- 
ated; and only the elastic tissue remains. The albuginea in these in- 
stances is usually thickened. When the lesion is still more extensive, 
no remnants of the seminiferous tubules can be found, except a few 
fragmented elastic tissue fibers, and the whole testicle is converted into 
a solid fibrous tissue containing but few nuclei. Exceptionally, the 
tubular epithelium may proliferate and form solid areas which may lead 
to an erroneous diagnosis of neoplasm; the presence of remains of the 
interstitial cells has led to the same error. Calcification may take place 
in the newly formed connective tissue. When the lesion is advanced, 
there is often a periorchitis which leads to thickening and fusion of the 
layers of the tunica vaginalis. In the gonorrheal cases the fibrosis in- 
volves the epididymis, also, while in chronic syphilitic processes without 
1 Simmonds, M., Virchows Arch., 1910, cci, 108. 
2 Fedsrmann, A., Virchows Arch., 1901, clxv, 469. REPRODUCTIVE ORGANS OF THE MALE 
1019 
gumma formation the epididymis is free from extensive lesions. If a 
few of the tubules escape the injury, spermatozoa may be formed, and 
if the epididymis is not diseased the patient may not be sterile. 
Tuberculous Orchitis may occur in connection with tuberculosis of the 
other genitourinary organs or of the lungs, in acute general miliary tuber- 
culosis, or independently. It usually originates in the epididymis, and 
may extend from there to the testis; or it may commence in the testis. 
The appearance which the testicles present when they are the seat of 
this form of inflammation is exceedingly varied and often difficult of 
interpretation. This is partly due to the complex structure of the organ, 
partly to the varied complicating simple inflammatory changes which 
the different parts of the organ undergo in connection with the tuber- 
culous lesion. 
Fig. 698.-Tuberculous Orchitis. 
We may find in the testicle small circumscribed masses of cells, visi- 
ble to the naked eye as whitish spots, which are sometimes composed of 
small spheroidal cells or of larger polyhedral or fusiform or round cells. 
These occur in the walls of seminiferous tubules and blood-vessels, and 
in the interstitial tissue. Sometimes associated with these smaller nod- 
ules, and sometimes not, we find larger, irregular, yellowish or gray 
cheesy masses, which may be formed by the confluence and degeneration 
of the smaller nodules (Fig. 698). The cheesy masses may break down 
and open externally, giving rise to fistulae, gangrenous inflammation, etc. 
Coincident with this distinctly tuberculous nodular formation of tis- 
sue, which is disposed to degenerative changes, there are various more 
or less diffuse alterations of the parenchyma and interstitial tissue of 
the organ which often constitute a most prominent feature of the lesion. 
The interstitial tissue may be more or less densely and diffusely infil- 1020 
REPRODUCTIVE ORGANS OF THE MALE 
trated with small spheroidal cells. The arteries are often the seat of 
obliterating endarteritis. The walls of the seminiferous tubules may be 
very much thickened, so that the lumen may be entirely obliterated. 
The epithelium lining the tubules may be fatty, disintegrated, and peeled 
off, or it may have largely disappeared*. The lumen of the tubules may 
be filled with a granular, nucleated mass which in transverse sections 
looks like a giant cell. The thickened walls of the tubules may be infil- 
trated with small spheroidal cells, so that the underlying stroma is 
scarcely visible. When this occurs in connection with a similar infiltra- 
tion of the interstitial tissue and the formation of giant cells in the lumina, 
we have structures which present the greatest resemblance to some forms 
of tubercle granula (Fig. 699), though not tuberculous in nature. 
Tuberculous inflammation may extend from the testis to the vas 
deferens, vesiculse seminales, and prostate. 
Syphilitic Orchitis.-This may occur in the form of a diffuse new for- 
mation of connective tissue, which may be localized or be widely dis- 
Fig. 699.-Chronic Orchitis with the Formation of Structures ResemblinC; Miliary Tubercles. 
a, Thickened interstitial tissue; b, mass of granular cells in the interstitial tissue; c, thickened 
membrana propria of seminiferous tubule; d, mass of separated epithelium in tubule; e, accumulation 
of small spheroidal cells around tubules; /, thickened membrana propria enclosing g, a multinuclear mass 
resembling a giant cell. 
tributed. The organ becomes dense and firm. Morphologically there 
is no constant difference between this form of orchitis and chronic indura- 
tive orchitis from other excitants; but occasionally the perivascular 
lymphocytic infiltration may give a clue to the origin. It may occur in 
children affected with congenital syphilis. Gummata may form in con- 
nection with the interstitial induration. These may disappear, leaving 
irregular cicatrices, yet have but little tendency to soften and break 
down as do the tuberculous lesions. 
The differential diagnosis between tuberculous and syphilitic orchitis 
is difficult.1 The vascular changes, the better preservation of the elastic 
fibers in gummata, and the infrequence of giant cells and well formed 
tubercles, may permit of a decision. The fact that testicular gummata do 
not soften so frequently as tubercles may assist in the differentiation. A 
i For a discussion of the histological differentiation between tuberculous and syphilitic orchitis, 
see Baumgarten, Verhandl. d. deutsch. path. Gesellsch., 1901, iii, 107. 1021 
REPRODUCTIVE ORGANS OF THE MALE 
positive Wassermann reaction points toward gumma, but does not exclude 
tuberculosis. 
In leprosy, inflammatory foci in the testicle are common, leading 
ultimately to a fibrosis.1 
Actinomycosis and glanders may rarely affect the testicle. 
TUMORS. 
There is scarcely an organ whose tumors have given rise to more dis- 
cussion-partly because no one.observer has had any wide experience, 
since new growths are not especially frequent in this organ,2 and partly 
because neoplasms at one time regarded as independent have come to be 
interpreted as predominating constituents of mixed tumors.3 Thus, a 
careful examination of such growths as adenoma, "carcinoma," sarcoma, 
chondroma, lipoma, myxoma, etc., has demonstrated in many cases the 
Imperfect striated muscle fibers lie in an embryonal connective tissue. 
Fig. 700.-Rhabdomyoma of the Testicle. 
presence of derivatives of all three germinal layers. A pure fibroma may 
possibly occur, though it is extremely rare, as is pure chondroma; myx- 
oma and lipoma probably do not arise apart from mixed tumors. Myo- 
mata have been observed, not, however, of strictly testicular origin, hav- 
ing sprung probably from the vas deferens, the walls of the epididymal 
canals,4 or the cremaster muscle (leiomyoma), or from the gubernaculum 
testis (rhabdomyoma, Fig. 700).5 They may represent, also, a portion 
of a mixed tumor. 
1 For a summary of leprous orchitis, consult Sebileau, Arch. gen. de m6d., 1899, i, 636, 757 (bibl.). 
2 Tumors are said to be somewhat more common in undescended testicles than in the normal gland. 
For bibl., see Bulkley, Surg., Gynec., and Obst., 1913, xvii, 703. For a general discussion of tumors of 
the testis, see Miyata, Arch. klin. Chir. (Langenbeck), 1913, ci, 426 (bibl.). 
1 For a discussion of the question, see Ewing, Surg., Gynec., and Obst., 1911, xii, 230 (bibl.); and 
Debernardi, Zieglers Beitr., 1907, xl, 534 (bibl.). 
4 For cancer and other tumors of the epididymis, see SaKaguchi, Frankfurt. Ztschr. f. Path., 1914, 
xv, 62 (bibl.). 
6 Beater, Virchows Arch., 1901, clxiii, 244 (bibl.). 1022 
REPRODUCTIVE ORGANS OF THE MALE 
Adenoma sometimes develops as part of a teratoma, but very rarely 
as an independent neoplasm.1 
The question of sarcoma is unsettled, the nature of the growths 
described as small round-cell or spindle-cell sarcoma being still undeter- 
mined. The former, most familiar of the new growths of the testis, is 
called also lymphadenoma and lymphosarcoma. 
Carcinoma is in a similarly doubtful position. Strictly speaking 
there is, of course, no such thing as carcinoma of the testis, since this 
gland is of mesodermal origin. 
Fig. 701.-Teratoma of the Testicle. 
Masses of hyaline cartilage at the left; new-formed atypical glandular structures at the right. 
A tumor2 called by many observers simply large round-cell tumor of 
the testis, in the absence of any definite information as to its actual 
character, is regarded by some pathologists as an independent carcinoma, 
by another group as a sarcoma, by others as a derivative of the spermato- 
blast (seminoma^ or of the interstitial cells of Leydig, and by still others 
as merely the predominating constituent of a teratoma. 
The type which is said to originate in the interstitial4 cells of the 
testis, though this derivation is not by any means universally accepted, 
is a firm, rapidly growing neoplasm which may metastasize. It is com- 
posed of interlacing strands of large cells looking somewhat like epithe- 
lium; these groups are interrupted by an acellular stroma but there is 
1 Pick, Berl. klin. Wchnschr., 1905, xlii, 502 (bibl.); Kaufmann, Deutsch, med. Wchnschr., 1908, 
xxxiv, 803. 
2 Debernardi, Zieglers Beitr., 1907, xl, 534 (bibl.); FranK, A., Frankfurt. Ztschr. f. Path., 1912, ix, 
206 (bibl.). 
3 Chevassu, Tumeurs du testicule, These de Paris, 1906. 
* Kaufmann, Verhandl. d. deutsch. path. Gesellsch., 1907, xi, 237 (bibl.); Deutsch, med. Wchnschr., 
1908, xxxiv, 803 (bibl.); Stoppato, Zieglers Beitr., 1911, 1, 113 (bibl.). REPRODUCTIVE ORGANS OF THE MALE 
1023 
no definite alveolar arrangement. The cells resemble the normal inter- 
stitial elements. The cytoplasm may be abundant like that of the liver 
cell, or smaller in amount and vacuolated. The nuclei are of moderate 
size (8 to 16 micra), vesicular, round, often eccentrically placed, and 
provided with one or two nucleoli. 
Teratoma.1-These neoplasms are described in the older text-books 
under the name cystoma or adenoma, but are now suspected by many to 
arise from dissociated blastomeres.2 A blastomere is one of the cells 
resulting from the first few divisions of the fertilized ovum. The earliest 
are totipotent, since any of them can produce all the tissues of the body. 
Fig. 702.-Chorionepithelioma of the Testicle. 
Showing syncytium and Langhans' cells and their relation to blood sinuses. 
Hence, they differ from their descendants, which become gradually multi- 
potent, or able to evolve many tissues though not all, and finally uni- 
potent, or capable of building but one. 
Teratomata of the testis are believed to arise at a time when the 
blastomere is totipotent, and these growths are, therefore, potentially 
tridermal, i.e., may contain derivatives of all three germinal layers (Fig. 
701). But one constituent may grow so vigorously as to overshadow 
1 Meyer, Rudolf, Frankfurt. Ztschr. f. Path., 1913, xiii, 215 (bibl.). 
2 Marchand, article Missbildungen, in Eulenberg's Real Encyclopadie der gesammten Heilkunde, 
3d ed., Vienna, 1897, Bd. xv, p. 508; Bonnet, Monatschr. f. Geburtsh. u. Gynak., 1901, xiii, 149; Wilms, 
Zeiglers Beitr., 1896, xix, 233; Deutsch. Ztschr. f. klin. Chir., 1898, xlix, 1; Die Mischgeschwiilste, 
Leipzig, 1899-1902. 1024 
REPRODUCTIVE ORGANS OF THE MALE 
or even suppress the others, so that the presence of one tissue only is 
not proof positive against a teratomatous origin. 
Not all pathologists accept the foregoing explanation. Thus it has 
been asked1 why teratomata occur almost always in the testis or ovary 
if they originate from the blastomeres in general, and it has been sug- 
gested that in the testis and ovary they arise from among those blasto- 
meres which eventually go to form these two organs. 
Now, since derivatives of all three layers are potentially present in 
a teratoma of the testis, the tumor, like a normal embryo, will tend to 
develop a chorion. Thus is explained the chorionepithelioma (Fig. 702) 
of the testis,2 a malignant and rapidly metastasizing neoplasm similar 
to that found in the female. 
PARASITES. 
Echinococcus may occur in the testis or epididymis. 
The Seminal Vesicles. 
The seminal vesicles may be the seat of acute or chronic inflammation, 
which is most frequently associated with inflammatory changes in adja- 
cent parts, prostate, urethra, etc. As a result of chronic inflammation 
the vesicles may be atrophied, or they may be greatly dilated, forming 
cysts due to constriction of the ducts. Tuberculous inflammation is 
usually secondary.3 
TUMORS. 
Carcinoma of the rectum or other genitourinary organs may second- 
arily involve the seminal vesicles. Primary tumors are very infrequent. 
Small concretions, sometimes containing masses of spermatozoa, are 
occasionally found in the seminal vesicles. Rhabdomyomata have been 
found in the seminal ducts.4 
The Prostate. 
DEGENERATION, ATROPHY, AND HYPERTROPHY. 
Fatty and hyaline degeneration of the epithelium and the muscle cells 
may occur in the prostate with or without hypertrophy. A moderate 
amount of brown pigment is often found in the muscle fibers and in the 
connective tissue about the gland in old age. 
Atrophy of the prostate may follow acute lesions, orchitis, orchidec- 
tomy, and ligature of the vas deferens, or may occur as a senile process. 
Usually the atrophy following orchidectomy and ligature of the vas is 
1 Ribbert, Die Geschwulstlehre, 2d ed., Bonn, 1914, p. 674; Adami, Principles of Pathology, Phila- 
delphia, 1st ed., 1908, i, 605. 
2 Schlagenhauf er, Wien. klin. Wchnschr., 1902, xv, 571; FranK, R. T., Jour. Am. Med. Assn., 1906, 
xlvi, 256 (bibl.); Risel, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1907, xi2, 928; Cookc, Bull. Johns 
Hopkins Hosp., 1915, xxvi, 215 (bibl.); Woglom, St. Luke's Hospital Medical and Surgical Reports, 
vol. iv, New York, 1917, p. 188 (bibl.). 
3 WalKer, G., Johns Hopkins Hosp. Rep., 1911, xvi, 1. 
4 Mdnclceberg, Virchows Arch., 1907, clxxxvii, 471. REPRODUCTIVE ORGANS OF THE MALE 
1025 
slight, and any improvement which occurs is due to reduction of the 
congestion of the gland and mucous membrane over it, rather than to a 
great reduction in the amount of connective tissue. 
Hypertrophy.1-Enlargement of the prostate-so-called hypertrophy 
-is of fairly frequent occurrence in old age; but occasionally it is seen 
before forty. It is rather more frequent among the better classes. The 
organ may be very greatly enlarged (Fig. 703), and may project forward 
into the bladder, or chiefly toward the rectum. The middle lobe of the 
gland is the one most frequently attacked and the one which causes the 
physical symptoms which call attention to the lesion by pressure upon 
Fig. 703.-Hypertrophy of the Prostate. 
the urethra, thus rendering urination difficult or impossible. Such par- 
tial or complete closure is regularly associated with other conditions, 
such as hypertrophy and dilatation of the bladder, trabeculation of the 
walls, or even the formation of diverticula. Dilatation of the ureter and 
hydronephrosis also may follow prostatic hypertrophy. If infection 
takes place cystitis, pyelitis, or suppurative pyelonephrosis may occur. 
Microscopical examination of the enlarged prostate shows a consider- 
able variety of pictures. The glandular hyperplasia may be extreme 
(Fig. 704), and the gland may be converted into what is practically a 
multilocular cyst. On the other hand, the fibro-muscular tissue may 
undergo a very great hyperplasia without marked increase in the glands. 
This hyperplasia may be diffuse or nodular, and this is equally true of 
1 For a discussion of pathological changes in the prostate, see Wilson, L. V., and McGrath, B. F. 
Surg., Gynec., and Obst., 1911, xiii, 647. 1026 
REPRODUCTIVE ORGANS OF THE MALE 
the hyperplasia of the glandular tissue. Corpora amylacea are regularly 
present, though not in as large numbers as in the normal prostate (Fig. 
708). The interstitial tissue especially about the gland is usually infil- 
trated with lymphocytes, and occasionally this infiltration is quite diffuse. 
When the hypertrophy of the gland is circumscribed, nodules of muscle 
and fibrous gland tissue which are formed near the periphery of the organ 
may project into the bladder and even become detached and be found 
as small movable tumors beneath the mucous membrane. 
This variation in the composition of the enlarged prostate leads to 
the different clinical types-the small hard enlargement, the nodular 
type, and the diffuse spongy vascular form 
Fig. 704.-"Hypertrophy"-Hyperplasia-of the Prostate. 
There is a glandular hyperplasia as well as hyperplasia of the fibromuscular stroma. 
In consequence of the enlargement of the gland the deep urethra is 
pushed up and, hence, is longer than normal; this lengthening may be 
increased by the formation across the urethral opening of a valve formed 
of prostatic tissue. 
The cause of prostatic hypertrophy is still unknown. It has been 
considered as a consequence of a productive inflammatory lesion of the 
connective tissue.1 This inflammatory thickening of the connective tis- 
sue leads to retention of the secretion and ultimately to a distention of 
the peripheral portion of the glandular structures. Others believe that 
the hypertrophy should be regarded as a tumor-like adenomatous growth,2 
and point to the extreme frequency with which carcinoma occurs, in 
1 Ciechanowski, Mitt. a. d. Grenzgeb. d. Med. u. Chir., 1900, vii, 183. 
* Ribbert, Zieglers Beitr., 1915, Ixi, 149. REPRODUCTIVE ORGANS OF THE MALE 
1027 
some series as high as 20 per cent.,1 though 10 per cent, is nearer the 
average. Still others have called attention to the analogous position 
occupied by the uterus and the prostate and have suggested that the 
hypertrophy was similar in nature to the myomata of the uterus. Even 
the rather far-fetched analogy with chronic cystic mastitis of the female 
breast has been cited as possibly pointing to the fact that the hypertrophy 
of the prostate represents a senile involutionary change. 
The recurrence of prostatic enlargement has been noted after removal 
of part of the gland, though without any evidence of tumor formation.2 
INFLAMMATION. (Prostatitis.) 
Acute exudative inflammation of the prostate may be induced by 
urethral gonorrhea, metastatic infection from other foci in the body, or 
Fig. 705.-Rhabdomyosarcoma of Prostate Gland. 
Showing area with abundant muscle fibers of embryonic type; striations only occasionally visible. 
extension of infections of the seminal vesicles and rectum. The acute 
process may become chronic without abscess formation, or large quanti- 
ties of pus may collect in the organ which can then be palpated as a 
swelling through the anterior rectal wall. These large abscesses may 
perforate into the rectum or into the urethra, and thus undergo spon- 
taneous cure. Smaller abscesses usually perforate into the urethra. On 
the other hand, the inflammation may extend to the capsule of the pros- 
tate and set up an extensive prostatic inflammation often with most 
serious consequences. 
Tuberculous inflammation of the prostate may be confined to that 
organ,3 but usually accompanies a similar lesion of some of the other 
1 Judd, E. S., Surg., Gynec., and Obst., 1915, xx, 274; and MacGowan, Jour. Am. Med. Assn., 1917, 
Ixviii, 521. 
2 Paul, T., Lancet, 1910, ii, 294. 
s Koch, G., Frankfurt. Ztschr. f. Path., 1907, i, 272. 1028 
REPRODUCTIVE ORGANS OF THE MALE 
genitourinary organs.1 Large cheesy masses are often formed, which may 
break down and open into the bladder or rectum. 
TUMORS.2 
Sarcoma of the prostate is very rare;3 a few cases of rhabdomyosar- 
coma have been reported (Fig. 705).4 Adenoma0 (Fig. 706) occurs either 
Fig. 706.-Adenoma of the Prostate. 
In the upper portion of the cut, at the right, are three nearly normal acini of the prostate, while 
the remainder shows various phases of new gland formation. The prostate, in addition to the circum- 
scribed tumor growth, was the seat of the usual glandular and interstitial hyperplasia. 
Fig. 707.-Glandular Hyperplasia of the Prostate with Cystic Dilatation. 
Some of the dilated glands contain corpora amylacea. 
with or without an increase in the fibromuscular interstitial tissue and 
gland hyperplasia. 
1 Halle, N., and Motz, B., Ann. d. mal. d. org. g6nito-urin., 1903, xxi, 481, 561. 
2 Foi bibl. of prostatic tumors, see McGrath, B. F., Jour. Am. Med. Assn., 1914, Ixiii, 1012; also 
Socin-Buraehardt, Deutsch. Chirurgie, Lief 53, 1902, which has a very complete list of references to 
papers on prostatic disease. 
3 Veil, W., Berl. klin. Wchnschr., 1908, xlv, 872, 924; Cumston, C. G., Internat. Abs. Surg., 1914, 
xviii, 417. 
1 Squier, J. B., Surg., Gynec., and Obst., 1916, xxiii, 341. 
6 Ribbert, Zieglers Beitr., 1915, Ixi, 149. 1029 
REPRODUCTIVE ORGANS OF THE MALE 
Carcinoma is of frequent occurrence in hypertrophied prostates, in- 
volving as high as 10 to 20 per cent, of carefully examined specimens in 
certain series.1 Such tumors are especially apt to form bone metastases. 
Secondary carcinoma is usually due to extension from the rectum. 
Cysts of the prostate (Fig. 707) are sometimes formed either as a 
result of occlusion of the ducts by hypertrophy of the interstitial tissue, 
by tumors, etc., or as a result of faulty development.2 
PARASITES AND CONCRETIONS. 
Echinococcus of the prostate has been described, but is rare. 
Concretions.-Small ovoidal or spheroidal, often brown or black 
bodies, having the characters of corpora amylacea (Fig. 708), are of very 
Fig. 708.-Corpora Amylacea in Glandular Hyperplasia of the Prostate. 
frequent occurrence in the alveoli of the prostate, particularly in old per- 
sons. We find a certain number of them in the prostates of nearly all old 
men, but they are sometimes present in great numbers. Larger, irreg- 
ular concretions, apparently formed by the coalescence or growth of the 
smaller ones, are less frequently found, and may be encrusted with lime 
salts. These concretions may give rise to ulceration of the ducts of the 
gland or to interference with the passage of urine, but usually they are 
of no practical importance. 
Cowper's Glands. 
Inflammatory processes, acute or chronic, may occur in these organs 
in connection with urethritis or prostatitis. Abscesses may form; the 
1 Judd, E. S., Surg., Gynec., and Obst., 1915, xx, 274; Gunn, L. G., Amer. Jour. Urol., 1915, xi, 
243. 
2 The occurrence of squamous epithelium in the ducts and sinuses of the prostate has been described: 
see Schmidt, Zieglers Beitr., 1906, xl, 120. 1030 
REPRODUCTIVE ORGANS OF THE MALE 
glands, either in acute or chronic inflammation, may become enlarged 
and encroach upon the lumen of the urethra. Retention cysts formed by 
the closure of the excretory ducts may also project into the urethral 
canal. 
The Male Mamma. 
There may be an abnormal number of mammae. In boys, at about 
the time of puberty, the mammae may be swollen and inflamed or they 
may secrete milk. Cases are recorded in which adult males possessed 
large mammae which secreted milk. The breasts may be enlarged from 
an increase of fat or of connective tissue. 
Fibroma, fibroadenoma, cystadenoma,1 sarcoma, cystosarcoma, myx- 
oma, and various forms of carcinoma2 may occur. 
Cysts of the male breast are not very infrequent. 
1 Unger, Virchows Arch., 1901, clxv, 550. 
2 For bibliography of carcinoma of the male breast, see Warfield, Bull. Johns Hopkins Hosp., 1901, 
xii, 305. CHAPTER XII. 
VOLUNTARY MUSCLE. 
ANATOMY. 
In the embryo, muscle fibers begin as round or oval cells with single 
nuclei. As development goes on, these cells elongate, and become oval 
or club shaped and the nuclei multiply, occupying a central clear area; 
while the cytoplasm quickly differentiates into fibrils bearing transverse 
striations. The fibrils are arranged in small groups which show on cross- 
section as polyhedral areas-Cohnheim's fields.1 The protoplasm is gran- 
ular, and some of these granules give an oxidase reaction,2 and under 
normal conditions contain glycogen. The muscle fibers are inclosed in 
a sarcolemma which is a clear, transparent, fibrous sheath, much tougher 
than the muscle fibers themselves, as they can be ruptured while the 
sarcolemma remains still inclosing the fibers. The nuclei, usually num- 
bering more than one in a muscle fiber, lie close along the inner surface 
of the sarcolemma. The muscle bundles are fastened together by a 
complex of connective tissue which carries elastic fibers, vessels, and 
nerves. When the muscle contracts, portions become double refractile, 
and electrical changes, which can be measured with special instruments, 
also take place. These reaction currents have been much studied of 
late for the elucidation of lesions of the muscle and the conducting 
systems.3 
Specialized groups of fibers, known as muscle spindles, are found in 
the muscles of the trunks and extremities. These groups, which comprise 
about twenty fibers, are separated from the rest of the muscle by a con- 
nective-tissue capsule. They do not atrophy when the nerves leading 
to the muscle are cut, but may show degenerative changes under cer- 
tain conditions, such as exophthalmic goiter. It has been thought that 
they are responsible for the muscle sense, but little is known as to their 
functions. 
RIGOR MORTIS. 
About two to four hours after death, coagulation of the protoplasm 
of the muscle fibers takes place, resulting in some shortening and stiffen- 
ing of the muscle; this continues as a rule for forty-eight hours, and then 
disappears. It is much more marked in persons with abundant muscu- 
lature, as it is dependent upon the amount of protein in the fibers. 
1 For details concerning the minute structure of muscle fibers, see Heidenhain, Plasma und Zelle, 
Jena, 1911, ii, 507. 
2 von Gierke, E., Munchen, med. Wchnschr., 1911, Iviii, 2315. 
3 For theories of muscular contraction, see Verworn, M., Allgemeine Physiologie, 5th ed., Jena, 1909; 
and Irritability, Silliman Lectures, New Haven, 1913; Robertson, Quarterly Jour. Exper. Physiol., 
1909, ii, 303; and Lillie, R. S., Science, 1912, N. S. xxxvi, 247. 
1031 1032 
VOLUNTARY MUSCLE 
Hence, in persons with fatty or degenerated muscle fibers, rigor mortis is 
very slight or is absent; this is the case in phosphorus poisoning. After 
hemorrhage and poisoning with strychnine or potassium cyanide there 
is a very rapid and marked rigor mortis. (For further details see page 
1188.) 
NECROSIS. 
Necrosis of muscle may be the local result of mechanical or chemical 
injury; it occurs in inflammatory foci, and may follow serious local dis- 
turbances of the circulation, as from pressure by tumors or cicatrices, etc. 
The muscle fibers may gradually lose their striations, become granular, 
and disintegrate, or the muscle substance may become homogeneous and 
strongly refractile and break into irregular masses. Necrotic muscle 
fibers are finally removed by the direct action of phagocytes or after 
various transformations leading to their solution. 
ATROPHY AND HYPERTROPHY. 
Simple Atrophy.-This may occur in old age, in prolonged exhausting 
diseases, or as a result of inactivity, pressure from a foreign body, tumors, 
Fig. 709.-Progressive Muscular Dystrophy (Soleus muscle, longitudinal section). 
a, Atrophied muscle fiber; b, degenerated muscle fiber; c, interstitial tissue; d, clusters of proliferated 
muscle nuclei. 
etc. Arthritic muscular atrophy due to acute or chronic inflammations 
of the joints belongs here, as the reflex inhibition of muscular movements 
owing to the inflammatory joint changes practically immobilizes the 
muscles attached to the part. The muscle fibers grow narrower, the 
degree of narrowing frequently varying considerably in different parts. 
They usually retain the striations, but these may be obscured by degen- 
erative changes. The sarcolemma may become thickened, and there 
may be a considerable increase in connective tissue between the muscle 
fibers and bundles. Brown pigment particles may accumulate in the 1033 
VOLUNTARY MUSCLE 
atrophied fibers.1 Nerve degeneration and anterior root changes may 
follow simple atrophy. 
Muscular atrophy in some cases follows injuries or overstraining of 
groups of muscles, and may occur as one of the sequelae of typhoid fever 
and diphtheria. 
Neurotic Atrophy.-This occurs when the nerves leading to the muscle 
are injured, and may follow lesions of the brain or spinal cord. Just 
how much the atrophy is dependent upon the nerve lesion and how much 
upon the enforced inactivity of the muscle is still under discussion. The 
muscles which have atrophied under the influence of a simple neuritis 
can be kept in fair condition by massage and electrical treatment. The 
atrophy following cerebral injuries is much slower than that induced by 
spinal or peripheral nerve lesions. 
a, Increased interstitial tissue; b, nearly normal muscle fibers; c, degenerated muscle fibers; d, atrophied 
muscle fibers; e, clusters of proliferated muscle nuclei. 
Fig. 710.-Progressive Muscular Dystrophy (Soleus muscle, transverse section). 
Progressive muscular atrophy of the Duchenne-Aran type is depend- 
ent upon nerve changes, even though the latter are accompanied by 
disease of the anterior horn cells (see page 1143). 
Progressive Muscular Dystrophy.-This lesion consists essentially in 
a combination of simple or degenerative atrophy of the muscle fibers with 
chronic interstitial inflammation, and is sometimes associated with 
proliferative changes in the muscle nuclei, which may lead to a temporary 
hypertrophy of the fibers. In the earlier stages of the disease the muscles 
may be pale and soft, but otherwise exhibit to the naked eye but little 
1 Ishida, M., Virchows Arch., 1912, ccx, 67. 1034 
VOLUNTARY MUSCLE 
alteration. Gradually, however, the muscle substance becomes replaced 
by connective tissue, so that in marked and advanced cases the muscles 
are converted into fibrous bands or cords, whose cicatricial contraction 
may induce great deformities. 
Microscopical examination shows in the early stages of the disease a 
proliferation of cells in the interstitial tissue, so that this may have the 
appearance of granulation or embryonal tissue, and, in some cases, marked 
proliferative changes in the muscle nuclei (Fig. 709), leading to the for- 
mation of new cells which may more or less replace the contractile 
substance within the sarcolemma. The new interstitial tissue increases 
in quantity and grows denser, and may crowd the muscle fibers apart 
(Fig. 710). The walls of the blood-vessels also may become thickened. 
Hand-in-hand with these interstitial alterations the atrophy of the muscle 
fibers proceeds. These may simply grow narrower, retaining their 
striations; or they may split up into longitudinal fibrillae, or transversely 
into discoid masses, and in this condition disappear. In other cases a 
certain amount of fatty or hyaline degeneration may be present. These 
degenerative and proliferative changes do not, as a rule, occur uniformly 
in the affected muscles, but some parts are affected earlier and more 
markedly than others. The atrophied muscle may be replaced by fat. 
This fatty alteration may be so extensive that the muscle is larger than 
normal, producing what has been termed a pseudohypertrophy. In such 
tissues the muscle fibers may be so infrequent that it is difficult to find 
them microscopically. 
Progressive muscular dystrophy is apt to commence in the small muscles 
of the extremities, in many cases in the muscles of the ball of the thumb. 
It may commence in the muscles of the shoulder, the arms, or the back. 
It may have a continuous extension, or it may jump single muscles or 
groups of muscles. Death may be induced by the affection of the 
muscles of respiration or deglutition. 
The causes of this lesion are in many cases unknown, and there is 
considerable lack of unanimity of opinion as to whether it is primarily a 
disease of the muscles or of the nervous system. In a considerable 
proportion of cases the muscle lesion is associated with atrophy of the 
ganglion cells in the anterior cornua of the spinal cord and the develop- 
ment of connective tissue about them. These changes, however, may 
be secondary to the general disease and not the cause of the atrophy.1 
In other cases these changes in the cord may apparently be absent. 
Recently the theory has been promulgated that muscular dystrophy may 
originate as a result of abnormal functioning on the part of the endocrine 
glands, leading in the muscle fibers to a defective storage of glycogen, the 
carbohydrate which is the source of muscular energy. The sugar con- 
tent of the blood is low, and the creatin in the urine is increased.2 
It is probable that there are a number of types of progressive muscu- 
1 von Werdt, F., Frankfurt. Ztschr. f. Path.', 1908, ii, 577. 
2 Janney, N. W., Goodhart, S. P., and Isaacson, V. I., Arch. Int. Med., 1918, xxi, 188; McCrudden, 
F. H., ibid., p. 256; McCrudden, F. H., and Sargent, C. S., ibid., 1916, xvii, 465; and 1918, xxi, 252; 
Timme, TV., Arch. Int. Med., 1917, xix, 79 (bibl.). VOLUNTARY MUSCLE 
1035 
lar dystrophy, which our present knowledge does not enable us clearly to 
distinguish.1 
Myasthenia Gravis.-This is a rare disease in which there is weakening 
and ultimate paresis of the striated muscles of the body without constant 
changes in the nervous system.2 The disease often begins with ptosis 
due to paralysis of the eye muscles; very frequently, also, the muscles 
of the face, larynx, and neck are involved, and as the disease progresses 
other groups of muscles may be affected. The important clinical symp- 
tom is the rapid exhaustion of the muscles under faradic stimulation. 
Of the causes of the disease almost nothing is known, though a his- 
tory of infection can be obtained in about 20 per cent, of the cases, and 
enlargement of the thymus has been reported in nearly 50 per cent.3 A 
relationship between the condition and changes in the thyroid, parathy- 
roids, suprarenals, and hypophysis4 has been suggested. 
The muscle fibers are usually normal ; but in almost all cases a lympho- 
cytic infiltration may be observed. A moderate fatty degeneration is 
probably dependent upon the slight atrophy which occasionally occurs. 
Edema and atrophy belong to the later phases of the disease. 
Atrophia Musculorum Lipomatosa (Pseudohypertrophy of the Muscles). 
-In some cases, hand-in-hand with the production of new connective 
tissue in the muscles and the atrophy of the muscle fibers, or after these 
changes have made considerable progress, there occurs a development 
of fat tissue between the fibers (Fig. 711) which may disguise any 
diminution in the size of the muscles, or in some cases may even give 
them the appearance of a great increase in size. This condition is of 
most frequent occurrence in children, and is most apt to appear in the 
gastrocnemii muscles. In the upper extremities the deltoid and triceps 
are most frequently involved. The lesion may be symmetrical, affecting 
similar muscles on both sides of the body, or it may be unilateral. Parts 
of muscle bellies may be affected. 
The cause of this form of atrophy is not definitely known. Various 
lesions of the spinal cord have been described as occurring with it; but, 
in many cases at least, alterations of the nervous system cannot be 
detected. A case5 has been described in which this lesion was marked 
in the gastrocnemii in connection with multiple false neuromata. Some 
of these cases undoubtedly belong to the pseudohypertrophic types of 
muscular dystrophy. 
Hypertrophy.-True hypertrophy of muscle as a pathological con- 
dition is rare, but it has been described in a few cases. It is usually 
confined to circumscribed groups of muscles. On microscopical exam- 
ination the diameter of the fibers is increased, sometimes considerably, 
i Timme, W., Arch. Int. Med., 1917, xix, 79 (bibl.). For details of classification and lesions, see 
the standard textbooks on neurology, and especially the monographs of Marburg and Jendrasski, in 
Lewandowsky, Handbuch d. Neurologic, Berlin, 1911, ii, part 1, pp. 278 and 321. 
2 Mandlebaum, F. S., and Celler, H. L., Jour. Exper. Med., 1908, x, 308 (bibl.) •,Patrick, H. TJour. 
Am. Med. Assn., 1902, xxxviii, 58; Marburg, O., Ztschr. f. Heilk., 1907, xxviii, 111; Bramwell, B., Brit. 
Med. Jour., 1901, ii, 769. 
3 For a report of a case of myasthenia gravis with thymoma, see Jones, W. A., Jour. Am. Med. Assn., 
1916, Ixvii, 1354. 
4 See Tilney, F., Neurographs, 1907, i, 920. 
& Prudden, Am. Jour. Med. Sc., 1880, Ixxix, 134. 1036 
VOLUNTARY MUSCLE 
though not uniformly. The transverse striation is unaltered and the 
muscle nuclei are in some cases enlarged. The cause of the change is 
unknown. 
Such an hypertrophy occurs in myotonia congenita (Thomsen's dis- 
ease) there being an increase in the size of the fibers and in the number 
of the nuclei. The transverse striations are less visible than normal; 
some fibers also show vacuolation. Clinically, the muscles are rigid 
when an attempt is made to contract them. The disease often occurs 
in several members of a family. 
Fig. 711.-Pseudohypertrophy of Gastrocnemius Muscle (Fatty Infiltration). 
The specimen is from the case mentioned on page 1035, accompanying multiple neuroma. 
DEGENERATION. 
Albuminous Degeneration of striated muscle occurs as a mark of toxe- 
mia in acute infectious diseases, and may lead to fatty degeneration. 
Fatty Degeneration, with greater or less destruction of the muscles, 
may commence with a simple swelling and fine granulation of the fibers. 
As the process goes on, smaller and larger fat droplets appear in the con- 
tractile substance, which loses its striations and becomes friable and may 
be entirely destroyed, leaving within the sarcolemma a mass of fatty 
detritus which may finally be absorbed and disappear. This alteration 
may occur in acute parenchymatous myositis in connection with various 
forms of atrophy, in prolonged exhausting diseases, and in phosphorus 
poisoning. It occurs, also, after transverse lesions of the spinal cord.1 
Fatty Infiltration of the muscle may occur in obesity and in alcoholics. 
1 Zipkin, R., Virchows Arch., 1906, clxxxv, 478. VOLUNTARY MUSCLE 
1037 
Hyaline Degeneration.-Under a variety of conditions the muscle 
fibers undergo a series of changes, leading to their conversion into a trans- 
lucent, highly refractile material, somewhat resembling amyloid, but not 
giving its microchemical reactions, and apparently more nearly allied to 
hyaline material. The lesion in the muscle which we are considering is 
often called waxy degeneration, from the peculiar appearances which the 
muscles present.1 When the lesion is far advanced and extensive the 
muscles are brittle and have a grayish-yellow, translucent appearance. 
Microscopical examination of various stages of hyaline degeneration of 
muscle shows that the contractile substance of the fibers becomes at first 
swollen and granular, and is gradually converted into hyaline material 
which may present the outlines of the swollen fibers, but is more fre- 
quently broken into larger and smaller shapeless clumps (Fig. 712), 
Fig. 712.-Hyaline Degeneration (So-called Waxy Degeneration) of Abdominal Muscle 
in Typhoid Fever. 
which may disintegrate and finally be absorbed. Hand-in-hand with 
these changes there usually occurs an increase in the interfibrillar con- 
nective tissue, and in certain cases there may be a proliferation of the 
muscle nuclei and a new formation of variously shaped cells within the 
sarcolemma which lead to the regeneration of the fibers. As a result of 
the brittleness of the degenerated muscles they are apt to rupture, and in 
this way hemorrhage may occur. 
This form of degeneration may occur in progressive muscular atrophy, 
in various infectious diseases, in trichinosis, with local inflammation, 
injuries, freezing, etc. It is, however, most marked and frequent in 
typhoid fever. In this disease the rectus abdominis and the adductors 
of the thigh are most frequently affected. 
Experimental investigations have shown that, under certain condi- 
tions, very similar appearances may be produced in the muscles by post- 
mortem changes, and by contractures due to strychnine poisoning and to 
high voltage electric currents.2 Various changes-some of them necrotic 
•-are at present incorrectly included under the name "hyaline degener- 
ation of the muscles." 
True amyloid degeneration is rare. 
A peculiar degeneration with atrophy of the striated muscle of the 
1 For an experimental study of the so-called waxy or Zenker's degeneration of muscle, see Thoma, 
Virchows Arch., 1906, clxxxvi, 64. 
Schmidt, M. B., Verhandl. d. deutsch. path. Gesellsch., 1910, xiv, 218. 1038 
VOLUNTARY MUSCLE 
uvula has been described, in which a series of bleb-like structures 
form along the fibers, which they may finally replace.1 
Calcification of individual muscle fibers is seen after blows or incised 
wounds, but is of rare occurrence.2 
Serous or Hydropic Infiltration of muscle fibers occurs under various 
conditions in association with other lesions. Larger and smaller spaces 
filled with clear fluid are present between the fibers and often over small 
areas largely replacing them. Such fluid-filled spaces are often called 
vacuoles. 
INJURIES, HEMORRHAGE, AND INFARCTION. 
Wounds and Rupture.-When the muscle fibers are severed by wounds 
or rupture there is more or less degeneration of the divided fibers, and 
the wound may heal by the production of granulation tissue, which 
gradually becomes converted into cicatricial tissue, thus binding the 
severed parts together. In some cases there is a moderate new formation 
of muscle fibers (page 84).3 When the wround does not gape, so that 
the severed ends are not much separated, there may be, it would seem, 
a direct re-establishment of muscular continuity by new development 
of muscle, without the formation of much new connective tissue. 
Hemorrhage.-This may occur as a result of mechanical injury, from 
rupture of the fibers by convulsive contraction, as in tetanus, when the 
muscle fibers are degenerated, as in typhoid fever, or in connection with 
certain general diseases, as scurvy, purpura, hemorrhagic diathesis, sep- 
ticemia, etc. The blood is usually readily absorbed. 
Embolic Infarction of Muscles in connection with heart disease has been 
described in a few cases, but it is rare. 
INFLAMMATION. (Myositis.) 
Suppurative Myositis.-In the early stages of this lesion the muscle is 
hyperemic and edematous, and the interstitial tissue more or less infil- 
trated with small spheroidal cells. If the inflammation becomes intense 
there may be an excessive accumulation of pus cells, either diffusely in 
the interstitial tissue or in larger and smaller masses. Hand-in-hand 
with this cell accumulation occur degenerative changes in the muscle 
fibers. By pressure their nutrition is interfered with and they undergo 
granular, fatty, or hyaline degeneration, and necrosis. They may com- 
pletely disintegrate; or gangrene may occur, so that larger and smaller 
masses of the infiltrated muscle tissue become soft and foul-smelling, and 
are converted into a mass of detritus in which but little muscle structure 
can be detected and which is intermingled with bacteria. In other cases 
there may be larger and smaller abscesses formed in the muscle, the 
muscle tissue itself degenerating and disintegrating and mixing with the 
contents of the abscess, or being pressed aside and undergoing atrophy 
and degeneration. In some cases, when the formation of pus is moderate 
1 Hoen, A. G., Jour. Exper. Med., 1898, iii, 549. 
2 Pielstiacer, F., Virchows Arch., 1909, cxcviii, 374 (bibl.). 
3 Schminctce, A., Zieglers Beitr., 1909, xlv, 424; Pielsticker, F., Virchows Arch., 1909, cxcviii, 385 
(bibl.). VOLUNTARY MUSCLE 
1039 
in amount, there may be restoration by formation of granulation tissue 
between the muscle fibers. This becomes gradually dense and firm, and 
leads to more or less atrophy of the muscle fibers by pressure.1 
Acute suppurative myositis may accompany wounds; it is very com- 
mon in acute phlegmonous inflammations of the skin and subcutaneous 
tissue, and often accompanies acute infectious diseases, such as pyemia, 
erysipelas, etc. In most cases the "pyogenic" cocci are present in the 
inflammatory foci. Suppuration not infrequently occurs in the muscles 
adjacent to the inflamed mucous membranes in diphtheria. 
Chronic Interstitial Myositis.-In this lesion there is a new formation 
of connective tissue between the muscle fibers or bundles of fibers. This 
new tissue is sometimes very cellular, resembling granulation tissue, and 
probably represents an early stage of the disease. In other cases (Fig. 
713) dense cicatricial tissue crowds the muscle fibers apart, inducing 
atrophy in them, and sometimes leading to their complete destruction. 
This lesion, the analogue of chronic interstitial inflammation of the 
internal organs, may occur in muscles adjacent to other parts which are 
the seat of chronic inflammatory proc- 
esses. It may occur in muscles which 
are not used. The new formation of 
fibrous tissue seems in some cases to 
be secondary to atrophy of the muscle 
fibers. In this case it would more 
appropriately be called replacement 
fibrous hyperplasia. Rheumatism is a 
frequent cause, as is also rupture of 
the muscle. The congenital wry neck 
or caput obstipum is a fibrous myositis 
due to rupture of the sternocleido- 
mastoid during delivery. 
Primary Acute Polymyositis. - 
Several observers2 have described an 
affection involving swelling of the muscles of the tongue, back, and ex- 
tremities, with local pain and fever. Voluntary movement is lost, and 
various rashes of the skin may occur (dermatomyositis). The muscles 
are brownish red in color, with yellowish spots; hemorrhages, and foci of 
hemorrhagic exudates with many leucocytes are present. There is de- 
generation of the muscle fibers. The disease may become chronic, and 
may be fatal. It is believed to be due to some form of autointoxication 
and may be associated with some infective focus in the body or with 
rheumatism. 
Myositis Ossificans.-Under conditions as yet imperfectly under- 
stood, there occasionally occurs, most often in young persons, a condition 
known as myositis ossificans progressiva multiplex.3 The process begins 
Fig. 713.-Chronic Interstitial Myositis 
1 See Lorenz, H., Die Muskelerkrankungen, Nothnagel, Spez. Path. u. Therap., Vienna, 1904, ll3, 1. 
2 See v. Strumpet, Deutsch Ztschr. f. Nervenh., 1891, i, 479; May esima, Deutsch. Ztschr. f. Chir., 
1910, civ, 318; Unverricht, Deutsch, med. Wchnschr., 1891, xvii, 41. 
3 For a study of myositis ossificans, consult Goto, S., Arch. f. klin. Chir. (Langenbeck), 1912-13, c, 
730; De Witt, L., Am. Jour. Med. Sc., 1900, cxx, 295 Cbibl.); Kidner, F. C., Jour. Am. Med. Assn., 
1917, Ixviii, 177 and Rosenstirn, J., Ann. Surg., 1918, Ixviii, 485. 1040 
VOLUNTARY MUSCLE 
in the fasciae, aponeuroses, tendons, or periosteum, and involves the mus- 
cles only secondarily. Three stages of the lesion can usually be made 
out: (1) A connective tissue hyperplasia; (2) a sclerosis of this connective 
tissue; and, (3) a formation of cartilage and bone in the sclerosed area. 
The bone is practically normal in structure. The muscle fibers un- 
dergo secondarily a greater or less degree of atrophy or degeneration. 
There may be fatty infiltration between the fibers, and various deformi- 
ties are produced by the shortening and progressive immobility of the 
affected parts. 
While inflammatory processes, including syphilis, can be ruled out 
as causes of the disease, trauma is certainly important; on the other hand, 
masses of bone may form spontaneously with no antecedent history of 
injury. 
While the above disease is a progressive and frequently a general one, 
there may be a local new formation of bone in muscle as a result of pro- 
longed or repeated mechanical irritation. Thus, in the adductors of the 
thigh in persons who are constantly in the saddle, or in the deltoid muscle 
soldiers who strike this part with their weapons in drill, there may be a 
formation of bone.1 In these instances the new growth of bone is de- 
pendent upon inflammatory processes leading to the formation of con- 
nective tissue which is later metaplastically altered into bone. The 
periosteum plays no part in the process unless the bone growth is directly 
in contact with this membrane. 
Tuberculous or Syphilitic Inflammation in the muscle is of occasional 
occurrence; the active processes are in the connective tissue and blood- 
vessels, the muscle fibers being secondarily involved in various phases 
of atrophy and degeneration. 
TUMORS.2 
Muscle tumors, which are rare, may be divided into three types: (1) 
Those developing in smooth muscle cells (leiomyoma); (2) those develop- 
ing in striated muscle cells (rhabdomyoma); and (3) those developing 
in the connective tissue of either variety of muscle. 
The most common site for the leiomyoma is the uterus, where it is 
the most frequent of all tumors (page 419). It is found also in other 
parts of the genitourinary tract, e.g., in the kidney,3 and in the gastro- 
intestinal tract4 and the skin.5 
For a discussion of rhabdomyoma, see page 421. 
Malignant tumors arising in the muscle itself are sometimes called 
sarcomata,6 though there is a considerable body of opinion in favor of 
retaining this term for tumors of connective tissue; and it would perhaps 
be better, therefore, to employ some such term as myosarcoma or malig- 
nant myoma1 (page 421). In employing the latter term, however, one 
1 See Gruber, Uber Histologie u. Pathogenese der circumskripten Muskelverknocherung, Jena, 1913. 
2 For a discussion of tumors of muscle, see Busse, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1903, 
ix1, 1226 (bibl.); Thorel, ibid., 1901, vi, 742 (bibl.). 
s Neurnberg, Frankfurt. Ztschr. f. Path., 1917, i, 433 (bibl.). 
* AnitschKov, Virchows Arch., 1911, ccv, 243. 
6 Lieber, Zieglers Beitr., 1915, lx, 449 (bibl.). 
6 Landois, Berl. klin. Wchnschr., 1912, xlix, 2274 (bibl.). 
' Ghon and Hintz, Zieglers Beitr., 1909, xlv, 89 (bibl.). 1041 
VOLUNTARY MUSCLE 
should not lose sight of the fact that, in the last analysis, malignancy is 
a clinical phenomenon, and is not necessarily correlated with the mor- 
phology of the tumor. 
Most new growths arise in the connective tissue of the muscle, where 
there have been found hemangioma,1 lymphangioma,2 fibroma,3 lipoma,4 
chondroma,5 and chondrolipoma.6 
The desmoid7 is an extremely hard fibroma which in rare cases may 
be multiple. It arises from the fasciae of the abdominal wall, most often 
from the sheath of the rectus muscle, and is found almost exclusively in 
women, particularly after repeated childbearing. 
Secondary tumors of muscle originate nearly always by extension, 
rarely by metastasis from a distant growth.8 
PARASITES. 
Trichinella spiralis is the most common parasite in the muscles and 
incites an acute myositis by invasion of the muscle fibers. The sarco- 
lemma remains, and the irritating excretions of the parasite set up an 
inflammatory reaction with involvement of the surrounding fibers and 
the determination to the site of many eosinophile cells. Ultimately, the 
fibrous capsule becomes dense, the exudate disappears, and calcification 
sets in about the dead parasite. 
Cysticercus cellulosae and echinococcus occasionally occur. 
1 Serra, Arch. f. klin. Chir. (Langenbeck), 1913-14, ciii, 1018; Borchard, Zieglers Beitr., 1914, Ivii, 30. 
2 Ritschel, Beitr. z. klin. Chir. (Bruns), 1895-96, xv, 99 (bibl.). 
3 Bidone, Monatschr. f. Geburtsh. u. Gynak., 1899, ix, 336. 
4 Morestin, Bull. Soc. anat. de Paris, 1897, Ixxii, 939; FraiKin, Jour, de med. de Bordeaux, 1897, 
xxvii, 573. 
5 Hansell, Beitr. z. klin. Chir. (Bruns), 1899, xxiii, 210 (bibl.). 
6 Kollaczelc, Beitr. z. klin. Chir. (Bruns), 1908-09, Ixi, 127 (bibl.). 
''Pfeiffer, Beitr. z. klin. Chir. (Bruns), 1904, xliv, 334 (bibl.); Andrews, Surg., Gynec., and Obst., 
1911, xii, 190. 
8 For an account of the changes produced in muscle fibers by invading tumors, see Fujinami, Vir- 
chows Arch., 1900, clxi, 115 (bibl.). CHAPTER XIII. 
THE BONES AND JOINTS. 
The Bones. 
General Considerations. 
It is not possible to understand the changes which the bones suffer under various 
abnormal conditions unless one holds in mind the physical peculiarities of this form 
of connective tissue and the ways in which the dense and solid structure is formed and 
dissolved and re-formed in the processes of development and growth. 
The striking character of bone, adapting it to serve as the supporting framework 
of the body, is the association with its organic tissue of the inorganic salts to which its 
hardness and solidity are due. But it is through connective tissue and blood-vessels 
and under the agency of highly specialized connective-tissue cells-osteoblasts, the 
"bone-builders," and osteoclasts, the "bone-destroyers"-that bone is formed and 
during life ceaselessly remoulded.1 
The general pathological processes to be observed in bone are fundamentally 
similar to those in the soft tissues of the body. Disturbance of circulation, necrosis, 
degenerations, inflammation, tumors, etc., are common. But their manifestations 
are modified and often complicated and obscured in part by the hardness of texture 
and durability of bone tissue, and especially by the frequent participation in the proc- 
esses of the osteoblasts and osteoclasts.2 Thus it is that many abnormalities of the 
circulation and their sequelae are less obvious than in other parts of the body; necrosis 
is masked by appearances due to the inorganic elements; while many of the inflamma- 
tory processes and tumors are regularly associated with the formation of new bone in 
such mass and measure as often to distort the bone and greatly complicate the 
picture. 
We have seen repeatedly, in studying the lesions of the viscera, that the primary 
pathological processes are modified by the tissues in which they are active. Attention 
is called to this feature in bone only because the regional modification is here so con- 
spicuously marked that one is liable to lose sight of the unity of the fundamental proc- 
esses and erroneously to conceive that the pathology of bone is a subject especially 
obscure, complex, and difficult.3 
ANOMALIES OF BONE DEVELOPMENT. 
Deficient Growth of Bone. 
Dwarfism.-This may be either local or general. In the former case 
it leads in children to shortening of the extremities when the epiphyseal 
cartilage is injured by trauma or by inflammation. Localized disease of 
the brain or cord may cause a local checking of the growth of the face 
or extremities. General interference with bone growth leads to a reduc- 
tion in size of the skeleton, which may be symmetrical, as in the true 
dwarfs, or distorted, as in the achondroplastic or cretinistic dwarfs. 
1 Hofmeister, F., Ergebn. d. Physiol. (Asher-Spiro), 1910, x, 435. 
2 Keith, A., Lancet, 1918, i, 250. 
3 For r6sum6 and bibl. of the pathology of bone, see Schmidt, M. B., Lubarsch-Ostertag, Ergebn. d. 
allg. Path., 1897, iv, 531; 1898, v, 895; and 1900-01, vii, 221. 
1042 1043 
THE BONES AND JOINTS 
The skull of the true dwarfs is apt to be somewhat large in proportion 
to the height of the body, but as ossification proceeds at a normal rate 
the brain is not injured; hence, the intelligence is usually good. As the 
bone failure in the achondroplastics is in the cartilaginous portion, the 
membranous bones of the calvarium may develop normally, and the 
intelligence be normal. The cause of the diminished bone production is 
not known. Hypophyseal lesions have been found in a number of cases.1 
In cretinism the idiocy is due to the athyreosis rather than to any lesions 
of the bones of the skull. 
Other forms of dwarfism are due to well recognized causes, among 
which are rickets (page 1052) and the nutritional defect known as infant- 
ilism.2 In the latter, various conditions have been suggested as factors, 
including defective digestion with poisoning from abnormal intestinal 
putrefaction, lack of secretion of the pancreas, insufficiency of the pitui- 
tary gland. The children are symmetrically small, and suffer from feeble 
digestion and delayed ossification of the bones. The latter are not 
fragile, but bend easily and green-stick fractures are not infrequent. 
Brain lesions, such as microcephalia, hydrocephalus, porencephalia, 
and mongolism, are often associated with dwarfism.3 
Achondroplasia (Chondrodystrophia Fetalis).-If the normal prolifer- 
ation of the cartilage of the long bones is checked, the limbs will not reach 
their usual length, while the growth of the other bony structures of the 
body will not be impeded. In achondroplasia, the inhibition of growth 
takes place before birth, and the disease is often so advanced that the 
child dies early. If it survives, the upper part of the skull grows nor- 
mally so that the head is large in proportion to the height (Fig. 714). 
The base of the skull may remain much smaller than normal, in some, 
but not all, instances because of premature synostosis of the sphenoid 
and occipital bones, which causes a sinking in of the bridge of the nose. 
The bones of the limbs, while short, develop fully in a lateral direction, 
and thus become even thicker than the corresponding normal bones. 
The muscles are often well developed; and these achondroplastic dwarfs 
when mature frequently possess great physical strength. The trunk is 
usually normal in size. The fingers are often flat and stumpy (Fig. 715). 
The thyroid gland is normal, showing that the disease has no relationship 
with cretinism, and that the changes in the bones are not those of rickets; 
it is, therefore, incorrect to use the term, fetal rickets A 
Osteogenesis Imperfecta (Fragilitas Ossium; Osteopsathyrosis).-In 
this disease, which is both hereditary and congenital, the osteoblasts of 
the internal and external periosteum form an imperfect type of bone. As 
the epiphyseal cartilages perform their functions properly, the bones are 
of normal length or nearly so, but the medullary cavity is large, the shaft 
thin, porous, and very fragile. Fractures may occur, and even undergo 
1 Benda, C., Berl. klin. Wchnschr., 1900, xxxvii, 1205; Hueter, C., Virchows Arch., 1905, clxxxii, 219. 
2 Herter, C. A., On Infantilism from Chronic Intestinal Infection, New York, 1908; and Strauch, A., 
Am. Jour. Med. Sc., 1914, cxlviii, 247. 
3 For further details, see page 499. 
4 See, for further details, Kaufmann., E., Zieglers Beitr., 1893, xiii, 32; Sumita, M., Deutsch. Ztschr. 
f. Chir., 1910, cvii, 1 and Wheeldon, T. F., Am. Jour. Dis. Child., 1920, xix, 1 (bibl.). 1044 
THE BONES AND JOINTS 
repair, before birth. If the child survives, which is rare, the bone fragil- 
ity, or osteopsathyrosis, may last for years or may gradually disappear.1 
While dwarfism is frequent, some affected individuals may be of short 
Showing shortened and deformed arms and legs, the trunk and head being approximately normal. 
Fig. 714.-Achondroplasia. 
stature only, others of normal height. Easy fracturability of the bones 
may be evident also in juvenile osteomalacia (page 1051). 
Showing characteristic deformity of the hands. (Photograph by Dr. Northrup.) 
Fig. 715.-Achondroplasia. 
Cretinism and Myxedema.-Dwarfs in whom the condition is due to 
absence of thyroid secretion show deformities similar to those seen in 
1 ». RecKlinghausen, F., Untersuchungen uber Rachitis u. Osteomalacie, Jena, 1910; Paltauf, Ueber 
den Zwergwuchs, Vienna, 1891; Bronson, E., Edinburgh Med. Jour., 1917, xviii, 240 (bibl.). THE BONES AND JOINTS 
1045 
achondroplasia-the shrunken nose and the short thick limbs (page 1043). 
The epiphyseal cartilages functionate imperfectly, and may remain un- 
ossified for many years.1 As is well known, the exhibition of thyroid 
gland will often cause a considerable bone growth, though this is not 
limited to cretins but may affect normal bones also.2 In congenital or 
infantile myxedema the same bone changes appear, but to a lesser extent. 
Excessive Growth of Bone. 
Gigantism.--This may be general or partial. The normal limits of 
height may be placed as about two meters; but a few symmetrically devel- 
oped giants are seen whose dimensions considerably exceed this, though 
usually the head is small in proportion to the body while the limbs are 
excessively long. The muscular development, as a rule, is poor; the 
bones are of imperfect quality; and spinal curvatures are frequent. In 
addition, evidences of status lymphaticus are sometimes present. No 
cause for the excessive size can be found, though a poor development of 
the generative organs is usual, and hypophyseal disease is probable.3 A 
similar overgrowth is observed in those castrated in childhood, since 
under those conditions the hypophyseal secretions are increased and the 
epiphyseal cartilages retain their activity for a long period.4 A large 
proportion of giants, however, are certainly acromegalics.5 
Partial gigantism is the result of some stimulation of the growing- 
bone. Various forms of inflammatory osteitis and arthritis excite bone 
growth, either directly or through hyperemia and venous congestion.6 
Acromegaly.7-The skeletal changes which follow the growth of 
tumors in the anterior lobe of the hypophysis are not in any way peculiar 
to the disease. They are rather the expression of an increase in the 
physiological activity of the bone-forming elements which results in a 
corresponding augmentation in the volume of the bone structures. The 
bones grow in length and also in thickness. The muscle insertions under- 
go hyperplasia, so that they become prominent raised plateau-like areas. 
The thickening of the hands and feet, on the contrary, is due, as shown 
by skiagrams, only in a slight degree to an increase in the volume of the 
bones, most of the enlargement consisting of an increase in the soft parts. 
The changes in the skull are due to enlargement of the frontal and other 
sinuses which lead to prominence of the orbital and supraorbital ridges; 
while the widening of the sella turcica is due to the increase in the size of 
the hypophysis. The increase in the length of the lower jaw, which pro- 
duces the remarkable prognathism, causing the lower teeth to project- in 
1 Dieterle, T., Jahrb. f. Kinderh., 1906, Ixiv, 465, 576. 
2 Bircher, E., Deutsch. Ztschr. f. Chir., 1909, xcviii, 75. 
3 Falta, W., The Ductless Glandular Diseases, Philadelphia, 1915. 
4 Tandler, J., Wien. klin. Wchnschr., 1910, xxiii, 459; Sellheim, H., Beitr. z. Geburtsh. u. Gynak., 
1899, ii, 236. 
6 For further details, see page 498. 
6 Wittelshbfer, R., Arch. f. klin. Chir. (Langenbeck), 1879, xxiv, 57; Hofmann, M., Beitr. z. klin. 
Chir. (Bruns), 1906, xlviii, 391; Wieland, E., Jahrb. f. Kinderh., 1907, Ixv, 519. 
7 Fischer, B., Frankfurt. Ztschr. f. Path., 1910, v, 351, 587; 1912, xi, 130; Biedl, A., The Internal 
Secretory Organs, New York, 1913; Leri, A., Lewandowsky,'Handb. d. Neurologic, 1913, iii, 283 (very 
complete bibl.). 1046 
THE BONES AND JOINTS 
front of the upper, is due to new osseous growth from the periosteum. 
If the acromegaly begins late in life when the activity of the epiphyseal 
cartilages has ceased, the height may not be greatly influenced. The 
bone produced is often somewhat rarefied by partial absorption; in rare 
instances there may be a great increase in the density of the bone owing 
to the deposition of new osseous material.1 
Hyperplastic Periostitis (Hypertrophic Pulmonary Arthropathy).-A 
peculiar periosteal osteogenesis affecting most frequently the terminal 
phalanges of the fingers and toes is observed in connection with chronic 
pulmonary tuberculosis, bronchiectasia, chronic empyema, chronic heart 
disease with much cyanosis, syphilis, chronic jaundice, and malignant 
tumors. The congestion and toxemia seem to be responsible for the 
incitement of the bony lesions. 
The thickening causes the end phalanges to assume a globular shape, 
and the enlarged nails are noticeably curved over the tip of the phalanx. 
Skiagraphs of hands so affected show that only rarely is the bone exten- 
sively involved, the enlargement being due largely or entirely to thick- 
ening of the periosteum. When the accompanying disease is very 
chronic, other bones may show alterations, especially the peripheral ex- 
tremities of the forearm and leg. The lesion is painless and the joints 
are not involved.2 
Leontiasis Ossea.-This is a rare and but little understood disease, in 
which there is a diffuse thickening of the bones of the face and skull, the 
hypertrophy of the cheek bones, jaws, and orbital ridges giving the face 
the leonine expression which the name signifies. The closure of the fora- 
mina of the skull may cause paralysis, blindness, and loss of the sense of 
smell. 
Microscopically, the enlarged bones are very dense and compact, the 
diploe often being obliterated. The thickness of the calvarium may be 
as great as four centimeters and the total quantity of bony material in 
the skull may be five times the normal. Whether the disease is the 
same as osteitis deformans (Paget's disease) is still in doubt.3 
Osteitis Fibrosa (von Recklinghausen's Disease).-This is a lesion 
of the bone which results in a local destruction of osseous tissue. Parallel 
with the bone destruction goes the formation of new bony or osteoid 
material, and, in addition, the normal bone-marrow is replaced by a soft 
fibrous material somewhat resembling sarcoma. In the later stages of the 
process, hemorrhages are apt to occur in the new-formed tissue, about 
which a large number of multinucleated giant cells usually form. The 
structures so produced resemble very closely the giant-cell sarcomata, 
but differ from them in the fact that sooner or later the new-formed bony 
substance undergoes a more or less complete absorption with the forma- 
tion of cystic areas containing a fluid of a dark brownish color due to the 
1 For other lesions of the disease, see page 496. 
2 Janeway, T. C., Am. Jour. Med. Sc., 1903, cxxvi, 563; Ebstein, P., Deutsch. Arch. f. klin. Med., 
1906, Ixxxix, 67; Beuttenmiiller, H., Berl. klin. Wchnschr., 1908, xlv, 1001 (icteric cases); Kruger, Vir- 
chows Arch., 1906, clxxxv 43; Marie, P., Rev. d. m6d., 1890, x, 1; Thompson, E. S., Med. Chir. Trans., 
1904, Ixxxvii, 85; Carper, Cosman, Gilmore, and Black, Am. Rev. Tuberc., 1921, 5, 357-387, 
• Schmidt, M. B., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1898, v, 895; Koch, M., Verhandl. d. 
deutsch. path. Gesellsch., 1909, xiii, 107; BocKenheimer, P„ Arch. f. klin. Chir. (Langenbeck), 1908. 
Ixxxv, 511. THE BONES AND JOINTS 
1047 
deposition of blood pigment. In case no hemorrhage has occurred, the 
softened wall and the cyst contents are colorless. When the disease 
attacks one of the long bones, the formation of the cysts and the softening 
of the surrounding bony structures often permit spontaneous frac- 
ture, or in less severe cases marked bending or softening of the bone. 
Where the process involves the bones of the face or skull, cyst formation 
is unusual. 
The lesions of osteitis fibrosa localize themselves most often in those 
portions of the bony system which are frequently injured by trauma. In 
the long bones, the most usual site is the diaphysis, though in younger 
persons the epiphysis may be most often involved. The most extensive 
tumors are usually those seen in the head of the tibia, where the growth 
projects in the form of rough masses which can be easily felt. The short 
bones of the feet and hands are very infrequently involved, the bones of 
the trunk much less often than those of the extremities. The clavicle 
is a frequent site, and the ribs are occasionally involved and may soften 
so that the thorax is altered in shape. The spinal column in severe cases 
may show considerable shortening. In the pelvis, spontaneous fractures 
are unusual, even though the tumor formation may be very extensive. 
A fairly frequent type occurs in the bones of the face, which may give 
rise to confusion with other forms of bony disease, such as Paget's disease 
(osteitis deformans) or leontiasis ossea. The upper or lower maxilla may 
be affected, and rarely the bones of the calvarium. Secondary changes 
are due to functional alterations in the muscles which may undergo 
atrophy and fatty degeneration owing to poor nutrition. The disease 
occurs most frequently in the second and third decade, in either a cir- 
cumscribed or a generalized form, some cases diagnosed as leontiasis ossea 
belonging to the latter type. The circumscribed form involves either a 
portion of a bone, appearing in the form of a cyst most frequently when 
in the metaphyses of the lower extremities, or a considerable portion of 
the skeleton, especially all the bones of the face. Skiagraphs of the con- 
dition show the bones to be of a spongy structure with lighter portions 
where the cystic softening has occurred. The bone itself is atrophied 
and shows rough contours as if the osseous portion had been eaten away. 
The disease may exist without any symptoms or may cause pain and 
a good deal of weakness. Attention is usually directed to it by the oc- 
currence of a spontaneous fracture, which may heal satisfactorily, or the 
appearance of a considerable tumor. If the disease remains of a circum- 
scribed type, it may cause no disturbance of health throughout life; but 
the generalized type usually leads to death in consequence of cachectic 
disturbances due to interference with bodily function. Only in excep- 
tional instances has a true sarcoma developed in the tissues with general 
involvement of the body and death following extension of the growth. 
Osteitis fibrosa must be differentiated from Paget's disease, osteo- 
malacia, syphilitic bone disease, and tuberculosis. The first, which was 
previously regarded as identical with osteitis fibrosa, is quite different 
in its course. The deformity of the bone is much greater; and the exten- 
sion of the disease is much more general throughout the skeletal system. 1048 
THE BONES AND JOINTS 
In fact, it is rather common to see Paget's disease involve almost all the 
bones; and for this reason general symptoms from the organs, such as 
the heart, kidney, and lungs, which are influenced by the occurrence of 
the bone changes, are apt to appear earlier in Paget's than in osteitis 
fibrosa, in which, indeed, they may never occur. Osteitis fibrosa, also, 
usually begins early, whereas Paget's rarely appears before the fortieth 
year. Paget's disease is especially apt to localize on the calvarium so that 
patients usually complain that their hats are too small; and bony frac- 
tures while common in osteitis fibrosa are rare in Paget's disease. The 
latter is apt to establish itself in a group of bones and then to involve 
others progressively, while osteitis fibrosa remains more or less confined 
to the bone originally attacked. Radiographically and microscopically, 
there is but little difference in the two lesions. 
Fig. 716.-Osteitis Fibrosa. 
Cellular type with giant cells. 
Osteomalacia usually involves the bones of the pelvis symmetrically 
and early. The extremities are involved only when the deformity of the 
trunk has progressed very far. In osteomalacia the pains that interfere 
with movements are very early and well marked, whereas in osteitis 
fibrosa they are absent or slight, and may clear up. In osteomalacia, 
also, there is increasing abnormal flexibility of the bone itself, because 
new formation of bone tissue does not occur. 
Bone syphilis occurring in periosteal form may produce lesions which 
have a great resemblance to those of osteitis fibrosa; in consequence of 
the rarefying osteitis there is a compensatory new production of bone 
which assumes the form of exostoses especially on the tibia, and these 
changes may be accompanied by spontaneous fractures and bending of 1049 
THE BONES AND JOINTS 
the bone which commonly are preceded by very severe pain. The pains 
of syphilis, however, are very much more severe during the night, and 
this observation, together with a positive Wassermann reaction, the his- 
tory of the patient, and the z-ray picture, will permit of a diagnosis. In 
syphilis the parts attacked are peculiarly eaten out so that the bone may 
be described as worm-eaten. 
Bone tuberculosis is not apt to be confused with osteitis fibrosa for the 
former more often occurs on the short bones of the hands or feet, and 
about the joints; and the formation of cold abscesses with sinuses and 
the general destruction of the bone without much attempt at repair will 
usually permit of a diagnosis. The development of sequestra, which is 
common in tuberculosis, does not occur in osteitis fibrosa. 
Fig. 717.-Osteitis Fibrosa, Dense Type. 
The differentiation from giant-cell sarcoma (Fig. 240, page 434) is 
not altogether easy, and the clinical history is very important for a diag- 
nosis. In osteitis there is usually, in addition to the giant-cell portions 
(Fig. 716), other parts of the tumor which do not contain such cells 
(Fig. 717), and from these the diagnosis can be made. Mitoses are not 
found in the connective-tissue cells of osteitis fibrosa, as they are in the 
cells of the tumor, and metastases have not been noticed even when the 
growth has existed for ten years or more.1 
Osteitis Deformans (Paget's Disease).-This is a chronic disease, 
affecting usually persons between the fifth and the eighth decennium. 
The process may be designated as an osteomyelitis fibrosa, and consists 
in the formation of a solid cellular connective tissue which replaces the 
bone substance and fills the medullary cavity. The destruction of the 
1 Haberer, H., Arch. f. klin. Chir. (Langenbeck), 1907, Ixxxii, 873; v. RecKlinghausen, Untersuchungen 
uber Rachitis und Osteomalacie, Jena, 1910; Klestadt, W., Beitr. z. klin. Chir. (Bruns), 1911, Ixxv, 681; 
Michalis, M., Uber Ostitis fibrosa, Inaug.-Diss., Berlin, 1913. 1050 
THE BONES AND JOINTS 
bone is accomplished not only by the osteoclasts, but also by invading 
blood-vessels and by halisteresis. Ultimately, poorly organized bone 
may form in the fibrous tissue. 
The most frequent site is the skull, although the tibia and femur are 
often involved ultimately, and, as the disease advances, may enlarge, 
soften, and, finally, undergo marked anterior curvature from the weight 
of the body; spontaneous fractures, however, are rare. Spinal curva- 
tures result from the softening of the bodies of the vertebrae. The bones 
of the skull thicken and enlarge, but are very spongy and may be pliable 
owing to the lack of lime salts. The bones of the face also enlarge, and 
confusion with leontiasis ossea may result.1 
ANOMALIES OF METABOLISM. 
Atrophy.-In old age or in senile conditions, the bones, especially 
those of the jaws, may become atrophied by the absorption of the hard 
tissue; the medullary spaces may be enlarged; the marrow tissue may 
contain less fat and may often be gelatinous in appearance. Senile 
kyphosis is often due to atrophy of the bodies of the vertebrae. 
As the result of lack of use or from any cause which interferes with 
the nutrition of the bone, such as paralysis of the muscles or diseases of 
the joints, the bones may atrophy. Good examples of this are the conical 
shape assumed by bone ends after amputation and the bone shortening 
seen after poliomyelitic paralysis. Such atrophy after relatively slight 
injury has been shown by skiagraphs to be frequent2 (see Fig. 733, page 
1071). 
The bone destruction may assume three types. The first is the result 
of the excess in the rate of physiological absorption by osteoclasts over 
that of the deposition of fresh bone by the osteoblasts; this is seen in 
pressure atrophy due to aneurysms or tumors, and is the process usually 
called rarefying osteitis. In the atrophy due to age, to inactivity, and 
to nerve lesions, there is a reduced osteoblastic new formation with a 
normal rate of osteoclastic destruction. The periosteum during these 
events may keep on building bone, so that the total volume appears 
greater though the weight per cubic centimeter may be less than that of 
normal bone. 
The second type is due to the perforation of the bone by new-formed 
capillaries, though just how these cause the resorption is unknown. The 
process is usually limited to small areas, and regeneration of bone may 
fill all the absorbed areas. 
The third process (halisteresis) begins with the removal of the lime 
salts of the bone; the resulting osteoid tissue is then dissolved. The 
phenomenon is seen chiefly in osteomalacia and rickets. 
The bones, sometimes as the result of atrophy and sometimes from 
1 Paget, J., Med. Chir. Trans., 1877, lx, 37; 1882, Ixv, 225; Stilling, H., Virchows Arch., 1890, cxix, 
542; Watson, TV. T., Bull. Johns Hopkins Hosp., 1898, ix, 133; Prince, M., Am. Jour. Med. Sc., 1902, 
cxxiv, 796; Fitz, R. H., ibid., p. 814; Vincent, Maladie osseuse de Paget, Paris, 1904; Higbee, W. 8., and 
Ellis, A.G., Jour. Med. Research, 1911, N. S. xix, 13 (bibl.); Vogel, K. M., Med. Record, 1911, Ixxx, 214; 
Norrie, V. H., and Wallace, G., Proc. New York Path. Soc., 1912, xii, 69. 
2 SudecK, P., Deutsch, med. Wchnschr., 1902, xxviii, 336. 1051 
THE BONES AND JOINTS 
causes which we do not understand, are unusually brittle and liable to 
fracture. The frequency of fracture of the hip in old persons is an ex- 
ample of such brittleness, the spontaneous fractures of tabes and syringo- 
myelia are examples of the neurotrophic types of osteoporosis (see page 
1050).1 
Osteomalacia.-This lesion consists of the softening of fully formed 
hard bone tissue by the removal of its inorganic salts {halisteresis} with, 
at the same time, a moderate amount of new formation of osteoid tissue.2 
To this regenerative process is due the repair of fractures by callus occa- 
sionally seen in the osteomalatic. The rare form of osteomalacia occur- 
ring in children3 is to be distinguished from rickets, whose lesions are 
due to a faulty development of bone, although in certain external char- 
acters and even in some histological processes the two diseases sometimes 
present considerable similarity. Osteomalacia usually occurs in adult 
females during pregnancy and after parturition; more rarely, it occurs 
in males, in females unassociated with the above conditions, and in chil- 
dren. A senile type is infrequent.4 
Microscopical examination shows that the decalcification occurs first 
in the periphery of the Haversian canals and in the inner layers of the 
walls of the marrow spaces. As the salts of lime are removed, the base- 
ment substance at first remains as a finely fibrillated material, still pre- 
serving the original lamellation; the bone cells may be changed in shape or 
degenerated. After a time the decalcified tissue may disintegrate and 
be absorbed, and its place may be occupied by new-formed marrow or 
granulation tissue. As the disease goes on, the medullary tissue is con- 
gested and red, the fat is absorbed, and there is a great accumulation of 
marrow cells; or the marrow may assume a gelatinous appearance. The 
decalcification and absorption of the bone from within may proceed so 
far that the bony substance in the cancellous tissue almost entirely dis- 
appears, and the compact bone is reduced to a thin, soft, decalcified 
tissue inclosed in the periosteum. The disease is not always continu- 
ously progressive, but may be subject to temporary cessation. 
Nothing definite is known as to its causation except that a consider- 
able percentage of cases are coincident with pregnancy. Removal of the 
ovaries has resulted in some instances in a cure of the disease.5 
As a result of the softened condition of the bones, the weight of the 
body and the actions of the muscles may induce a series of deformities 
which are sometimes excessive: curvatures of the spine, complete and 
incomplete fractures of the bone; distortions of the pelvis, sternum, etc. 
There is a tendency to a general involvement of the bones, but the changes 
are sometimes confined to single bones or to groups of bones. The cra- 
nium is rarely much affected, and when it is diseased the lesion is at the 
base. In the puerperal type, the first symptoms point to the pelvis as 
the usual site of the lesion. In males and non-parturient females, the 
1 For neuropathic types, see Grunert, Deutsch. Ztschr. f. Chir., 1905, Ixxvi, 254. 
2 Ribbert, Anat. Untersuch. uber die Osteomalacie, Bibi. Med., 1893, Abt. C., H. 2; v. Reckling- 
hausen, Untersuchungen iiber Rachitis u. Osteomalacie, Jena, 1910. 
3 Schmidt, M. B., Verhandl. d. deutsch. path. Gesellsch., 1909, xiii, 3. 
4 Weber, O., Virchows Arch., 1867, xxxviii, 1. 
8 Fehling, H., Arch. f. Gynak., 1891, xxxix, 468. 1052 
THE BONES AND JOINTS 
spinal column and thorax are first affected, and there is usually a rapid 
spread to other parts of the skeleton. 
Rachitis (Rickets).-Rickets is a metabolic disease affecting the bone, 
in which proper ossification does not take place.1 It occurs usually 
during the first two years of life, but may be seen as late as the twentieth 
year. Although it had long been held that the disease might be con- 
genital,2 this view has of late been abandoned.3 Its cause is still unknown 
though recent experimental studies have added much to our knowledge.4 
The physiological growth of bones presents three phases. They 
grow in length by the production of bone in the cartilage between the 
epiphysis and diaphysis; in thickness, by the growth of bone from 
the inner layers of the periosteum. At the same time the medullary 
canal is enlarged, in proportion to the growth of the bone, by the disap- 
pearance of the inner layers of bone. 
In rickets these three phases of growth are abnormal. The carti- 
laginous and subperiosteal cell growth which precedes ossification, goes 
on with increased rapidity and exuberance and in an irregular manner, 
both between the epiphyses and diaphyses and beneath the periosteum, 
while the actual ossification is imperfect, irregular, or wanting. Even 
the lime salts of the previously ossified bone may be removed by halis- 
teresis. At the same time the dilatation of the medullary cavity goes 
on irregularly and often to an excessive degree. The marrow may be 
replaced by fibrous tissue in which imperfect bone or osteoid tissue may 
develop. Microscopic examination of the region in a rachitic bone be- 
tween the epiphysis and diaphysis (Fig. 718), shows that the cartilage cells 
are not regularly arranged in rows along a definite zone in advance of the 
line of ossification, as in normal development, but that there is an irreg- 
ular heaping-up of cartilage cells, sometimes in rows, sometimes not, 
over an ill-defined and irregular area. The zone of calcification also, 
instead of being narrow, regular, and sharply defined, is lacking in uni- 
formity. Areas of calcification may be isolated in the region of prolifer- 
ating cartilage cells, or calcification may be altogether absent over con- 
siderable areas. 
Corresponding to these irregularities the ossification zone is also irreg- 
ular. New-formed bone and marrow cavities containing blood-vessels 
may lie in the midst of the cartilage, or masses of cartilage may lie deep 
in the region which should be completely ossified. In other places it 
seems as if the cartilage tissue were directly converted by metaplasia into 
an ill-formed bone or osteoid tissue. It will readily be seen from this 
that the medullary spaces of the new-formed bone are irregular, and this 
abnormality is enhanced by the premature intramedullary absorption of 
the bone. 
1 See Schmorl, Deutsch. Arch. f. klin. Med., 1905, Ixxxv, 170; and Ergebn. d. inn. Med. u. Kinder- 
heilk., 1909, iv, 403. For general studies of the lesion, see v. RecKlinghausen, Untersuchungen uber 
Rachitis u. Osteomalacie, Jena, 1910; Schmorl, Verhandl. d. deutsch. path. Gesellsch., 1905, ix, 248; 
1909, xiii, 40; Schmidt, M. B., ibid., 1909, xiii, 3; Dyrenfurth, F., Virchows Arch., 1906, clxxxvi, 321; 
Goetsch, W., Zieglers Beitr., 1906, xxxix, 218. 
2 Salvetti, C., Zieglers Beitr., 1894, xvi, 29 (bibl.). 
s Escher, Jahrb. f. Kinderheilk., 1902, Ivi, 613; Wieland, Ergebn. d. inn. Med. u. Kinderheilk., 1910, 
vi, 64. 
* Sherman, H. C., and Pappenheimer, A. M., Jour. Exper. Med., 1921, xxxiv, 189. THE BONES AND JOINTS 
1053 
Similar irregularity in the bone formation may be seen beneath the 
periosteum. An excessive proliferation of cells in the inner layers of 
the periosteum, the irregular calcification which occurs about them, and 
the absence of uniformity in the elaboration of ill-structured bone, con- 
spire to produce an irregular, spongy bone tissue instead of the compact, 
lamellated tissue which is so necessary here for the solidity of the struc- 
ture. The increased cell growth between the epiphyses and diaphyses 
produces the peculiar knobby swellings which are characteristic of 
rickets. The diseased areas show marked congestion. 
The result of these processes is that the bones do not possess solidity 
and cannot resist the traction of the muscles or outside pressure. The 
epiphyses may be displaced or bent, especially in the ribs, less frequently 
in the long bones. The long bones and the pelvic bones may be bent 
Fig. 718.-Rachitic Bone. 
Showing ossification zone in a longitudinal section of a rib. 
into a variety of forms (Fig. 719). Incomplete fractures are not infre- 
quent. Complete fractures do not usually occur until the later stages of 
the disease, when the bones have become more solid. The head is often 
square; the cranium may be unnaturally large for the size of the face, 
due either to edema or to a mild hydrocephalus; the fontanelles and 
sutures may remain open; the bones may be soft, porous, and hyperemic, 
while at their edges there may be rough, bony projections beneath the 
pericranium. Sometimes, especially in the occipital bone, there are 
rounded defects in the bone, filled only with a fibrous membrane; this 
constitutes one of the forms of craniotabes (Fig. 720). The defects are 
probably due to the pressure of the edematous brain from within plus the 
pressure from the weight of the head on the pillow from without. 
It does not fall within the scope of this work to describe the various 
deformities which may occur as a result of this disease. The familiar 
pigeon breast; the rows of knobs along the sides of the chest from bend- 1054 
THE BONES AND JOINTS 
ing and dilatation of the ribs at the point of junction of cartilage and 
bone (rachitic rosary)', the knock-knees, bow-legs, spinal curvatures, etc., 
may all be the result of rachitic weakening of the bones. 
After a time the rachitic process may stop and the bones take on a more 
normal character. The porous bone and osteoid tissue become compact 
and even unnaturally dense; the swellings at the epiphyses disappear; many 
Fig. 719.-Rickets. 
Showing irregular ossification and bending of the long bones. 
of the deformed bones may become of a normal shape. In severe cases, 
however, the deformities continue through life; especially there is a ces- 
sation of the growth of the bones in their long axis, so that the persons 
affected are dwarfed. 
The disease may have an acute or a chronic character. The acute 
form begins usually during the first six months of life. The children are 
apt to suffer from vomiting, diarrhea, profuse sweating, chronic bron- 1055 
THE BONES AND JOINTS 
chitis and pneumonia, general anemia, and wasting. Either they die or 
the rachitic process is gradually developed. The chronic form is seen in 
older children, and often in those apparently healthy. The changes in 
the bones may take place without constitutional symptoms, though there 
are often catarrhal bronchitis, pneumonia, and anemia, with enlargement 
of the spleen. Occasionally, the anemia is very severe (von Jaksch type) 
and may cause death. 
This skull of a child is large, its bones are thin, with holes due to faulty development and 
covered only by a thin, fibrous membrane. 
Fig. 720.-Craniotabes. 
Moller-Barlow Disease (Osteotabes Infantum).-This is a disease of 
infants, occurring usually in the first year of life, and is due apparently 
to feeding with boiled milk or artificial foods. Clinically and patholog- 
ically it resembles the scurvy of adults1 and like the latter can often be 
cured by the addition to the diet of fresh fruit juices. The bone changes 
are the important lesion. The normal cellular marrow is replaced by a 
loose, poorly vascularized fibrous tissue, with absorption of the bony 
tissue. The bone ceases to grow while the normal resorptive activities 
continue, resulting in rarefaction of the bone trabeculae and imperfect 
ossification at the epiphyseal junctions. The epiphyses are, in conse- 
quence, easily separated from the diaphyses, and the rib cartilages from 
the ribs. Fracture of the diaphysis is not infrequent. Coincident with 
these bone changes a hemorrhagic diathesis makes its appearance, and 
blood accumulates under the periosteum of the long bones and skull, in 
the marrow cavity, and, in severe cases, in the skin, mucous membranes, 
eyelids, orbit, and kidney.2 The gums may swell, become spongy, and 
1 Looser, E., Jahrb. f. Kinderheilk., 1905, Ixii, 743; Schmorl, G., ibid., 1907, Ixv, 50. 
2 Heubner, O., Berl. klin. Wchnschr., 1903, xi, 285; Weiss, S., Arch. f. Kinderh., 1905, xli, 43; Fraenkel, 
E., Fortschr. a. d. Geb. d. Rontgenstrahlen, 1904, vii, 62; 1906, x, 1; 1908, xii, 151, Erganz. Heft, 
1911-12, xviii, 172. 1056 
bleed. If the disease is cured under proper feeding, the alterations in the 
normal osteogenesis and the subperiosteal hemorrhages may lead to per- 
manent deformities and bony overgrowths (see also page 495). 
Rickets is present in about half the cases, though the two diseases 
are of an entirely different nature.1 
THE BONES AND JOINTS 
DISTURBANCES OF CIRCULATION. 
Hyperemia.-The evidences of this condition are most apparent to the 
naked eye in the periosteum and marrow, particularly the latter. Hyper- 
emia occurs usually as an accompaniment of inflammatory processes in 
the bone; when it is marked, the periosteum is swollen and red; the 
compact bone tissue may appear of a pink color, while the marrow, either 
by an increase in the amount of blood or absorption of its fat, or both, 
may be of a uniform dark red color or mottled with red and reddish 
yellow. 
Hemorrhage.-This may be due to wounds and injuries and to in- 
flammatory and necrotic processes; hemorrhages often accompany adult 
and infantile scurvy, purpura, hemorrhagic diathesis, and leukemia. 
Clots of considerable size between the periosteum and bone may lead to 
serious consequences by cutting off the blood supply to the superficial 
layers of bone and thus inducing necrosis. But when not infected 
through contact with the air or by microorganisms brought in the circu- 
latory channels, they are not usually of serious import, and are readily 
absorbed, though the periosteum may be stimulated to new and irregular 
bone formation. The smaller hemorrhages of the medulla are not usu- 
ally of much importance. The destruction of the extravasated blood 
may lead to extensive pigmentation of the marrow. 
INFLAMMATION. 
The periosteum, bone tissue, and marrow are so intimately connected 
that in most cases they all share to a greater or less degree in the patho- 
logical alterations of the bones. But as sometimes one, sometimes 
another, is most markedly involved, it is convenient to consider sepa- 
rately here the inflammatory changes by which they are respectively 
affected. 
Periostitis. 
Exudative inflammation in the periosteum is essentially similar to 
this form of inflammation in other parts of the body, except as it is 
modified by the relationships of the connective tissue and blood-vessels 
to the hard bone and by the presence and performances of the osteoblasts 
and associated cells peculiar to bone. 
We may distinguish several forms of periosteal inflammation. 
1 Schmorl, G., Zieglers Beitr., 1901, xxx, 215; Schodel and Nauwercic, Moller-Barlow'sche Krankheit, 
Jena, 1900. THE BONES AND JOINTS 
1057 
Simple Exudative Periostitis.-This is apt to occur in children and 
ill-nourished persons after comparatively slight injuries or from unknown 
causes. The periosteum is thickened, succulent, congested, and more or 
less abundantly infiltrated with leucocytes. It becomes less firmly 
adherent to the bone, and the cells of the inner layers are increased in 
number. This form of inflammation may terminate in resolution, or it 
may lead to other phases of inflammation. Even in the mild cases, the 
irritation often leads to the formation of small nodules or spicules of bone 
(osteophytes) under the periosteum (see Ossifying Periostitis). 
Suppurative Periostitis may begin as a simple or as a purulent inflam- 
mation. The pus is formed in the inner layers of the periosteum, and 
between it and the bone. The outer layers of the periosteum may for 
a long time resist the suppurative process. The accumulation of pus 
may dissect up the membrane from the bone and leave the latter bare. 
The pus thus formed may remain in this position for a long time, 
or be absorbed, or become dry and cheesy, or it may burst through 
the periosteum and lead to abscesses in the soft parts. The bone, if 
separated from its nutrient membrane, may remain unchanged, but 
more frequently necrosis or inflammation of the bone itself is set up. 
Such a periostitis may run an acute or a chronic course. 
Sometimes suppurative periostitis takes on a very malignant 
character. Pus is developed not only beneath, but in the periosteum, 
forming abscesses filled with foul pus. The periosteum breaks dowm 
into a gangrenous, foul-smelling mass, and the same change may affect 
the neighboring soft parts. The medulla may take part in the process 
and break down into a purulent, gangrenous mass. Hemorrhages may 
complicate the process. The lymph-nodes may be enlarged and swollen; 
abscesses may form in different parts of the body; and the patient may 
die with the symptoms of pyemia. The streptococcus and staphylococcus 
pyogenes are the most common excitants of suppurative inflammation. 
Fibrous Periostitis.-This is a chronic form of inflammation, resulting 
in the development of new connective tissue in the periosteum, which 
becomes thickened and dense and usually adherent to the bone. It 
may accompany necrosis, chronic arthritis, chronic ulcers of adjacent soft 
parts, etc., or follow simple acute periostitis. It may in many instances 
be regarded as a conservative process of a reparative character. 
Ossifying Periostitis results in the formation of new bone from the 
inner layers of the periosteum. The masses of new-formed bone, called 
osteophytes, are of variable shape. They may form a thin, velvet-like, 
villous layer (Fig. 721); or appear as little spicula; or form larger, rounded 
masses (Fig. 722 and 723), or a thick, uniform layer extending over a 
large part of a bone. They may have at first a loose, spongy character, 
and be loosely connected with the old bone. But layers of compact 
bone tissue are formed within their medullary spaces, which are thus 
gradually filled, and they join the old bone so that they may finally 
become as compact as or even more compact and dense than normal bone 
to which they are firmly joined. The hyperostoses and exostoses thus 1058 
THE BONES AND JOINTS 
Fig. 721.-Ossifying Periostitis. 
An irregular layer of new bone is forming between the periosteum and the old bone. 
Fig. 722.-Ossifying Periostitis-Tibia. 
Large exostoses at the end of the bone. The process involves the joint, and the bone is enlarged. 
Fig. 723.-Ossifying Periostitis With Large Exostoses-Femur. 
A large part of the shaft is thickened and covered with ragged platelets of new-formed bone 
while above large rough exostoses project. This bone has been the seat of rarefying and formative 
osteitis. THE BONES AND JOINTS 
1059 
formed may remain indefinitely, or they may gradually become smaller 
and finally disappear by absorption. 
The formation of new bone in osteophytes, or in dense masses beneath 
and in the periosteum, occurs as a result of the same process by which 
bone tissue is normally formed. The osteoblasts, which are developed 
along the blood-vessels, possess the power of depositing osseous basement 
substance about themselves and so forming bone. Pathological new 
formation of bone differs from the normal mainly in the conditions under 
which it occurs. The blood-vessels around which the pathological bone 
develops, grow out of the old vessels, as in the formation of granulation 
tissue, are irregularly arranged, and are subject to a variety of abnormal 
nutritive and mechanical conditions, so that the new bone is usually 
formed, not in a series of definite systems of lamellae, but, as above 
Fig. 724.-Tuberculosis of the Joint. 
Shows caries with extensive destruction of the bone. 
described, in a series of irregular spicula or masses. Moreover, as will be 
seen further on, the conditions under which it is formed being liable to 
change, and itself serving no definite purpose in the economy, as does 
normal bone, pathological new bone is often an evanescent structure. 
The details of its disappearance will be considered below. 
Syphilitic Periostitis.-Syphilitic infection may excite simple, purulent, 
fibrous, or ossifying periostitis. In addition to these, gummata (page 
306) may be developed in the periosteum in long bones, most frequently 
on the shaft, where they cause a more or less fusiform enlargement. The 
bone tissue is usually more or less involved. The gummata may be 
absorbed or undergo cheesy degeneration, or be converted into fibrous 
tissue, or they may suppurate. 
Tuberculous Periostitis.-In badly nourished persons, particularly in 
children suffering from scrofula, chronic purulent periostitis is frequently 1060 
THE BONES AND JOINTS 
associated with the formation of miliary tubercles. Abscesses are apt 
to form in and about the periosteum, and when these are evacuated gran- 
ulation tissue, which contains miliary tubercles, may develop. The bone 
is apt to be involved to a greater or less extent in simple inflammatory 
changes or caries (Fig. 724). 
Osteitis. 
Inflammation in bone tissue is dependent upon the same general con- 
ditions and presents essentially the same series of phenomena as inflam- 
mation in other kinds of connective tissue. But it is variously modified 
in detail by the peculiar dense and unyielding character of the basement 
substance, and by certain peculiarities of the blood supply and the 
nutritive conditions under which the cells are placed. In simple exuda- 
tive inflammation the same series of phenomena occurs in connection with 
the blood-vessels as in other tissues, resulting in the production of serum, 
fibrin, and pus; but these changes are limited in extent, and they are 
constantly associated with striking alterations in the basement sub- 
stance. It is these secondary alterations in the basement substance 
which lend to inflammations of the bone their most essential characters, 
and in the prominence which these assume the fundamental alterations 
are often overlooked. The most common of these secondary alterations 
are the absorption of the hard basement substance of the bone and 
its replacement by, or conversion into, young cellular forms of fibrillar 
connective tissue or marrow tissue, and the formation, in a more or 
less typical manner, of new bone. The active phenomena of inflamma- 
tion in bone are processes of the blood-vessels and the fibrillar connective 
tissue as in other parts of the body, the hard bone substance being in a 
certain sense only secondarily involved. 
As a result of these changes the bone in simple inflammation becomes 
more vascular, and, with an increase of spaces filled with granulation or 
marrow tissue, more porous at the expense of the dense basement sub- 
stance; or the new-formed spaces or the marrow cavities may be con- 
stantly encroached upon by the new-formed bone lamellae on their walls, 
so that the bone becomes more compact; or as is frequently the case, 
both series of changes occur either simultaneously in different regions, 
or follow each other, or are variously associated together. Very fre- 
quently one or the other of the opposing forms of alteration predominates, 
or one may occur to the exclusion of the other, and we thus have two 
prominent forms of inflammation, which are called rarefying osteitis 
or osteoporosis, and condensing osteitis or osteosclerosis. The exact 
nature of the conditions under which in one case the bones become 
more, in another less dense, we do not understand. Nor is the exact way 
in which the osteoclasts dissolve hard bone, or the osteoblasts secure and 
deposit inorganic salts and become bone cells as yet clear. Furthermore, 
more or less characteristic forms of inflammation may occur in syphilitic 
and tuberculous infection-syphilitic and tuberculous osteitis. Suppura- 
tive osteitis may further complicate the process. 1061 
THE BONES AND JOINTS 
In addition to these phases of inflammation in bone, and in frequent 
and varied association with them, there are alterations leading to death 
and destruction of bone tissue in greater or less amount, which are called 
caries and necrosis. Finally, any of these forms, and commonly several 
of them at once, are variously associated with more or less marked 
inflammatory or degenerative alterations of the periosteum on the one 
hand, of the marrow tissue on the other, or of both combined. 
Rarefying Osteitis consists essentially in the formation in the marrow 
spaces, or Haversian canals, or beneath the periosteum, of new, very cel- 
lular and vascular tissue, resembling granulation or young marrow tissue, 
under whose influence the basement substance of the bone is absorbed. 
This absorption of the bone takes place largely as bone is absorbed in 
normal growth, namely under the influence of certain large cells, which 
are grouped around the blood-vessels. If a thin section of bone which 
Fig. 725.-Rarefying Osteitis in Ulna of Child. 
a, Isolated bone fragment with rough edges; b, marrow tissue; c, Howship's lacuna; with osteoclast 
is undergoing absorption be examined (Fig. 725), the edges of the bone 
which border on the vascular surfaces are found irregularly indented by 
deep or shallow depressions, sometimes simple, sometimes quite complex. 
These are called Howship's lacunae and are usually filled or lined by larger 
and smaller granular, frequently multinuclear cells-the so-called osteo- 
clasts. In the larger lacunae there may be granulation tissue with loops of 
blood-vessels, with or without osteoclasts. Under the influence of the 
osteoclasts or of the new vascular tissue, the bone is gradually ab- 
sorbed. 
On the other hand, there may be irregular branching channels through 
the bone across the lamellae, which appear to be due to the enlargement 
and coalescence of the lacunae and canaliculi, without the direct influence 
of blood-vessels or other cells than the fixed cells of the bone. The tissue 
which replaces the absorbed bone may be very rich in small spheroidal 
cells, or it may be more or less fibrillar. 1062 
THE BONES AND JOINTS 
As a result of this process irregular islets of bone tissue may be 
entirely separated from adjacent bone and surrounded by a more or less 
fibrillar vascular tissue; this is most apt to occur in the cancellous tissue. 
Or the originally compact bone may become traversed by a series of larger 
and smaller, irregularly branching, communicating channels with ragged 
walls. These progressive alterations may cease, and be succeeded by a 
new formation of bone along the edges of the channels or cavities. 
Rarefying osteitis may occur as an independent process from unknown 
causes; it is often associated with syphilis, with diseases of the joints, 
with fractures or other injuries to the bone; it often forms a predominant 
feature in tuberculous inflammation of the bones. It is chiefly by a 
rarefying osteitis that bone tissue is eroded and destroyed in the vicinity 
of tumors, aneurysms, etc., which exert pressure on the bones. By the 
same process the sharp ends of fractured bones may be rounded off as 
healing proceeds. 
When this form of inflammation occurs in cancellous bone tissue the 
marrow is red or gelatinous, and the bony septa may disappear altogether, 
so that in extreme cases there may be, instead of cancellous bone, a mass 
of granulation tissue. When the process occurs in the articular extrem- 
ity of a bone the granulating medulla may send little offshoots through 
the articular cartilage. These may become fused together and inflam- 
mation of the joint may follow. The walls of the shafts of the long 
bones may be converted into spongy tissue. If, as is sometimes the case, 
an ossifying periostitis occurs at the same time, the bone is thickened but 
spongy; or sometimes there are concentric layers of compact bone tissue, 
separated by rarefied bone. 
Condensing Osteitis (Osteosclerosis).-This lesion is characterized by 
the new formation of bone in the walls of the marrow cavities or Haver- 
sian canals. The bone is formed under the influence of the blood-vessels 
and osteoblasts, as in normal bone formation, but with less regularity. 
It may result in the conversion of cancellous tissue into compact bone, 
in the filling up of the medullary cavity of long bones with more or less 
dense bone tissue. The compact bone, owing to the filling of its Haver- 
sian canals, may become very dense and ivory-like. When the medullary 
cavities of long bones are involved the yellow marrow is converted into 
red marrow by the absorption of fat and by increased vascularity. This 
change is due, in part at least, to the condensation, so to speak, into 
definite areas, of the marrow tissue invisible in the fat, and also to the 
destruction of the marrow in other areas, as a result of which functional 
hyperplasia of the remaining marrow occurs. Severe and even fatal 
anemia may result if the osteosclerosis is extensive, and a secondary 
osteosclerosis may in rare instances follow the development of a leukemia 
or a severe anemia.1 
Osteosclerosis is frequently associated with ossifying periostitis. It 
often follows rarefying osteitis, and then the Howship's lacunae resulting 
from the original absorption process may be filled and covered in with 
new bone lamellae (Fig. 726). The presence in the bone-marrow of cer- 
i Assmann, HZieglers Beitr., 1907, xli, 565 (bibl.). THE BONES AND JOINTS 
1063 
tain types of metastatic carcinoma, especially prostatic, may lead to an 
extensive osteosclerosis.1 It is apt to occur in connection with necrosis 
or chronic inflammation of adjacent soft parts, and is then a reparative 
and conservative process, but it sometimes occurs independently under 
unknown conditions. 
Suppurative Osteitis (Abscess of Bone).-This process occurs usually in 
the ends of the long bones, and is associated with rarefying osteitis. As 
the bone tissue is absorbed, a circumscribed cavity may be formed in the 
bone, filled with pus, and lined with granulation tissue. 
Less frequently abscesses are formed in the shaft of a long bone by 
circumscribed suppuration of the medulla. Such abscesses may occur in 
old people and may be of long duration. They may gradually enlarge 
Fig. 726.-•Condensing Osteitis, or Osteosclerosis, in Ulna of Child 
a, Fragment of old bone with roughened, sinuous edges; &, old Howship's lacunae covered with more 
recently formed bone lamellae; c, d, new Haversian canals. 
and be accompanied by an ossifying periostitis, so that the bone is ex- 
panded. The abscesses in suppurative osteitis sometimes develop rapidly 
and may perforate. On the other hand, instead of abscesses, there may 
be a diffuse infiltration with pus of the Haversian canals or of the spaces 
formed by rarefying osteitis (see Osteomyelitis, below). Staphylococcus 
aureus is usually found in the pus. 
The lesion of phosphorus poisoning is of this type. It begins with a 
productive osteitis and periostitis which, by infection from the mouth 
becomes a suppurative process involving both the periosteum and the 
bone. 
Osteomyelitis.-The tissues of the medulla so frequently share in the 
inflammatory processes in bone that many conditions described as osteitis 
are really osteomyelitis. It is customary, however, to reserve the latter 
name for those cases in which the medulla is primarily or chiefly involved. 
1 v. Recklinghausen, Festschrift f. Virchow, Berlin, 1891 . 1064 
THE BONES AND JOINTS 
Acute Infectious Osteomyelitis.-This may occur as the result of 
a local injury which permits the access, or favors the development, of 
pyogenic microorganisms; it may be metastatic, resulting from the 
transportation of infectious material from other parts of the body in septi- 
cemia and pyemia, in typhoid fever, in the exanthematous fevers, and 
under other conditions; or it may occur without evidence of local predis- 
position or of infectious processes in other parts of the body. 
The lesions of acute infectious osteomyelitis are, in the large majority 
of cases at least, due to the presence and action of the pyogenic cocci, 
the Staphylococcus pyogenes and the Streptococcus pyogenes, and in 
many of its forms it may be regarded as one of the phases of septicemia 
or septicopyemia. 
While the lesions vary widely, the following general description is 
applicable to a considerable proportion of the cases: 
At the commencement of the disease, which usually begins in the shaft 
of one of the long bones, there are hyperemia and edema of the medulla, 
so that on inspection the marrow is found to be soft and of a dark red color. 
A diffuse suppuration now rapidly ensues, and the marrow becomes 
streaked or mottled with gray. Occasionally, though not often, larger 
and smaller abscesses may form in the marrow. The inflammatory areas 
may be circumscribed; or, in the more malignant cases, the entire mar- 
row may become rapidly involved. The cancellous tissue of one or both 
of the epiphyses usually becomes affected. The disease, however, is 
not commonly confined to the medullary spaces. The periosteum 
becomes edematous and infiltrated with pus, and the surrounding soft 
parts may become the seat of intense inflammatory changes. Abscesses 
of the periosteum or surrounding tissues are apt to form. As a result of 
these changes, necrosis of greater or less portions of the bone may ensue 
with the formation of larger or smaller sequestra (see p. 1068). The 
medullary cavity may become enlarged as pus accumulates, and the wall 
of the bone may be broken through, permitting the discharge of pus 
outward. Sometimes several bones are involved at once. Secondary 
involvement of the joints is very frequent. Here there may be only a 
serous or purulent exudation; or the acute and destructive inflammatory 
process may extend beneath the joint and produce extensive alterations. 
In young persons the epiphyses very frequently become separated from 
the shaft by the destruction of the cartilage which binds them together. 
In the severer cases, which are often called, par excellence, malignant 
osteomyelitis, the changes may be very rapid and destructive. The 
medulla is disintegrated and gangrenous; the joints are soon involved; 
necrosis of large portions of the bone, sometimes of the whole shaft, 
occurs, the periosteum and surrounding parts become gangrenous; the 
veins contain thrombi, and pyemic infarctions and abscesses may form 
in various parts of the body.1 
1 Consult, for an elaborate treatment of acute osteomyelitis in its relationship to other forms of 
inflammation, with bibl., Jordan, Beitr. z. klin. Chir, (Bruns), 1893, x, 587. For a study of this condi- 
tion in childhood, see Koplik and Van Arsdale, Am. Jour. Med. Sc., 1892, ciii, 422 and 535. THE BONES AND JOINTS 
1065 
Chronic Osteomyelitis.-In prolonged cases of osteomyelitis there 
is apt to be more or less ossifying periostitis and osteosclerosis, and 
fistulae may form in the bone, through which the exudates are discharged.1 
Tuberculous Osteitis is primarily a tuberculous inflammation of the 
soft parts of bone with associated rarefying and formative processes in 
the hard bone. The tubercles are sometimes small and scattered (Fig. 
727), sometimes they unite to form larger foci or large diffuse caseous 
masses. There may be extensive involvement of the medulla. Rare- 
fying and condensing osteitis and necrosis often accompany the tuber- 
culous process. Thus the bone frequently becomes spongy or fragile 
A miliary tubercle formed in the cancellous tissue near the joint in tuberculous arthritis. 
Fig. 727.-Tuberculous Osteitis- 
(Fig. 724). Much of the new tissue formed in tuberculosis of the bones 
is simple granulation tissue or fibrous tissue of reparative character.2 
Not infrequently an exudative inflammation occurs, with the for- 
mation of the so-called cold abscesses. This abscess formation in bone 
as well as in soft parts may be due to the tubercle bacillus alone. But 
concurrent infection of tuberculous areas often takes place, the pyogenic 
or other organisms gaining access to the involved region either through 
the blood-channels or by surface openings, fistulse, sinuses, etc. 
Tuberculous inflammation is most frequent in early life and, save 
for the smaller bones, such as the phalanges, metacarpal, metatarsal, it 
rarely involves the shafts of bones.3 In young children, however, the 
disease involves the phalanges of the hands and feet in the form of spindle- 
1 For a resume of the deformities resulting from osteomyelitis, consult Park, R., Med. Record, 
1895, xlviii, 613. 
2 For a review of recent opinions on bone tuberculosis, see Fraser, J., Jour. Am. Med. Assn., 
1915, Ixiv, 17. 
3 For a study of the relative prevalence of human and bovine types of tubercle bacilli in bone and 
joint tuberculosis of children, see Fraser, J., Jour. Exper. Med., 1912, xvi, 432 (bibl.); Griffith, A. S., Jour. 
Path, and Bacterio!., 1916, xxi, 54; and Cobbett, The Causes of Tuberculosis, Cambridge, 1917. 1066 
THE BONES AND JOINTS 
shaped swellings {spina ventosa). This is produced by deposition of new 
bone by the periosteum while the central spongy portion is progressively 
absorbed. A similar type is sometimes seen in the ulna and tibia. It 
is often associated with tuberculous involvement of the joints (Fig. 724). 
The bovine type of bacillus is present in about one-fourth of the cases. 
Syphilitic Osteitis.-Syphilitic infection may lead to one or other of the 
forms of osteitis just described, or gummatous nodules may form. Syph- 
ilitic osteitis usually commences in the periosteum, which becomes 
thickened and infiltrated with cells, so that 
there may be a circumscribed thickening 
of the periosteum, with or without distinct 
gummata. The vessels which extend from 
the periosteum into the bone become sur- 
rounded by new cellular tissue, which 
causes an enlargement of the canals. At 
this stage, if the periosteum be stripped off, 
it drags with it the vessels surrounded by 
the new cell growth, leaving the bone be- 
neath with numerous small perforations ex- 
tending inward. As the disease progresses 
the channels in the bone enlarge by a 
rarefying osteitis and coalesce, forming 
large, irregular defects filled with new 
fibrous tissue (Fig. 728). In these masses 
of new tissue, cheesy degeneration may oc- 
cur, so that the new growth has more or 
less of the character of a gumma. In the 
vicinity of these gumma-filled spaces a con- 
densing osteitis may occur, both in the 
substance of the bone and on the surface, 
in the form of osteophytes, so that the 
opening in the bone may be surrounded by 
an elevated, irregular ring of bone tissue. 
All this may occur beneath the uninvolved 
skin, or the skin may participate by a sup- 
purative inflammation, resulting in ulcera- 
tion. These processes may be circum- 
scribed or involve a large part of a bone. 
It is not infrequently associated with necro- 
sis of larger and smaller portions of bone. The syphilitic tissue may be 
absorbed and its place be more or less filled with fibrous tissue. Syphilitic 
osteitis is most frequent in the cranial bones, but may occur elsewhere, 
as in the sternum, clavicle, tibia and fibula, the ribs, etc. 
Congenital Syphilis.-The bones of young children in this condition 
may show increased density or evidences of periostitis, or irregular thick- 
enings, particularly of the skull. Characteristic lesions are frequently 
found in the long bones in still-born or young children who are the vic- 
tims of hereditary syphilis. These lesions are found for the most part 
Fig. 72S -Syphilitic Osteitis 
and Periostitis of Ulna. THE BONES AND JOINTS 
1067 
along the border zone between the epiphysis and diaphysis. In normal 
ossification of the long bones, the border line between the calcification 
and ossification zones is narrow, sharply defined, and straight, or lightly 
and evenly curved. In syphilitic bones, on the contrary, this line is 
broader and uneven, and presents various modifications, which merge into 
one another, so that all intermediate forms may be seen. In a lesion of 
moderate grade there may be, between the cartilage and the new-formed 
spongy bone, a white or reddish-white zone, about two millimeters in 
breadth, with very irregular borders, consisting of calcified cartilage, in 
which the linear groups of cartilage cells are more abundant than normal. 
In more pronounced lesions the calcified zone, still containing an unusual 
number of cartilage cells, is broader and still more irregular and less 
sharply outlined against the ossification zone. The cartilage just beyond 
it is softer and almost gelatinous, and may contain numerous blood-ves- 
sels, or islets of connective tissue, of calcification, or of irregular ossification. 
Finally the bone may be pouched out at the sides around the ossification 
and calcification zones, and the perichondrium and periosteum thickened. 
The whitish, irregular, calcified zone is hard and friable. Between this 
and the new-formed bone there is an irregular, soft, gray or grayish 
yellow zone, from two to four millimeters in thickness, which forms a loose, 
readily separated connection between the cartilage and the diaphysis. 
The white, friable zone consists mainly of irregular rows of degenerated 
and distorted cartilage cells lying in a calcified basement substance, of 
irregular masses of atypical bone tissue, and of blood-vessels surrounded 
by variously shaped cells. The soft zone consists of more or less vascular 
tissue with homogeneous basement substance, and round and spindle- 
shaped cells. This soft zone is not sharply outlined against the adjoining 
new-formed spongy bone, which, instead of consisting of the normal 
marrow spaces with bony lamellae between them, is largely composed of 
granulation tissue. 
Different phases of this faulty development may be seen in different 
bones in the same individual. According to Wegner the lesion is usually 
most advanced in the lower end of the femur, then in the lower ends of 
the leg bones and of the forearm, then in the upper ends of the tibia, 
femur, and fibula. 
Not infrequently there is fatty degeneration of the marrow cells and 
blood-vessels, giving the marrow a reddish yellow color. These altera- 
tions of the bones may occur, not only in children who have gummata in 
other parts of the body, but also in those in whom other evidences of 
syphilitic infection are absent. So uniform is their occurrence that their 
presence alone suffices for the establishment of a diagnosis. 
NECROSIS. 
Necrosis is the death of a larger or smaller portion of bone. This 
may be induced by conditions which deprive the bone of its proper vas- 
cular supply from the periosteum and medulla. It may be associated 
with suppurative periostitis, osteomyelitis, and osteitis, traumatic sepa- 1068 
THE BONES AND JOINTS 
ration of the periosteum, ulcers of neighboring soft parts, emboli, the 
action of phosphorus vapor, and exhaustive infectious diseases. Necro- 
sis is a pure form of gangrene, differing from gangrene of soft parts in 
that the dead bone has at first, and may retain for a long time, the general 
outward characters of the normal bone; while in dead soft parts rapid 
absorption may occur, or, should bacteria of various forms be presenter 
gain access to the dead tissue, putrefaction, with complex changes, may 
ensue. 
When a portion of bone has died, inflammation occurs at the dividing- 
line between the dead and living bone. This inflammation has the char- 
acters of a rarefying osteitis (see above), and finally separates the dead 
from the living bone. The dead bone, or sequestrum, may remain smooth 
and unaltered (Fig. 729), or it may be eroded by the influence of sur- 
rounding pus or granulation tissue or osteoclasts. In this way it is pos- 
sible for the sequestrum, if it be small, to be entirely absorbed. More 
frequently there is a production of new bone around the sequestrum, 
Fig. 729.-Necrosis of Bone. 
Showing sequestrum of dead bone partially surrounded by new-formed subperiosteal bone, 
with thickening of the shaft. 
either beneath the periosteum or in the substance of the bone, and this 
becomes lined with granulation tissue, from which pus may continue to 
be formed, bathing the sequestrum. 
Necrosis may involve the superficial layers, or the entire thickness of 
the wall of a long bone, or only the spongy tissue and inner layers, or an 
entire bone, or a number of different portions of the same bone; but it is 
most apt to occur in compact bone. 
The death and separation of the bone may be soon followed by the 
growth of new bone to repair the loss. The periosteum, the medulla, 
and the surrounding soft tissues may all take part in this new growth. 
The new bone is usually irregular, rough, and perforated with openings 
through which pus formed around the sequestrum may be discharged. 
If the sequestrum be removed, healing may occur by the formation of 
new bone; but the bone is usually more or less distorted by the irregular 
new ossification. Bacteria persist for a long time in sequestra, and are 
responsible for the acute inflammatory processes sometimes seen after 
aseptic operations on diseased bones.1 
1 Taylor and Davies, Ann. Surg., 1917, lxvi, 522, 1069 
THE BONES AND JOINTS 
Phosphorus Necrosis.-Under the influence of phosphorus vapor, 
periostitis and osteitis, particularly of the jaw, are apt to occur, and 
usually lead to more or less extensive necrosis, generally associated with 
prolonged and often extensive suppuration. 
CARIES. 
Caries of bone is essentially an ulcerative osteitis resulting in progres- 
sive molecular destruction of the bone tissue. It differs from necrosis in 
that, in the latter larger and smaller masses of bone die, while in caries the 
destruction is molecular and gradual 
(Fig. 730). It may occur in connec- 
tion with any form of osteitis, with 
periostitis and osteomyelitis, or it 
may be secondary to inflammatory or 
destructive processes in the joints or 
adjacent soft parts. The depressed 
surfaces of bones in which caries is 
progressing are rough and more or 
less finely jagged, and may be covered 
with granulations. The minute 
changes by which ulceration and 
destruction of the bone are pro- 
duced in caries are somewhat analo- 
gous with those in rarefying osteitis, 
but there are marked degenerative 
changes in the bone cells, which may 
become fatty or converted into a 
granular material. Moreover, the 
basement substance of the bone, in- 
stead of being absorbed, may disin- 
tegrate, with the formation of larger 
and smaller masses of detritus. 
Sometimes the lime salts are re- 
moved from the basement substance, 
which is converted into atypical 
fibrillar tissue and fatty and granu- 
lar detritus. Very extensive sup- 
purations and necrosis may be asso- 
ciated with caries. 
Long-continued caries, especially 
in badly nourished individuals, is apt 
to become complicated with tubercu- 
lous inflammation. 
There is very little tendency to spontaneous healing in caries, but it 
may occur, and the defects produced may be more or less supplied by 
means of new-formed bone. 
Fig. 730.-Caries of the Vertebrae. 1070 
THE BONES AND JOINTS 
HEALING OF WOUNDS AND FRACTURES OF BONE. 
The process of healing in bone after fracture is, when uncomplicated, 
at first similar to that in ordinary healing in fibrous tissue. The blood 
and other exudates and the tissue detritus are gradually absorbed or dis- 
posed of by phagocytes. By a proliferation of connective-tissue cells of 
the region a larger or smaller mass of granulation tissue is formed. This 
granulation tissue does not at first differ in appearance from similar tis- 
sue formed elsewhere in the body in the reparative phase of exudative 
inflammation. 
But soon, under the influence of the especially endowed cells of cartilage 
or bone or periosteum, but especially of the last, the granulation tissue 
becomes partially replaced either by cartilage or by a substance resem- 
Fig. 731.-New-formed Cartilage and Osteoid Tissue from Callus after Fracture 
of the Femur. 
bling bone in general appearance but containing no lime salts. This is 
called osteoid tissue. These new cartilaginous and osteoid tissues, which 
are apt to occur together, form irregular masses or interlacing trabeculae 
in the stroma of granulation tissue. This constitutes the so-called callus 
of a uniting fracture (Fig. 731). 
Gradually the osteoid tissue becomes osseous, and the masses of car- 
tilage and bands of periosteal and other fibrous tissue, under transfor- 
mations practically identical with those seen in normal development, are 
converted into bone. Thus by gradual absorption and re-formation of 
bone in the usually redundant provisional bony mass, and by the re- 
adjustment of its vascular channels, the healing, with more or less per- 
manent deformity, is accomplished (Fig. 732). 
If the conditions are not favorable, the healing of fractures may occur 
only by fibrous-tissue formation, so that so-called "false joints" may THE BONES AND JOINTS 
1071 
result (Fig. 733). The healing of other injuries and losses of substance 
occurs by a process similar to that described. 
ALTERATIONS OF THE BONE-MARROW IN 
LEUKEMIA AND ANEMIA. 
In some cases of acute leukemia there 
is but little change in the bone-marrow, 
but in the chronic forms, especially when 
of long duration, there may be great alter- 
ations in this blood-producing organ. The 
change most often seen is a more or less 
complete replacement of the fatty marrow 
in the shafts of the long bones by the ac- 
cumulation, in lymphatic leukemia, of 
lymphocytes of various types, and, in the 
myelogenous form, of myelocytes of all 
varieties. In addition, the marrow con- 
tains large numbers of nucleated red cells, 
phagocytic cells often containing red cells, 
Fig. 732.-Healed Bone after 
Fracture. 
Fig. 733.-Ununited Fracture of Radius with 
Healed Fracture of Ulna after Insertion of a 
Metal Plate. 
Shows redundant hard bone about 
seat of fracture. 
The pressure atrophy of the bone is well shown about 
the screw on the left of the cut. 
and not infrequently considerable numbers of small octahedral crystals 
(Charcot's crystals). All these types of cells are apt to be arranged in 
foci; that is, there may be a small area composed chiefly of nucleated 
red cells, another area of myelocytes, and so on. 1072 
THE BONES AND JOINTS 
The degree to which this accumulation of cells occurs varies much in 
different cases, and the gross appearances of the marrow are consequently 
very diverse. In some cases the marrow is soft and has a uniform red 
Fig. 734.-Hyperplastic Bone-marrow of Rib. 
From a case of purpura hsemorrhagica. 
appearance, or it is variously mottled with gray and red. Occasionally 
circumscribed hemorrhages are seen. In another class of cases, in which 
the cell accumulation is more excessive, the marrow may be gray, 
grayish yellow, or puriform in appearance (Fig. 734). 
Fig. 735.-Normal Bone-marrow from Shaft of Femur. 
The marrow shows little but fat tissue with occasional darker patches containing a few red cells, often 
nucleated, some leucocytes, and a few of the characteristic megalokaryocytes of the marrow. 
These changes may occur in the central marrow cavity, as well as in 
the marrow spaces of the spongy bone. They may be present in several 1073 
THE BONES AND JOINTS 
or many of the bones. They are usually accompanied by analogous 
changes in the spleen and lymph-nodes (Fig. 735). 
In certain cases of acute and chronic anemia, particularly in the perni- 
cious and progressive varieties, the marrow, especially of the larger long 
bones, may lose its yellow color from absorption of the fat, and become 
red. Microscopical examination of the marrow under these conditions 
may show myelocytes and sometimes an abundance of developing nucle- 
ated red blood-cells and Charcot's crystals. 
In many of the acute infectious diseases, typhus fever and typhoid 
fever, ulcerative endocarditis, recurrent fever, etc., the bone-marrow has 
been found to be hyperemic, and to contain an excess of myelocytes. 
All these lesions of the marrow, although our knowledge of them 
is still very incomplete, together with what is known of the physiological 
functions of the marrow, point to a close relationship between the mar- 
row and the spleen and lymph-nodes as blood-producing organs. 
Closely related to the leukemias are two forms of tumors of bone 
arising in the bone-marrow-chloroma and myeloma. 
Chloroma.-Under the name chloroma is grouped a series of tumors 
which are closely related to the leukemias on the one hand and to the 
myelomata on the other They are distinguished from the latter by the 
greenish color which they possess and by the fact that they occur in 
children and young individuals, while myeloma is a disease of adult life. 
The tumor masses most frequently involve the bones of the skull, the 
orbit, and nearby regions, but occur also in the loose connective tissue 
along the spinal column, and secondarily involve the lymphatic tissue, 
lymph-nodes, muscles, and thymus, as well as the bone-marrow. In 
some instances diffuse infiltration of the internal organs also occurs.1 
Microscopically, two types of chloroma can be distinguished, one 
composed of lymphocytes, the other composed of myelocytes. The 
lymph-nodes of the body are more often extensively involved in the first 
than in the second form, in which the invasion is apt to be diffuse and 
the bone-marrow especially is involved. 
While the green color of the tumor is important in the differential 
diagnosis between chloroma and myeloma, it is not constant, and may 
be present in some of the tumors and not in others in the same case. A 
similar greenish tone may be found in typical leukemia in the masses in 
the bone-marrow and also very rarely in chronic lymph-node tuberculosis. 
Bence-Jones' albumose has been found in the urine of cases of chloroma 
of the myelocytic type. 
Myeloma.-Under this name is included a peculiar group of tumors, 
which, while they resemble the sarcomata in many respects, are distinct 
from them in their histogenic relationships; that is, they are derived from 
the special cells of the bone-marrow, and not from the periosteum. These 
tumors are usually multiple, appearing simultaneously in many parts of 
the bony structures.2 They form grayish or reddish masses in the spongy 
1 See page 542 for bibliography and further details. 
2 Wright, Trans. Assn. Arn. Phys., 1900, xv, 137; Christian, H. A., Jour. Exper. Med., 1907, ix, 325; 
and Vance, B. M., Am. Jour. Med. Sc., 1916, clii, 693 (bibl.); Summers, D., Multiple myelomas and 
their ability to metastasize, Ann. Surg., 1918, Ixvii, 687. 1074 
THE BONES AND JOINTS 
bone or in the medullary canal and as they grow excite active resorption 
of the bone. Spontaneous fractures are frequent and bending of the bone 
from loss of lime salts is occasionally seen. Metastases in other organs are 
rare.1 Another interesting point is the presence in the urine in many 
of these cases of a peculiar protein called Bence-Jones' albumose, 
which coagulates on heating and dissolves on further heating in the boiling 
liquid, only to reappear again as it cools. This protein is not absolutely 
characteristic of myeloma as it has been found also in some of the leu- 
kemias and in isolated instances in chloroma, myxedema, chondrosar- 
coma, and osteomalacia. 
Microscopically, the tumors are composed of four varieties of cells: 
myelocytes or myeloblasts, lymphocytes, red cells, and plasma cells. In 
the first type of tumor, which may very well be designated myelocytoma 
(Fig. 736), the cells are large, with oval or irregular nuclei, and many of 
Fig. 736.-Myeloma, Myeloblastic Type. 
them show characteristic granulations of the ncutrophile myelocytes and 
give the oxidase tests. Giant cells may be present in small numbers. 
Tumors formed largely of red cells (erythrocytoma or erythroblastoma) are 
extremely rare,2 while new growths composed largely of plasma cells are 
the most frequent variety. 
TUMORS. 
The tumors of bone all belong to the connective-tissue group, arising 
as they do from either the periosteum, bone-marrow, or cartilage. They 
may involve either the periosteum, or the compact bone, or the medulla, 
or, as is more frequently the case, two or more of these structures may be 
involved at once. Tumors of the bone are usually accompanied by vari- 
1 Pepper, O. H. P., and Pearce, R. M., Jour. Med. Research, 1917, N. S. xxxii, 171 (bibl.). 
2 Norris, C., Proc. New York Path. Soc., 1906, vi, 128; Ribbert, Centralbl. f. allg. Path., 1901, xv, 
337. THE BONES AND JOINTS 
1075 
ous secondary and sometimes very marked alterations of the bone tissue, 
osteoporosis, osteosclerosis, ossifying periostitis, etc. The new growths 
are very apt to undergo calcification and ossification. Many are de- 
pendent for their origin upon anomalies in the development of the skeleton 
or follow diseases of the bone, such as Paget's disease, osteitis fibrosa, and 
similar conditions. A traumatic origin has been suggested for many of 
the osseous tumors, but in a large proportion of instances it has been 
found on careful study of the lesion that the tumor has antedated the 
injury. This is especially true of fractures following the slow-growing 
and relatively benign medullary giant-cell sarcomata. 
Fig. 737.-Osteoma of Humerus. 
Eburnated type. 
Fibromata may grow from either the periosteum or the medulla. 
Their most common seat is in the periosteum of the bones of the head and 
face. They are apt to form polypoid tumors projecting into the posterior 
nares, pharynx, mouth, and antrum of Highmore. Central fibromata, 
i.e., those growing from the medulla, are rare. They usually occur in 
the lower jaw, but have been found in the ends of the long bones, the 
phalanges of the fingers, and the vertebrae. Many of the fibromata 
arising in the lower jaw are merely granulation tissue masses whose vas- 
cularity has diminished as the tumor has aged, leaving a firm fibrous 
mass filling a tooth socket. Such fibromata can hardly be considered 1076 
THE BONES AND JOINTS 
as true tumors, but they comprise a portion of the group of neoplasms 
known as epulides. The fibromata may calcify or ossify, contain cysts, 
and not infrequently occur in combination with sarcoma. 
Myxomata are of occasional occurrence in bone, while myxosarcomata 
are fairly frequent. 
Osteomata.-New formations of bone as a result of inflammatory proc- 
esses are, as we have already seen, of frequent occurrence in bone, and 
although not, strictly speaking, tumors, some of their forms are very 
closely allied to them, and they may therefore be conveniently mentioned 
here. New growths of bone which arise from the surfaces are called 
exostoses (see Fig. 723) or enostoses, according to their origin from the 
external surface or from the interior of the bone. They may contain all 
the constituents of normal bone: bone, medulla, vessels, periosteum, 
and cartilage. The new bone may be compact (Fig. 737) and like ivory, 
or spongy (Fig. 738), or contain large cavities filled with marrow. 
Fig. 738.-Osteoma of Lower Jaw. 
Rapidly growing fibrous type. 
The shape of exostoses varies greatly; they may be in the form of 
sharp, narrow spicula and processes, and, occurring in connection with 
periostitis, are called osteophytes. They may be polypoid in shape, or 
form rounded tumors with a broad base. They may form a general 
enlargement of the bone with much roughening of the surface; this con- 
dition is often called hyperostosis. 
The bone beneath these new growths may be normal, or sclerosed, or 
rarefied, or the medullary cavity of the bone may communicate with that THE BONES AND JOINTS 
1077 
of the exostosis. Exostoses are usually developed from the periosteum, 
sometimes in the insertion of tendons and ligaments. They are very 
frequently multiple, and may occur at all ages, even during uterine life. 
Enostoses are developed in the interior of bones from the medulla. 
They may increase in size, with absorption of the surrounding bone, un- 
til they project from the surface like exostoses. Their most frequent 
situation is in the bones of the cranium and face. 
Chondromata.-These tumors may be single or multiple, and most fre- 
quently grow from the interior of the bone, but sometimes from the 
periosteum. They are prone to form various combinations with other 
forms of tumors, as fibroma, myxoma, sarcoma, etc. They are frequently 
congenital, and are most common in young people. They occur most 
frequently in the bones of the hand and foot (Fig. 739). 
Jig. 739.-Chondroma of Humerus. 
There is a form of chondroma, called osteoid chondroma, which de- 
velops beneath the periosteum, most frequently in the femur and tibia 
near the knee-joint, forming a club-shaped enlargement of the bone. The 
characteristic of the tissue composing these tumors is that it resembles 
somewhat the immature bone tissue which is seen beneath the periosteum 
in developing bone. It differs from cartilage in the irregular shape of 
its cells, in the fibrillation and density of the basement substance, and in 
its general vascularity. On the other hand, it has not the inorganic con- 
tents or appearance of true bone. It resembles considerably the callus 
tissue forming about fractures of the bones. It may, however, and most 
frequently does, become converted, in some parts of the tumor, into true 
bone. On the other hand, combinations with sarcomatous tissue are of 
frequent occurrence (see below). 
Sarcoma is especially common in the bones. It grows from the inner 
layers of the periosteum or from the medulla, so that we may distinguish 1078 
THE BONES AND JOINTS 
a periosteal and a myelogenic sarcoma (Fig. 740). Sometimes the tumor 
involves the bone itself so early that it is impossible to say whether the 
tumor began in the periosteum or in the medulla. There is also a variety 
which grows close to the outside of the periosteum and becomes connected 
with it-parosteal sarcoma. 
The periosteal sarcomata usually belong to the varieties fibro-, myxo-, 
chondro-, and osteo-sarcoma, more rarely to the medullary variety. 
They commence in the inner layers of the periosteum, pushing this mem- 
brane outward. After a time the periosteum is involved and the tumor 
invades the surrounding soft parts. The bone beneath may remain nor- 
mal, or may be eroded and gradually disappear until the tumor is con- 
tinuous with the medulla. Portions of the tumor may be calcified, or a 
growth of new bone may accompany its growth. The new bone usually 
Fig. 740.-Myelogenic Sarcoma of Bone, with Giant Cells. 
takes the form of plates, or spicula, radiating outward (Fig. 741). The 
minute structure of these tumors is very variable. The simplest-the 
fibrosarcomata-are composed of fusiform, round, stellate, and some- 
times giant cells (myeloplaxes), in varying proportions, packed closely 
in a fibrous stroma. In the medullary form the stroma is diminished 
to a minimum and the round cells are most numerous. In the chondro- 
and myxo-sarcoma the basement substance may be hyaline or mucous, 
and the cells may follow the type of cartilage and mucous tissue more or 
less closely. There is a mixed form of tumor, called osteoid sarcoma, which 
is very apt to spread and to form metastases especially in the lungs. 
The growth consists in part of tissue corresponding to fibrosarcoma and 
round-cell sarcoma. In addition to this there occurs, in greater or less 
quantity, immature bone tissue, called osteoid tissue, which may in part 
become calcified, the calcification usually occurring in the central por- 
tions, leaving a softer peripheral zone. This form of tumor is most apt 
to occur at the ends of the long bones, and may form tumors of large 
size. It is often called, on account of its tendency to extend and to form THE BONES AND JOINTS 
1079 
metastases, malignant osteoma or osteoid cancer. Angiosarcomata are of 
frequent occurrence in bone. 
Sarcomata may originate in the medulla-myeloid sarcoma-and may 
grow rapidly, the bone surrounding them being destroyed so that they 
project as rounded tumors. Most frequently new bone is formed be- 
neath the periosteum, so that the tumor is inclosed in a thin, bony shell 
Fig. 741.-Sarcoma of the Bone-Periosteal. 
The growth has invaded the shaft of the bone, which is fractured. Spicula of bone, new- 
formed in the tumor, may be seen below, passing outward from the periosteum. 
(Fig. 742); sometimes there are also plates of bone in the tumor; some- 
times the periosteum is unaltered; sometimes it is perforated and the 
tumor invades the surrounding soft parts. The tumors are frequently 
very soft, vascular, and hemorrhagic in parts, and are usually of the 
spindle-cell or round-cell variety, and not infrequently contain giant cells. 
Fig. 742.-Myelogenic Sarcoma of the Sternum. 
In recent years there has been much discussion concerning the nature 
of these tumors. It has been found that those which are rich in giant 
cells are, despite their sarcomatous morphology, relatively or absolutely 
benign, and do not recur after thorough curettage of the cavity in which 
the tumor lies (page 434). There has been a great deal of discussion also 
as to the nature of the giant cells which occui in these tumors; some ob- 1080 
THE BONES AND JOINTS 
servers1 consider them to be purely phagocytic, while others believe that 
they correspond to the osteoblasts of normal bone, and still others that 
they are true tumor cells. Instances have been reported in which the 
center of the tumor was softened, forming a cyst with hemorrhagic con- 
tents. There is a question whether these are truly myeloid tumors or 
whether they should not be classed with osteitis fibrosa in which con- 
dition giant cells are not infrequently present. 
A similar type of tumor is very frequent on the tendon sheaths and 
the periosteum of the fingers (Fig. 240, page 434), and here, too, the 
clinical course shows the tumor to be of very low malignancy. Some of 
the tumors of this site contain cartilage also. While the question has 
not yet been settled, it is evident that it is not possible on the mere 
Fig. 743.t-Multiple Giant-cell Tumors of Bone. 
Preparation by Dr. H. S. Martland. 
morphology to draw definite conclusions as to their clinical features. 
Some are unquestionably malignant, recurring repeatedly; one tumor of 
the antrum of Highmore, seen by the writer (Wood), has been removed 
seven times during fourteen years, and the patient is still in fair health. 
On the other hand, other tumors of exactly the same morphology have 
not recurred after simple removal. The formation of metastases at a 
distance almost never occurs with tumors of this type, though nodules 
may appear either in the marrow or under the periosteum at a consider- 
able distance from the site of the primary tumor. Occasionally, how- 
ever, the tumors may be multiple in origin and some may undergo spon- 
taneous disappearance at the same time that others are forming (Fig. 743).2 
1 See Mallory, F. B., Principles of Pathologic Histology, Philadelphia, 1914, p. 280. Mallory thinks 
that many of these giant cells are due to fusion of endothelial leucocytes which have been attracted to 
the tumor by foreign bodies, while another type is the true tumor cell and can be distinguished by the 
presence of multiple mitoses which do not occur in the form due to fusion of endothelial cells. See 
also Barrie, G., Ann. Surg., 1917, Ixv, 151. Ewing, Arch. Surg., 1922, iv, 485. 
2 For a report of two unusual giant-cell tumors of this type, see Martland, H. S., Proc. New York 
Path. Soc., 1915, xv, 119; Haussling and Martland, Ann. Surg., 1916, Ixiii, 454. 1081 
Sarcomata may originate in the outer layers of the periosteum-par- 
osteal. They may be as firmly connected with the bone as is the peri- 
osteal form. The periosteum may remain intact between the tumor and 
the bone, or it may disappear and leave them in apposition. This form 
is most often of the spindle-cell variety. Endotheliomata of bone have 
been described, but in most, cases if not in all, are sarcomata or hyper- 
nephromata. Lipoma is rare. 
Angioma and Lymphangioma.-A very large number of the tumors 
which have been described under these names are really very vascular 
sarcomata. Cavernous angiomata may form between the periosteum 
and bone and be intimately connected with the latter. There are several 
cases described of cavities filled with blood in the interior of bones, which 
it is difficult to interpret. They have mostly been found in the head of 
the tibia. They are said to have consisted of single sacs composed of 
thickened periosteum, lined with plates of bone, and filled with fluid and 
clotted blood. No large vessels communicated with the sacs, but their 
walls were covered with a rich vascular plexus, branches of which opened 
into the cavity of the sac. Some of these vascular cysts are undoubtedly 
forms of osteitis fibrosa. Care should be taken not to confuse them with 
the very vascular fibromata, myxomata, and sarcomata of bone, or with 
aneurysm (see page 438). 
Carcinoma.-Because of the lack of epithelial structures, primary 
carcinoma does not occur in the bones. Most of the neoplasms thus 
named have doubtless been sarcomata or hypernephromata. Secondary 
carcinoma, on the other hand, as a result of metastases or local exten- 
sion, is not infrequent. Metastatic carcinoma may occur in the bones 
of various parts of the body at the same time, and are most apt to be 
secondary to carcinoma of the mamma or prostate; but metastases from 
the thyroid are not infrequent.1 
The blood picture of a myelogenous leukemia is sometimes seen 
when the marrow is extensively invaded by metastatic carcinoma. 
This is probably due to stimulation of the marrow by the metabolic 
products of the rapidly growing masses of tumor cells. 
Cysts2 not due to parasites occur most frequently in the long bones, 
particularly in the femur, humerus, fibula, and tibia and are not infre- 
quent in the metacarpals. Cysts of this type are not lined with epi- 
thelium, being produced by softening following some alteration of the 
bone. Originally (Virchow), they were thought to be the result of lique- 
faction of misplaced islands of epiphyseal cartilage, and the walls of 
many of these cysts do show cartilaginous elements; but this explanation 
has been abandoned as not valid in all cases. It is now believed that 
many of the bone cysts are due to a localized osteitis fibrosa3 (page 1046), 
others to softening as a result of local infectious processes. Giant cells 
THE BONES AND JOINTS 
1 Kanoky, J. P„ Surg., Gynec., and Obst., 1916, xxii, 679 (bibl.). 
2 Bloodgood, J. C., Jour. Am. Med. Assn., 1904, xliii, 1124; Progressive Med., 1904, vi, 181; S/cinner; 
M., Surg., Gynec., and Obst., 1915, xx, 570; Tietze, Ergebn. d. Chir. u. Orthop., 1911, ii, 32 (bibl.), 
Lexer, Arch. f. klin. Chir. (Langenbeck), 1906, Ixxxi, 363 (good bibl.). 
3 Bockenheimer, Arch. f. klin. Chir. (Langenbeck), 1906, Ixxxi, 236; Haberer, Arch. f. klin. Chir. 
(Langenbeck), 1910, xciii, 791. 1082 
THE BONES AND JOINTS 
of the same type as those seen in osteitis fibrosa may be found in the 
lining membrane. The contents of the cyst are usually a thin serosan- 
guineous fluid, but it may contain myxomatous or soft fibrous material. 
The cysts may be multiloculated, trabeculae being formed by bone, and 
in most cases are situated near or in the epiphysis. Fractures are not 
infrequent when the cyst is extensive, and the traumatic origin of the 
cysts has long been assumed; but as with tumors this is neither probable 
nor has it been proved. 
In the bones of the jaw, especially the inferior maxilla, there arise 
tumors and cysts peculiar to this region, since in the process of develop- 
ment of the teeth from the embryonic enamel organ masses of specialized 
epithelium may be left deep in the substance of the jaw, to give rise later 
either to solid tumors or to cysts lined with epithelium. Of the solid 
tumors of this region there have already been discussed adamantinoma 
(page 448) and odontoma (page 406). Both types are usually benign, 
but the former may on occasion become highly malignant. 
The cysts developing in the jaw1 are, as just stated, peculiar because 
of their epithelial lining. Three groups of true cysts are generally recog- 
nized: (1) Those arising from the root tissues; (2) follicle cysts, derived 
from the enamel organ and usually single; and (3) multilocular cysts 
arising in the jaw and growing extensively, usually distending the bone 
and rarefying it. The multilocular cysts may convert the entire jaw 
into a spongy mass, the bony walls being reduced to a few millimeters 
in thickness. The root cysts are usually correlated with inflammatory 
lesions in the teeth, but must be carefully differentiated from peridental 
abscess. They rarely possess an epithelial lining, for the cells, if origi- 
nally present, desquamate under the inflammatory process so frequently 
present from infection of the cyst cavity. Occasionally, however, small 
areas of epithelium may persist, and in a few instances ciliated epithelium 
has been observed. The follicle cysts are usually lined with cylindrical 
epithelium, are filled with thin mucus, and may or may not contain a 
tooth. The multilocular cysts are usually lined with epithelium and 
contain a slimy, mucoid secretion, in which cholesterin crystals are some- 
times found, but as the cysts are often infected, the walls may be covered 
with granulation tissue only. Many of the multilocular cysts are un- 
doubtedly derived from the peridental epithelial remnants left during 
the development of the tooth, and hence are related to the adamantinoma; 
in fact, the French writers call them epithelioma adamantinum cysticum. 
Dermoid cysts are occasionally found in connection with the bones, 
particularly of the skull. 
Echinococcus cysts also occur,2 and often cause spontaneous fracture. 
The Joints. 
For a description of the dislocations, misplacements, and injuries of 
the joints we refer to works on surgery. 
1 The literature of tumors and cysts of the jaw up to 1897 has been collected by Goebel, C., Centralbl. 
f. allg. Path., 1897, viii, 128. A more recent study, with complete bibl., is by Schmidt, M. B., Lubarsch- 
Ostertag, Ergebn. d. allg. Path., 1900-01, vii, 221. 
2 Walker, C. A., and Cummins, W. T., Jour. Am. Med. Assn., 1917, Ixviii, 839 (bibl.). 1083 
THE BONES AND JOINTS 
DEGENERATION. 
Fatty degeneration of the cartilage cells, mucous degeneration, and 
fibrillation of the stroma with softening, and often roughening, of the 
joint surfaces, calcification, and amyloid degeneration, may occur in 
inflammation, or as a senile alteration, or under other conditions. The 
cartilage is usually, under these conditions, whiter and more opaque 
than normal. 
Exudative Arthritis.-The earlier stages of acute inflammation of the 
synovial membranes are better known from experiments on animals than 
from post-mortem examinations. Among the early changes are swelling 
and congestion of the membrane, with increased growth and desqua- 
mation of the lining cells, and infiltration of the membrane with lymphoid 
cells. These conditions are soon followed by an exudation. The exact 
origin of much of the exudate is not clear. 
In Serous Arthritis the accumulation of serum within the synovial sac 
is the most prominent lesion. The disease may terminate in recovery, or 
become chronic, or pass into the suppurative form. It may be incited 
by contusions, penetrating wounds, gonorrhea, or rheumatism, or it may 
occur without evident cause. 
Serofibrinous Arthritis may occur under the same conditions as those 
which lead to simple serous inflammation. The fibrin may be present 
largely as flocculi in the serum, or it may form false membranes over the 
surfaces of the joint. 
Suppurative Arthritis may follow or be associated with the above forms 
of inflammation. The synovial membrane is thickened and cloudy, and 
there may be but a moderate amount of pus in the joint, and a slight 
degree of infiltration of the synovial membrane with pus cells. Under 
these conditions resolution may occur. 
In other cases the accumulation of pus in the cavity may be great, 
the synovial membrane and its surrounding tissue densely infiltrated 
with pus cells. Under these conditions granulation tissue is apt to 
form and the cartilages of the joints may become involved. There are 
swelling and proliferation or degeneration of the cartilage cells; the 
basement substance becomes disintegrated, ulcerates, and exposes the 
bone, in which osteitis, caries, rarefaction, etc., may occur. The new- 
formed granulation tissue may penetrate the cartilage, absorbing the base- 
ment substance, and by metaplasia the cartilage tissue may be converted 
into embryonal or granulation tissue. The pus may break through 
the capsule of the joint and form large abscesses in the adjacent soft 
parts. Sometimes the inflammation is not only suppurative but gan- 
grenous, and runs a rapidly fatal course. The synovial membrane, articu- 
lar cartilages, and ends of the bone all undergo a rapid suppuration 
and gangrene. Acute arthritis may be incited by trauma, or it may 
be associated with pyemia, smallpox, measles, scarlet fever, pneumonia,1 
INFLAMMATION. (Arthritis.) 
1 For bibliography of pneumococcic arthritis, see Cave, E. J., Lancet, 1901, i, 82. 1084 
THE BONES AND JOINTS 
gonorrhea, diphtheria, mumps, typhus fever, glanders, the puerperal 
condition, or other infectious diseases.1 In these cases the process is apt 
to be suppurative, and is induced by various forms of bacteria. 
Chronic Arthritis may begin as such, or it may be the result of previous 
acute inflammation. There is an increase of fluid in the joint. This 
fluid is thin and serous, or is thickened with flocculi of fibrin and epi- 
thelial and lymphoid cells, or is thick, syrupy, or even gelatinous. The 
synovial membrane is at first congested, its tufts are prominent. Later it 
becomes thickened, sclerosed, and anemic; the lining cells are destroyed, 
and the tufts become large and projecting. From the distention of the 
capsule there may be subluxations or luxations of the joint, or the cap- 
sule may be ruptured. 
Rheumatic Arthritis.-An acute inflammation, usually exudative in 
character and involving one joint after another, is characteristic of acute 
articular rheumatism. The exudate is usually serous. 
A chronic form of so-called rheumatic arthritis is most common in 
elderly persons, usually affecting several joints and advancing slowly and 
steadily. There is a fibrous thickening of the synovial membrane and 
the adjacent tissue. Fluid accumulations are not common. The articu- 
lar cartilages are apt to degenerate or ossify, or become softened and 
fibrillated, and they may disappear. The contracting synovial mem- 
branes and fibrous tissue render the joints stiff and may cause consider- 
able deformity. Not infrequently fibrous and bony ankyloses are formed 
between the ends of the bones. 
Arthritis Deformans.-This name has been applied to a variety of 
chronic inflammation of the joints which, combined with degeneration of 
parts of the joint and the new formation of bone, may result in marked 
deformities of the part. The disease usually occurs in elderly persons and 
is apt to involve several joints, most frequently the hip, knee, fingers, and 
feet. It may be idiopathic, or due to rheumatism or to injuries, or follow 
an acute arthritis. The capsules of the affected joints are thickened and 
sclerosed. The synovial fluid is at first increased in quantity; later, 
diminished and thickened. The tufts of the synovial membrane become 
much enlarged and vascular; they may be converted into cartilage. 
Sometimes the capsule becomes ossified. The new bone grows from the 
edge of the cartilage within the capsule and its articular surface is covered 
with cartilage. The articular cartilages are much changed. The base- 
ment substance splits into tufts, while the cartilage cells are increased in 
number. Or the basement substance becomes fibrous; or it is split into 
lamellae and the cartilage cells are multiplied; or there are fatty degener- 
ation and atrophy. 
As a result of these changes, larger or smaller portions of the cartilage 
are destroyed and the bone beneath is laid bare. The exposed bone may 
become compact and of an ivory smoothness. The ends of the bones are 
much deformed. They are flattened and made broader by irregular new 
growths of bone, while at the same time they atrophy. The new growth 
of bone starts from the articular cartilages. The cartilage cells increase 
1 For chronic streptococcus arthritis, see Davis, D. J., Jour. Am. Med. Assn., 1913, Ixi, 724. THE BONES AND JOINTS 
1085 
in number and the basement substance grows in quantity. This growth 
is most excessive at the edge of the cartilage, so that a projecting rim is 
formed there. This projecting rim may ossify next the bone, and at the 
same time new cartilage may form on its surface, so that we may find 
large masses of bone covered with cartilage. All these changes occur in 
various combinations and sequences, so that joints in this condition pre- 
sent the greatest variety of appearances.1 
Arthritis Uratica (Gouty Arthritis).-This lesion is characterized by the 
deposit of salts of uric acid in the cartilages, bones, and ligaments, and 
also in the cavities of joints. The deposits may be in the form of stellate 
masses of acicular crystals in and about the cartilage cells or in the base- 
ment substance; or they may be deposited in the fibrillar connective- 
tissue structures of the joint in single crystals, or in the subcutaneous 
tissue about the joint as white concretions. The deposits may occur in 
repeated attacks of the disease, and are accompanied by acute inflam- 
matory changes. They may lead to various forms of chronic inflamma- 
tion of the joints. 
Tuberculous Arthritis.-This process may commence in the synovial 
membrane of the joint, or may extend to the joint from adjacent bone. 
It is characterized by the formation of tubercle tissue and granulation 
tissue, sometimes in great quantity, and is usually associated with second- 
ary inflammatory and degenerative changes of surrounding parts. 
According to the prominence of one or other of these secondary altera- 
tions, several forms of tuberculous arthritis may be distinguished. If 
there is an excessive growth of granulation tissue without much suppura- 
tion, this constitutes a fungous form. Sometimes there is extensive 
suppuration, so that the cavity of the joint may be filled with pus, which 
may be discharged through openings in the skin; or there may be more 
or less extensive formation of abscesses, or infiltration of the soft parts 
about the joint with pus. In other cases there is disintegration of the 
new-formed tuberculous tissue and of the tissues of the joint-ulcerative 
form. The cartilage basement substance may become split into frag- 
ments and the cells degenerate, and thus deep and destructive ulcers 
of the cartilage may be formed. Or the new tissue may work its way 
through the cartilage into the bone beneath, by absorption of the base- 
ment substance of the cartilage, with or without proliferation of its cells. 
Caries and necrosis of the underlying bone may lead to extensive de- 
struction. Hand-in-hand with these alterations subperiosteal new 
formation of bone may occur, or sclerosis of the adjacent bone tissue. 
There may also be a great increase of fibrous tissue about the joint. 
The type of lesion depends in considerable degree upon the joint 
involved. 
This disease is most common in children and young persons. The 
so-called scrofulous diathesis is said to foster it, but local injuries are 
frequently the predisposing factors. It is most common in the large 
joints. It may occur in connection with tuberculous inflammation in 
1 For a valuable study of arthritis deformans, see Nichols and Richardson, Jour. Med. Research, 1909, 
N. S. xvi. 149. 1086 
THE BONES AND JOINTS 
other parts of the body, but it is frequently quite local, and may remain 
so for a very long time or permanently, since general infection from tuber- 
culous arthritis is comparatively infrequent. 
The process is usually slow, and may end in death. If recovery takes 
place before the cartilages and bones are involved, the topography of the 
joint is maintained; but it may be stiffened, or even immovable, from 
the contraction of the new fibrous tissue around it. If the cartilages and 
bones are diseased the joint is destroyed, and either bony or fibrous 
ankylosis results. Sometimes, from the change in the articulating sur- 
faces and the contraction of the muscles and the new fibrous tissue, 
partial or complete dislocations are produced. 
Occasionally miliary tubercles occur in the synovial membranes in 
cases of general miliary tuberculosis, with but little accompanying simple 
inflammatory change. 
Syphilitic Arthritis.-Syphilitic changes in the joints are frequent in 
congenital luetics, and exudative arthritis has been observed, especially 
in the knee-joint and the spine. In adults there may be a subacute 
arthritis in the eruptive phase with the accumulation of serous exudate 
in the joint. In the tertiary stage gummata may form in the synovial 
membranes, setting up a perisynovitis and synovitis by exudation into 
the capsule, or the lesion may be primary in the bone and extend through 
the cartilage with final destruction of the joint. 
An entirely different type of lesion is seen in neuropathic arthritis of 
tabes dorsalis and syringomyelia. A number of forms have been ob- 
served, one of which progresses in much the same fashion as arthritis de- 
formans, which has led to the suggestion that these tabetic changes are 
simply a modified type of this form of joint disease; but the sudden 
appearance of the fluid, the acute swelling, the great destruction of the 
joint tissues, and the rapid and painless course are not characteristic of 
arthritis deformans. These joint changes may be very extreme and lead 
to the separation of considerable fragments of bone or cartilage which lie 
free in the joint and ultimately are smoothed off by the rubbing which 
occurs during motion. The destruction of the synovial membrane is 
frequently so extensive that spontaneous dislocation occurs, rendering 
locomotion impossible. In another form very extensive production of 
bone and cartilage may occur, greatly increasing the size of the opposed 
joint surfaces. Bone so formed is very spongy and may undergo spon- 
taneous fracture. 
TUMORS. 
Secondary tumors of the joints as a result of local extension from the 
adjacent parts are not uncommon, and the tumors may be of various 
kinds. Primary tumors of the joints, on the contrary, are not very 
common. For example, some seventeen instances of sarcoma of the 
knee-joint are recorded, and the occurrence of tumors of this nature in 
other joints is of like infrequence. In most cases there is a diffuse thick- 
ening of the capsule due to tumor invasion. The tumor is usually of 
the myeloid variety with numerous giant cells. One instance of a xantho- THE BONES AND JOINTS 
1087 
sarcoma has been recorded,1 and a few round-cell sarcomata have been 
observed. 
Lipoma.-A new growth of fat tissue may begin in the other portions 
of the synovial membrane, push this inward, and project into the joint 
in a mass of tufts-lipoma arborescens. 
Fibroma occurs as a hypertrophy of the little tufts and fringes of the 
synovial membrane. In this way large polypoid and dendritic bodies 
are formed. The pedicles of these growths may atrophy and even dis- 
appear, so that the growths are left free in the cavities of the joints. 
Corpora aliena Articulorum (Loose Cartilages in the Joints).-This 
name is given to bodies of various structure and origin, which are found 
free or attached by slender pedicles in the cavities of the joints. They are 
most frequently found in the knee; next in order of frequency in the 
elbow, hip, ankle, shoulder, and maxillary joints. They may be single 
or in hundreds. Their size varies from that of a pin's head to that of 
the patella. They are polypoid, rounded, egg-shaped, or almond- 
shaped; their surface is smooth or faceted, or rough and mulberry-like. 
They are composed of fibrous tissue, cartilage, fat, or bone, either pure 
or mixed in various proportions. 
These bodies are most formed often by hyperplasia of the synovial 
tufts and the production in them of cartilage and bone. The usual 
process is that small plates of cartilage form on the inner surface of the 
synovial membrane, which increases in size while their outer layers 
ossify. These may remain fixed in the synovial membrane; or they pro- 
ject and become detached from it, and they then appear as flattened, 
concave bodies composed of bone covered with cartilage on one side. 
On the other hand, cartilage and bone may form outside the synovial 
membrane from the periosteum or the edges of the articular cartilages, 
and, pushing inward, may later become detached. 
Rarely portions of the articular cartilages may be detached by vio- 
lence or disease; or masses of fibrin, blood-clot, and other concretions 
may form in the joints in arthritis deformans, or under conditions which 
we do not understand.2 
The Bursae. 
Some of the large bursae are preformed; others originate in connective 
tissue, a portion of which atrophies; fluid then collects in the cavity, and 
later an imperfect endothelial lining may form. The same process is 
responsible for the formation of the mucus-containing cysts (ganglia^ 
which occur so frequently about the wrist joints. After trauma, blood 
may collect in a bursa, distend it, and later undergo organization or 
complete resorption. Acute suppurative inflammation may take place 
if bacteria obtain entrance to the bursal cavity. Chronic inflammation, 
however, is a much more important and frequent lesion of the bursse, 
1 Ziillig, J., Cor.-Bl. f. schweiz. Aerzte, 1917, xlvii, 1368. 
2 For further details, see Borth, Arch. f. klin. Chir. (Langenbeck), 1898, Ivi, 507; Boerner, Deutsch. 
Ztschr. f. Chir., 1903, Ixx, 363; and Schmieden, Arch. f. klin. Chir. (Langenbeck), 1900, Ixii, 542. 
3 Thorn, J., Arch. f. klin. Chir. (Langenbeck), 1896, lii, 593. 1088 
THE BONES AND JOINTS 
the most characteristic example being the swelling and inflammation of 
the prepatellar bursae in those who have to spend much time on their 
knees (housemaid, s knee in cleaning women). The process is a connective 
tissue thickening of the wall of the bursa, distention of the lumen with 
exudate, and in some instances a complete organization of the contents 
with obliteration of the cavity itself. If any exudate remains it is thick 
and is often colored with blood. Small bodies of hyaline material, called 
Fig. 744.-Calcification of Subacromial Bursa. 
An arrow points to the remains of the bursa. 
rice bodies, may exist in considerable numbers in the inflamed bursa. 
Ultimately, the exudate may undergo calcification with the obliteration 
of the cavity This occurs not infrequently in or about the subacromial 
bursa,1 which is peculiarly subject to injury (Fig. 744). 
Tuberculous inflammation may occur in a bursa, usually in connec- 
tion with tuberculosis of the neighboring bone. The cavity is distended 
by the effusion, and tubercles with characteristic giant cells may be 
found in the walls. 
1 Smith, M. K., Med. Record, 1917, xci, 406. CHAPTER XIV. 
THE NERVOUS SYSTEM.1 
The Membranes and the Ventricles. 
The Dura Mater Cerebralis. 
The cranial dura mater consists of two layers, an outer, which forms the internal 
periosteum of the cranial bones and carries the meningeal arteries and veins, and an 
inner, which is more delicate in structure than the outer dense layer and is richly 
vascular. The dural sinuses are inclosed between these two layers. The inner layer 
of the dura is reduplicated in certain locations, forming the tentorium, the falx 
cerebri, the falx cerebelli, and the diaphragma sellae. Lesions of the dura mater, 
therefore, are apt to be associated with lesions of the cranial bones, of the pia mater, or 
of the venous sinuses. 
In young children the dura mater adheres closely to the inner surface of the cranial 
bones, in adults it is more readily detached, and in old persons it is again more adher- 
ent. Chronic inflammation of the external layers of the dura mater also renders it 
more adherent to the bones. The intimate relationship of the membranes with the 
brain and cord leads to the simultaneous affection of both by many inflammatory 
and other processes; but for clarity of consideration it is better to consider the lesions 
of the two under separate heads. 
HEMORRHAGE. 
Extravasated blood may lie between the dura mater and the cranial 
bones, in the substance of the membrane, or between the dura mater and 
the arachnoid. 
Hemorrhages between the dura mater and the cranial bones are usu- 
ally due to blows and injuries of the head, are often of considerable size, 
separating the membrane from the bones, and may compress the brain. 
They are often associated with laceration of the brain, and with hemor- 
rhages between the dura mater and arachnoid. 
Hemorrhages between the dura mater and the pia-arachnoid may take 
place from the vessels of either membrane. Those from the vessels of 
the dura may result from chronic pachymeningitis. 
Hemorrhages into the substance of the dura mater are not frequent 
and are usually small. 
Pressure on the head of the infant in delivery may cause extravasa- 
tions of blood between the bones and the dura mater, as well as between 
the bones and the pericranium. 
THROMBOSIS. 
Thrombosis of the venous sinuses is not uncommon. It is often associ- 
ated with inflammation of the dura mater and with injuries and inflam- 
1 The detailed anatomy of the brain can not be considered here. The student should consult 
Quain's Anatomy, vol. iii, part i, 11th ed., London, 1909; Lewandowsky's Handbuch d. Neurologie, 
Berlin, 1910-14; Bing, Regional Diagnosis in Affections of the Brain and Spinal Cord, 2d ed., New 
York, 1913; Tilney, F., and Riley, H. A., The Form and Functions of the Central Nervous System, 
New York, 1921. 
1089 1090 
mations of the brain and pia mater, of the cranial bones, of the middle 
ear, and of the scalp. Like thrombosis in other parts of the body, it 
may occur in the infectious and exhausting diseases. It may occur in 
apparently healthy persons without discoverable cause. The thrombi 
may be red or white, and firm. They may induce no secondary changes, 
or they may extend into the veins and induce hemorrhagic softening of 
the involved areas of the brain. A secondary hydrocephalus is occa- 
sionally a consequence of such thrombosis. 
THE NERVOUS SYSTEM 
INFLAMMATION. (Pachymeningitis.) 
This may involve the external layers of the membrane, pachymenin- 
gitis externa, or the internal layers, pachymeningitis interna. It may be 
either acute or chronic. The tissues of the substance of the dura mater 
participate to a greater or less degree in these changes, but the chief 
lesions are upon the surfaces. 
Acute Pachymeningitis Externa is usually secondary to injuries or dis- 
eases of the cranial bones; thus it may be incited by fractures of the 
skull, either depressed or not, osteitis, caries, and suppurative inflamma- 
tion of the internal and middle ear and of the mastoid cells. The dura 
Fig. 745.-Pachymeningitis Interna Hemorrhagica-Chronic. 
At the left near the vessels are connective-tissue cells containing blood-pigment. 
mater is commonly congested and swollen, and may contain small ecchy- 
moses. The inflammation is usually suppurative, and pus may accu- 
mulate between the membrane and the bone, or in the substance of the 
membrane. The areas of inflammation are not usually extensive. It 
sometimes leads to thrombosis of the venous sinuses, and sometimes gan- 
grene of the dura mater occurs. The inflammation may extend to the 
inner surface of the dura mater, or to the pia mater and brain, or it may 
remain localized and undergo resolution. 
Acute Pachymeningitis Interna may be secondary to inflammation of 
the external surface, or it may occur as a complication in pyemia, puer- 
peral fever, chronic diffuse nephritis, in the exanthemata and erysipe- THE NERVOUS SYSTEM 
1091 
las, or independently. There is a general or circumscribed production 
of fibrin and pus, so that the internal surface of the membrane is lined 
with a layer of soft, yellow exudate. 
Simple Chronic Pachymeningitis consists in the formation of new con- 
nective tissue in the dura mater, by which it becomes thicker and in 
many cases abnormally adherent to the bones of the skull. This thick- 
ening may be general or circumscribed, and may involve the entire 
thickness of the membrane. Not infrequently, when the external layers 
are especially involved, firm adhesions to the skull occur, with ossifi- 
cation of the outer layers, so that shreds of the membrane containing 
little masses of bone (osteophytes) remain sticking to the skull when 
the membrane is stripped off. 
Pachymeningitis Interna Haemorrhagica.-This is an important form 
of chronic inflammation of the internal layer of the dura mater, character- 
ized by the formation of layers of new delicate 
connective tissue with numerous very thin-walled 
blood-vessels from which the blood is prone to 
escape. The membrane may at first appear as 
a delicate fibrinous pellicle, with small red spots 
scattered through it, or it may look like a simple 
reddish or brown staining of the inner surface of 
the dura mater. Microscopical examination 
shows this membrane to consist of numerous 
blood-vessels, mostly capillaries with very thin 
walls, which may be distended or pouched, and which have grown out 
from the vessels of the dura mater (Fig. 745). Between the vessels is a 
homogeneous or slightly differentiated basement substance, containing a 
variable number of spheroidal, fusiform, or branching cells. Red blood- 
cells in variable quantity, blood pigment in various forms, frequently in- 
closed in the new cells, and small calcareous concretions (brain sand) (Fig. 
746) also lie in the intervascular spaces. In more advanced stages the 
new membrane may become greatly thickened, its outermost layers being 
changed into dense fibrous tissue with obliteration of the vessels; while 
the more recently formed layers are similar in structure to those at first 
developed. Considerable blood usually escapes by diapedesis from the 
vessels of the new membrane in all stages of its formation. The vessels 
are also very liable to rupture, giving rise to extensive hemorrhages 
either into the substance of the membrane or between it and the pia- 
arachnoid. Sometimes masses of new tissue and blood, from half an 
inch to an inch or more in thickness, are formed in this way, greatly 
compressing the brain. These new membranes are most frequently 
formed over the convexity of the brain, but may extend over nearly the 
entire surface of the dura mater. Sometimes, when old, the entire 
membrane, densely pigmented and firm, lies loosely beneath the dura 
mater without compressing the brain or giving any clinical indication 
of its presence. The membrane may induce chronic changes in the pia 
mater, with or without accompanying changes in the cortical portion of 
the brain. 
Rarely, serum accumulates between the layers of the new membranes 
Fig. 746.-Brain Sand from 
Pachymeningitis Interna. 1092 
THE NERVOUS SYSTEM 
and in this way cysts of large size may be formed. In rare cases diffuse 
suppuration of the entire new membrane occurs. The slighter degrees 
of this form of inflammation may occasion no symptoms during life. 
They are not infrequently found in persons suffering from various chronic 
brain lesions and from chronic alcoholism, but they may occur unasso- 
ciated with complicating lesions. The more advanced forms of the lesions 
are frequently found in idiots, epileptics, etc. 
Tuberculous Pachymeningitis may occur secondarily to that form of 
inflammation in the pia mater or the bones, or as a part of general miliary 
tuberculosis. The tubercles may be situated on either surface of the 
membrane or in its substance, and may be single or aggregated, forming 
large masses. 
Syphilitic Pachymeningitis manifests itself by the formation of gum- 
mata upon either the external or internal surface of the dura mater or, 
more frequently, by a diffuse syphilitic inflammation. These gummata 
may be single or multiple, and may vary greatly in size. They may be 
accompanied by simple inflammatory changes in the dura mater in their 
vicinity. They may undergo suppuration with the formation of abscess. 
The inflammation may extend to the pia mater, inducing simple or 
syphilitic meningitis and adhesions between the dura mater and pia- 
arachnoid. The gummata may, on the other hand, when occurring on 
the outer surface of the membrane, cause absorption and perforation of 
the bones of the skull. 
TUMORS. 
Fibromata and lipomata occur rarely in the dura mater and are of 
small size. 
Small chondromata are sometimes found connected with the dura 
mater at the base of the brain. Small, soft, translucent growths some- 
what resembling cartilage are seen under the dura. They are derived 
from remnants of the chorda dorsalis which remain in the clivus. Occa- 
sionally, this tissue may develop into large tumors with malignant quali- 
ties (see under Chordoma, page 403). 
Osteomata.-In addition to the formation of osteophytes in chronic 
external pachymeningitis, plates and, more rarely, globular masses of 
bone may be formed in the dura mater, unconnected with the bones 
of the skull. They are most frequently found in the falx cerebri, but 
may occur elsewhere. The new bone may be dense or loose in texture, 
and usually produces no symptoms. 
Hemangiomata and lymphangiomata may occur in the dura and pia. 
Endotheliomata.1-These tumors may grow inward or outward, caus- 
ing pressure on the brain or absorption and perforation of the bones; they 
often attain considerable size. Some of these tumors somewhat resemble 
certain forms of epithelioma, and have often been described as primary 
carcinomata. They vary in character, being sometimes formed of 
1 Dagonet, Arch, de m6d. exp6r., 1892, iv, 361; Hassin, G. B„ Histopathology of carcinoma of the 
cerebral meninges, Arch. Neurol, and Psychiat., 1919, i, 705; Lissauer, M., Zur Kenntnisder Meningitis 
carcinomatosa, Deutsch, med. Wchnschr., 1911, xxxvii, 16; Mallory, F. B., The type cell of the so-called 
dural endothelioma, Jour. Med. Research, 1919-20, xli, 349. THE NERVOUS SYSTEM 
1093 
densely packed masses of flattened cells with little fibrous stroma (Fig. 
249, page 441), sometimes tabulated with considerable dense stroma in 
narrow or broad bands. In other cases, the polyhedral or cuboidal cells 
are conspicuously grouped around blood-vessels. Again, the cells form 
concentric, densely packed masses, either around vessels or around a 
Fig. 747.-Psammoma of the Dura Mater. 
central cell group (Fig. 250, page 441). These form one of the types of 
psammoma, and the concentric borders are often calcified. 
Sarcomata are the most common tumors of the dura mater, and of 
these the spindle-cell forms are of more, the round-cell and polyhedral- 
cell forms of less, frequent occurrence; the melanotic types are very rare. 
They may grow from either surface of the membrane. Giant-cell sarcoma 
is derived usually from the bone and invades the dura secondarily. 
Fig. 748.-Psammoma of Brain. 
Some of the round- and polyhedral-cell forms are soft and very vascular, 
and are apt to involve the neighboring pia mater and brain tissue, or the 
bones of the skull, which they may perforate. They sometimes project 
through the opening in the skull as fungous, bleeding masses. Myeloma 
and chloroma form a portion of the round-cell group. 1094 
THE NERVOUS SYSTEM 
Psammomata are small globular tumors, often multiple and peduncu- 
lated, growing from the inner surface of the dura mater. They are 
usually composed of tissue, fibrous, sarcomatous, or endotheliomatous 
in character, and contain variously shaped calcareous concretions similar 
in appearance to the so-called brain sand1 (Fig. 747 and 748). 
The Pia Mater Cerebralis and the Arachnoid. 
The external surface of the brain is invested by a connective-tissue membrane 
which covers the convolutions, dips down into the sulci, and extends into the ventricles. 
This membrane is abundantly supplied with blood-vessels, and from it numerous ves- 
sels extend into the brain, so that any disturbance in the circulation of the blood in 
the pia mater involves a disturbance in the circulation of the blood in the brain also. 
The connective tissue which makes up the pia mater is arranged in a series of 
membranes and fibers reinforced by elastic tissue, forming a spongy membrane con- 
taining numerous cavities more or less filled with fluid. These cavities are continuous 
with the perivascular spaces which surround the vessels that pass from the pia mater 
into the brain. The outer layers of the pia mater are the most compact, and are 
covered on their outside surface by a continuous layer of endothelial cells. This 
external layer, the arachnoid, is a serous membranous sac, consisting of an outer layer, 
in contact with the dura, and an inner layer, in contact with the pia, which completely 
incloses the brain and spinal cord, but does not dip into the sulci and fissures of the 
brain. The space between the arachnoid and the pia is the subarachnoid space, and 
contains the cerebrospinal fluid. At some points the arachnoid is widely separated 
from the pia, thereby forming wide spaces filled with fluid, which are known as the 
cisterns. The deeper layers of the pia contain the blood-vessels. The membranes and 
fibers which compose the pia mater are partly coated with cells which have irregular 
and delicate cell bodies and large, distinct nuclei. 
Along the borders of the longitudinal fissure, and, more rarely, on the under sur- 
face of the brain, are a number of small, white, firm, irregular bodies, the Pacchionian 
bodies or granulations, which are reduplications and thickenings of the arachnoid. 
They vary in size, in number, and in the extent of the surface of the hemispheres 
which they cover, increase with age, and are more numerous in males than in females. 
They serve as filters for the cerebrospinal fluid, which makes its escape into the general 
circulation through them. They may perforate the dura mater, or, more rarely, the 
wall of the longitudinal sinus, and may produce erosions of the skull bones. They are 
composed of fibrous tissue and may undergo fatty or calcareous degeneration. 
The pia mater is frequently thickened, opaque, and white, either in diffuse patches 
or, more commonly, along the course of the vessels. In other cases single or multiple 
small white spots, of the size of a pin's head or smaller, may be seen in the membrane, 
not appreciably elevated above the surface, but due to localized thickening. These 
slight opacities of the pia mater are commonly believed to be dependent upon repeated 
congestions of the membrane or upon chronic meningitis, but there is no evidence that 
this is always the case. They are most frequently found in old persons, but may exist 
at any age, and do not necessarily indicate the pre-existence of disease. 
The amount of blood contained in the vessels of the pia mater after death varies 
greatly, and is by no means a reliable indication of the amount present during life. 
In edema of the brain and pia mater the vessels of the latter may contain but a small 
amount of blood. 
General Characters of the Pia Mater and of the Arachnoid. 
EDEMA. 
The quantity of serum beneath the pia mater and infiltrating its 
tissue is very variable in amount. It may accumulate as a result of 
atrophy of the brain substance or of venous hyperemia, and sometimes 
is, and sometimes is not, accompanied by edema of the brain substance. 
1 For a study of psammoma, consult Ernsc, P., Zieglers Beitr., 1892, xi, 234 THE NERVOUS SYSTEM 
1095 
It may be diffuse or localized. It is not infrequent to find in hospital 
patients suffering from chronic nephritis, cardiac or pulmonary disease, 
or chronic alcoholism, a very considerable amount of serum in this situa- 
tion, though the patient has been free from cerebral symptoms. In 
other cases a serous effusion may accompany grave cerebral symptoms. 
It is necessary to be very careful in judging of the importance of this 
accumulation of fluid, especially in determining the cause of death in 
the absence of other marked lesions. 
It should always be borne in mind that an accumulation of fluid 
beneath the pia mater and in its meshes may occur as a result of post- 
mortem changes.1 
HYPEREMIA AND HEMORRHAGE. 
Hyperemia.-The pia mater may be hyperemic in early stages of 
meningitis, in delirium tremens, in epileptic convulsions, in infectious 
diseases, and in poisoning. The hyperemia may be due to the pressure 
of exudates or tumors on the veins, or to general or local lesions of the 
circulatory system. The time which elapsed between death and the 
autopsy, the position in which the body has lain, and the coagulability 
of the blood, may have an important bearing upon the amount and 
situation of blood in the pia. 
Hemorrhage.-This may occur either into the space between the dura 
and the arachnoid or between the arachnoid and the pia -inter meningeal 
hemorrhage-or in the meshes of the pia or between the latter and the 
brain. It may be due to injury, to rupture of aneurysms or otherwise 
diseased blood-vessels, to thromboses of the venous sinuses, or to condi- 
tions which we are unable to ascertain. Hemorrhages without known 
cause not infrequently occur in the substance of the pia mater in young 
children, but in adults they are apt to be the result of injury. Multiple 
ecchymoses, however, in the substance of the pia mater sometimes occur 
in infectious diseases and also in acute inflammation of the pia mater. 
Hemorrhages in the brain substance may lead to the accumulation of 
blood beneath or in the meshes of the pia mater. Intermeningeal 
hemorrhage in infants as a result of injury during birth is not uncommon. 
Small, or sometimes considerable, extravasations of blood may occur 
from diapedesis, and sometimes, as a result of chronic congestion, degener- 
ated blood-pigment collects along the walls of the vessels. The extra- 
vasated blood in meningeal hemorrhage, if small in quantity, may be 
largely absorbed, leaving a greater or smaller accumulation of pigment 
at the seat of the hemorrhage. Such pigmentations may last for a long 
time. 
INFLAMMATION. (Meningitis; Leptomeningitis.) 
We distinguish acute, chronic, tuberculous, and syphilitic meningitis. 
Acute Meningitis may occur as the characteristic lesion of epidemic 
cerebrospinal meningitis; it is a not very infrequent complication of 
pneumonia, influenza, typhus and typhoid fever, the exanthemata, and 
1 For study of edema of the pia arachnoid, see Stillman, C. K., Arch. Int. Med., 1911, viii, 193. 1096 
THE NERVOUS SYSTEM 
chronic diffuse nephritis; it may be secondary to injuries and inflamma- 
tion of the cranial bones, of the dura mater, and of the middle ear, and 
it sometimes occurs as an independent infectious process. 
In acute meningitis the inflammatory process is apt to extend down- 
ward and involve the pia mater of the cord. It may also involve the 
ependyma of the ventricles, and cause the distention of these cavities 
with serum. This latter condition is especially frequent in young 
children. 
It is convenient to consider two varieties of acute meningitis, one in 
which there is cell proliferation with little or no exudate, the other in 
which exudate is present. In many cases at least, the first may be the 
early stage of the latter form. 
1. Acute Cellular Meningitis.-The pia mater is congested, its 
surface is dry and lustreless, and it is somewhat opaque. The changes 
in the gross appearance of the membrane are not marked and are easily 
overlooked, but the minute changes are more decided. There is a pro- 
Showing distention of the meshes of the pia mater of the brain with fluid, in which are 
leucocytes and exfoliated endothelium, the latter undergoing proliferation. 
Fig. 749.-Acute Exudative Meningitis. 
liferation of the endothelial and connective-tissue cells of the pia, and 
often a moderate collection of fluid and leucocytes in the meshes of the 
pia. This cell proliferation may involve the pia mater over most of the 
surface of the brain. This form of meningitis is of frequent occurrence 
and is attended with the ordinary clinical symptoms of acute meningitis. 
2. Acute Exudative Meningitis is characterized by the accumu- 
lation, chiefly in the meshes of the pia mater and along the walls of the 
blood-vessels, of variable quantities of serum, fibrin, and pus. Some- 
times one, sometimes another of these preponderates, giving rise to 
serous, fibrinous, or purulent forms of the inflammation. The absolute 
quantities of the exudation also vary greatly. In some cases death 
may occur with so slight a formation of exudate that to the naked eye 
the pia mater may look quite normal or perhaps only moderately hyper- 
emic or edematous; the microscope, however, will reveal in these cases 
pus cells in small numbers, newly formed connective-tissue cells (Fig. 749 THE NERVOUS SYSTEM 
1097 
and Fig. 750), and sometimes flakes of fibrin in the meshes of the pia and 
along the walls of the vessels. In other cases turbid serum in the meshes 
of the membrane is all that can be seen and the microscope shows the 
turbidity to be due to pus cells or to a small amount of fibrin. Again, 
either with or without marked edema of the pia mater, yellowish stripes 
are seen along the sides of the veins, sometimes appearing like faint 
Fig. 750.-Acute Exudative Meningitis. 
Proliferation of connective-tissue cells and extravasation of leucocytes in the adventitia of a 
small blood-vessel of the pia mater. 
turbid streaks, at other times dense, opaque, thick, and wide, and almost 
concealing the vessels. These are due to the accumulation of pus cells 
and fibrin in large quantities along the vessels, and are best seen and 
most abundant around the larger veins which pass over the sulci. In 
still other cases the infiltration with pus and fibrin is so dense, thick, 
and general, that the brain tissues, convolutions, and most of the vessels 
a, Convolutions of cerebrum; b, pia mater thickly infiltrated with pus; c, blood-vessels entering 
brain from pia and surrounded by a zone of pus cells; d, congested blood-vessels of pia mater; e, smaller 
blood-vessels of pia, around which pus cells are collected in dense masses. 
Fig. 751.-Acute Exudative Meningitis. 
of the pia mater themselves are concealed by it. This pus is usually of 
a greenish yellow color, and is sometimes so thick as to form a sort of 
cast of the brain surface at the seat of the lesion (Fig. 751). Sometimes 
extravasated red blood-cells are mingled with the other exudations, as 
the result of diapedesis. Microscopical examination shows numerous 
white blood-cells sticking to the walls of the veins and capillaries, or 1098 
THE NERVOUS SYSTEM 
blocking the vessels. It is evident that a large part of the pus cells 
accumulate as the result of emigration. The connective-tissue cells of 
the pia mater may be detached from their places or degenerated. The 
endothelial cells and other connective-tissue cells may proliferate. In 
some cases there are considerable accumulations of pus between the pia 
mater and the brain substance and along the vessels which enter the 
latter. More rarely pus is found upon the free surface of the membrane. 
The brain substance may be compressed by the accumulated exudate, 
so that the convolutions are flattened. The cortical portion of the brain 
may be simply infiltrated with serum-edematous-or it may undergo 
degenerative changes, or it may be the seat of punctate hemorrhages. 
Not infrequently the inflammation extends to the ventricles, which may 
contain purulent serum, and to the pia mater of the cord. This form of 
inflammation is most frequent on the convexity of the brain, but may 
Fig. 752.-Fatty Degeneration of Cells Along the Blood-vessels of the Pia Mater 
after Exudative Meningitis. 
From the pia mater of a child five years old. 
extend or even be confined to the base. It may be localized, but fre- 
quently extends widely over the surfaces of the hemispheres. 
When recovery from acute exudative meningitis occurs there may be 
fatty degeneration of the cells which have accumulated in the pia mater, 
particularly along the vessels (Fig. 752), and this may produce white 
patches in the membrane and threads along the blood-vessels, which 
resemble the appearance of an accumulation of exudate in the acute 
stage. Fatty degeneration of the blood-vessels and cells of the pia 
mater may also occur without acute inflammatory changes. 
Sometimes, in children and young adults, inflammatory changes in 
the ventricles persist for days and weeks after the subsidence of the 
inflammation of the pia mater. 
For a discussion of the bacterial excitants of exudative meningitis 
see page 254.1 
1 The close topographic relationships which the nasal cavities and the middle ear bear to the 
meninges are significant in this connection on account of the possibility of the transmission to the 
brain membranes of bacteria not uncommonly present and usually harmless in the former situations. THE NERVOUS SYSTEM 
1099 
Chronic Meningitis.-The entire pia mater may be involved or the 
inflammation may be confined to the base alone (basilar meningitis), or to 
the convexity alone, or to circumscribed patches of the membrane. The 
pia mater is thickened and opaque, the thickening being sometimes very 
considerable. There is a formation of new connective tissue and this 
may be associated with accumulation of pus, fibrin, and serum; the rela- 
tive quantity of these inflammatory products varies in different cases. 
Firm and sometimes extensive adhesions may be formed between the 
dura mater and the pia mater. Not infrequently the cortical portions 
of the brain participate in the process, and there is an infiltration of small 
spheroidal cells around the blood-vessels, thickening of the walls of the 
vessels, and degenerative changes and atrophy of the nerve tissue. New 
connective tissue may also form in the brain substance, which may 
become closely adherent to the pia mater. The ventricles of the brain 
also may contain an increased amount of serum and may be dilated, 
the ependyma may be thickened and roughened. This form of inflam- 
There is an area of caseation at the center; on the right of this are two giant cells; there is 
a peripheral zone of small cells. The leucocytes are increased in the meshes of the pia. 
Fig. 753.-Miliary Tubercle of the Pia Mater of a Child. 
mation may be the result of injury or disease of the cranial bones, or 
secondary to chronic pachymeningitis or to inflammation of the brain 
substance. It may occur in the vicinity of tumors of the brain or menin- 
ges. It may be a complication of chronic diffuse nephritis and cerebral 
arteriosclerosis or the result of chronic alcoholic poisoning. It may occur 
in marked form in general paresis of the insane. 
Tuberculous Meningitis.1-This is especially characterized by the for- 
mation in the pia mater of miliary tubercles, associated with more or less 
well-marked exudative inflammation. It may occur in adults or in 
children, but is more common in the latter. The dura mater may be 
unchanged, or its inner surface may be sprinkled with miliary tubercles. 
The pia mater may or may not be congested; it may look dry on the sur- 
face or it may be edematous. Usually the brain seems to fill the cere- 
bral cavity to an unusual degree, and the convolutions are flattened. If 
the pia mater be edematous the serum may be clear, or turbid with pus 
and fibrin. The membrane may present any of the general appearances 
of exudative meningitis, but always in addition to these, and sometimes 
without them, are found miliary tubercles. These may be few and widely 
scattered, or present in great numbers. They are most numerous along 
the blood-vessels, but may occur anywhere. They are usually abundant 
1 For a thorough study of the clinical symptoms and pathology of tuberculous meningitis, see Meyers, 
A. E., Am. Jour. Dis Child., 1915, ix, 407. 1100 
THE NERVOUS SYSTEM 
at the base of the brain. On the convexity they are most common along 
the surfaces of the sulci. Some of the tubercles are so small as to be 
scarcely visible or entirely invisible to the naked eye; others are as large 
as a pin's head or larger. They may be formed in the membranous 
prolongations of the pia mater which dip into the sulci, around the ves- 
sels which enter the brain substance, in the choroid plexus and ependyma 
of the ventricles, and may exist in the spinal cord. The miliary tubercles 
have the usual structural characters of focal tuberculosis in connective 
tissue (Fig. 753). 
In children the ventricles are usually more or less distended by an 
accumulation of transparent or turbid serum, and the walls of the ven- 
Fig. 754.-A Miliaky Tubercle of the Ependyma of the Lateral Ventricle. 
This shows an early stage of tubercle formation on the ependyma without marked caseation. 
tricles may be studded with miliary tubercles (see Fig. 754). In adults 
the ventricles are less frequently involved. The brain tissue around 
the ventricles is often softened. The central canal of the spinal cord 
may also be dilated. It is the dilatation of the ventricles which causes 
the flattening of the convolutions, and the flattening is usually in direct 
proportion to the amount of accumulated fluid. 
Owing to the frequency of the dilatation of the ventricles with serum 
in children, the disease is often called acute hydrocephalus. In both 
children and adults the tuberculous inflammation may produce large 
masses of tuberculous tissue, which undergo cheesy degeneration, and 
may involve the brain tissue. In almost all cases of tuberculous menin- 
gitis there is tuberculous inflammation in other parts of the body. 
Miliary tubercles in the choroid of the eye are present in a considerable 
proportion of cases. The cortex of the brain may be hyperemic, and 
punctate hemorrhages may be present in the cortex and in the pia mater. 1101 
THE NERVOUS SYSTEM 
Syphilitic Meningitis.-In this form of inflammation, which is usually 
circumscribed, there is a development of gummata of various sizes, 
frequently associated with simple inflammation of the membrane, either 
with the formation of serum, fibrin, and pus, or with the development 
cf new connective tissue and consequent thickening of the membrane. 
The gummata may form in the pia mater covering the convexity, or at 
the base of the brain. They may grow outward, involving the dura 
mater; or inward, encroaching upon or involving the brain tissue. 
Although usually circumscribed, syphilitic inflammation may occur as 
a diffuse thickening of the membrane, usually over the base of the brain 
and along the blood-vessels and involving the sheaths of the cranial 
nerves. The ependymal lining of the ventricles often presents a granular 
appearance due to reduplications of the ependymal cells. The syphilitic 
nodules, including the gummata and new-formed connective tissue, are 
often very small, but may be as large as a hen's egg. (See, for further 
details, page 1174.) 
TUMORS. 
Hematoma^-In chronic pachymeningitis of long standing the new 
connective tissue may form large, flat cysts between the dura mater and 
the pia mater, which may compress the surface of the brain. The blood 
originally contained in these cysts may be absorbed and replaced by 
serum, the attachments to the dura mater may disappear, and the whole 
appearance becomes that of an independent cyst between the dura mater 
and the pia mater. Fibroma, lipoma, myxoma, chondroma, osteoma, 
and cholesteatoma (page 1173) are of rare occurrence. 
Endotheliomata.-These tumors are of not infrequent occurrence, and 
may grow from the pia of the cerebrum or cerebellum or from the choroid 
plexus. They may be single or multiple. 
Some of them are composed of a connective-tissue stroma which 
incloses regular spaces filled with large, flat, nucleated cells. These may 
resemble carcinoma. Some of them are composed of a connective-tissue 
stroma which forms cavities lined with cylindrical epithelium. In such 
tumors the stroma may grow so as to form papillae covered with cylin- 
drical epithelium; or in addition there may be mucous degeneration of 
the stroma. In some of them there is a connective-tissue stroma which 
contains large numbers of blood-vessels. Around these blood-vessels are 
arranged regular masses of polyhedral cells (Fig. 755 and 756). 
In some endotheliomata the stroma is scanty. The cells are numer- 
ous, large, flat, and arranged in little globular masses or nests (Fig. 249, 
page 441). If in these little nests there is a deposition of the salts of 
lime, forming concretions like the so-called 11 brain sand," the tumor is 
called a psammoma. Some of the tumors seem to be formed of very thin, 
nucleated membranes arranged concentrically like the layers of an onion.1 
Sarcoma.-Tumors belonging to the ordinary types of round-cell and 
fusiform-cell sarcoma and of myxosarcoma are occasionally found. 
1 For a critical review of these and other pial tumors, with bibliography, see Bostroem, E., Centralbl, 
f. allg. Path., 1897, viii, 1. 1102 
THE NERVOUS SYSTEM 
Fig. 755.-Endothelioma of the Cerebellum Originating in the Pia Mater. 
Showing general appearance of the tumor (see Fig. 756). 
c- 
B- 
A- 
B- 
C 
Fia 756.-Endothelioma of the Pia Mater of the Cerebellum. 
From specimen shown in Fig. 755, more highly magnified. A, Section of pia mater dipping into 
a sulcus; B, tumor cells growing at each side of the pia; C, surface of cerebellar convolutions. THE NERVOUS SYSTEM 
1103 
Cysts.-Small cysts are often found in the choroid plexus. Rarely 
such cysts may reach a larger size, even as large as a pigeon's egg. Cysts 
of the pia mater containing serum, with walls and septa of connective 
tissue, and compressing the brain have been described. 
Variously shaped pigment cells not infrequently occur in the pia mater, 
either scattered or sometimes in considerable masses; they seem to have 
little pathological significance, except as forming the starting point of 
the very infrequent melanotic tumors which occur in this region. Not 
infrequently thin plates of newly formed bone are found in the pia mater, 
associated with a thickening of the membrane. 
PARASITES. 
Cysticercus has been observed in the pia mater. 
The Dura Mater Spinalis. 
The dura mater spinalis, unlike that of the brain, does not serve as periosteum 
to the bones forming the cavity, so that the lesions of the two membranes differ 
somewhat. 
HEMORRHAGE. 
Hemorrhage may occur, as the result of injury, between the dura 
mater and periosteum, or it may occur in tetanus, as a result of circula- 
tory changes induced by muscular spasm, or in the asphyxia of newborn 
children. Small hemorrhages on the surfaces of the membrane may 
occur as the result of inflammation. Serous fluid may accumulate outside 
of the dura mater as a result of post-mortem changes, or in connection 
with circulatory or inflammatory changes in the membranes. 
INFLAMMATION. (Pachymeningitis.) 
Acute external pachymeningitis is usually secondary to disease or 
injury of the spinal column, and may result in collections of pus between 
the dura mater and periosteum, usually most abundant posteriorly. 
Hemorrhagic pachymeningitis occurs in the dura mater spinalis, with the 
formation of products similar to those observed in the brain, in the 
chronic insane, and in drunkards. Simple chronic pachymeningitis 
interna, with the formation of new connective tissue containing brain 
sand, is not infrequent. The new tissue may form minute projections 
from the surface, or, -when more abundant, may take the form of psam- 
momata. Tuberculous inflammation of the dura mater spinalis may 
occur in connection with tuberculous meningitis, or be secondary to 
tuberculous inflammation of the vertebrae. 
TUMORS. 
Fibromata, lipomata, chondromata, myxomata, endotheliomata,1 and 
alveolar sarcomata occur in the dura mater spinalis as primary tumors. 
1 Howe, H. S., Extensive spinal arachnoid fibroblastoma, Neurol. Bull., 1921, iii, 216.  THE NERVOUS SYSTEM 
1104 
Carcinomata and sarcomata may be found as secondary tumors. Small 
plates of newly formed bone are of rare occurrence. 
PARASITES. 
Echinococcus developing outside of the spinal canal may perforate the 
dura mater; or the cysts may lie between the dura mater and the pia 
mater. 
The Pia Mater Spinalis and the Arachnoid. 
It is difficult in most cases in the pia mater, as well as in the dura mater spinalis 
and in the spinal cord, to judge with certainty, from the appearances after death, of 
the blood contents of the vessels of these parts during life. The same is true of abnor- 
mal quantities of serum found after death. The veins of the pia mater, especially in 
the posterior region, may be greatly distended with blood after death, without pre- 
existing disease; and the intermeningeal space may contain much fluid under the same 
condition. 
Between the pia and the dura is a definite membrane, the arachnoid. It contains 
no blood-vessels, and receives its nutrition from the spinal fluid which circulates in 
the space between the arachnoid and the pia, the so-called subarachnoid space. 
HEMORRHAGE. 
Hemorrhages may occur from injury, in connection with severe con- 
vulsions, or in general diseases such as the hemorrhagic diathesis, scurvy 
smallpox, etc. The hemorrhages under these conditions, except from 
injury, are not usually extensive. But in some cases of injury or cere- 
bral apoplexy, from the bursting of aneurysms of the basilar or vertebral 
arteries, and in other cases in which we cannot find a cause, a very large 
quantity of blood may collect between the dura and pia mater. 
INFLAMMATION. (Meningitis.) 
Acute exudative spinal meningitis occurs under essentially the same 
conditions and with essentially the same post-mortem appearances as 
acute cerebral meningitis, though it is less frequent. The exudate is 
apt to be most abundant in the posterior portions. It may be asso- 
ciated with a similar inflammation of the pia mater cerebralis, and the 
inner surface of the dura mater may be involved. The disease may be 
circumscribed, but usually affects the entire length of the membrane. 
Chronic spinal meningitis is not infrequent, manifesting itself in the 
formation of larger or smaller patches of new connective tissue or in 
thickenings of the pia mater. The pia-arachnoid and dura mater may 
thus be firmly united in places by adhesions, or the pia mater may become 
closely adherent to the substance of the cord. 
Not very infrequently large numbers of pigment cells are found in 
the pia mater spinalis, sometimes giving it a distinct gray or blackish 
color. This change is not due to a previous malarial infection. 
Tuberculous inflammation is usually associated with a similar condi- 
tion of the pia mater cerebralis, in which case the lesion is most marked in 
the upper portions of the cord; but it may extend over the entire mem- THE NERVOUS SYSTEM 
1105 
brane. The conditions under which it occurs and the character of the 
lesions are similar in both. 
TUMORS. 
Fibromata, myxomata, sarcomata, and endotheliomata have been 
found. 
Small plates of cartilage and bone (Fig. 757) are sometimes found in 
the pia mater. 
PARASITES. 
Cysticercus sometimes occurs in the meshes of the pia mater 
Fig. 757.-Plates of Bone in the Pia Mater Spinalis 
THE VENTRICLES OF THE BRAIN. THE EPENDYMA AND 
CHOROID PLEXUS. 
GENERAL CONSIDERATIONS. 
As the lymph-spaces of the pia mater and the ventricles of the brain 
are in communication, it might be supposed that they would share alike 
in the accumulation of fluids. This, however, is not the case. The 
membranes of the brain may be highly edematous while the ventricles 
contain about the normal quantity of fluid; or, on the other hand, the 
ventricles may be widely dilated and the pia mater unusually dry. Many 
of these varying conditions may be understood by remembering that the 
skull and spinal canal form a closed cavity, and that accumulations of 
fluid in one part must be at the expense of some material occupying 
other parts, either blood, serum, or brain tissue. It is not always easy 
to see, however, exactly how the compensation occurs. 
There may be an unusual amount of fluid in the ventricles of the 
brain as a result of post-mortem change; in connection with senile or 
other atrophy of the brain, or in the general vascular changes which lead 
to edema of the brain; in connection with inflammation of the meninges 
or of the ependyma; or under conditions which we do not understand, 
as in some cases of congenital and acquired hydrocephalus. Accumula- 
tions of fluid in the ventricles are often called internal hydrocephalus to 
distinguish them from accumulations in the meninges-external hydro- 
cephalus. 1106 
THE NERVOUS SYSTEM 
INFLAMMATION. (Ependymitis.) 
Acute Ependymitis.-In this condition, which may occur by itself, but 
is usually associated with inflammation of other parts of the brain, the 
ependyma is congested, the vessels are more prominent than usual and 
are often tortuous. The ependyma and the adjacent brain tissue may be 
thickened and infiltrated with pus cells, and the surface of the ependyma 
covered with fibrin and pus in variable quantity (Fig. 758). The cavi- 
ties of the ventricles may contain purulent serum. Small hemorrhages 
may also be present in the tissue of the ependyma. This, as well as 
other forms of inflammation, is more common in the lateral ventricles 
than in the others, but not infrequently involves the fourth ventricle. 
The choroid plexus may participate in the inflammatory changes of the 
ependyma. Tuberculous inflammation of the ependyma is, as above 
mentioned, a not infrequent accompaniment of tuberculous meningitis. 
Fig. 758.-Acute Ependymitis. 
Showing replacement of the epithelium of the ventricle by inflammatory exudate: collections 
of pus cells near the epithelium and about the adjacent small blood-vessels. 
Chronic Ependymitis.-This lesion, which is much more common than 
simple acute inflammation of the ependyma, occurs under a variety of 
conditions, being most frequently seen in paresis, cerebral arterio- 
sclerosis, and chronic encephalitic states. The ependyma is thicker, 
whiter, and more opaque than normal, so that the vessels may be nearly 
or quite invisible. The thickenings may occur in patches or diffusely, 
and the surface of the ependyma may be smooth, or roughened and 
granular. On microscopical examination the surface of the ependyma 
may be covered with the usual epithelium, but the new neuroglia tissue 
which forms beneath it often raises it up in places, causing the roughness 
of the surface. The new tissue is usually rather loose in texture and THE NERVOUS SYSTEM 
1107 
may contain many small spheroidal cells; but it may be dense in texture 
and contain few cells. The brain tissue beneath the thickened ependyma 
may be softened or infiltrated with cells. The sides of the ventricles 
may be grown together in places by the adhesion of the thickened and 
roughened ependyma. The ventricles usually contain more serum than 
normal, and sometimes this accumulation is so great as to cause an enor- 
mous dilatation of them. The accumulation of fluid and the dilatation of 
the ventricles being the most marked feature in all this class of lesions, 
they are often called chronic hydrocephalus, but in many cases we have no 
evidence that the change in the ependyma is an important or even 
primary factor. 
Hydrocephalus.1-We may, for convenience of study, consider three 
classes of cases of hydrocephalus: first, congenital hydrocephalus in 
young children; second, secondary hydrocephalus in children and adults; 
third, primary hydrocephalus in adults. 
For an understanding of the conditions which lead to hydrocephalus, 
it is important to recall some of the facts concerning the production and 
distribution of the cerebrospinal fluid.2 The fluid is presumably a true 
secretion from the ependymal cells of the choroid plexuses. Additional 
fluid may be supplied by the cerebral lymphatics, which empty into the 
spaces of the arachnoid. The major quantity is set free in the lateral 
ventricles, passing by the foramen of Monro to the mesial ventricles, 
from which it escapes by the foramina of Luschka and Magendie into 
the subarachnoid spaces. From here the excess of fluid enters the dural 
sinuses, probably through the intermediary of the arachnoid villi, and 
also from the subarachnoid space through the process of osmosis. We 
may, therefore, again classify hydrocephalus into, first, obstructive 
hydrocephalus, due to obstruction at any part of the path which the fluid 
traverses, and, second, nondestructive hydrocephalus, due to increased 
secretion or diminished absorption of the fluid. It will thus be obvious 
that inflammatory or mechanical obstruction along any portion of the 
tortuous course followed by the cerebrospinal fluid may set up stasis; 
and it is not difficult to see that even thrombosis of the sinuses may 
accomplish the same interference with the necessary removal of the 
continuously secreted fluid, whose amount, it has been estimated, is not 
less than 500 c.c. per twenty-four hours. 
1. Congenital Hydrocephalus.-The lesion may be in an advanced 
stage at the time of birth, or it may be scarcely evident or but moder- 
ately developed. It may progress rapidly and cause the early death 
of the child, or it may develop gradually or come to a standstill. In 
the more marked forms of the disease the ventricles are widely dilated 
(Fig. 759) and filled with serum, which is usually transparent. Not only 
the lateral ventricles, but also the third and fifth, may be involved; the 
fourth is less apt to participate in the lesion, although it is sometimes 
dilated, as well as the central canal of the cord. 
i Consult Margulis, Arch. f. Psychiat., 1912,1, 31; and Dandy, W. E„ and Blackfan, K. D., Am. Jour. 
Dis. Child., 1914, viii, 406; 1917, xiv, 424. 
2 For information concerning cerebrospinal fluid, see Boyd, WPhysiology and pathology of the 
cerebrospinal fluid, New York, 1920; and Levinson, A., Cerebrospinal fluid in health and in disease, 
St. Louis, 1919; also Mott, F. W., Lectures on the cerebrospinal fluid, Lancet, 1910, ii, 1, 79; and Weed, 
L. H., Theories of drainage of cerebrospinal fluid, Jour. Med. Research, 1914-15, N. S. xxvi, 21; The 
cerebrospinal fluid, Physiol. Reviews, 1922, ii, 171 (bibl.). 1108 
THE NERVOUS SYSTEM 
The distention, especially of the lateral ventricles, may be so great 
that the brain tissue over the vertex is crowded up into a thin layer 
beneath the dura mater, or it may be entirely destroyed. When the dila- 
tation of the ventricles is considerable, the convolutions are flattened 
and may be almost entirely obliterated. The skull bones may be thin 
and bulging over the forehead and vertex; the fontanelles and sutures 
widely open. The ependyma in these cases is usually thick and rough, 
but it may be softened, and the blood-vessels may be dilated. The basal 
portions of the brain may be flattened, but are usually much less affected 
than the upper portions. The brain tissue is usually soft and anemic. 
In advanced cases there is often atrophy of the lateral columns. 
2. Secondary Hydrocephalus.-This may occur in children and 
adults, and may be a result of epidemic cerebrospinal meningitis, of 
acute meningitis, or of chronic meningitis, either simple or tuberculous. 
It sometimes occurs in chronic alcoholic poisoning and in general paraly- 
sis of the insane. It may be caused by the presence of echinococcus 
in the ventricles, blocking the free outflow of cerebrospinal fluid. The 
presence of a tumor may exert sufficient pressure to prevent the 
Fig. 759.-Congenital, Hydrocephalus in Child. About half natural size. 
a, a, Dilated lateral ventricles; b, cornua, unequally dilated; c, third ventricle; d, middle commissure. 
outflow of the secretion of the ependymal cells; and, in rare instances, 
obstruction may be due to the crowding of the pons and posterior portion 
of the cerebellum into the foramen magnum, as a result either of rapidly 
increasing intracerebral pressure or of the incautious and rapid removal 
of large quantities of fluid by lumbar puncture. The amount of dilata- 
tion of the ventricles varies greatly in these cases, but it is never so great 
as in congenital hydrocephalus, and is not accompanied by the changes 
in the shape of the skull which form so prominent a feature in the latter 
disease, since the bones are firmer and the sutures united. In this form 
of chronic hydrocephalus the changes in the ependyma above described 
are usually more or less well marked, and they may be associated with 
the production of fibrin and pus. 
3. Primary Hydrocephalus in Adults.-The conditions leading 
to this form of lesion are not understood. It is apt to occur in persons 1109 
THE NERVOUS SYSTEM 
over thirty years of age. Sometimes one, sometimes both lateral ven- 
tricles are dilated. The dilatation is usually moderate, sometimes very 
slight and never so great as in congenital hydrocephalus. The ven- 
tricles usually contain transparent serum, and the ependyma is thickened 
and roughened. A chronic leptomeningitis is not infrequent. In some 
cases the hydrocephalus is the only lesion found to account for the death 
of the patient.1 
TUMORS. 
New formations of connective tissue in the ependyma, although usu- 
ally diffuse, may be circumscribed and form small, projecting connective- 
tissue nodules which may be classed among the fibromata. Small fibro- 
mata are sometimes detached from the walls of the ventricles and lie 
free in the cavity. Small lipomata, angiomata, cystic sarcomata,2 
"peritheliomata,"3 and gliomata1 occur rarely, and may arise from the 
walls of the ventricle or the plexus. Chondromata and angiomata may 
occur in the choroid plexus, the latter sometimes being as large as a hen's 
egg. The choroid plexus is not infrequently the seat of transparent 
cysts, usually of small size; they may contain clear fluid, colloid material, 
droplets of fat, or calcareous particles. The cysts have no special patho- 
logical significance. Dermoid cysts containing hairs have been found in 
the ventricles.5 
Very rarely papillary epithelial tumors arise from the cells covering 
the choroid plexus, and cysts containing mucus may be found in them, 
as well as epithelial pearls. They are not malignant, as a rule, and re- 
main confined to the ventricular cavity.6 
The calcareous bodies called "brain sand" (Fig. 746), which are 
aggregations of particles of carbonate and phosphate of lime with a small 
amount of phosphate of ammonia and magnesium mixed with more or 
less organic matter, occur frequently in the choroid plexus, and corpora 
amylacea may occur here and beneath the ependyma. 
PARASITES. 
Cysticercus7 and echinococcus cysts are sometimes attached to the 
walls of the ventricles or may be free in their cavities. In the latter 
case, echinococcus may, by obstructing the flow of fluid from the ven- 
tricles, incite hydrocephalus, or by pressure may cause glycosuria. 
Blastomycetes have been found in the ventricles and in cysts in the 
brain substance.8 
1 For theories of causation of hydrocephalus, see Weber, L. W., Arch. f. Psychiat., 1906, xli, 64. For 
studies on the cerebrospinal fluid, including its relation to hydrocephalus, see Cushing, H., Weed, 
L. H., and Wegefarth, P., Jour. Med. Research, 1914-15, N. S. xxvi, 1. 
2 Hirsch, K., Berl. klin. Wchnschr., 1892, xxix, 727, 751. 
3 Watzold, Zieglers Beitr., 1905, xxxviii, 388. 
4 Mallory, F. B., Jour. Med. Research, 1902, iii, 1; Link, Zieglers Beitr., 1903, xxxiii, 98. 
6 Bostroem, Centralbl. f. allg. Path., 1897, viii, 1 (bibl.). 
6 Saxer, Zieglers Beitr., 1902, xxxii, 276; and Hort, Arch. f. Psychiat., 1910, xlvii, 739. 
7 Kocher, R. A., Zieglers Beitr., 1911, 1, 338 (bibl); and Sato, T., Deutsch. Ztschr. f. Nervenh., 
1904, xxvii, 24. 
8 v. Hansemann, Verhandl. d. deutsch. path. Gesellsch., 1906, ix, 21. 1110 
THE NERVOUS SYSTEM 
The Brain and Spinal Cord. 
Cyclopia.-This malformation consists in an arrest of development affecting the 
cerebrum, which, instead of separating into two hemispheres, remains single, with one 
ventricle, the rudiments of the eyes usually uniting to form one eye (Fig. 187). This 
single eye is in the middle of the face, near the place of the root of the nose, in a single 
orbit. Over this is an irregular body representing the nose. The rest of the face is 
well formed. The eyeball may be wanting entirely, or there may be two eyes joined 
together, or, more seldom, two separate eyes. The orbit is surrounded by rudiments 
of four eyelids. The frontal bone is single, the nasal bones are undeveloped; the 
ethmoid, vomer, and turbinate bones are absent. The optic nerve is double, single, or 
absent. There may be hydrocephalus. Such children are incapable of prolonged 
existence. 
Anencephalia.-This malformation may be of various degrees. The brain may 
be entirely absent, the base of the cranium being covered with a thick membrane, into 
which the nerves pass. The membranes may form a sort of cyst containing blood and 
serum or portions of brain. Of the cranial bones, only those which form the base of 
the skull are present {acrania). The scalp is usually partly or entirely absent over 
the opening in the skull; the eyes are prominent, and the forehead slopes sharply 
backward. This malformation may occur in otherwise well-developed children. 
Hydrocephalus.-This lesion has been already considered above. It is proba- 
ble that in some cases hydrocephalus internus is due to a primary partial anencephalia, 
and that the accumulation of fluid is of secondary occurrence. In rare cases, only 
part of one lateral ventricle is hydrocephalic, giving to the head a protuberance on 
one side. The viability of the fetus depends upon the degree of the hydrocephalus. 
Hydrocephalus externus is an accumulation of serum beneath the pia mater, or, accord- 
ing to some authors, between the pia and arachnoid membrane. It causes dilatation 
of the cranium and compression of the brain. It is of very rare occurrence, and may 
also be secondary to partial anencephalia. 
Cephalocele, or Brain Hernia.-When abnormal openings exist in the skull 
from malformation, the contents of the cerebral cavity are apt to protrude in the 
form of larger or smaller sacs. This may occur in cases of well-marked anencephalia 
or in cases in which the brain is well developed. The protruding sac formed of the 
meninges may or may not be covered with skin. If the contents of the sac are simply 
fluid, the lesion is called hydromeningocele; if composed of brain substance, encephalo- 
cele (Fig. 191); if the sac contain both fluid and brain substance, it is called hydren- 
cephalocele. The sacs may be very small or as large as a child's head. They may 
protrude from the top of the skull in acrania. They most frequently protrude 
through openings in the occipital bone, often hanging down in large sacs upon the 
neck; also at the root of the nose, along the line of the sutures, at the base of the skull, 
and elsewhere. 
Microcephalia.-This is an abnormally small size of the brain, with a correspond- 
ingly small cranium. The diminution in size affects principally the cerebral hemi- 
spheres, though the other parts of the brain are also small. Thus the cerebellum may 
be of extremely small size. The cord may be smaller than normal, in which case the 
diminution in size is apt to show a direct dependence upon the cerebral lesions, the 
direct and the crossed pyramidal tracts being most affected. There may also be 
present imperfect development of the posterior columns and of the direct cerebellar 
tracts. The convolutions are few and simple, the cavities often dilated with serum; 
on the membranes there may be traces of inflammation. The cranium is small, the 
face large, the rest of the body small. This malformation is in some cases caused by 
inflammation or dropsy of the brain during fetal life. It is endemic in some countries, 
and may affect a number of persons in the same family; but single cases often occur. 
The fetus is viable. Absence or incomplete development of portions of the brain 
may occur, not only in idiots, but in persons whose minds are perfect.1 
Malformations of the Brain. 
1 For a general consideration of malformations of the central nervous system, consult Thoma, 
Pathology and Pathological Anatomy, English translation, vo . i, 206 et seq.; and Ernst, P., Schwalbe, 
Die Morphologie der Missbildungen des Menschen u. der Tiere, Jena, 1909, vol. iii, part 2, p. 67. 1111 
THE NERVOUS SYSTEM 
Malformations of the Spinal Cord. 
The malformations of the spinal cord may be conveniently classed as follows: 
I. Congenital Deformities Associated with Monstrosities, and Incompati- 
ble with Extra-uterine Life. 
These may be divided into: 
1. Amyelia, or absence of the spinal cord. This is almost invariably associated 
with absence of the brain. 
2. Atelomyelia, or partial development of the spinal cord. This is often seen in the 
anencephalous or acephalic monsters, where, corresponding to the incompletely devel- 
oped brain, there may be various degrees of defective development of the cord. 
3. Diastematomyelia, a condition in which a portion or the whole of the cord is 
split into two lateral halves. Each half of the cord is developed in its own membranes 
and gives rise to its own nerve roots. There may be union at one or more points to 
form a single cord. 
4. Diplomyelia, or a formation of two spinal cords-a duplication of the spinal 
cord. This happens in the various kinds of double monsters. 
Fig. 760.-Hydeomyelia 
In the section from which this drawing was made, the epithelial cells surrounding the dilated 
central canal were well preserved. 
II. Minor Congenital Malformations not Inconsistent with the Mainte- 
nance of Life. 
1. Hydrorrhachis interna is a defective closure or arrangement of the divisions of 
the primary fetal central canal often resulting in the dilatation of the central canal 
by fluid (Hydromyelia, Fig. 760). This dilatation may be moderate, or so extreme 
that but little of the substance of the cord is left as a thin shell around the central 
cavity. When they have not been destroyed by atrophy, epithelial cells may be 
found lining the cavity. 
This condition may be accidentally found after death. Its presence may also be 
indicated by its association with spina bifida.1 
2. Heterotopia, or misplacement of the substances of the cord. 
(a) There may be misplaced portions of the gray matter. 
(6) Portions of the white matter may be arranged in an unusual manner. 
3. Anomalies of the Spinal Nerve Roots. 
4. Asymmetries of the Spinal Cord. 
III. Malformations of the Spinal Cord Acquired during Extrauterine 
Life or Secondary to Defective Development in Other Parts of the Body. 
1. Distortions following other cord lesions. 
2. Asymmetry of the cord due to arrested development after birth or to secondary 
1 Under this subdivision the condition known as hydrorrhachis externa may be conveniently alluded 
to, which consists in an abnormal congenital accumulation of fluid between the meninges of the cord, 
causing more or less diminution in the volume of the latter. 1112 
atrophy of portions of the cord in association with defective development or absence 
of some other part of the body. 
3. Asymmetry of the cord with congenital defects of the extremities or muscles, 
such as intrauterine or other amputations, clubfoot, etc. 
4. Variations in the volume of the cord as a whole. 
False Heterotopia.-Congenital displacement of the gray or white matter of the 
spinal cord-heterotopia-has been frequently described. It has been shown,1 how- 
ever, that in a large proportion of cases the so-called heterotopia is an artefact (Fig. 
761) and has been caused by bruises or careless handling of the cord during its removal 
from the body or in the process of examination or hardening. 
Spina Bifida.-In the majority of cases hydrorrhachis is accompanied by a more 
or less complete lack of closure of the spinal canal posteriorly, so that the collections 
of fluid within may pouch outward through the opening in the form of a sac. The sac 
may be covered by skin, or this may be absent, either from the beginning or as a result 
of thinning and rupture. The walls of the sac may consist of the dura mater and the 
pia mater, or, in cases of hydrorrhachis externa, of the dura mater alone. When both 
are present they are usually more or less fused together. Inside of the membranes of 
the sac there may be a shell of distended nerve tissue of the cord; or the spinal cord 
may be split posteriorly and the sides crowded sideways; or there may be a rudimen- 
tary fragment of the cord suspended in the sac or attached to the walls; or the cord 
may be but little changed and remain inside the spinal canal. The openings in the 
spinal canal may be due to the complete or partial absence of the vertebral arches, or 
more rarely the sac may protrude through 
openings between the completely formed 
arches. Spina bifida most frequently occurs 
in the lumbar and sacral regions, but it may 
occur in the dorsal or cervical regions, or the 
canal may be open over its entire length. 
Very rarely it is open on the anterior sur- 
face. The protruding sac may be very small 
or as large as a child's head. The fluid in the 
sac is usually clear, but may be turbid from 
flocculi of degenerated nerve tissue.2 
THE NERVOUS SYSTEM 
SACRAL TUMORS AND CYSTS.3 
In addition to the malformations 
of the lower end of the spinal cord, a 
variety of types of complex congenital 
tumors are seen in the region of the 
sacrum and coccyx. The majority 
are developed in connection with de- 
velopmental malformations about the 
postanal gut and neurenteric canal, for during embryonic life there is a 
connection between the spinal canal and the intestine in this region. 
Some of the tumors are, however, evidently of bigerminal origin, for they 
are made up of fragments of another fetus.4 Others are found to contain 
Fig. 761.-False Heterotopia. Section, 
from Cervical Region of Spinal Cord. 
Showing artificial displacement of the 
structures by an experimental bruise ("false 
heterotopia") after the removal of the cord 
from the body. (Van Gieson.) 
1 For a study of artefacts of the nervous system, see Von Gieson, I., New York Med. Jour , 1892, 
vi, 337, 365, 421. 
2 For further anatomical details, see the standard text-books on surgery, and Lecene, Proust, and 
Tixier, Precis de pathologic chirurgicale, Paris, 1909. 
3 Keen and Coplin, Surg., Gynec., and Obst., 1906, iii, 661 (bibl.); Borst, Centralbl. f. allg. Path., 
1898, ix, 449 (good bibl).; Prym, Frankfurt. Ztschr. f. Path., 1912, ix, 1 (neuroepithelioma); Nakayama, 
Arch. f. Entwcklngsmechn. d. Organ., 1905, xix, 475 (teratoid tumors); Hagen, W., Beitr. z. klin. Chir. 
(Bruns), 1904, xlii, 646; Englemann, Arch. f. klin. Chir. (Langenbeck), 1903-1904, Ixxii, 942; Schramm, 
Wien. klin. Wchnschr., 1910, xxiii, 55 (complex tumors); Markoe, F. H., and Schley, W. S., Am. Jour 
Med. Sc., 1902, cxxiii, 820; Mallory, F. B , Jour. Med. Research, 1902, N. S. iii, 1. 
4 For illustrations, see Bland-Sutton, Tumours: Innocent and Malignant, 5th ed., New York, 1917, 
pp. 425, 443. and 444. THE NERVOUS SYSTEM 
1113 
nerves, parts of eyes, kidney, thyroid, mamma, intestine, and other adult 
tissues. A less complex type is the cystosarcoma, which is composed of 
mixtures of sarcomatous or embryonic connective tissue, embedded in 
Fig. 762.-Nedboepithelioma from Tumob of Sacbum. 
Fig. 763.-Lining of Wall of Cyst fbom Sacbal Region. 
which are epithelial cysts. Dermoid tumors and lymphangiomata are 
also found. Of the simpler tumor types lipoma, chondroma, neuro- 
blastoma (Fig. 762), and the ordinary types of sarcoma have been de- 1114 
THE NERVOUS SYSTEM 
scribed. In addition to these tumors, remnants of the neurenteric canal 
may be found quite frequently in the form of the so-called postanal 
dimples, shallow depressions over the top of the coccyx. These dimples 
may be deep so that a sinus is formed lined by skin containing hair, 
sweat and sebaceous glands. The tissues may become infected, and all 
the skin structures be destroyed by the suppurative process, so that the 
determination of the nature of the sinus may be difficult. In some in- 
stances the fistulae may connect with the spinal canal and be lined with 
cylindrical or ciliated epithelium. Closed cysts lined with either squam- 
ous or columnar epithelium are also found in this region (Fig. 763). 
CONGENITAL DISEASES OF THE BRAIN. 
Three types of mental deficiency are generally recognized which 
grade into each other and are distinguished only by arbitrary divisions. 
A moron represents the highest class. Such persons are merely 
children mentally, and the examination of the central nervous system 
shows no constant anatomical differences from the normal. The brain 
weight may equal or exceed that of the most intelligent of the human 
race. 
The imbecile is the next grade and in some instances the brain anat- 
omically is normal; in others the brain is smaller and may show some 
increase in the neuroglia; or congenital defects such as porencephalus, hy- 
drocephalus may be present or other changes many of them probably due 
to vascular or inflammatory lesions at an early age. In some cases para- 
lysis may exist, either monoplegic or diaplegic, due often to hemorrhages 
following prolonged and difficult labor or instrumental trauma. These 
children may have a perfectly normal mentality or may grade through 
severe imbecility into the lowest type, depending upon the site and extent 
of the lesion. Some imbeciles undoubtedly owe their condition to con- 
genital syphilis and it has been recently recognized that there may be cor- 
related with this infection a type of juvenile general paralysis in those 
who are ordinarily classed as imbeciles. 
By some writers the Mongolian type of idiocy is considered to belong 
in the syphilitic group1 but in general the opinion is that syphilis when 
present is only a coincident process and has no etiological relationship 
to the disease. Cases of this type of idiocy are easily recognized by 
their small size, Mongolian features, furrowed tongue (lingua scrotalis), 
short stubby fingers. Enlargement of the sella turcica has been noted.2 
Constant brain lesions have not been described though the organ is small 
and the modelling rudimentary. Malformations of the face, ears, palate, 
and genital organs are frequent. The basal metabolism is not lowered 
which differentiates the patients from cretins or congenital myxcedeinics.3 
Mental Deficiency. 
1 Stevens, H. C., Jour. Am. Med. Assn., 1915, Ixiv, 1636. 
2 Timme, W., Arch. Neurol. & Psychiat., 1921, v, 568. 
3 For Mongolian idiocy, see review of recent literature, Am. Jour. Dis. of Child., 1919, xviii, 146-148; 
Tumpeer, I. H., Jour. Am. Med. Assn., 1922, Ixxix, 14. THE NERVOUS SYSTEM 
1114a 
Another well marked group of idiots are the cretins whose condition 
is due to atrophy or abnormal functional activity of the thyroid gland 
(see pp. 486 and 1044). The brain is small and the ventricles may be 
dilated. The exhibition of thyroid substance in young cretins sometimes 
produces considerable intellectual improvement showing that the brain 
is not seriously altered but in others the amentia persists unimproved. 
In idiots not of the Mongolian or cretin type, the most frequent lesion 
is atrophy of the brain substance following vascular changes occurring 
either previous to or following birth. Meningeal hemorrhage is com- 
monly the primary lesion in these cases. The site of the hemorrhage deter- 
mines to a certain extent the symptoms of the patient. If the motor areas 
are involved, paralyses of various types are to be expected. A great thick- 
ening of the dura, in the earlier stages of the hemorrhagic type and 
later becoming fibrous (see pp. 1091, 1095, 1099) may be a dominant 
lesion. This new formation may compress the brain substance simply, 
or may cause extensive pressure atrophy. If the vascular lesion extends 
to the vessels supplying a definite portion of the brain, atrophy often 
accompanied by extensive sclerosis may result. 
Another type of lesion seen in the brains of idiots is the hydrocephalic 
form, either primary or secondary (see p. 1107). Very extensive destruc- 
tion of the brain substance may result, occasionally the cerebral cortex 
being reduced so that its thickness may not exceed a millimeter. 
In secondary hydrocephalus due to inflammatory lesions or tumors, 
the atrophy of the brain is not as great, but owing to the rapidity of the 
development of the pressure the life of the patient is apt to be short, even 
though complete amentia may not have been produced. Accompanying 
the hydrocephalus may be independent congenital malformations with 
diminished size or absence of portions of the whole cerebrum, of one 
hemisphere, the corpus callosum, or of the cerebellum. In other in- 
stances, especially in the microcephalic idiots, there may be no striking 
gross pathological changes in the brain. The organ may simply present 
a condition of arrested development with the persistence of fetal mor- 
phology, both as regards the naked eye appearance of the organ and its 
microscopical features. Usually, however, detailed study of these 
brains reveals changes of an inflammatory nature suggesting that prenatal 
infections or toxic agents may play a part in the etiology. There may be 
a compensatory hydrocephalus or a thickening of the skull in these 
cases of small brains, and occasionally an external hydrocephalus accom- 
panies agenesis of the cortex. Such collections of fluids are likewise 
apt to be present together with skull thickening in idiots with poren- 
cephaly and microgyria. 
While, as a rule, alterations in the size and shape of the skull are 
regular external accompaniments of idiocy, a large number of other 
"stigmata of degeneration" are often present. The most varied defects 
of the face such as hare-lip, cleft palate, deformities of the ears, and of the 
extremities are frequently seen. Mental deficiency has even been noted in 
connection with hemihypertrophy of the body, which must be regarded 
as a form of asymmetry dating back to an early embryonic stage. 1114b 
THE NERVOUS SYSTEM 
The nervous systems of epileptics present no uniform pathological 
changes. In fact, there are many cases in which careful macroscopic 
as well as microscopic examinations of the brains reveal nothing of unusual 
appearance. On the other hand, there are other cases which present all 
degrees of pathological changes ranging from mere simple degeneration 
of the nervous tissue and replacement by neurolgia to complete loss 
of one or more lobes and even of an entire hemisphere. The changes 
often reported in medical literature, i.e., hemorrhages, cloudy swelling, 
chromatolysis, and neuronophagy, may be accounted for by the injuries 
received during convulsions, and by the immediate causes of death in 
these cases, such as status epilepticusor an acute infection like pneumonia. 
From the viewpoint of pathology, epilepsy cannot be regarded as the 
result of a distinct anatomical lesion. 
Epilepsy. 
This is a congenital cerebral lesion characterized by the presence of 
tumor-like masses of glia tissue in various portions of the brain, from 
which varying degrees of idiocy or epilepsy result.1 In addition to the 
lesions in the brain, tumors of the type of adenoma sebaceum are often 
found in the skin; in a considerable number of cases tumors are present 
also in the heart and in the kidney. Most of the patients die early. 
The gliomatous changes involve individual convolutions or groups of 
convolutions, and may give rise to small tumors in the lateral ventricles 
and occasionally on the dura of the brain and cord. Heterotopic islands 
of cortical material may be present in the brain substance. Microscopic- 
ally, the growth is a gliosis differing from the ordinary type by the pres- 
ence of very large irregular cells whose nature has not yet been estab- 
lished. Some of these resemble the cells of the glia; others resemble 
ganglion cells. The sclerotic areas contain very few nerve fibers. In the 
fresh condition, the new growth of tissue is recognizable by the fact that 
it is lighter in color than the rest of the brain and is much firmer. Owing 
to this greater density the mass may project somewdiat above the general 
level of the convolutions. There is, however, no sharp boundary be- 
tween the normal brain and the gliosis. 
The cardiac tumors are rhabdomyomata composed of embryonal mus- 
cle cells.2 The skin lesions are those of adenoma sebaceum (Fig. 264, 
page 452), which are composed of alveoli filled with epithelial cells re- 
sembling those of the sebaceous glands. Usually the tumors are small, 
but they may measure several centimeters in diameter. 
The kidney tumors are present in about 25 per cent, of the cases, 
and may be of the type of hypernephromata or sarcomata, but they 
may also be exceedingly complex, containing striated muscle fibers, 
epithelial tubules, and other structures evidently due to some congenital 
displacement.3 
Tuberous Cerebral Sclerosis. 
1 Neurath, R., Lubarsch-Ostertag, Ergebn. <1. allg. Path., 1908, xii, 732 (bibl.); Bundschuh, E., 
Zieglers Beitr., 1912, liv, 278 (bibl.). 
2 Wolbach, S. B., Jour. Med. Research, 1907, N. S. xi, 495. 
3 Kirpicznik, J., Virchows Arch., 1910, ccii, 358. THE NERVOUS SYSTEM 
1115 
Amaurotic Family Idiocy (Tay-Sachs Disease). 
This is a type of congenital affection of the brain causing idiocy, mus- 
cular weakness, and a rapidly developing blindness. The retinal macula 
shows a cherry-red central spot surrounded by a pale area, a condition 
which is of importance in diagnosis during life. Death occurs usually 
within two years of the beginning of the disease. A number of children 
in the same family are apt to be affected; and all but one of the reported 
cases have been in Hebrews. 
Grossly, the brain is poorly developed, the tissue is firm and hard. 
Microscopically, there is a widespread degeneration of the ganglion cells 
of the brain, cord, and spinal ganglia. The cells show a swelling of the 
cytoplasm and dendrites, and alteration and, ultimately, disappearance 
of the Nissl bodies, with destruction of the cell fibrils.1 Finally, the 
fiber tracts in brain and cord degenerate. Inflammatory and vascular 
lesions are not present; nor do the tissues show evidence of syphilitic 
infection. 
A juvenile type not limited to the Hebrew race, and occurring in 
children of from six to fourteen years, has been described.2 The macular 
spot is not found in this form and an optic atrophy only is present. The 
ganglion cells are not so completely altered as in the infantile group; the 
cortex and spinal cord are not much changed. The retina shows loss 
of the rods and cones. 
INJURIES OF THE BRAIN.3 
The brain may be wounded directly by a foreign body, or indirectly 
by fragments of bone driven into it, or it may be lacerated by severe 
contusion without fracture or solution of continuity of the skull. Very 
severe injuries of the brain are often caused in parts of the organ remote 
from the seat of violence; thus blows on the skull frequently cause lacera- 
tion of the brain on the opposite side. This is called injury by contrecoup. 
It is very difficult to estimate the degree of injury which must cause 
death, since some persons die from slight, and others recover from very 
severe, wounds of the brain. In incised wounds of the brain more or 
less hemorrhage occurs at the seat of lesion, and the brain tissue in the 
vicinity soon undergoes degenerative changes. These may be compara- 
tively slight or extensive. Inflammatory reaction may occur in the 
vicinity, and the adjacent brain tissue, as well as the hemorrhagic and 
degenerated area, may become infiltrated with pus cells. After a time 
the injured and degenerated area may become surrounded by new-formed 
connective tissue, and the decomposed extravasated blood and detritus 
of brain tissue, more or less fatty, may be absorbed. In this way the 
part heals, leaving a somewhat pigmented cicatrix. The healing is in 
most cases very slow. The pia mater may participate to a marked degree 
in the inflammatory healing process. 
After wounds which involve the removal of portions of the cranial 
1 For details, see Sachs, B., Jour. Nerv. and Ment. Dis., 1903, xxx, 1; Sachs, B., and Strauss, I., 
Jour. Exper. Med., 1910, xii, 685; Bing, Ergebn. d. inn. Med. u. Kinderh., 1909, iv, 82. 
2 Spielmeyer, W., Nissl and Alzheimer, Histologische und histopathologische Arbeiten, Jena, 1908, 
ii, 193 (bibl.). 
3 For detailed discussions, see Macklin, C. C., and Macklin, M. T., study of brain repair in rat by 
use of trypan blue, Arch. Neurol, and Psychiat., 1920, iii, 353; and Essick, C. R., Pathology of experi- 
mental traumatic abscess of the brain, Arch. Neurol, and Psychiat., 1919, i, 673. 1116 
THE NERVOUS SYSTEM 
bones, it is not uncommon after a few days to see a bleeding fungous 
mass projecting through the opening. This mass, sometimes wrongly 
called hernia cerebri, consists of degenerated brain tissue, blood, and 
granulation tissue, with more or less pus. The brain tissue below it is 
degenerated, soft, broken down, and purulent, and there is often abscess 
in the adjacent brain tissue. Such wounds may finally heal by the absorp- 
tion of the broken-down brain tissue and blood, and its replacement by 
granulation tissue. 
Lacerations of the brain tissue without fracture may appear shortly 
after the injury as simple, more or less circumscribed areas of capillary 
hemorrhage; the brain tissue about these may degenerate, pus may 
form, and abscesses be developed; or the degenerated and lacerated tis- 
sue may be gradually replaced by granulation tissue which finally forms 
a cicatrix. The process of degeneration and softening and of healing 
in such lacerations of brain tissue may occur very slowly indeed, even 
occupying years, and not infrequently the degenerative changes are very 
extensive and progressive. In many cases, of course, the injury is so 
extensive, or involves such important parts of the organ, that very little 
or no inflammatory or degenerative change takes place before death. 
INJURIES OF THE CORD. 
The spinal cord may be compressed or lacerated by penetrating 
wounds, by fracture or dislocation of the vertebrae, or by concussion 
without injury to the vertebrae. The spinal cord is found simply disin- 
tegrated, or there may be much hemorrhage and the disintegrated nerve 
tissue be mixed with blood. If life continue, the nerve elements may 
degenerate; Gluge's corpuscles and free fat droplets may form; blood 
pigments may be formed; and when inflammation supervenes more or 
less pus may be intermingled with the degenerated material. There may 
be marked changes in the minute structure of the cord, without any 
change being evident to the naked eye. 
The secondary effects of injuries to nerves are described in the sec- 
tion on degenerations following injury. After amputation of a limb, 
there often occur swellings of the peripheral ends of the divided nerve 
trunks. These bulbous ends are called false or amputation neuromata. 
Usually they contain a considerable proportion of nerve fibers mingled 
with scar tissue, the relative amounts varying in different specimens. 
INJURIES OF THE NERVES. 
HYPERTROPHY AND ATROPHY OF THE BRAIN. 
True Hypertrophy of the brain is rare, and probably always congeni- 
tal. An increase in the size of the brain from the proliferation of the 
neuroglia sometimes occurs in children either before or after birth, less 
frequently in youths, and very seldom in adults. The white substance of 
the hemispheres is increased in amount. If it takes place before the ossi- 
fication of the cranium, the bones are separated at the sutures and fon- 
tanelles; if aftei* this, the inner table of the skull may be eroded and THE NERVOUS SYSTEM 
1117 
thinned. When the cranium is opened the dura mater appears tense and 
anemic, the convolutions of the brain are flattened, the brain substance 
is firm and anemic, the ventricles are small, the ganglia and cerebellum 
are either of normal size or compressed. 
The disease is usually very chronic, and destroys life with symptoms 
of compression of the brain. There may, however, be acute exacerbations. 
Atrophy.-This may occur as a senile change, or, in chronic alcohol, 
opium, or lead poisoning, in paresis, and in chronic meningitis, or from 
local interference with the circulation. In children who are much re- 
duced by chronic diseases atrophy of the brain may accompany atrophy 
of the rest of the body. 
Fig. 764.-Atrophy of a Circumscribed Portion of Brain Convolutions in a Child. 
From a lesion of the corresponding blood-vessels. 
The atrophy affects principally the cerebral hemispheres, and may be 
uniform or more marked in some parts than in others, involving the 
whole of a hemisphere or of a lobe or only single convolutions or groups 
of these (Fig. 764). The convolutions are small, the sulci broad, the 
ventricles usually dilated, the brain tissue is firm, the gray matter discol- 
ored, the white substance grayish in color; the blood-vessels may be 
dilated. The basal ganglia may be small. Serum accumulates in the 
pia mater and in the ventricles; the pia mater, and often the skull, 
become thickened; the brain tissue may be edematous or contain small 
hemorrhages. The nerve elements of the brain tissue are those most 
involved in the atrophy, the diminished areas being usually harder and 
firmer than normal. The neuroglia is usually increased. 1118 
THE NERVOUS SYSTEM 
This may occur in any portion of the brain or its meninges from the 
decomposition of extravasated blood. In persons affected by malaria 
the gray matter of the brain has sometimes a dark or even blackish 
appearance. This color is due to the presence of black pigment granules 
within the capillary blood-vessels. The obstruction to the vessels by 
masses of these pigment granules may cause capillary apoplexies. The 
pigment may also be found in the walls and in the lumina of the vessels 
of the pia mater. Pigmentation of the brain is seen in ochronosis, also.1 
Pigment patches of congenital origin are not infrequently seen in the 
pia mater. They may be due to the presence of branching pigmented 
cells.2 Melanosarcomata may develop from such chromatophores.3 
PIGMENTATION OF THE BRAIN. 
CIRCULATORY AND VASCULAR CHANGES IN THE BRAIN AND SPINAL CORD 
Anatomical Considerations. 
In studying the circulatory changes in the brain and cord certain peculiarities in 
that circulation should be borne in mind. The vessels which nourish the brain arise 
from a remarkable anastomosis of large arterial trunks at its base, known as the circle 
of Willis (see diagram, Fig. 765). From this "circle" pass 
off to each hemisphere three main branches-the anterior, 
the middle, and the posterior cerebral. These arteries 
ramify in the pia, where they anastomose freely. From 
this anastomosis small branches are given off which 
penetrate the brain substance, the shorter breaking up 
into capillaries in the gray matter, the longer passing to 
the underlying white matter. After entering the cortex 
there is no further anastomosis, the capillaries of a corti- 
cal artery passing directly over into a venous system of 
capillaries without communicating with capillaries of 
other arteries. They are thus "terminal arteries." In 
addition to these arteries, which supply the hemispheres, 
branches from the circle of Willis are distributed to the 
basal ganglia. These arteries are much larger than those 
which pass from the pia into the cortex, and beyond the 
circle of Willis do not form anastomoses with one another. 
Thus it is that occlusions of the arteries supplying the 
basal ganglia are much more serious, aside from the im- 
portance of the parts involved, than of those passing to 
the cortex. 
Three main arteries furnish blood to the cord: the 
anterior spinal, lying along the opening of the anterior 
median fissure, and two posterior spinal, lying near the 
entrances of the posterior roots. Branches of these 
arteries anastomose in the pia, and from this pial network 
branches pass directly into the substance of the cord. 
The largest, a branch of the anterior spinal, passes into 
the pia of the anterior fissure, and, penetrating the cord, 
is distributed to the gray matter of the anterior horn, 
and to the median gray matter as far back as Clarke's column. Smaller arteries from 
the posterior spinal supply the posterior regions of the cord. These arteries, like 
those in the brain, are terminal in the sense that, while anastomosing freely in the 
pia, after penetrating the substance of the cord they form no further anastomoses. 
Fig. 765.-Diagram of the 
Circle of Willis and Asso- 
ciated Vessels. 
a, Anterior cerebral; b, an- 
terior communicating; c, in- 
ternal carotids; d, middle cere- 
bral; e, posterior communicat- 
ing; f, posterior cerebral; g, 
basilar; h, vertebral. 
1 Pick, Berl. klin. Wchnschr., 1906, xliii, 478. 
2 Virchow, Virchows Arch., 1859, xvi, 180. 
8 Stoerk, Wien. klin. Wchnschr., 1904, xvii, 184; Pick, Berl. klin. Wchnschr., 1906, xliii, 884. THE NERVOUS SYSTEM 
1119 
In structure the vessels of the brain differ from those of the rest of the body 
sufficiently to warrant mention here. The intima and the elastic membrane are 
much closer to each other than in the other vessels; longitudinal elastic fibers are 
very scarce; and the internal elastic lamina is very much thicker in the cerebral ves- 
sels of large caliber than elsewhere. At the point of contact between the muscular 
layers and the adventitia there is, however, in the larger vessels, especially the verte- 
bral and the basilar, a layer of coarse elastic fibers running longitudinally. There 
are no vasa vasorum in the larger cerebral arteries. The smaller vessels are composed 
solely of endothelium and elastic tissue with a thin elastic layer between them and 
occasional muscle fibers; the last are absent from the capillaries. The small veins 
possess an elastic lamina not present in the larger, so that they can not be distinguished 
from small arteries. About the vessels are lymph-spaces, called the Virchow-Robin 
lymph-spaces, which may contain embolic tumor cells or leucocytes in inflammatory 
lesions of the brain. These Virchow-Robin lymph-spaces drain into the subarachnoid 
spaces. Between the vessel and the nerve tissue there is interposed a thin layer of 
neuroglial tissues, the perivascular limiting neuroglial membrane. The great vas- 
cularity of the brain in comparison to its bulk, the close relationship of the vessels to 
the substance, the great importance of the perfect competence of such circulation 
because of the serious lesions which rapidly follow interference with the blood flow; 
all these make arteriosclerosis a very much more important phenomenon in the cerebral 
vessels than in other organs of the body. 
Hyperemia and Anemia 
The appearance of the brain tissue after death does not always 
furnish reliable indications of its blood contents during life, though 
it is perhaps more to be depended on than the appearance of the meninges. 
Some of the more common conditions determining hyperemia which 
are mentioned above as influencing the meninges apply also to the sub- 
stance of the brain. 
Active hyperemia may occur in various inflammatory conditions of 
the brain. Hyperemia of the brain is quite common in deaths from 
insolation and after conditions accompanied by acute delirium, such as 
delirium tremens. Passive hyperemia may occur in conditions similar 
to those which determine congestions in other organs of the body, such 
as chronic diseases of the heart or lungs. It may be induced by anything 
which prevents venous return, such as intracranial tumors which com- 
press the sinuses, or by thrombosis. 
In sections of hyperemic brains the small blood-points from the cut 
ends of small vessels are more numerous and conspicuous than under 
normal conditions, and the brain tissue, particularly the gray matter, 
may have a diffuse red color. If excessive, the convolutions may be 
somewhat flattened, the brain tissue and pia mater may be edematous, 
and the ventricles may contain fluid. The congestion of the vessels may 
be general or localized. 
Anemia of the brain may be either local or general. It may depend 
upon a general anemia or upon general disturbances of the circulation, 
such as mitral stenosis or regurgitation; or upon local interference with 
the arterial blood supply, such as complete or partial obstruction of the 1120 
THE NERVOUS SYSTEM 
arteries from thrombi, emboli, inflammatory changes, spasmodic con- 
tractions, etc., or from tumors, exudations, and blood extravasations 
pressing upon the vessels from without. In edema of the meninges, and 
in the presence of internal hydrocephalus, the brain tissue is apt to be 
anemic. The brain tissue in anemia looks whiter than usual, the con- 
trast between the gray and the white matter is less marked, and the 
small blood-points usually seen on section from divided vessels may be 
very inconspicuous or almost entirely absent. Anemia, when local and 
long continued, leads to softening, with destruction of the ganglion cells 
and the appearance of fatty and granular cells in the affected area. 
Edema. 
Edema of the brain tissue may accompany either general or localized 
hyperemia, or it may accompany anemia, and it seems in most cases, 
though nor always, to be dependent upon conditions which induce these 
alterations in the blood contents of the brain, such as sinus thrombosis, 
brain tumors, etc. It is, perhaps, most common in conditions which 
determine a passive hyperemia. In some cases of marked impoverish- 
ment of the blood a so-called hydremic edema of the brain is found. This 
is not infrequent after death from uremia. 
In edema the brain tissue appears unusually wet and shiny. The 
same underlying condition is apt to determine an exudation into the 
membranes and ventricles. There is usually considerable distention of 
the perivascular lymph-spaces. 
Marked edema of the brain may exist without brain symptoms. On 
the other hand, persons may die comatose with no other gross lesion than 
edema, either with or without edema of the pia mater. This is seen 
with especial frequency in acute and chronic alcohol poisoning, but may 
occur under other conditions. A careful microscopical examination of 
the brain under these conditions will frequently reveal structural lesions 
of more serious import than the edema. Occasionally edema is seen in 
very acute cerebrospinal meningococcal infections, when death has 
occurred before the inflammatory lesions have reached a macroscopic 
stage. 
Under the designation of 11 serous apoplexy," edema of the brain was 
formerly considered, in the absence of other lesions, of importance as a 
cause of death. But increased knowledge has led to the general belief 
that simple cerebral edema as an independent condition has not the sig- 
nificance formerly ascribed to it, and it should be accepted, if ever, with 
great reserve as a cause of death. 
Hemorrhage. 
Hemorrhages in the substance of the brain may be very small and 
punctate, and are then usually called capillary hemorrhages; or they may 
result in the collection in the brain tissue of masses of blood of consider- 1121 
THE NERVOUS SYSTEM 
able size, which are called apoplectic foci or clots. These forms of hem- 
orrhages may be associated, or a number of capillary hemorrhages may 
join to form an extensive clot. 
Capillary hemorrhages may appear, on section of the brain, like the 
severed ends of hyperemic blood-vessels, or the tissue about them may 
be more or less tinged with blood. Microscopically, the perivascular 
spaces are distended with blood, which may have escaped into them. 
This is associated with more or less broken-down brain tissue. The 
hemorrhages may be single, but are frequently multiple, so that the brain 
tissue is besprinkled with blood-points. Degeneration of the extrava- 
sated blood may give rise in later stages to reddish or brown or yellowish 
circumscribed discoloration of the brain tissue, due to granules and crys- 
tals of blood pigment intermingled with broken-down brain tissue, with 
more or less fatty degeneration of its elements. Capillary hemorrhages 
may be due to fatty degeneration of the vessels leading to rupture; or 
the extravasation may be due to diapedesis; or it may depend upon con- 
ditions which we do not understand. The hemorrhages frequently 
occur in the vicinity of apoplectic clots and tumors, and may be due to 
thrombosis of the veins or of the sinuses of the dura mater; they not 
infrequently occur in acute encephalitis, in congestive hyperemia, in 
acute mania, and in delirium tremens; and they may be associated with 
general diseases, such as scurvy, purpura haemorrhagica, typhus fever, 
pyemia, ulcerative endocarditis, etc., and with embolic softening. 
The cerebral symptoms which follow serious traumatic injuries to 
the brain have been illuminated of late by the numerous opportunities 
afforded for the study of the brains of those who have died from shell 
explosions, no visible external injuries being found.1 As a rule, the brain 
and cord are the only organs affected in persons dying either immediately 
or some time after exposure to shell shock. In the brains of those who 
have lived for some time, there are found extreme congestion and an 
extraordinary number of minute punctiform hemorrhages of the spinal 
vessels and at the terminations of the small capillaries at the surface of 
the brain. No large hemorrhages are found, as a rule, and no intra- 
cerebral petechiae. There may be ecchymoses about the large sinuses 
and the cerebrospinal fluid is almost always blood tinged. Subarachnoid 
hemorrhages or even complete separation have been noted also. When 
the disease has existed for some time, degenerative changes in the ganglion 
cells and in the neuroglia, and secondary degenerations in the fiber tracts 
of the brain and the columns of the cord can be found.2 
Apoplectic foci may result from the coalescence of numerous capillary 
hemorrhages; from injury; or from rupture of diseased arteries, either 
with or without changes in the blood pressure. Hemorrhages from 
1 For a study of the causes of death from shell shock, see Mott, F. W., Brit. Med. Jour., 1917, ii, 612. 
See also Lhermitte, J., Ann. de m6d., 1917, iv, 294; and Guillain, G., and Barre, J. A., ibid., 1917, v, 
598 (bibl.). For an experimental study of the traumatic lesions of the central nervous system, see 
JaKob, A., Nissl and Alzheimer, Histologische und histopathologische Arbeiten, Jena, 1913, v, 182 (bibl.). 
2 The great force which acts upon the brain may be estimated from the fact that the air pressure 
following the explosion of a large shell at a distance of 3 meters has been computed to be 1 kilo per 
square centimeter. If the area of the calvarium be estimated to be roughly 500 square centimeters, 
this would mean that the skull received a blow of 500 kilos. 1122 
THE NERVOUS SYSTEM 
injury to the skull may occur as well without as with fracture, and may 
be situated over the vertex or at the base of the brain. They vary in 
extent and location, depending upon the character and point of the 
injury and the size of the vessels involved. The so-called spontaneous 
hemorrhages, other than those of capillary origin, which give rise to 
masses of blood and broken-down brain tissue, may vary in size from that 
of a pea to those occupying a large part of a hemisphere. They are due, 
in a small proportion of cases, to the rupture of aneurysms, but usually 
arise from weakening of the walls of the arteries, from arteritis, atheroma, 
or fatty degeneration. These latter lesions doubtless give rise in most 
cases to the formation of pseudoaneurysms whose rupture is in so many 
cases the immediate cause of the hemorrhage. A source of extensive 
spontaneous hemorrhage may be a softened glioma, which may escape 
detection unless a careful microscopic examination is made of the brain 
surrounding the clot. Occasionally infectious thrombi form in the larger 
cerebral vessels, invade the walls, so that weakening results, and give rise 
to aneurysm-like dilatations which may ultimately rupture and cause 
extensive hemorrhages, usually at the base of the brain. 
Aneurysms of the cerebral arteries may be as large as a pea or hazel- 
nut, but those most frequently met with and causing apoplexy are usually 
small--called miliary aneurysms-and may be microscopic in size, 
varying from this up to that of a large pin's head or larger. They may 
be sacculate or fusiform, and frequently exist in considerable num- 
bers. Encapsulated mural hematomata produced by the rupture of a 
small vessel or destruction of the external coats by a dissecting aneurysm 
should not be confused with the true aneurysmal type of lesion. Aneu- 
rysms may occur in any of the small arteries of the brain, but are said to 
be most frequent on the branches of the middle cerebral artery. The 
statement that the bursting of miliary aneurysms is the exclusive cause 
of spontaneous apoplectic clots is doubtful.1 
As to the immediate cause of rupture, either of aneurysms or of other- 
wise diseased blood-vessels in the brain, we are in many cases entirely 
ignorant. In some cases it seems to be due to an increased arterial ten- 
sion in such diseases of the heart as induce this change, as in the cardiac 
hypertrophy which may accompany some forms of chronic diffuse 
nephritis; or it may result from unusual exertion or mental excitement. 
Hemorrhages most frequently occur in the corpora striata and optic 
thalami (Fig. 766), and in the brain tissue in their vicinity, and here they 
are most common in the parts supplied by the branches of the middle 
cerebral artery. The possibility of hemorrhage in the floor of the fourth 
ventricle should be borne in mind in investigating cases of sudden death 
from obscure causes. 
Hemorrhages frequently seriously affect other portions of the brain 
than those immediately supplied by the ruptured vessels. Thus hemor- 
1 For extensive studies on the nature and importance of aneurysms of the cerebral vessels, see Ellis, 
A. G., Proc. Path. Soc., Philadelphia, 1909, N. S. xii, 197; and Pick, L., Berl. klin. Wchnschr., 1910, 
xlvii, 325, 382. Shennan, T., Miliary aneurysms in relation to cerebral hemorrhage, Edinburgh Med. 
Jour., 1915, xv, 245; Raeder, 0. J., Repeated multiple minute corticospinal hemorrhages with miliary 
aneurysms in case of arteriosclerosis, Arch. Neurol, and Psychiat., 1921, v, 270. THE NERVOUS SYSTEM 
1123 
rhages in the cortical substance or beneath the pia mater may force their 
way deep into the brain substance; or, in hemorrhage in the brain sub- 
stance, the blood may burst into the ventricles1 or work its way into the 
intermeningeal space, and, either at the seat of its occurrence or in the 
situations into which it is forced, may give rise to serious compression 
of the brain. Portions of the brain containing large extravasations may 
be enlarged, the tissue anemic from pressure, the convolutions flattened, 
The hemorrhage involves the right basal ganglia and adjoining brain tissue. The blood is in 
both lateral ventricles. The right side of the brain (the upper side in the figure) is pressed out with 
flattening of the convolutions. 
Fig. 766.-Large Hemorrhage in the Brain. "Cerebral Apoplexy." 
and the surface dry. As the blood is poured out, the brain tissue is usu- 
ally torn and lacerated, so that the apoplectic clot often consists of 
detritus of brain tissue intermingled with blood. If, however, the blood 
is poured out from a single vessel, the brain tissue may be pressed aside, 
and the greater portion of the mass may consist of blood. 
The appearances presented by hemorrhages in the brain vary greatly, 
depending upon the time which has elapsed since their occurrence. If 
i Tilney, F., and Casamajor, L., Hemorrhage into the basal cisterns and ventricles, Neurol. Bull., 
1918, i, 161. 1124 
THE NERVOUS SYSTEM 
life continue, the edema which usually soon occurs in the vicinity of the 
hemorrhage disappears and the clot becomes drier and firmer; gradually 
the blood undergoes the usual series of changes seen in extravasation; 
the hemoglobin decomposes, forming granules and crystals of blood pig- 
ment; and the blood-cells and fibrin undergo degeneration and absorption; 
the detritus of brain tissue undergoes fatty or myelinic degeneration, the 
fatty and other particles being taken up by large phagocytic cells. As 
these alterations occur the color changes to reddish brown, orange, or 
yellow, and the adjacent brain tissue may be discolored by imbibition. 
Inflammatory reaction may occur in the vicinity, leading either to the 
formation of a more or less pigmented cicatrix, or to a cyst with yellow- 
ish fluid contents and a fibrous, more or less pigmented wall formed of 
glia and connective tissue, the latter being supplied by the vascular 
sheaths. The process of degeneration and absorption of the blood and 
broken-down brain tissue, and their replacement by a cyst or by a cica- 
Fig. 767.-Section of the Spinal Cord Showing Hemorrhage into the Gray Matter 
and Extending Lengthwise of the Cord. (An early phase of hematomyelopore.) 
This lesion is sometimes called hematomyelia. 
trix, is a slow one, and the cysts and cicatrices may resemble those formed 
at the seat of embolic softening. Not infrequently we find in the brain 
of a person dead from recent apoplexy the remains of old clots presenting 
some one of the above-described stages of absorption. The apoplectic 
cysts and cicatrices persist for a long time after their formation. 
Secondary degenerations (page 1141) following hemorrhages depend 
entirely upon the cells destroyed or the fiber tracts interrupted. Most 
common are degenerations of the pyramidal tracts from hemorrhages 
into the sensory-motor region of the cortex, or from hemorrhages into 
the internal capsule (lenticulostriate artery). Hemorrhages involving 
the optic centers or the optic fibers lead to degeneration in the optic 
tracts. Hemorrhages into other portions of the brain, by destroying 
commissural cells or interrupting their fibers, lead to degeneration of 
intracranial fiber tracts. THE NERVOUS SYSTEM 
1125 
Hemorrhage in the spinal cord is much less frequent than in the brain, 
but may occur either as capillary apoplexy or as larger apoplectic clots. 
Capillary hemorrhages, similar in appearance to those of the brain, may 
occur as the result of injury, or near areas of softening or tumors, or may 
accompany severe convulsions, as in tetanus. Apoplectic clots, which 
are comparatively rare in the spinal cord, are usually small, commonly 
not more than one centimeter in diameter, and are similar in their appear- 
ance, and in the changes subsequent to their formation, to those in the 
brain. They are usually the result of injury, but may occur spontane- 
ously. These so-called spontaneous hemorrhages are undoubtedly in 
most cases the result of inflammation. They may occur in any acute 
disease of the cord, and are an especially frequent complication of acute 
myelitis. Hemorrhage into the cord, occurring in the course of an 
The section shows at one point a cyst-like cavity in the spinal cord, originating in a hemorrhage 
in the posterior root (see Fig. 767) and extending nearly the entire length of the cord. The cavity 
is lined by tissue detritus and neuroglia. 
Fig. 768.-Hematomyelopore. 
acute infectious disease, is probably, as a rule, due to an unrecognized 
myelitis or acute degeneration. Hemorrhages in the course of a chronic 
myelitis are not common, and are probably due to a softening dependent 
on interference with nutrition. Hemorrhages into the cord have been 
reported in syphilitic myelitis, in syringomyelia, and in tumors of the 
cord. Gliomata especially are often very vascular, and their thin-walled 
vessels are subject to rupture. Sometimes, however, hemorrhagic foci are 
found in the spinal cord without traumatism or evidence of inflammatory 
change. In caisson disease, hemorrhages may occur secondary to rup- 
ture of the capillaries or softening of the cord tissue. They may occur, 
also, after spinal anesthesia and during delivery. 
Larger hemorrhages naturally follow the lines of least resistance, and 
their long diameter corresponds to that of the cord. To such columnar 1126 
THE NERVOUS SYSTEM 
hemorrhages, usually traumatic in origin, the name hematomyelia has 
been applied (Fig. 767). The term is being now more properly used to 
cover the general subject of hemorrhage into the spinal cord.1 
The smaller capillary hemorrhages may be entirely absorbed. They 
may, on the other hand, form microscopic sclerotic areas. The larger 
hemorrhages determine a considerable destruction of tissue. They may 
be absorbed and replaced by fibrous tissue, or the central area may break 
down into a fluid or semi-fluid mass of blood and tissue, with a more or 
less definite fibrous wall (Fig. 768). To these columnar cavities or canals 
the term hematomyelopore has been applied.2 To a similar condition in 
which proliferation of the neuroglia is the most marked feature, the name 
of false or secondary syringomyelia has been given. 
Thrombosis and Embolism. 
Thrombi may form in. the arteries as a result of any degenerative or 
inflammatory process in their walls leading to a roughening or death of 
the intima, or from pressure from without, or they may occur in vessels 
in whose walls we can detect no primary lesion. The most common 
causes are atheroma and simple endarteritis. Thrombi may also form 
around an embolus which does not entirely occlude the vessel. Infec- 
tious thrombi may lead to destruction of the walls of the vessel, with 
consequent hemorrhage. 
Emboli of the cerebral arteries most commonly arise from acute or 
chronic endocarditis or cardiac thrombi; they may arise from aneurysms 
or atheroma of the aorta, from the carotid or vertebral arteries, or from 
the pulmonary veins. The materials constituting emboli vary greatly, 
depending on their mode of origin (page 35). The effects on the brain 
tissue of emboli and thrombi of the arteries are essentially the same 
in their main features. In some cases, however, in which large emboli, 
usually from endocarditis, suddenly block up a large vessel, the individual 
may die almost instantly without other apparent lesion than the stoppage 
of the vessel. 
In general, the first effect of the occlusion of an artery is to deprive 
the region to which it is distributed of blood. In arteries whose branches 
anastomose, the affected area is soon supplied with blood by the estab- 
lishment of a collateral circulation. In terminal arteries, on the other 
hand, the blocking of the vessel is followed, as a rule, by degenerative 
changes and softening in the brain tissue. The appearances which these 
degenerated areas present vary greatly, depending upon the stage of the 
degeneration and the amount of blood which may be extravasated. 
Dense infiltrations of the brain tissue with blood, as in hemorrhagic 
infarctions from emboli in other parts of the body, do not usually occur, 
although considerable blood may be extravasated. Areas of softening 
in which there is little extravasation of blood are usually white or yellow 
in color, white or yellow softening. When much blood is present the proc- 
1 For a case of hemorrhage of the spinal cord, see Rice, H. W., Jour. Am. Med. Assn., 1910, liv, 1783. 
For bibl. of the subject, see Lewandowski, M., Handbuch d. Neurologic, Berlin, 1911, ii, 550. 
2 For study of hematomyelopore, see Van Gieson, I., New York Polyclinic, 1897, x, 87. 1127 
THE NERVOUS SYSTEM 
ess is frequently called red softening. Yellow softening is probably often 
only a secondary stage of the red, resulting from absorption of most of the 
pigment. The term "white softening" is often used interchangeably 
with " yellow." It is also applied to that condition into which the latter 
passes after more complete liquefaction, and after fatty changes have 
taken place. Young proliferating neuroglia tissue often give a glisten- 
ing white appearance to the lesion. 
The tissue in the affected area gradually softens and may become dif- 
fluent. Microscopically, the softened tissue is seen to consist of more or 
less fluid with broken-down brain tissue, fragments of nerve fibers, drop- 
Fig. 769.-Degenerated Cells, Cholesterin Crystals, and Corpora Amylacea from 
Brain Tissue in Embolic Softening. 
a, Fatty ganglion cells; b, corpora amylacea; c, cell containing very large number of fat droplets 
(compound granular or Gluge's corpuscles); d, cholesterin crystals. 
lets of myelin, nerve cells, shreds of neuroglia tissue and blood-vessels, 
and red and white blood-cells. The evidence of degeneration is seen 
in the presence of fat granules and droplets, larger and smaller cells 
densely crowded with droplets of fat (Gluge's corpuscles or compound 
granular corpuscles). Various kinds of cells and cell fragments, more or 
less granular and fatty, and also corpora amylacea, blood-pigment, fat 
crystals, and cholesterin crystals, may be found (Fig. 769). The walls 
of the blood-vessels may also be in a condition of fatty degeneration 
(Fig. 770). The color of the softened mass will of course depend upon 
the relative amounts of these elements. 
The tissue may remain for a long time in the soft condition, or it 
may be absorbed and replaced by a connective-tissue cicatrix which 
may be more or less pigmented; or a wall of connective and glial tissue 1128 
THE NERVOUS SYSTEM 
may form about it, converting it into a well-defined cyst, with or without 
pigmented walls; or the mass may dry and form a dense, structureless 
nodule. Acute inflammatory changes may occur about the dead tissue. 
In cases of infectious emboli numerous abscesses may be formed in addi- 
tion to their mechanical action. 
Thrombi are most frequent in the internal carotids, less frequent in the 
middle cerebral, basilar, and vertebrals. They may occur, but still less 
frequently, in other cerebral arteries. Emboli are most common in the 
middle cerebral artery, next in the internal carotid, and then in the basi- 
lar. The relative frequency with which embolism occurs in the middle 
cerebral artery is attributable to the directness with which the blood 
passes into this artery from the heart. The great significance attaching 
to embolism of the middle cerebral artery is evident when we remember 
that its branches within the brain are terminal arteries, and are dis- 
The walls of the vessels, particularly the endothelial cells, contain fat granules and fat droplets, 
Fig. 770.-Blood-vessels From an Area of Embolic Softening of Brain. 
tributed to such important structures as the lenticular and caudate 
nuclei, the internal capsule, and the optic thalamus. 
Thrombosis and embolism also occur in the vessels of the spinal cord, 
though less frequently than in those of the brain. 
Lesions of the Vessel Walls in the Brain and Cord. 
The mural changes in the vessels are not peculiar to the nervous sys- 
tem: the most frequent is that known as atheroma or arteriosclerosis, 
which is especially common in the system of arterial trunks forming 
the circle of Willis. Fatty degeneration is often found in the vessel 
walls coincident with the increase in the connective-tissue elements. 
Calcification may occur and may be so extensive that the whole or a 
greater part of the circle of Willis is converted into a series of hard 
tubes usually somewhat larger than normal.1 More commonly the cal- 
careous areas are irregular in their distribution, giving to the vessels a 
i Marburg, 0., Zur Pathologie der grossen Hirngefasse, Wien. klin. Wchnschr., 1902, xv, 1216; 
Pick, A., Calcification of finer cerebral vessels, Amer. Jour. Insanity, 1905, Ixi, 417; Schmincke, A., 
Encephalitis interstitialis Virchow mit Gliose und Verkalkung, Ztschr. f. die ges. Neurol, u. Psy- 
chiat., 1920, lx, 290; Bassoe, P., and Hassin, G. B., Calcification of cerebral vessels, Arch. Neurol, and 
Psychiat., 1921, vi, 359. 1129 
THE NERVOUS SYSTEM 
nodular appearance. Fatty degeneration also occurs, though more 
rarely, as an independent lesion affecting the muscular coat. Hyaline 
degeneration may also occur either as an independent lesion, which is 
quite frequent in the brain of idiots, or as the initial lesion of a sclerosis. 
The alterations in the brain substance associated with arteriosclerosis 
are usually the coarse hemorrhagic lesions of apoplexy; but in a certain 
number of brains with arteriosclerotic changes no gross lesions occur, 
and there are only minute focal areas of necrosis, most often in the gray 
substance of the cortex.1 Limited secondary changes follow either the 
necrosis or the softening. These arteriosclerotic alterations in the brain 
are distinct from those due to paresis or senile dementia, both the latter 
involving the brain in a diffuse fashion and showing more or less charac- 
teristic structures. 
DEGENERATION AND INFLAMMATION IN THE BRAIN, SPINAL CORD, AND 
NERVES. 
Review of Normal Morphology. 
While the scope of this work does not warrant a detailed description of the mor- 
phology of the nervous system,2 our appreciation of the pathological changes to which 
it is subject is so dependent upon an accurate knowledge of its morphology, that, 
before proceeding further, a brief resume of some of the more fundamental points in its 
structure and architecture cannot wisely be omitted. 
The studies of Golgi and of his successors in the use of his technique have led to the 
so-called neurone conception of nervous-system structure. According to this view, 
the neurone represents the structural unit of the nervous system. The neurone is the 
nerve cell with all its prolongations, and the nervous system in toto is but an orderly 
association of an immense number of these neurone units. Although these neurones 
differ from one another as to details of structure they still present an essential 
similarity. 
The neurone is first distinguishable as a small round cell in the epiblastic lining of 
the embryonic neural canal. Such a cell is entirely devoid of processes It soon, 
however, becomes pyriform, and from the tip of the pear grows out a process, which is 
the axis-cylinder process or axone. Later other processes appear as outgrowths of the 
cell body. These, are the protoplasmic processes or dendrites. Each adult neurone 
then consists of a cell body, and passing off from this cell body two kinds of processes 
(Fig. 771 and 772). 
The Cell Body.-Our knowledge of the internal structure of the nerve cell has been 
greatly increased in the last few years by the application of a special technique devised 
by Nissl.3 Subjected to this technique, nerve cells present two very different types of 
reaction. Certain cells, such, for example, as the cells of the granule layers of the 
cerebellum and of the olfactory lobe, stain only as to their nuclei, the cell bodies them- 
selves remaining entirely unstained. To such cells Nissl has given the name of caryo- 
chromes. It is obvious that the method of Nissl gives no insight into the structure of 
these cells. The majority of nerve cells, however, react both as to their nuclei and 
as to their cell bodies to the Nissl stain. These cells Nissl designates as somatochromes. 
Such a cell presents the following appearance (Plate XV, 1). There is a nucleus 
identical in structure with nuclei found in other cells. It is bounded by a nuclear 
i Marie, Rev. de m6d., 1901, xxi, 281. 
2 For this the reader is referred to Barner, L. F-, The Nervous System, New York, 1899; Von Gehuch- 
ten, A., Anatomie du syst^me nerveux de 1'homme, 4th ed„ Louvain, 1906; Dejerine, Anatomie des 
centres nerveux, Paris, 1895; Edinger, Bau der nerven. Zentralorgane, Leipzig, 1911; Nissl and Alz- 
heimer, Histologische u. histopathologische Arbeiten, Jena, 1904-12; Tilney, F., and Riley, H. A., The 
Form and Functions of the Central Nervous System, New York, 1921. 
3 See Nissl's method of staining, p. 1181. 1130 
THE NERVOUS SYSTEM 
membrane and traversed by a network which takes a comparatively light blue stain. 
Within the nucleus is a nucleolus staining an intense blue. In the cell body two 
distinct elements appear: a clear ground substance, unstained; and scattered through 
it deep staining masses, known as chromophilic bodies. These chromophilic bodies 
are granular, and differ in size, shape, and arrangement. These differences have 
served as a basis of classification. Presenting 
variations in different types of cells, their appear- 
ance in a given type remains constant. Most in- 
vestigators, while differing in details, agree in 
ascribing to the unstainable substance a definite 
structure. This structure is usually described as 
composed of a fibrillar or reticular network lying 
in a more or less homogenous ground substance. 
With the use of the ordinary technique of Nissl, all 
of the cell body, excepting the chromophilic bodies, 
remains unstained and apparently structureless. 
Our ideas as to the physiology of these different 
elements of the nerve cell rest largely upon a 
theoretical basis. It has been shown that the 
nerve cell represents the genetic center of the 
neurone. From the behavior of the processes, 
when cut off from the nerve cell, it is evident that 
the cell body represents the nutritive or trophic 
center of the neurone. It seems probable that 
from the stand-point of neurone activity, the cell 
body represents the functional center of the 
neurone, while the processes act as organs of re- 
ception or distribution. Certain facts, such as 
the entire absence of the chromatic substance in 
many nerve cells, in the axones of all nerve cells, 
and its diminution during functional activity and 
in fatigue, together with its behavior under certain 
pathological conditions, lend weight to the view 
that the stainable substance of Nissl represents a 
food element of the cell. The achromatic element, 
on the other hand, is continuous with the fibrillae 
of the axone, and is considered by most investi- 
gators as representing the essential nervous 
mechanism of the cell. The relation of the Nissl 
picture to the conditions existing in the proto- 
plasm of the living cell still remains an unsolved 
problem. The importance of the Nissl method 
from the standpoint of pathology lies in the fact 
that when subjected to a given technique, a given 
type of nerve cell presents always the same ap- 
pearance, and that this appearance furnishes a 
norm of comparison with cells showing patho- 
logical changes which have been subjected to the 
same technique. 
Pigment.-In addition to the elements already 
described, more or less pigment in the shape of 
fine brownish yellow granules is often present in nerve cells (Plate XV). It is not 
found in cells of the new-born. It increases with age, and in old age often fills up a 
large part of the cell body. Its significance is not known. 
The protoplasmic processes or dendrites are-at least the larger trunks-of the 
same structure as the cell body (Plate XV, 1). That these larger trunks have func- 
tions similar to those of the cell body seems probable from the fact that the axone 
not infrequently takes origin from a large dendritic trunk instead of directly from the 
body of the cell. The chromatic substance is present in the dendrites, as elongated 
Fig. 771.-Neurone (Nerve Cell 
or Ganglion Cell and Processes) 
from Human Cerebral Cortex. 
Showing main or apical dendrite 
passing upward and numerous smaller 
dendrites coming off from the main 
dendrite and from the body of the cell. 
A. single axone (axis-cylinder process) 
passes downward from the base of the 
cell, giving off two collaterals. THE NERVOUS SYSTEM 
1131 
rods with triangular masses at the points of bifurcation. The achromatic elements 
are apparently of the same character as in the body of the cell. The protoplasmic 
processes divide dichotomously, becoming rapidly smaller, and end at a compara- 
tively short distance from the cell body.1 Stained by the method of Golgi, the 
dendrites are seen to be covered with minute projections or gemmules, often ending 
in a small bulb. These processes carry impulses toward the cell. 
The axis-cylinder process or axone-so called from its often becoming the 
axis-cylinder of a nerve fiber-is usually single. It generally arises directly from 
the body of the cell, but may arise, as already mentioned, fiom one of the larger 
protoplasmic trunks. It is differentiated from the dendrites in Nissl preparations 
by always taking origin from an area in the cell body free from chromatic sub- 
stance, the axone hill, and by being itself entirely achromatic (Plate XV, 1); in Golgi 
specimens, it is recognized by its straight course, uniform diameter, andsmooth outline 
(Fig. 771). It sends off few branches, and these at right angles (collaterals.) This 
axone may extend a great distance from the cell 
body; for example, the axones of certain motor cells 
of the spinal cord extend to the muscles of the 
hands or feet. Both the axone proper and its 
collaterals end in terminal arborizations. Their 
conductivity is cellulifugal-that is, they always 
carry impulses from the cell. In certain cells the 
axis-cylinder processes branch rapidly and end in 
the gray matter in the vicinity of their cells cf 
origin (Fig. 772). An axone may pass from its 
cell of origin to its termination uncovered by any 
sheath. Such axones are found in certain portions 
of the gray matter. An axone may be enveloped 
only by a thin membrane, the sheath of Schwann, 
as, e.g., the fibers of Remak found mainly in the 
sympathetic system. An axone may be sur- 
rounded by a myelin sheath alone, as in the white 
matter of the brain and cord, or by both a 
myelin sheath and a sheath of Schwann, as in 
the fibers of the peripheral nerves, with the excep- 
tion of the olfactory and optic. 
According to the strict neurone conception of 
nervous-system structure, each neurone is considered a complete morphological 
and, to a lesser degree, physiological entity. It has no anatomical connection 
with any other neurone. Association between neurones takes place by contact or 
contiguity, and never by continuity of their protoplasm. The passage of an impulse 
is always from the terminal arborizations of axones or collaterals to the dendrites or 
cell body of the other neurone. 
The validity of the neurone theory has been recently called in question by such 
prominent neurologists as Held, Apathy, Bethe, and Nissl,2 on the ground that in 
many cases axones pass directly into the protoplasm of another neurone and that 
the neurofibrils are sometimes continuous throughout a series of neurones. Nissl 
in a critical review upon the present status of the neurone theory announces his belief 
that the entire neurone concept has been proved fallacious and must be abandoned. 
Admitting that the discovery of anastomoses between neurones and of the 
continuity of the neurofibrils must be accepted as invalidating some of our ideas as 
to the separateness of the neurone units, it can still hardly be considered as over- 
throwing the entire neurone theory. Embryologically, morphologically, and 
physiologically the neurone shows a marked degree of individuality, and the fact 
that neurones sometimes, usually, or even always, anastomose no more warrants 
the giving up of the neurone as essentially a unit than did the discovery of the fact 
Fig. 772.-Neurone (Nerve-Cell 
or Ganglion-Cell Processes) . From 
the Granular Layer of the Cere- 
bellar Cortex of a Guinea-Pig. 
The short axone passes off to the 
left and terminates near its cell of 
origin. 
1 Exception, peripheral arm of spinal ganglion cell. 
2 For a critical view of the opinions of these writers consult Van Gehuchten, A., Anatomie du systeme 
nerveux de 1'homme, 4th ed., Louvain, 1906. Explanation of Plate XV.1 
1. Normal Ganglion Cell. Large motor cell from anterior horn of human spinal cord, showing 
the nucleus in its normal central position with its nucleolus. In the body of the cell are seen the 
chromophilic bodies of various shapes and sizes. Three main protoplasmic trunks or dendrites 
pass off from the upper portion of the cell. In these the chromophilic bodies are rod-shaped. The 
largest process branches at a short distance from the cell. To the left is seen the axone or axis- 
cylinder process free from chromatic substance, as is also that portion of the cell from which it 
takes origin (axone hill). 
2. Ganglion Cell from the Anterior Horn of the Human Spinal Cord of a Case of Alcoholic 
Neuritis. Showing eccentricity of the nucleus and a large central area of the cell body free 
from chromatic substance (central chromatolysis), with an arrangement of the remaining chromo- 
philic bodies around the periphery. (The similarity between the appearance of this cell and the 
one shown in Fig. 6 should be noted.) 
3. Ganglion Cell from the Anterior Horn of the Spinal Cord of a Rabbit Inoculated with 
Rabic Virus and Killed Shortly After the Onset of Symptoms. Shows an early stage of 
chromatolysis; the chromophilic bodies being pale, ragged, and vacuolated. 
4. Ganglion Cell from the Anterior Horn of the Spinal Cord of a Rabbit which Died on the 
Ninth Day After Inoculation with Rabic Virus. Shows extreme chromatolysis, only a 
few fine granules of chromatic substance remaining at the periphery. The cell is swollen, the 
nucleus has disappeared, and the cell body and processes are stained more deeply with the erythrosin 
than is the case in normal cells. 
5. Normal Ganglion Cell from a Human Spinal Ganglion of the Posterior Root. Showing 
central position of the nucleus and the concentric arrangement of the chromophilic bodies. 
6. Ganglion Cell from the Posterior Root Ganglion of a Rabbit Three Weeks After Section 
of the Sciatic Nerve. The cell shows extreme eccentricity of the nucleus with central chro- 
matolysis and a peripheral arrangement of the remaining chromophilic bodies-axonal degeneration. 
(There also remains in the central portion of the cell some chromatic substance in the shape of 
fine granules forming an irregular reticulum. The similarity between this picture and the one 
shown in Fig. 2 is apparent.) 
7. Portion of a Posterior Root Ganglion from a Case of Tabes Dorsalis. Showing degeneration 
in the ganglion cells with increase in the interstitial connective tissue. 
8. Two Pyramidal Cells from the Normal Human Cerebral Cortex. While the pyramidal 
cells in the human cortex vary considerably in the amount of chromatic substance which they 
contain, these are of an average type. 
9. Two Pyramidal Cells of the Human Cerebral Cortex from a Case of Eclampsia. These 
cells show marked chromatolysis. 
10-13. Anterior Horn Cells of the Spinal Cord from a Case of Pellagra. Showing coarse 
Nissl granules (Fig. 10), clumping of the granules and disappearance of the nuclear boundaries 
(Fig. 11), pigmentation with absence of nuclei (Fig. 12), and absence of nucleus and breaking up 
of Nissl granules (Fig. 13). 
1 In the staining of the specimens from which these drawings were made, Held's modification of 
Nissl's method was used. This consists essentially in a preliminary staining of the sections with a 
one per cent, aqueous solution of erythrosin. In the case of the specimens used for the last four 
drawings (Fig. 10-13), the regular Nissl staining method without the erythrosin counterstain was 
employed. 
1132 Pathology-Delafield & Prudden. 
Plate XV. 
FIG.10. 
FIG 5 
FIG. I. 
FIG II- 
FIG 6 
FIG.2 . 
FIG. 12. 
FIG.3 . 
FIG. 7 
FIG 13 
FIG.8 
FIG-4- . 
FIG. 9. 
Lesions of Ganglion Celis.-(Stained by Nissl's Method) 
sackctt t minims cphp.m y. THE NERVOUS SYSTEM 
1133 
that the protoplasm of epithelial cells was continuous through intercellular " bridges" 
necessitate the giving up of the epithelial cell as the structural unit of epithelium. 
The cell bodies of neurones are grouped mainly in the gray matter of the brain and 
cord, in the ganglia of cranial, spinal, and sympathetic nerves, and in the peripheral 
end organs of certain of the nerves of special sense. Protoplasmic processes ramify 
mainly within the gray matter.1 While some terminate in the gray matter in the 
immediate vicinity of their cells of origin, it is the axones that make up the bulk of 
the white matter of the brain, cord, and peripheral nerves. 
Neuroglia.-In addition to the extensions inward of the pia mater and the con- 
nective tissue of the blood-vessels, there is found in both gray and white matter a 
tissue, supportive and protective in function, and 
peculiar to the nervous system-the neuroglia. 
Like the neurone, it originates in the epiblastic cells 
lining the embryonic neural canal. These cells, 
at first morphologically identical, soon differentiate 
into neuroblasts or future neurones, and spongio- 
blasts, or future neuroglia cells. In the adult two 
main types of neuroglia cells are found, spider cells 
(Fig. 773), with spine-like, straight, unbranching 
processes, and mossy cells (Fig. 774) with thick, 
rough, branching arms. The former are found 
chiefly in the white matter, the latter in the gray 
matter in connection with blood-vessels. As in the 
case of the nerve cell, the processes of these cells do 
not anastomose, but interlace, forming a dense 
feltwork. By a special stain, Weigert demon- 
strates neuroglia cell nuclei and separate fibrils. 
It seems probable that this method fails to show the body of the cell, while staining 
its nuclei and the fibrils which pass through it. 
It would thus appear that the architecture of the central nervous system, consid- 
ered as an organ, is analogous to that of other organs. It has in the neurone its paren- 
chyma, and this parenchyma is supported and bound together by a framework of 
connective tissue. The essential difference lies in the fact that in the neurone is the 
highest morphological differentiation which protoplasm has attained, representing 
chemically the most complex molecules known. In the axone, sometimes a meter or 
more in length, of a cell of microscopic dimensions, there is a distribution of cell 
protoplasm, such as occurs in no other tissue or organ. The neuroglia also, while 
without question a tissue supportive in func- 
tion, is embryologically and morphologically 
different from other forms of connective tissue.2 
Fig. 773.-Neuroglia Cell-Spider 
Type-Human Cerebrum. 
DEGENERATION. 
Neurone Degeneration. 
Degenerative changes may affect the 
entire neurone or any of its parts. Such 
changes may result from direct injury 
to some part of the neurone, to diminu- 
tion or modification of its nutritive sup- 
ply, to various toxic conditions, etc. 
I. Changes in the Neurone from In- 
jury to One of Its Parts.-(a) Changes in the Axone Resulting from 
Separation from Its Cell Body.-That changes, presumably of a 
Fig. 774.-Neuroglia Cell-Mossy 
Type-Human Cerebrum. 
1 Exception, peripheral arm of spinal ganglion cell. 
2 For detailed investigation of neuroglia, see Weigert, C., Gesammelte Abhandlungen, Berlin, 1906, 
ii, 582; and Alzheimer, A., Nissl and Alzheimer, Histologische und histopathologische Arbeiten, Jena, 
1910, iii, 401. 1134 
THE NERVOUS SYSTEM 
degenerative character, occur in the peripheral end of a nerve when its 
connection with the central nervous system is broken has -long been 
known. This degeneration takes place as well in the central as in the 
peripheral nervous system, and is complete, involving every portion 
of the axone distal to the point of section. The changes are not 
progressive from the point of lesion, but occur at nearly the same time 
in all parts of the distal stump. These changes consist in a breaking 
up of the medullary sheath into segments (Fig. 775), which in turn dis- 
integrate, forming variously shaped masses of myelin, among which 
may be seen the axis-cylinder, the whole being inclosed by the neu- 
rilemma. The method of Marchi (page 1181), 
which differentiates between fat and myelin, 
showrs that coincident with the breaking up of 
the myelin there is an appearance of fat drop- 
lets. These fat droplets increase in number 
pari passu with the decrease in myelin, but 
also ultimately disappear. During the progress 
of these changes in the medullary sheath, the 
axis-cylinder at first segments and then under- 
goes dissolution. The neurilemma, on the 
other hand, appears to take no part in the 
degenerative process. On the contrary, it 
and its nuclei remain intact to take part later in regenerative changes, 
should these occur. If there is no reunion of the severed ends of the 
axone, the peripheral portion completely disappears, its place being 
taken by connective tissue. 
(6) Changes in Dendrites Resulting from Their Separation 
from Their Cell Bodies.-If we consider, as some observers do,1 that 
the peripheral arm of the spinal ganglion cell is a protoplasmic process, 
making a physiological rather than a morphological differentiation, we 
find that the same law holds good for dendrites as for axones when 
separated from their cell bodies. Thus in the divided peripheral nerve 
those fibers which are the processes of the spinal ganglion cells undergo 
the same degenerative changes as do the fibers which are processes 
of cells of the anterior horn. Most dendritic processes are, however, 
so short and terminate in the gray matter so near the cells from which 
they originate that experimental separation of the process from its 
cell body is impracticable. In view of the fate of the axone, however, 
and the relation of the dendrites to the cell body, there can be 
little doubt that as complete degeneration follows the severance of a 
protoplasmic process from its cell of origin as follows in the case of 
the axone. 
(c) Changes in the Proximal Stump and in the Cell Body Re- 
sulting from Lesion to the Axone.-The fundamental principle 
of the law of Waller was the complete degeneration of the distal portion 
of the divided nerve, while the proximal stump remained intact. Our 
present conceptions, however, of the interdependence of the different 
Fig. 775.-Neurone Degenera- 
tion after Injury. 
Teased nerve fibers from distal 
portion of sciatic nerve of rabbit 
three weeks after division of the 
nerve. Osmic-acid stain. The 
large and small black masses 
represent disintegrated myelin 
and fat droplets. 
1 Van Gehuchten, A., Anatomie du systeme nerveux de 1'homme, 4th ed., Louvain, 1906. 1135 
THE NERVOUS SYSTEM 
parts of the neurone, and of the axone as the outlet for neurone energy, 
would lead us to expect certain changes of an atrophic nature in the 
proximal stump and in the cell body, as a result of separation from its 
axone and consequent inability to functionate. That such changes take 
place recent improvements in cytological technique have enabled us 
to determine. The method of Marchi shows that degenerative changes 
occur, not only in the distal, but in the proximal end of the divided 
nerve. These changes take place more slowly than in the distal portion, 
but are apparently identical in character. 
In the body of the cell the method of Nissl demonstrates marked 
changes after section of the axone. These changes may be observed 
Fig. 776.-A, Fibrils in normal anterior horn cell. B, Fibrils in degenerated cell after separation 
from its motor nerve. After Bielschowsky. Bielschowsky fibril stain. 
within twenty-four hours after the injury. They consist in a diminu- 
tion in the chromatic elements of the cell, chromatolysis. This is most 
marked in the central portion (central chromatolysis), a distinct ring 
of chromophilic bodies around the periphery often remaining. The 
nucleus usually migrates toward the periphery and may even bulge 
from the cell. The fibrils in the cell body also show changes (Fig. 776, 
A and B). In the case of the hypoglossal nerve in the rabbit, these 
changes reach their maximum in from two to three weeks. The future 
of some of these cells is complete degeneration. Others apparently un- 
dergo hypertrophy and regeneration. The fibrils, as demonstrated by 
the silver impregnation methods, decrease in number and stain only at 
the periphery of the cell and in the dendrites. The cell may not regen- 
erate after this phase. If regeneration does take place, however, the 
cell may enlarge and the fibers reappear; but ultimately the cell may again 1136 
THE NERVOUS SYSTEM 
degenerate and the fibers disappear.1 The intensity of the reaction of 
the nerve cell to injury to its axone depends upon the severity of the 
injury. Thus cutting the nerve is followed by more prompt and marked 
changes in the nerve cell than simple compression, while pulling out the 
nerve roots is followed by a still more intense reaction. Again, there is a 
difference in the resisting-powers of different types of cells. Thus the 
motor cells of the anterior horn are peculiarly resistant to injury to their 
axones, as are also the spinal ganglion cells to injury to their central 
processes. Again, between cells of the same type there are marked vari- 
ations in resisting-powers. Thus the motor cells of the anterior horn 
are much more resistant than the cells of the motor cranial nuclei.2 
(d) Changes in the Cell Body Resulting from Lesions to Its 
Dendrites.-In the study of the effect upon the cell body of a lesion 
depriving it of one or all of its dendritic processes, we meet with the 
same experimental obstacles already mentioned in connection with 
changes in the dendrites. It is, again, only in the peripheral arm of the 
spinal ganglion cell that we have a cellulipetal process of any considerable 
length. Section of this process results in changes in the spinal gan- 
glion cell quite similar in character to the so-called " axonal " degenera- 
tion (Plate XV, 6). If we consider that a cell's dendrites probably 
furnish its most important avenue for the reception of impulses, it follows 
that a neurone may be thrown as completely out of circuit, as it were, 
by injury to its dendrites as by injury to its axons. Interesting experi- 
ments3 have been carried out in the attempt to bring about the same 
functional effect as would result from section of a cell's dendrites, by 
inhibiting afferent impulses. Cutting the posterior roots resulted in 
changes in the cells of the anterior horn. The inference was that these 
changes were induced by an inhibition of the customary normal stimu- 
lation by means of the afferent impulses reaching the cells through their 
dendritic processes. 
II. Changes in the Neurone from Interference With Its Nutrition.- 
Changes apparently of a degenerative character have been described in 
neurones as a result of interference with nutrition Thus it has been4 
found that by temporarily applying a ligature to the abdominal aorta, 
an acute necrosis of the cells of the lumbar cord can be induced. Later 
experiments of a similar nature followed by the Marchi staining showed 
that the degenerative process affected not ony the cell bodies, but the 
entire neurone. Similar degenerative changes have been induced by 
experimentally produced multiple emboli, cells in the vicinity of the 
occluded vessels being in marked contrast to cells from regions whose 
vessels remained patent. Definite degenerative changes have been seen5 
1 For studies of regeneration of peripheral nerve fibers, see Kennedy, Brit. Med. Jour., 1904, ii, 729; 
Head and Ham, Jour. Physiol., 1904-05, xxxii, 9; and Doininow, B., Nissl and Alzheimer, Histologisehe 
und Histopathologische Arbeiten, Jena, 1911, iv, 445. 
2 For review and bibl. of changes in the nerve cell and in the proximal stump after section of a 
peripheral nerve, consult Barker, L. F., The Nervous System, New York, 1899; and da Fano, Zieglers 
Beitr., 1908, xliv, 495. 
3 See Warrington, W. B., Jour. Physiol., 1898, xxiii, 112, for study of the structural alterations in 
nerve cells. 
'See Brieger and. Ehrlich, Ztschr. f. klin. Med., 1884, vii, Suppl., 155. 
6 For study of ganglion cells, see Ewing, J., Arch. Neurol, and Psycho-Path., 1898, i, 263. THE NERVOUS SYSTEM 
1137 
in nerve cells as a result of anemia consecutive to pressure from cerebral 
hemorrhage and to thrombosis of the basilar artery. Less marked 
changes have been observed in cases of general malnutrition and in severe 
anemias, except the pernicious form, in which extensive cerebral and 
spinal lesions, due perhaps to a special toxin, may occur.1 
III. Effects of Toxins upon Neurones.2-Changes of a degenerative 
character occur in neurones as a result of the action of toxins. These 
toxins may be introduced into the body from without, for example, such 
poisons as alcohol, arsenic, lead, strychnin, etc.; they may be elaborated 
within the body as the result of faulty metabolism, for example, in ure- 
mia, eclampsia, etc., or as a result of the action of bacteria, as in tetanus, 
rabies (Plate XV, 3, 4, and 8), diphtheria, etc., or of the Plasmodium 
malarise. The effects of these poisons upon the neurone vary with dif- 
ferent poisons and in different types of neurones. The effects of the 
same poison upon a given type of neurone also vary according to its 
rapidity of action, whether rapidly fatal or extending over a considerable 
period of time. Again, given the same poison and the same time of 
action, not all neurones even of the same type show an equal suscepti- 
bility. 
These changes in the neurone from the action of toxins may affect one 
or all of its structural elements, and vary from the slightest appreciable 
loss of staining qualities of the chromophilic bodies to complete destruc- 
tion of the neurone. In the chromophilic bodies the essential change 
seems to be a decrease in the amount of chromatic substance, chromatoly- 
sis. This may be evidenced merely by a decreased staining intensity, 
the chromatic masses appearing abnormally pale; the bodies may have a 
ragged or frayed-out appearance at their edges; they may be shrunken, 
or, retaining their normal shape and size, become vacuolated (Plate 
XV, 3); they may completely disintegrate, giving to the cell a diffuse 
granular appearance; they may disappear, leaving the cell entirely devoid 
of chromatic substance. The chromatic masses in the dendrites seem in 
many cases to be more resistant or less exposed than are those in the body 
of the cell, often remaining unchanged at a time when the latter show an 
advanced degree of chromatolysis. During these changes in the chro- 
matic element the cyto-reticulum may remain apparently normal or it 
may more or less completely disintegrate. This disintegration usually 
marks the more advanced degenerative changes (Plate XV, 4). 
In the truly achromatic element of the cell or cytoplasm, our present 
methods of staining fail to demonstrate lesions except in the finer fibrillar 
structures. Diffuse staining of this basement substance is a common 
phenomenon of chromatolysis, but seems more properly referable to a 
diffusion of the fine granules resulting from disintegration of the chro- 
matic masses than to any changes in the cytoplasm itself. Disappear- 
ance of the formed elements of the cell often leaves clear holes or vacuoles 
in the cell body or gives the appearance of cracks or fissures. The 
nucleus may remain normal; it may swell and its contour become abnor- 
1 Wolman, H. W., Arch. Int. Med., 1918, xxi, 791 (bibl.). 
2 Meyer, A., On parenchymatous systemic degenerations mainly in the central nervous system 
Brain, 1901, xxiv, 47. 1138 
THE NERVOUS SYSTEM 
mally distinct; it often takes a diffuse stain; later it shrinks, becomes 
crenated, its reticulum and limiting membrane break up and its outline 
is lost. During these nuclear changes the nucleolus may also disinte- 
grate, but it is often extremely resistant, remaining apparently unchanged 
after most of the other parts of the cell have become unrecognizable. 
Concurrent with these changes in internal structure are changes in the 
shape and size of the cell. Its contour becomes irregular, and its edges 
present an eroded appearance; the cell body shrinks away from its cell 
space, breaks up, and ultimately disappears. The dendrites undergo 
alterations similar to those in the body of the cell. They shrink, become 
separated from the cell body, and finally disintegrate. 
That part of the neurone which shows most marked evidences of its 
effect is not necessarily the part upon which the poison is most directly 
acting. Thus a toxin affecting directly the cell body may cause the 
earliest and most pronounced changes far out in its dendritic or axonal 
processes, that is, in those parts of the neurone farthest removed from 
the trophic center. 
To the action of a specific poison certain neurones seem less resistant 
than others. Thus, to the action of lead those neurones governing the 
extensor muscles of the wrist seem especially susceptible, The cells of 
the motor nucleus of the trigeminus seem to be less resistant than other 
motor cells to the poison of tetanus. Again, the frequency with which 
tabes dorsalis is associated with a syphilitic history seems to indicate a 
special susceptibility to the syphilitic poison on the part of the peripheral 
sensory neurone. 
Comparing the changes in the nerve cell in toxemias (Plate XV, 3 and 4) with 
those induced by lesions to its axone-axonal degeneration (Plate XV, 6)-we note 
that while in the latter the chromatolysis is central in character, beginning in the 
region of the axone hill and nucleus, in the former the changes begin at the periphery, 
the portion of the cell in most direct relation to the surrounding lymph. In axonal 
degeneration the nucleus is usually eccentric. In toxemia it usually remains central, 
at least until the process of degeneration is far advanced. While this distinction holds 
good in general and while the phenomena of central chromatolysis and eccentricity 
of the nucleus regularly follow injury to the axone, we are not yet warranted in stating 
that such changes never occur except after some injury, or that the presence of such 
changes in the cell can be explained only on the basis of injury to its axis-cylinder. 
IV. Effects of Fatigue upon Neurones.-Studies of the effect of fa- 
tigue upon the neurone have been made in animals after prolonged mus- 
cular activity and after electrical stimulation. Changes have been 
described which consist in a decrease in the size of the cell body, a de- 
crease in the size of the nucleus, often with distortion, and a marked 
increase or decrease in the amount of chromatic substance with more or 
less diffuse staining of both cell body and nucleus.1 There is no agree- 
ment as to the direct relationship of these changes to fatigue, and many 
observers deny that such morphological alterations are constant in this 
condition.2 Changes consist in a decrease in the size of the cell body, 
1 Hodge, Jour. Morphol., 1892, vii, 1; Dolley, D. H., Jour. Med. Research, 1909, N. S. xvi, 95; and 
Jour. Am. Med. Assn., 1917, Ixviii, 756; Crile, G. TP., A Physical Interpretation of Shock, Exhaustion, 
and Restoration, New York, 1921. 
2 Kocher, R. A., Jour. Am. Med. Assn., 1916, Ixvii, 278. THE NERVOUS SYSTEM 
1139 
a decrease in the size of the nucleus, often with distortion, and a marked 
increase or decrease in the amount of chromatic substance with more or 
less diffuse staining of both cell body and nucleus. 
It seems not at all improbable that the clinical pictures presented by certain psy- 
choses and neuroses are the expression of the effects upon the neurones of prolonged 
fatigue. Certain local expressions of neurone exhaustion, as, for example, writer's 
cramp, may possibly also be placed in the same category. 
As to the significance of those changes in the nerve cell, which are marked by dim- 
inution in the chromatic substance alone, and to which the term "chromatolysis" has 
been given, there is a considerable difference of opinion. Marinescu considers them 
of the nature of degeneration, while Van Gehuchten1 is inclined to look upon the phe- 
nomenon as conservative in character, a means by which the neurone assumes a con- 
dition most advantageous for self-defence. It has been shown that even an extreme 
degree of chromatolysis is not incompatible with function. Marinescu insists that so 
long as the changes are confined to the chromatic substance recovery is possible, no 
matter how extensive the alterations, while changes in the achromatic elements are 
always permanent in character. 
REGENERATION. 
Regeneration of nerve tissue in the sense of an actual reproduction 
of neurones probably never occurs in the adult human nervous system.2 
As has been noted, extreme chromatolysis may be succeeded by complete 
recovery. In the case of axonal chromatolysis, the degenerative process 
usually reaches its maximum in about three weeks. Regeneration of 
chromophilic bodies then begins. This reconstructive process is slow, 
the cells often requiring months to return to a normal condition. At 
some stage of the process there is usually an overproduction of chro- 
matic substance, and the cells appear darker than normal. 
Primary union between the ends of divided nerve fibers does not 
occur. Complete degeneration of the distal portion always precedes the 
regenerative process. In this reconstruction the nuclei of the neurilemma 
seem to play an important part; they increase in number, and there is 
also an increase in the protoplasm which surrounds them. With union 
of the divided ends, the axones of the central stump may grow out again, 
if the ganglion cells be intact, and ultimately resume function. The 
myelin first reappears as droplets which coalesce and finally form a 
complete sheath. This reconstructive process in the nerve fiber is ex- 
tremely slow, often requiring many months for its completion.3 
Replacement Neuroglia Hyperplasia.4-Under various conditions 
in which there is destruction of the parenchyma, as, for example, in 
ascending and descending degenerations of the spinal cord, there occurs a 
compensatory increase in the interstitial elements. This new tissue is at 
first cellular, most of the cells being of the spider variety. Later there 
1 See Van Gehuchten, A., Anatomie du systeme nerveux de 1'homme, 4th ed., Louvain, 1906. 
2 For review and literature on regeneration, see BarKer, L. F., The Nervous System, New York, 
1899, p. 245 and following. 
3 For studies of the regeneration of peripheral nerve fibers, see Kennedy, Brit. Med. Jour., 1904, ii, 
729; Head and Ham, Jour. Physiol., 1904-05, xxxii, 9; and Doiniicow, B., Nissl and Alzheimer, Histo- 
logische und histopathologische Arbeiten, Jena, 1911, iv, 445; and Huber, G. C., Transplantation of 
peripheral nerves, Arch. Neurol, and Psychiat., 1919, ii, 466; 1920, iii, 437. 
1 Alzheimer, A., Beitrage zur Kenntnis der pathologischen Neuroglia und ihrer Beziehungen den 
Abbauvorgangen in Nervengewebe, Nissl und Alzheimer, Histologische und histopathologische Arbeiten, 
Jena, 1910, iii. 1140 
THE NERVOUS SYSTEM 
is an increase in the neuroglia fibers, and the tissue often becomes dense 
and hard. What part the mossy cells or other less common types of 
neuroglia cells take in the proliferative process is as yet unknown. 
With the increase in fibers there are often shrinkage and the formation of 
dense fibrous tissue. This replacement hyperplasia in neuroglia seems 
quite similar in nature to replacement connective-tissue hyperplasia in 
other organs, and is often wrongly considered inflammatory. 
Degenerations Affecting Systems of Neurones. 
General Considerations Concerning Neurone Systems. 
Before considering the subject of systemic degeneration we may refer briefly to 
the situation in the nervous system of certain of the more important groups of neu- 
rones and the paths which their axones take. 
That the cell bodies of neurones are grouped in the gray matter of the brain, cord, 
and ganglia, and in the end organs of certain nerves of special sense, has already been 
mentioned. This grouping of neurones serves definite physiological ends. Their cell 
bodies form centers or nuclei, while their axones are collected into bundles or fiber 
tracts. Thus, in the region of the fissure of Rolando are grouped the centers of those 
neurones which have to do with voluntary motion, and what is known as cerebral 
localization means the grouping of cell bodies of neurones for specific function. After 
the known localizations are eliminated, there still remains unaccounted for the greater 
part of the cerebral cortex, and our present belief is that these neurones are neurones 
of association by which the various centers are brought into physiological relationship. 
Some understanding of this neurone grouping, and especially of the arrangement of 
their neuraxones as fiber tracts of the cord, is essential to an appreciation of those 
degenerations which affect definite systems of neurones. 
Peripheral Motor Neurones.-These neurones have their cell bodies in the 
gray matter of the anterior horn and in the motor nuclei of the cranial nerves. Their 
neuraxones pass out as the motor fibers of the cranial and of the spinal nerves. The 
entire neurone lies upon the same side of the body; that is, the peripheral motor neu- 
rone is "direct." 
The Upper or Corticospinal Motor Neurones have their cell bodies situated 
mainly in the cerebral cortex near the fissure of Rolando. Their neuraxones converg- 
ing, pass through the internal capsule, pons, and medulla, sending off fibers to the 
motor nuclei of the cranial nerves. In the medulla the tract comes to the surface as 
the anterior pyramids. At the junction of medulla and cord occurs the pyramidal 
decussation in which most of the fibers of the tract cross to the opposite lateral region 
of the cord, to be known as the crossed pyramidal tract, while a minority remain on the 
same side, to pass down the cord as the direct pyramidal tract. As the tracts descend, 
fibers continuously leave them to terminate, those of the crossed tract in the gray 
matter of the same side, those of the direct tract, after passing through the anterior 
commissure, in the gray matter of the opposite side. The corticospinal motor tract 
is a crossed tract.1 These tracts present variations in size and length. They are 
often asymmetrical. The crossed tract extends to the lower sacral cord. The direct 
tract usually ends about the mid-dorsal region, though it has been followed as low 
as the second lumbar segment. 
The Sensory (Afferent) Tract, like the motor, consists of two segments, an 
upper and a lower. 
The lower or peripheral sensory neurone tract has its cell bodies in the ganglia of the 
spinal and of the cranial nerves. Their peripheral arms, which Van Gehuchten con- 
siders protoplasmic processes, are axis-cylinders of cranial or of spinal nerves. Their 
central processes or axones pass into the cord as the fibers of the posterior roots and 
enter the posterior columns. Here they divide into ascending and descending arms. 
Certain recent observations tend to show that there may be a small number of "direct" fiben 
in the so-called crossed pyramidal tract. THE NERVOUS SYSTEM 
1141 
The descending arm is short, and with its collateral branches soon terminates in the 
gray matter of the same side of the cord. The ascending arm may also be short, and 
with its collaterals terminates as does the descending. It may pass a considerable 
distance up the cord and then end in the gray matter. It may, as one of the long 
fibers of the posterior columns, continue upward to the medulla, where it terminates 
in one of the posterior column nuclei. These long fibers pass inward as they pass 
upward, so that the lower the origin of the fiber the more mesial is its position in the 
upper part of the cord. The entire neurone lies upon the same side of the cord. The 
lower sensory, like the lower motor neurone, is direct. 
Upper Sensory Neurones.-The arrangement of these neurones is extremely com- 
plex, and only those whose axones enter into the formation of distinct tracts of the 
cord will be here mentioned. Of the above-described central arms of the peripheral 
sensory neurones, some of the shorter enter the gray matter of the cord and with their 
collaterals terminate around motor cells (reflexes). Others terminate around cells 
whose axones cross to the opposite side of the cord and pass upward as the antero- 
lateral ascending tract, or tract of Gowers. Other fibers terminate around cells of the 
column of Clarke, the axones of which pass upward as the direct cerebellar tract. 
In addition to these main fiber tracts, there are in all regions of the cord fibers 
which are commissural in character. These fibers are the axones of cells situated in 
the gray matter of the cord, and after passing a short distance up or down and sending 
collaterals into the gray matter, themselves re-enter the gray matter and terminate 
there. These short fibers make up the so-called ground bundles or fundamental col- 
umns of the cord. They attain their greatest development in those regions of the 
cord where the reflex centers are most extensive, that is, in the lumbar and cervical 
enlargements. 
Secondary Degenerations. 
Secondary degenerations are dependent upon the fact already noted, 
that, the cell body being the trophic center of the neurone, the axone 
when separated from its cell body dies. 
Descending Degeneration.-Any cortical lesion, such as embolic 
softening and apoplectic clots, which destroys the nerve cells, or any 
lesion of the brain or cord which interrupts the axone tracts of the cortico- 
spinal system of neurones, determines a complete degeneration of the 
affected axones (Fig. 777). The course of these axones has been de- 
scribed. Thus a lesion of the brain affecting motor neurones is fol- 
lowed by a degeneration in the motor tract of the same side down to the 
pyramidal decussation, and below that point, in the direct motor tract 
on the same side and in the crossed tract on the opposite side, the num- 
ber of degenerated fibers being proportionate to the number of cells de- 
stroyed or axones interrupted. In a number of cases of descending de- 
generation due to cerebral lesions, degenerated fibers were found in the 
crossed pyramidal tract on the same side as the lesion. This degenera- 
tion was not present in all cases, and in no case was it so marked as the 
degeneration in the opposite lateral tract. The explanation is that 
in some cords a small number of fibers instead of decussating pass down 
into the cord in the lateral tract of the same side. 
In descending degeneration due to a lesion below the pyramidal de- 
cussation a somewhat different picture is presented. In a complete trans- 
verse lesion there is degeneration of both crossed and of both direct py- 
ramidal tracts. If the lesion is unilateral the degenerations are upon the 
same side as the lesion. The areas of degeneration are also larger and 1142 
THE NERVOUS SYSTEM 
less sharply defined than in cerebral lesions. Then in addition to the 
degeneration of the pyramidal tracts there is a degeneration of a con- 
Fig. 777.-Secondary Descending Degeneration. 
From hemorrhage into the internal capsule, almost complete degeneration of the direct pyramidal 
tract on the same side as the lesion and of the crossed pyramidal tract on the opposite side. There 
were a few degenerated fibers in the crossed tract on the same side as the lesion. 
Following complete crushing of the cord about two segments below the level at which the section 
was taken. Degeneration is almost complete in the columns of Goll, of Gowers,-and the direct cere- 
bellar tracts. A few normal fibers are seen in the columns of Burdach. These are the ascending 
axones of spinal ganglion cells between the point of injury and the level of the section, and are seen 
to occupy that part of the posterior columns adjacent to the posterior horns. 
Fig. 778.-Secondary Ascending Degeneration. 
siderable number of fibers in a crescent-shaped area lying near the periph- 
ery of the anterolateral region and extending from the crossed to the 
direct tract. Degeneration of these fibers has been described1 after 
1 Marchi, Riv. sper. di freniat., 1891, xvii, 367. THE NERVOUS SYSTEM 
1143 
removal of the cerebellum. They have been considered as descending 
cerebellar fibers. The so-called comma-shape degeneration in the pos- 
terior columns is sometimes present. Others1 regard these fibers, which 
are situated about the middle of the posterior columns, as descending 
axones of spinal ganglion cells, while still others2 think that they are 
more probably descending branches of commissural neurones. In the 
fundamental columns the degeneration extends but a short distance be- 
low the seat of injury, and of course affects only descending axones. 
Ascending Degeneration.-Any lesion which destroys the spinal 
ganglion cells or which interrupts their axones determines a secondary 
ascending degeneration in the posterior columns (Fig. 778). Any lesion 
of the cord which interrupts the tract of Gowers or the direct cerebellar 
tract is followed by degeneration of the fibers of these tracts above the 
lesion (Fig. 778). Immediately above the lesion there is complete de- 
generation of the tracts. As we pass upward new undegenerated fibers 
from the spinal ganglia above the lesion enter the column of Burdach, 
so that there appears in the posterior columns a constantly increasing 
number of normal fibers. Also in the column of Gowers undegenerated 
fibers appear as one passes upward from the lesion. Some of these fibers 
probably have their origin in the gray matter of the cord, and the num- 
ber of normal fibers is in proportion to the number of these cells be- 
tween the lesion and the point at which the section is taken. Descending 
fibers in these columns have already been mentioned. They, of course, 
do not degenerate. If the lesion be above Clarke's columns the degen- 
eration in the cerebellar tracts remains complete; if not, the number of 
normal fibers is in proportion to the number of Clarke's column cells 
between the lesion and the point of section. The ascending fibers of the 
fundamental columns also degenerate, but are so short that they cannot 
usually be traced beyond the area of direct action of the traumatism. 
Primary Degenerations. 
Degeneration of the Peripheral Motor Neurones. 
Progressive spinal muscular atrophy is the clinical designation of a 
disease, the underlying lesion of which is a progressive atrophy or de- 
generation of the lower motor neurones. There is a degeneration of 
the large motor cells of the anterior horns and of their processes.3 This 
degeneration goes on to complete destruction of some neurones. With 
the loss of nerve tissue proper there is a compensatory growth of neu- 
roglia. In a well-advanced case, section of the cord shows a marked 
diminution in the number of anterior horn cells and an atrophic condition 
of the horn itself and of the anterior roots. The lesion usually begins in 
the cervical region; more rarely it starts in the lumbar cord. The de- 
generation may extend to the motor cranial nerve nuclei, giving the 
1 Schultze, On Comma-shaped Degeneration of the Posterior Columns, Arch. f. Psychiat., 1889, xi, 
770. 
2 Tooth, H. H„ Gulstonian Lectures on Secondary Degenerations of the Spinal Cord, London. 1889. 
3 Huenekens, E. J., and Bell, E. T., Infantile spinal progressive muscular atrophy (Werdnig-Hoff- 
mann), Amer. Jour. Dis. Chil., 1920, xx, 496. 1144 
THE NERVOUS SYSTEM 
picture of a progressive bulbar paralysis. The medullary nuclei most 
commonly involved are the hypoglossal and the spinal accessory. Less 
often the degeneration affects the cells of origin of the fifth and seventh. 
Degeneration of the peripheral nerves has been described. The muscu- 
lar lesions correspond to the lesions in the cord, the muscles of the hand 
and arm being usually first affected. The affected muscles are pale and 
infiltrated with fat. The fibers shrink, and the contents of the sarco- 
lemma sheath become granular and finally disappear, leaving nothing but 
the sheath and the nuclei. This lesion is sometimes described as a 
chronic anterior poliomyelitis. Both its clinical history and its pathol- 
ogy, however, indicate the degeneration as the initial lesion and the 
neuroglia increase as secondary-a replacement hyperplasia. The vas- 
cular lesions which have been found also point to a primary degenerative 
change. The disease is probably syphilitic in origin in about one-fifth 
of the cases; heavy muscular labor and hereditary weakness of the affected 
neurones are unquestioned factors, also. 
Degeneration of the Corticospinal Motor Neurones. 
Spastic Paraplegia-Spastic Spinal Paralysis.-This may be described 
as a primary lesion of the upper or corticospinal motor neurones. Arte- 
riosclerosis and syphilis may be etiological factors.1 It is probable that 
the lesion affects the entire neurone. As a distinct pathological entity 
the condition is extremely rare. Whether it originates in a degeneration 
of the cell bodies of these neurones in the cortex is not known. The 
lateral columns and especially the pyramidal tracts are degenerated, and 
there is a replacement gliosis. The clinical picture of spastic paraplegia 
due to compression, to a transverse myelitis, or to a multiple sclerosis, 
is not uncommon. The type of spastic paraplegia appearing in child- 
hood is due to a faulty development of the corticospinal motor neurones, 
rather than to their degeneration {Little's disease).2 Probably some cases 
are due to porencephalus, polioencephalitis, or birth injuries inhibiting 
the development of the pyramidal tracts. 
Degeneration of Both Peripheral and Corticospinal Motor 
Neurones. 
Amyotrophic Lateral Sclerosis.-This is a primary progressive degener- 
ation involving both corticospinal and spinoperipheral motor neurones. 
The appearance of the transverse section of the cord is a combination of 
that in spastic paraplegia and that in progressive muscular atrophy. 
There is a degeneration of the cells of the anterior horn with atrophy of 
the horn itself, and a degeneration of the fibers of the direct and of the 
crossed pyramidal tracts (Fig. 779). The lesion in the horns is usually 
most pronounced in the cervical region. The extent of involvement of 
1 M ingazzini, G., Family spastic paralysis of spinal type on a heredosyphilitic basis, Arch. Neurol, 
and Psychiat., 1921, v, 637. 
2 Marie, Lectures on Diseases of the Spinal Cord, London, New Sydenham Soc., 1895, 1145 
THE NERVOUS SYSTEM 
ths motor tracts of the cord is extremely variable. The degeneration, 
which is the initial lesion, is accompanied by a replacement gliosis, and 
the picture presented on section of the cord is that of a sclerosis of the 
motor tracts and of the anterior horns. Quite frequently the sclerosis 
is not wholly confined to the motor tracts, but extends into the neighbor- 
ing anterior and lateral tracts, especially in the cervical region. The 
degeneration in these tracts has been traced through the medulla, pons, 
and crus to the cortex, where changes have been observed in the large 
pyramidal cells. In the gray matter of the medulla are also found 
changes analogous to those in the anterior horns, consisting in degenera- 
tion of the cells of the motor cranial-nerve nuclei (hypoglossal, spinal 
accessory, pneumogastric, glossopharyngeal, and facial). The atrophy 
of the muscles innervated by these nerves gives the clinical picture of 
Fig. 779.-Amyotrophic Lateral Sclerosis. 
Degeneration of the crossed pyramidal and of the direct pyramidal tracts. In this case there was 
but little atrophy of the anterior horns. Very few cells, however, were present in the anterior horns 
and there was an increase in the connective tissue of the horns. 
glosso-labio-laryngeal paralysis or progressive bulbar paralysis. The 
medullary lesion may occur without any corresponding lesion of the cord, 
thus giving rise to a bulbar paralysis without any spinal symptoms. The 
seat of the initial lesion, whether in the cell bodies in the cortex or in 
their axones, is as yet undetermined. The fact that disturbances of 
nutrition acting primarily upon the cell body are frequently most evi- 
denced by changes in parts of the neurone farthest from the trophic 
center has already been mentioned. The muscle changes are those of a 
progressive muscular atrophy. 
Degeneration of the Peripheral Sensory Neurones. (Tabes Dor- 
salis-Posterior Spinal Sclerosis-Locomotor Ataxia.) 
The essential lesion of tabes is a primary progressive degeneration of 
the peripheral sensory neurone system. As its older title indicates, the 1146 
THE NERVOUS SYSTEM 
clinical picture of locomotor ataxia had been attributed to a primary 
sclerosis of the posterior columns. This was not because in these col- 
umns was the only lesion, but because, owing to the close packing to- 
gether here of the sensory axones, this lesion was the most conspicuous. 
The distribution of the lesion is coextensive with the peripheral sensory 
neurone system (page 1140). Any part of the system may be affected or 
the lesion may involve practically the whole system; again, the entire 
neurone may be affected, or only part of the neurone, or one part more 
than other parts. In general it may be said that it is the central process 
of the neurone, which enters the cord in the posterior nerve roots that 
shows the earliest and most extensive changes. 
It is convenient to classify the lesions of tabes according to the anat- 
omy of the peripheral sensory neurone system, as follows: 
1. The Peripheral Processes.-(a) The sensory nerve endings. Changes 
of a degenerative character have been described in the sensory nerve 
endings of the skin, joints, and muscle. Especially well marked are 
lesions of the (sensory) muscle spindles which are almost constant. 
(6) The peripheral nerves. Degenerations of the peripheral nerves 
are common. Like similar conditions due to toxic agents, they are usu- 
ally referred to as a neuritis. The changes in both axones and medullary 
sheaths are, however, degenerative in character and similar to those of 
a Wallerian degeneration. The lesion is confined wholly to the sensory 
fibers, the motor fibers remaining intact. It is usually most pronounced 
in the smaller peripheral branches of the nerves. Degeneration of the 
optic nerve-so-called optic neuritis1-occurs in from ten to twenty per 
cent, of cases. Degeneration of the auditory2 nerve and of the sensory 
fibers of the pneumogastric, glossopharyngeal, and trigeminus is of 
less frequent occurrence. 
2. The Cell Bodies.-Marked degenerative changes in the cells of the 
spinal and analogous cranial ganglia and in the retina have been described. 
In a number of cases they have been found early in the disease. There is 
a reduction both in number and in size of the ganglion cells, with a replace- 
ment neuroglia hyperplasia. Chromatolysis with nuclear eccentricity 
has also been observed.3 
3. The Central Processes.-(a) The sensory nerve roots, consisting as 
they do of the central processes of the spinal ganglion cells, show more 
or less complete degeneration. It is, in fact, in this part of the neurone 
that the earliest and most conspicuous changes are usually found. The 
extent and location of the degeneration vary. In the more common 
type of the disease-lumbar tabes-the earliest lesions appear in the 
posterior roots of the lumbar nerves. Only a few of the roots are at first 
affected, and only some of the fibers in these roots. With the progress 
of the disease more fibers are involved and the degeneration extends 
downward to the sacral roots and upward to those of the dorsal and cer- 
1 Stargardt, Ueber die Ursachen des Sehnervenschwundes bei Tabes und der progressiven para- 
lyse, Arch. f. Psychiat., 1913, li, 711. 
2 Knick, A., and Zaloziecki, A., Ueber Acusticuserkrankungen im Friihstadium der Lues, inbesondere 
nach Salvarsan, Berl. klin. Wchnschr., 1912, xlix, 639. 
3 In Plate XV, 7, is seen a portion of a spinal ganglion from a case of advanced tabes. In addition 
to a degeneration of the cells present, there was a marked reduction in the number of cells in the ganglion. 1147 
THE NERVOUS SYSTEM 
vical nerves. In specimens stained by Weigert's method the con- 
trast between the darkly stained anterior root fibers and the almost 
unstained posterior root fibers is often marked. 
(6) The spinal cord. On removing the cord in a case of advanced 
tabes, certain changes are usually apparent to the naked eye. The pia 
mater between the two posterior horns is apt to be thickened, of a dull 
appearance, and adherent to the cord. This, in contrast to the normal 
condition of the rest of the pia, gives the effect of a narrow band ex- 
tending the length of the cord. The posterior columns may be depressed, 
of a grayish color, and firmer than the rest of the cord. On section the 
contrast between the posterior columns and the rest of the white matter 
of the cord is often very distinct. In cords removed from patients dying 
during the earlier stages of the disease there are often no macroscopic 
lesions. 
Cervical region, showing an early stage of the lesion. 
Fig. 780.-Tabes Dorsalis. 
The microscopic appearances vary, depending on the stage, extent, 
and location of the lesion (Fig. 780). 
In a case which comes to autopsy early in the disease the appearance 
of the lesion differs from that in a case of advanced tabes. As already 
noted, the most marked changes are in the posterior columns. In the 
more common type of the disease in which the degeneration begins in 
the lumbar region, sections of the cord at this level show certain quite 
well-defined areas of degeneration. The zone of Lissauer early shows 
marked degenerative changes. This zone extends across the entering 
fibers of the posterior root which divide the zone into two parts. The de- 
generation of the outer part has been wrongly described by some writers 
as a lateral-column degeneration. It will be remembered that these 
fibers are short fibers which have entered the cord in the nearest posterior 
root. Degeneration usually appears early in that part of the column of 
Burdach which borders the posterior horn. The column of Goll varies 
as to the extent of involvement. In many cases it is only slightly af- 
fected, in others the degeneration is marked. As the fibers of this column 1148 
THE NERVOUS SYSTEM 
come mainly from the last lumbar and first two sacral segments, it 
is seen that its condition depends entirely upon the integrity of these 
roots. The fibers of the posterior columns have two sources: (1) enter- 
ing fibers of the posterior roots; (2) fibers from cells in the gray matter 
of the cord. The latter are situated mainly in a narrow strip behind the 
posterior commissure and in the median oval area of Flechsig. These 
fibers are unaffected in tabes. 
The degenerations seen in sections of the dorsal and cervical cord 
in lumbar tabes are dependent upon an ascending degeneration of the 
fibers affected below. The columns of Goll are thus usually affected, 
while the columns of Burdach are often only slightly involved. If at 
any level of the cord degenerated root fibers enter the cord, there results 
Fig. 781.-Tabes Dorsalis. 
a degeneration in the zone of Lissauer and in the band of fibers lying 
along the posterior horn at that level. 
Rarely the tabetic process begins in the cervical region. In these 
cases section of the cervical cord shows not only normal endogenous 
fibers, but a normal condition of the column of Goll and of such part of 
the column of Burdach as originated below the level of the lesion. Some- 
times the dorsal roots are affected with the cervical. In cervical tabes 
the cord below the affected region is normal, while above is the lesion of 
an ascending degeneration. The lesion may in any case be asymmetrical, 
one root of a segment being affected while the other remains normal. 
In cases of advanced tabes (Fig. 781) there are often almost no nor- 
mal nerve fibers in the posterior columns, the columns of Goll, of Bur- 
dach, and of Lissauer presenting little but dense fibrous tissue. The 
posterior fissure may be completely obliterated. There usually remain, 
however, even in advanced tabes, undegenerated fibers bordering the pos- 
terior commissure and the adjacent parts of the posterior horns. The 
median area of Flechsig also remains intact. As already noted, these 
fibers are endogenous. 
Cervical region, showing an advanced stage of the lesion. THE NERVOUS SYSTEM 
1149 
The microscopical appearance of the degenerated areas varies with the 
stage of the process (Fig. 782). The new connective tissue may be at 
first quite cellular; later the fibrillar elements predominate and the 
tissue becomes dense and firm. Of the nerve roots some have disap- 
peared, others show degeneration of their medullary sheaths and axis- 
cylinders. Some few normal fibers are usually present even in advanced 
sclerosis. The blood-vessels often have thickened walls and may show 
lymphoid and plasma cells in the Virchow-Robin spaces. There may be 
corpora amylacea and fat globules, the latter either free or collected in 
cells. The pia is infiltrated with lymphoid and plasma cells and, in the 
chronic stages of the disease, is rich in fibrous tissue. 
The lesion of tabes is not, however, confined to the posterior columns. 
The fibers of these columns are constantly sending collaterals and termi- 
nals into the gray matter. Most of these pass into the posterior horns, 
A portion of sclerosed area in the posterior columns of the spinal cord, a, New-formed connective 
tissue; b, blood-vessels; c, nerve fibers; d, atrophied nerve fibers. 
Fig. 782.-Posterior Spinal Sclerosis. (Tabes Dorsalis.) 
an especially well-marked group entering Clarke's cell column. The 
posterior horns are therefore usually smaller than normal, with a marked 
reduction in the number of fibers entering them from the posterior col- 
umns, while the columns of Clarke show a diminution in the number of 
delicate fibrils which normally surround the ganglion cells. 
Changes have also been described in the spinal root of the fifth cranial 
nerve and in the fasciculus solitarius which consists of afferent fibers of 
the vagus and glossopharyngeal nerves. These fibers are analogous to 
those of the posterior columns, and the changes in them are similar. 
Degenerations of a secondary character may occur in those systems 
of neurones which are more or less dependent upon the peripheral sen- 
sory neurone system for their impulses. Thus the cells of Clarke's col- 
umn may be affected, with resulting degeneration of their axones which 
make up the direct cerebellar tract. This degeneration extends through 
the restiform body to the termination of the tract in the cerebellum. 1150 
THE NERVOUS SYSTEM 
The cells of the gray matter whose axones form Gowers' tract may be 
degenerated with consequent degeneration of the fibers of this tract. 
In the medulla the cells of the nucleus gracilis and nucleus cuneatus 
may be affected, thus determining an ascending degeneration along the 
tracts followed by their axones. Degeneration of the cells of the anterior 
horns of a similar character has been seen. These changes in the ante- 
rior-horn cells have been accepted by some investigators as explanatory 
of the various trophic disturbances which so frequently occur during 
the course of tabes. Similar changes have been found in the nuclei of 
two of the motor cranial nerves, the oculomotor and the hypoglossal. 
Others ascribe the trophic disturbances to a peripheral neuritis. Marie1 
describes a case interesting in this connection, in which there was marked 
hemiatrophy of the tongue with distinct changes in both main and acces- 
sory nuclei of the hypoglossal nerve on the same side, the opposite nuclei 
being normal. Similar cases of tabes, with laryngeal crises in which there 
were pronounced degenerative changes in the pneumogastric nucleus and 
in the ascending root of the glossopharyngeal, have been reported. 
Changes have been described in the cells of the cerebral cortex. They 
are similar to those found in dementia paralytica, but less marked. 
Although various hypotheses have been advanced in explanation of the tabetic 
lesion, present knowledge favors the view that tabes is due to a degeneration of the 
posterior spinal roots.2 Nageotte3 accounted for the posterior column degeneration 
on the basis of an inflammatory process of the radicular nerve, which includes both 
sensory and motor roots and extends mesially from the spinal ganglion to the spinal 
cord. The motor fibers escape because of their great resistance; the sensory fibers 
are more delicate and degenerate. The inflammatory process involves the epineurium, 
perineurium, and endoneurium. Obersteiner and Redlich4 claimed that the posterior 
roots, in passing through the pia lining the spinal cord, were compressed partly by 
the inflammatory exudate in the pia and partly by the shrinking pia and by pressure 
from the sclerosed vessels. Later, Redlich,5 in his explanation of the tabetic process, 
admitted the possibility of a toxic factor acting upon the intramedullary portion of the 
posterior roots. Spiller6 emphasized the meningeal lesions in tabes and insisted that 
tabes should be regarded as a cerebrospinal disease. Bresowsky,7 in an exhaustive 
study of a large number of cases, arrived at the conclusion that the extensive inflamma- 
tory meningeal process serves as a toxic agent on the posterior roots. Schaller2 
concluded from his pathological material that in tabes there is probably a primary 
syphilitic pial and arachnoid meningitis which is the basis for the subsequent tabes. 
The subacute inflammatory meningitis produces root degeneration by direct extension 
of the meningeal lesions to the nerve roots, causing a meningo-radiculitis, by pressure 
constriction from the sclerosed meninges, by toxic products engendered by this 
inflammation, and by increased spinal fluid, these factors working alone or in conjunc- 
tion with one another. Occasionally one finds anterior root degeneration changes 
giving a picture of amyotrophic tabes.8 Tabes is now regarded as one of the many 
anatomical changes caused by the Treponema pallidum. The disease is ten times as 
frequent in males as in females. 
1 Marie, Lectures on Diseases of the Spinal Cord, New Sydenham Soc., London, 1895. 
2 Schaller, W. F., Pathogenesis of tabes dorsalis, Arch. Neurol, and Psychiat., 1919, i, 749. 
3 Nageotte, J., La 16sion primitive du tabes, Bull, de la soc. anat. de Paris, 1894, viii, 808. 
4 Obersteiner, H., and Redlich, E., Ueber Wesen und Pathogenese der tabischen Hinterstrangsde- 
generation, Arbeiten a. d. Inst. f. Anat., u. Physiol, d. Centralnervensystems, Wien, 1894. (Abstr. 
Neurol. Centralbl., 1894, xiii, 454.) 
6 Redlich, E., Die Pathologic der tabischen Hinterstrangserkrankung, Jena, 1897. 
6 Spiller, W. G., Pathology of tabes dorsalis, Internat. Med. Mag., 1897, vi, 321. 
7 Bresowsky, M., Uber die Veranderungen der Meningen bei Tabes und ihre pathogenetische Bedeu- 
tung, Arbeit, a. d. Neurol. Inst., Wien, 1912-13, xx, 1. 
8 Wilson, S. A. K., Tabetic amyotrophy, Rev. Neurol, and Psychiat., 1911, ix, 401. THE NERVOUS SYSTEM 
1151 
Ataxic Paraplegia-Subacute Combined Sclerosis.-This is 
a disease of uncertain etiology, in which there are degenerative changes 
in both motor and sensory neurone systems (Fig. 783). The tracts usu- 
ally involved are those of Burdach and of Goll, the direct cerebellar 
tracts, and the crossed pyramidal tracts. Less commonly the degenera- 
tion extends to the tracts of Gowers and to the direct pyramidal tracts. 
It seems probable that the lesion in the cord is not always the expression 
of the same pathological process, and that in many cases it is not the 
result of a true systemic degeneration. In perhaps the minority of cases 
the lesion corresponds to the tract systems of the cord and probably 
represents a combined sensory-motor degeneration. Such are those rare 
cases in which the degeneration affects all of the above-mentioned tracts. 
The pia is thickened; the vessels are sclerotic; and the cord, owing to 
the atrophy, is shortened. The lesion affects the myelin principally, 
and the axones become involved only late in the disease, giving a picture 
of Wallerian degeneration. There is an active glial proliferation, and 
active phagocytic glia cells are present which remove the degenerating 
myelin. The adventitial spaces of the vessels are filled with phagocytic 
cells. The degeneration is most marked at the periphery of the cord, 
which, on cross section, presents many vacuoles in this region, giving it 
a cribriform appearance.1 
According to Dejerine, the appearance of a combined system disease may be 
induced by the chronic meningitis, which exists over the posterior columns in tabes, 
extending forward over the direct cerebellar tract, the productive inflammation finally 
spreading to this tract and to the crossed pyramidal. In these cases that part of the 
Showing degeneration and sclerosis in the columns of Goll, the direct and the crossed pyramidal tracts, 
and the direct cerebellar tract. 
Fig. 783.-Combined System Disease. 
latter tract which lies deepest, i.e., close to the gray matter, usually remains unin- 
volved. Marie lays particular stress upon the arterial systems of the cord as the 
prime factor in many cases, calling attention to the fact that the lesion, as it is most 
commonly found, coincides almost exactly with the distribution of the posterior 
spinal arteries. By others the lesion is ascribed to a multiple sclerosis, the restriction 
of the degeneration to definite tracts being only apparent. It is possible that in some 
cases the pathological picture of a combined sclerosis may be due to secondary 
1 Hassin, G. B., Histopathological findings in two cases of subacute (combined) cord degeneration, 
Med. Record, 1917, xci, 885. 1152 
THE NERVOUS SYSTEM 
degeneration following myelitis. It is obvious that authors differ as to its exact 
classification. It is most frequently encountered in chronic wasting diseases, perni- 
cious anemia, and lead and ergot poisoning. 
A subacute type of combined system degeneration has been described by Russell.1 
The degeneration involved the same tracts affected in the more chronic type, and was 
often very extensive at some levels of the cords studied, there being only a thin layer 
of normal fibers covering the gray matter. 
Under the name of diffuse degeneration of the spinal cord, a somewhat similar 
condition has been described,2 the question as to the systemic nature of the process 
being left open. 
Traumatic and Sclerotic Cord Lesions. 
Chronic Interstitial Myelitis.-Under this heading are embraced a 
variety of lesions which probably differ from one another somewhat 
in the nature of the changes involved, but more in the seat of the disease. 
We shall consider without special classification the most important 
forms. 
Chronic Transverse Myelitis.-In certain cases of pressure on the 
spinal cord from a tumor or from displacement of the bones of the verte- 
bral column, etc., the cord, instead of becoming softened or undergoing 
acute inflammatory changes, becomes the seat of a localized formation 
of new connective tissue with consecutive atrophy of more or less of the 
nerve elements in the gray and white matter. The cord becomes in this 
way harder, and sometimes shrunken at the seat of lesion, and gray in 
color. This change may be followed by ascending and descending 
degeneration. 
Showing irregular areas in which there are atrophy of the nerve fibers and their replacement by connect- 
ive tissue. 
Fig. 784.-Multiple Sclerosis in the Spinal Cord. 
Chronic Disseminated Myelitis-Multiple Sclerosis.3-This lesion, 
similar in its nature to multiple sclerosis of the brain, often occurs with 
it. It consists in the formation, in more or less numerous scattered, cir- 
cumscribed areas, of new connective tissue, derived from the neuroglia. 
1 Russel, Batten, and Collier, Brain, London, 1900, xxiii, 39. 
"Putnam and Taylor, Jour. Nerv. and Ment. Dis., 1901, xxviii, 1, 74. 
3 Dawson, J. IF., and Bruce, A., Histology of disseminated sclerosis, Rev. Neurol, and Psychiat., 
1917, xv, 47; xvi, 12; Klingman, T., Histogenesis of multiple sclerosis, Arch. Neurol, and Psychiat., 1919, 
39, 193. THE NERVOUS SYSTEM 
1153 
Primarily it is a disease of the myelin sheaths. At first these break up 
into fat droplets which are stained black by the Marchi stain. Fat 
granular glia cells appear and remove the degenerating droplets of myelin 
The fiber-forming glia cells then make their appearance and replace the 
degenerated myelin with glia fibers which eventually form the glia 
sclerosis or glia scars. The degeneration of the myelin sheath is an acute 
process, while the formation of sclerotic plaques is chronic in nature.1 
The new connective tissue consists of the characteristic branching 
neuroglia cells, surrounded by a more or less dense network of fine 
fibrillae, many, if not most, of which seem to be branches of the neuroglia 
cells. Corpora amylacea and sometimes fat droplets, either free or con- 
tained in cells, may be present in the sclerosed areas. 
The areas of sclerosis may involve both gray and white matter, and 
may be very small or large (Fig. 784). If very small or in early stages 
of formation, they may not be recognizable by the naked eye, but when 
visible they are grayish, translucent, and firmer than the surrounding 
tissue, and may or may not present a depressed surface; they sometimes 
project above the general level. The cause of this as of all other forms 
of so-called idiopathic interstitial myelitis is very obscure. As noted in 
multiple sclerosis in the brain, secondary degenerations are rare, and 
probably for the reason there given. The degeneration does not follow 
along the tracts of the cord, and sections of the cord only a few millimeters 
apart will show different areas of degeneration and sclerosis. 
Syringomyelia.2 
This lesion of the spinal cord consists in the production of gliomatous 
tissue in the vicinity of the central canal, and its subsequent partial 
disintegration with the formation of one or more cavities within the 
substance of the cord (Fig. 794). The cavities, which are filled with 
fluid, vary greatly in size, shape, and extent, and, while usually situated 
in the central region of the cord, may involve the anterior and posterior 
cornua and invade the posterior columns. There may be two communi- 
cating cavities, and these may, but usually do not, open into the central 
canal. The longitudinal extent of these cavities varies greatly. The 
lower cervical and upper dorsal regions are most frequently involved. 
The cavity is usually lined with tissue somewhat denser than that which 
makes up the bulk of the tumor. The gliomatous tissue which forms 
the basis of the lesion in syringomyelia probably originates from the 
layer of neuroglia or ependyma which surrounds or extends away from 
the central canal. The ependymal lining of the central canal is redupli- 
cated and broken in places. There is an increase in the number of 
capillaries, and the pia is definitely hyperplastic. Small hemorrhages 
and foci of myelitis may be found. The disease may last for years; it is 
principally a lesion of the glia, which may be regarded as being deficient 
1 Spiller, W. G., Subacute form of multiple sclerosis, Arch. Neurol, and Psychiat., 1919, i, 219; 
Marinesco, G., fitude sur 1'origine et la nature de la sclerose en plaques, Rev. Neurol., 1919, xxvi, 481. 
2 Hassin G. B., Histopathology and histogenesis of syringomyelia, Arch. Neurol, and Phychiat., 
1920, iii, 130. 1154 
THE NERVOUS SYSTEM 
from early life. Anesthesia to pain and temperature, but not to touch, 
and trophic disturbances are prominent symptoms. 
Syringomyelia is frequently mistaken for hydromyelia, which is a 
congenital malformation, in which the longitudinal cavity in the cord 
is at some period lined with epithelial cells. Syringomyelia has also 
been confused with hematomyelopore. 
There seems, furthermore, to be a class of lesions of the cord, usually 
classed as syringomyelia, in which cavities of various forms coexist with 
a tumor in the vicinity of the central canal. But these cavities appear 
to be formed not by a breaking down of the tumor tissue, but in some 
other way as yet little understood. 
Friedreich's Ataxia. {Hereditary Ataxia.) 
This disease, while often referred to as hereditary ataxia, has more of 
a family than of a distinctly hereditary character.1 Clinically, the dis- 
ease is characterized by ataxia, beginning in the lower limbs and gradu- 
ally ascending so that even speech may be interfered with. Paralysis 
and contractions are the final results. Its pathology is marked by a 
decrease in the size of the spinal cord, the diameter of which is often 
not more than three-quarters that of the normal cord. Degeneration 
of the columns of Goll is usually quite complete. Less marked degenera- 
tion is found in the columns of Burdach, in the direct cerebellar and in 
the crossed pyramidal tracts. The marginal tract of Lissauer may or 
may not be affected. In the posterior horns and in the columns of 
Clarke the condition resembles that in tabes. There may be atrophy of 
the cerebellum. An extensive gliosis exists in the diseased areas. 
Marie notes in addition, atrophy and disappearance of the cells of Clarke's column. 
Blocq and Marinescu2 describe degeneration of the posterior root fibers similar to that 
found in tabes. Friedreich3 and Rutimeyer4 find atrophy of the anterior horn cells. 
The determining cause of the disease and the nature of the morbid process are as yet 
undetermined. It seems probable that the condition of the cord may be more prop- 
erly considered an abnormality of development rather than a degeneration. 
Cerebellar Ataxia. 
Atrophy of the cerebellum was noted as sometimes occurring in Fried- 
reich's ataxia. In that disease, however, the cord lesion was most 
marked. In cerebellar ataxia the lesion of the cord is slight or absent, 
the chief lesion being an atrophy of the cerebellum. This atrophy is 
accompanied by little or no sclerosis, the organ being simply smaller 
than normal.5 Whether cerebellar ataxia is to be considered as an entity 
separate from the preceding is doubtful.6 
1 Lloyd, J. H., and Newcomer, H. S., a case of Friedreich's ataxia, Arch. Neurol, and Psychiat., 1921, 
vi, 157; Pfeiffer, J. A. F., a case of hereditary ataxia (Friedreich) with anatomic findings, ibid., 1922, 
vii, 341. 
2 Blocq, P., and Marinescu, G., Compt. rend, de la Soc. de Biol., 1890, ii, 118. 
3 Friedrich, N., Virchows Arch., 1881, Ixxxvi, 421. 
4 Rutimeyer, L., Virchows Arch., 1887, ex, 215. 
8 Londe, H5r6do-ataxie-c€r6belleuse, Paris, 1895. 
6 See Oppenheim, Lehrb. d. Nervenkrankh., 6th ed., Berlin, 1913, p. 240. THE NERVOUS SYSTEM 
1155 
Acute Inflammation of the Brain. (Encephalitis.) 
Acute Encephalitis.-Inflammatory processes in the nervous system, 
whether of an exudative or of a productive type, are frequently consecu- 
tive to or coincident with the more severe forms of degeneration or other 
lesions, thus making differentiation of the processes often extremely dif- 
ficult. It has been already mentioned that the brain tissue about hem- 
orrhages and areas of embolic and thrombotic softening may undergo 
inflammatory changes leading to the formation of new connective tissue. 
There is a class of cases in which localized areas of the brain undergo 
softening, with more or less extravasation of red and white blood-cells 
and hyperemia, so that the softened material consists, as seen under the 
microscope, of detritus of brain tissue in a condition of fatty degenera- 
tion, often with more or less pus cells and pigment. When such areas are 
red in color from intermingled blood-cells or pigment, the condition is 
called red inflammatory softening. When fatty degeneration prevails, and 
the red blood-cells or their derivatives are not abundant, the softened 
area looks yellow or yellowish-white, and this is often called yellow in- 
flammatory softening. The origin of these processes is very obscure and 
their inflammatory nature not well defined. 
Abscess of the Brain.-Small multiple abscesses of the brain may 
occur in pyemia. Large abscesses of the brain are usually single; they 
may attain a large size. They are most frequent in the cerebral and 
cerebellar hemisphere, rare in the basal ganglia, the pons, and the medulla 
oblongata.1 
There may be an irregular cavity containing thin pus and softened 
brain tissue.2 The walls of the cavity are ragged and infiltrated with 
pus, and outside of the walls is a zone of edematous and softened brain 
tissue. If the abscess be near the pia mater, meningitis may follow; if 
it be near the lateral ventricles, it may rupture into them; if it be near 
the sinuses of the dura mater, it may induce thrombosis. An abscess 
may in time become inclosed in a capsule of connective tissue. In acute 
suppuration the abscess is not encapsulated, and the suppurative process 
is very diffuse. The ganglion cells undergo all gradations of degenera- 
tion, from mere cloudy swelling and chromatolysis to complete disintegra- 
tion. The glial elements undergo proliferation. The blood-vessels are 
congested, and the Virchow-Robin spaces are filled with lymphocytes and 
plasma cells. Thrombosed vessels are also present. 
In the chronic suppurative processes,3 the abscess is walled off from 
the rest of the brain tissue by a firm dense fibrous capsule. The abscess is 
composed of a central necrotic area, an encapsulating dense membrane, 
and an outer zone of engorged vessels. The encapsulating membrane has 
three distinct layers, an inner collagenous layer, a middle delicate layer 
containing numerous fibroblasts, plasma cells, connective tissue fibers, 
1 For a study of acute encephalitis and brain abscess, see Southard, E. E., Osler and McCrae, 
Modern Medicine, Philadelphia, 1915, v, 359. 
2 Essick, C. R., Pathology of experimental traumatic abscess of brain, Arch. Neurol, and Psychiat., 
1919, i, 673. 
3 Hassin, G. B., Histopathology of brain abscess, Arch. Neurol, and Psychiat., 1920, iii, 616. 1156 
THE NERVOUS SYSTEM 
and blood-vessels, and an outer layer containing many collagen fibers, 
plasma cells, fibroblasts and distended blood-vessels. 
Abscess of the brain is most frequently secondary to chronic suppu- 
rative otitis (42.5 per cent., Gowers), much less frequently to acute 
otitis. With the otitis there may also be caries of the temporal bone, sup- 
puration of the mastoid cells, and inflammation of the dura mater. The 
abscess is usually situated deep in the brain, commonly in the temporo- 
sphenoidal, the frontal, the occipital or the parietal lobes, or in the 
cerebellum; rarely it is continuous with the inflamed dura mater and 
bone. Abscess may follow chronic lesions in the orbit, caries of vari- 
ous parts of the cranial bones, and sinus infections. 
Abscess of the brain frequently follows traumatism, blows, or falls 
on the head. Such injuries may not damage the skull, or may produce 
fractures or necrosis. There is often a considerable interval between 
the time when the injury is inflicted and the development of the symptoms. 
When the cranial bones are uninjured the abscess is usually deep in 
the brain; when there is necrosis of the bones the abscess may be super- 
ficial; when the bones are fractured the abscess may be either superficial 
or deep. The abscess develops rarely in the opposite side of the brain. 
In acute exudative meningitis from various excitants there may be an 
infiltration of the brain with leucocytes; this may be especially marked 
in the perivascular tissue and around the ganglion cells. 
Acute Disseminated Encephalitis,1 hematogenous in character, may 
develope during the progress of an infectious disease. It is most com- 
mon in infective endocarditis, in pyemia, and in cerebrospinal meningitis. 
It may be associated with acute anterior poliomyelitis, pneumonia, and 
epidemic influenza. The lesion consists of disseminated foci of inflam- 
mation, or minute multiple abscesses. Some of these are microscopic in 
size, others may be seen with the naked eye. The smallest show simply 
small lymphocytic and plasma-cell infiltration of the walls of one or 
more small vessels and of the surrounding tissue. The larger spots, 
which undoubtedly take origin in the same way, are seen to be softer 
than the rest of the tissue, and resemble red or yellow softening, accord- 
ing to the amount of red blood-cell extravasation. Congestion is usu- 
ally marked. There may be distinct hemorrhages. Degenerative 
changes with disintegration of the exudate usually set in and determine 
destructive changes in the neighboring neurone and neuroglia ele- 
ments. The ganglion cells show cloudy swelling, chromatolysis, and 
eccentrically situated nuclei. Neuronophagy is also present. At the 
periphery of one of these abscesses the neuroglia, instead of being in a 
degenerating condition, usually shows proliferation. The more minute 
inflammatory foci may undergo complete resolution with absorption 
of the exudate. In the larger abscesses there may be absorption of the 
exudate and of the products of degeneration, and a replacement neuroglia 
hyperplasia, ultimately resulting in a sclerotic patch. 
1 Under the head of "Acute Parenchymatous Encephalitis" has been described a lesion of the 
ganglion cells without vascular or interstitial changes. These lesions are the result of toxemias of 
either endogenous or exogenous nature. They are more properly classed as parenchymatous degenera- 
tion. THE NERVOUS SYSTEM 
1157 
Suppurative encephalitis may occur as a result of traumatism or from 
extension of suppurative meningitis. 
A form of encephalitis which has been designated acute non-suppu- 
rative hemorrhagic encephalitis, has been described.1 The lesion con- 
sists in the occurrence of multiple hemorrhagic, inflammatory foci, which 
are non-suppurative, and which are accompanied by leucocytic infiltra- 
tion. These foci may occur in any part of the brain, but are most numer- 
ous in the white matter of the brain and basal ganglia. Some of these 
hemorrhages may be quite large. 
ACUTE EPIDEMIC ENCEPHALITIS (Encephalitis Lethargica.)2 
This is an acute epidemic disease which has only recently been recog- 
nized. The symptoms are extremely variable as is the course of the 
disease. Many mild cases unquestionably occur which pass undiagnosed. 
In other instances the patient dies in a few days with symptoms of an 
acute encephalitis. 
Clinically some eight or ten varieties have been distinguished. The 
most general symptoms are marked asthenia with prolonged somnolence. 
Palsy of the cranial nerves is a frequent accompaniment. Some of the 
cases resemble poliomyelitis; others are maniacal. In the late stages the 
syndrome resembling paralysis agitans may appear. The lesions are as 
variable as the symptoms but in the encephalitic type certain changes are 
fairly constant.3 On gross examination the brain appears congested 
and the vessels markedly engorged. The dura mater is normal. The 
pia arachnoid is edematous, and may present minute hemorrhages. The 
brain stem shows the greatest amount of congestion. Microscopically, the 
brain stem, basal ganglia, pons, and medulla are the regions of the greatest 
inflammatory reaction, although any part of the brain may be intensely 
involved. The cerebellum is least affected. There is marked infiltration 
of the Virchow-Robin spaces with lymphocytes and, to a lesser degree, 
with plasma cells and larger cells of mesodermic origin. Thrombosis of 
the vessels in the acute stage is very rare. Throughout the parenchyma, 
and apparently without any connection with perivascular exudation, 
there are masses of inflammatory cells, mostly lymphocytes and, to a 
considerably lesser extent, plasma and endothelial cells. Hemorrhagic 
areas are abundant especially near blood-vessels. The endothelial cells 
of the blood-vessels are swollen and appear to proliferate, as is manifested 
by the numerous mitotic figures in these cells. The nervous tissue proper, 
both the ganglion cells and the glia cells, are relatively little involved 
considering the intensity of the general inflammatory process. In the 
regions of greatest inflammatory reaction, the ganglion cells may show 
1 Putnam, Jour. Nerv. and Ment. Dis., 1897, xxiv, 1 (bibl.). 
2 A useful collection of clinical reports will be found in Tilney, F., and Howe, H. S., Epidemic En- 
cephalitis, New York, 1920. 
3 Bassoe, P., and Hassin, G. B., Histopathology of epidemic lethargic encephalitis, Arch. Neurol, 
and Psychiat., 1919, ii, 24; Buzzard, E. F., and Greenfield, J. G., Lethargic encephalitis; its sequel® and 
morbid anatomy, Brain, 1920, xlii, 305; Schroeder, P., Encephalitis und Myelitis, Monatschr. f. Psychiat. 
u. Neurol., 1918, xliii, 146; Macnalty, A. S., The morbid histology, bacteriology and experimental 
pathology of encephalitis lethargica, Brit. Jour. Exper. Path., 1921, ii, 141 (bibl.). 1158 
THE NERVOUS SYSTEM 
cloudy swelling, chromatolysis, eccentrically situated nuclei, and even 
neuronophagy. In these areas, there is considerable neuroglia prolifera- 
tion especially of the small round glia cell type. There is considerable 
edema present, and under the microscope this is evident as poorly staining 
homogeneous areas within the parenchyma. The spinal cord, especially 
in the cervical region, presents similar findings, but to a markedly less 
degree. Strauss and Loewe have recovered a filterable virus from their 
pathological material and by inoculation of this virus into rabbits have 
been able to reproduce both the clinical and the pathological pictures of 
the disease.1 
Acute Inflammation of the Spinal Cord. (Acute Myelitis.) 
Inflammation in the spinal cord is quite analogous to inflammation 
in the brain. 
Acute Disseminated Myelitis2 runs a rapid course and proves fatal in a 
short time.3 The inflammation may involve nearly the whole length of 
the cord, but is usually more intense in some places than in others. The 
cord is swollen and congested, it is infiltrated with pus cells, the connect- 
ive tissue is swollen, and there is degeneration of the nerve elements 
proper.4 
More frequently an acute myelitis is localized. It involves but 
a small portion of the length of the cord, while laterally it may com- 
pletely cross it, and is hence spoken of as a transverse myelitis. When 
the cord is removed and laid upon the table, if the lesion is marked, a 
flattening of the cord at its seat may 
be observed; or when the finger is 
passed gently along the organ, the af- 
fected segment will be found softer than 
the rest of the cord, sometimes almost 
diffluent. When a section is made 
through the affected portion, the nerve 
tissue may appear white or red or yel- 
lowish or grayish. 
Microscopical examination shows 
different appearances, depending upon 
the stage of the degenerative or in- 
flammatory process.5 There may be 
much blood, or, if the lesion has existed for some time, blood pigment; 
also fragments of more or less degenerated nerve fibers and ganglion 
Fig. 785.-Degenerated Tissue from 
Acute Myelitis. 
1 Loewe, L., and Strauss, I., Studies in epidemic (lethargic) encephalitis, Jour. Inf. Dis., 1920, xxvii, 
250. 
2 Acute parenchymatous myelitis, like its analogue in the brain, is a lesion of the ganglion cells, 
and is more properly classed as a degeneration. Embolic and thrombotic softenings are more rare 
in the cord than in the brain, and are necessarily much more restricted in extent. When of an inflam- 
matory character they resemble the similar brain lesion and are red or yellow according to the amount 
of extravasation. For bibl. see Schmaus, H., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1903, ix1, 313. 
3 Morris, L. M., and Jacobson, V. C., Acute ascending myelitis of infectious type, Arch. Neurol, and 
Psychiat., 1921, vi, 509. 
4 Hassin, G. B., Histopathologic changes in five cases of myelitis, Med. Record, 1916, xc, 619. 
6 Bassoe, P., and Hassin, G. B., Myelitis and myelomalacia, Arch. Neurol, and Psychiat., 1921, vi, 
32. THE NERVOUS SYSTEM 
1159 
cells (Fig. 785), myelin droplets, free fat granules, larger and smaller 
cells filled with fat granules (Gluge's corpuscles), pus cells, granular 
matter, neuroglia cells, and sometimes corpora amylacea. The various 
proportions of these elements give rise to the different gross appearances 
which the diseased part presents. In earlier stages of the lesion the 
blood-vessels may be dilated, the nerve fibers and cells swollen; or the 
walls of the blood-vessels may be thickened or fatty, or surrounded by a 
sheath of leucocytes and cells derived from the connective-tissue cells of 
the adventitia.1 There is. a marked glia reaction The large fat granular 
glia cells absorb the degenerating myelin and transport it to the neighbor- 
hood of mesodermic tissue. They almost replace the degenerating areas. 
The advential spaces are distended with cellular infiltration. The pia 
spaces are also distended with leucocytes, erythrocytes, and plasma cells. 
The subarachnoid space contains considerable debris. There is a large 
amount of proliferation of the endothelial cells. 
The lesion is apt to commence in the gray matter or at its edge, and 
then extend first laterally and afterward upward and downward. 
In a certain number of cases the degenerated material may be 
absorbed and a cicatrix or cyst formed. After the least extensive forms 
of the lesion there may be a restoration of the functions of the cord. 
Secondary degeneration, both ascending and descending, may occur 
in this form of myelitis, varying in extent according to the size of the 
primary lesion. The terms central myelitis, peripheral myelitis, and uni- 
lateral myelitis, are sometimes used to designate localizations of the lesion. 
Acute Poliomyelitis.-This name is applied to a group of cases of 
acute infectious disease characterized by a variety of clinical symptoms, 
Fig. 786.-Acute Anterior Poliomyelitis. 
Death seven weeks after onset. Showing gliomatous tissue in both horns, with cavity formation in 
one of them. 
the most evident of which are due to changes in the anterior horn cells 
of the spinal cord.2 For this reason, the disease is sometimes called 
acute anterior poliomyelitis. Because it often appears in children, it is 
1 Lotmar, F., Beitrage zur Histologie der acuten Myelitis und Encephalitis, sowie verwandter Pro- 
zesse, Nissl and Alzheimer Histologische und Histopathologische Arbeiten, Jena, 1913, vi, 245. 
2 Peabody, Draper, and Dochez, A clinical study of acute poliomyelitis, Monograph No. 4, Rocke- 
feller Inst., New York, 1912. 1160 
THE NERVOUS SYSTEM 
known also as infantile paralysis; and is also called Heine-Medin'sdisease, 
from Heine, who, in 1840, first differentiated the condition from similar 
neurological affections, and Medin, who published in an important mono- 
graph the results of his observations on the great Swedish epidemic of 
1887. 
While the spinal type of the disease is the most frequent, encephalitic, 
cerebellar, bulbar, polyneuritic, and meningitic forms are now recognized; 
and it is probable that there are many abortive cases in which the nervous 
system escapes damage. Wickman1 was the first to recognize from clin- 
ical observation that the disease was of an infectious nature, and Land- 
steiner and Popper2 first successfully transmitted the disease to monkeys. 
Shortly afterward, Flexner and Lewis confirmed their work and greatly 
extended our knowledge of the nature of the disease. Noguchi finally 
isolated the organism (see page 332). 
In the acute stage of the disease, evidences of nasopharyngeal in- 
flammation are often found, the spleen is occasionally enlarged, and 
Fig. 787.-Perivascular Infiltration in Cobd in Case of Acute Anterior Poliomyelitis. 
Preparation of Dr. Simon Flexner. 
moderate hyperplasia of the lymphoid structures occurs. The cerebro- 
spinal fluid is clear and increased in amount, later becoming opalescent, 
and contains a large number of lymphocytes. The pia is congested, the 
spinal cord is hyperemic, the congestion being especially noticeable in 
the gray substance. Dilated vessels and minute capillary hemorrhages 
are not infrequent. There is often extensive edema of all the tissues of 
the spinal cord. In addition to the cord changes, there may be edema 
and hyperemia of the brain substance with minute hemorrhages, but 
usually the gross alterations in the brain are not at all evident to the 
naked eye. In late cases, the spinal cord may show macroscopic altera- 
tions, even so extensive as to lead to an asymmetrical distortion from 
atrophy of the anterior horn. Areas of softening may occur in the an- 
terior horn (Fig. 786). The nerve bundles arising from the affected area 
are diminished in size. 
1 Wickman, I., Acute Poliomyelitis, Nerv. and Ment. Dis., Monograph Series, No. 16, NewYork, 
1913 (trans, of article in Lewandowsky, Handb. d. Neurologie, Berlin, 1911, ii, 807 (full bibl.). 
2 Landsteiner and Popper, Ztsehr. f. Immunitatsforsch., Orig., 1909, ii, 377. THE NERVOUS SYSTEM 
1161 
Microscopically, there is usually a round-cell infiltration in the pia, 
the cells being most frequently lymphocytes; polyneuclears, however, are 
not rare; plasma cells are very scanty. This infiltration is often espe- 
Fig. 788.-Ganglion Cell Lesions in Acute Anterior Poliomyelitis. 
Preparation of Dr. Simon Flexner. 
cially marked about the vessels and in the region of the active lesions in 
the anterior horn. The dura usually escapes involvement. In the 
spinal cord the veins and capillaries are often greatly distended with 
blood; thrombi are rare. Minute hemorrhages are not at all infrequent 
A, Normal ganglion cells surrounded by nerve fibers; B, degenerated ganglion cells; C, granular masses 
at place of ganglion cells; D, small cavity containing fluid. 
Fig. 789.-Poliomyelitis Anteriob. 
and may be widely distributed in the anterior horn. The smaller vessels 
are surrounded by a collar of lymphocytes usually lying in the perivascu- 
lar lymph-spaces and spreading out, when the lesion is extensive, into 
the surrounding nerve tissue (Fig. 787). The arteries show less of this 
perivascular infiltration. Collections of round cells, also, may be demon- 
strated in the brain or cord, are sometimes found in groups surrounding 
and invading as phagocytes the damaged ganglion cells, and, after 1162 
THE NERVOUS SYSTEM 
destruction of the latter, may remain in the tissues as areas of infiltration 
(Fig. 788). These groups of neuronophages are found also in experi- 
mental poliomyelitis in monkeys. The ganglion cells, especially those 
of the anterior horn of the spinal cord, show a variety of changes depend- 
ing upon the stage of the disease. The cell body is found early to be 
swollen, with disintegration of the Nissl granules. The nucleus may 
remain normal in position and appearance, but when extensive destruc- 
tion occurs it is altered into a mass of chromatin and occasionally under- 
goes karyolytic destruction. The intracellular neurofibrils also atrophy. 
While these cell changes are most marked in the spinal cord, and are 
often limited to a certain region of that organ, moderate lesions are 
usually present, in addition, in all cases in the brain and medulla. So, 
too, the perivascular exudate is often present in the brain in cases not 
giving cerebral symptoms. On the other hand, the lesion may be that 
of an acute encephalitis, with changes more extensive and more marked 
than those usually seen in the spinal cord. As the process becomes 
chronic, phagocytosis of the ganglion cells is completed, the perivascular 
infiltration diminishes, and secondary hyperplasia of the neuroglia and 
of connective tissue begins (Fig. 789). The extent of the changes natur- 
ally depends upon the amount of the destruction in the acute stage. 
Many ganglion cells may escape permanent damage, but there may be 
no normal ganglion cells present in the anterior horns of considerable 
areas of the spinal cord if the lesion has been extensive. Atrophy of the 
anterior roots, the intraspinal tracts, and the muscles supplied from the 
diseased area is regularly found. Occasionally degenerations are seen 
in the anterolateral and cerebellar tracts and the posterior columns of 
the cord. 
Acute Ascending Paralysis-Landry's Paralysis.-This is a rare 
disease characterized clinically by a rapidly ascending paralysis, beginning 
in the lower extremities and progressing 
upward to involve the body, arms, and 
head.1 Recently a number of cases have 
been reported in which the lesion was an 
acute myelitis with or without an accom- 
panying polyneuritis, and congestion, hem- 
orrhages, and circumvascular infiltration 
(Fig. 790), the ganglion cells being in 
various stages of degeneration.2 Lesions 
occasionally seen in other organs consist of acute splenic enlarge- 
ment, swelling of the mesenteric nodes, and infarcts in the intestine and 
lung. A great variety of parasites have been isolated from the lesions, 
including streptococcus, anthrax and tubercle bacilli, and an organism of 
the Friedlander type. In many instances the disease is evidently an acute 
infectious myelitis with various inciting agents. That the organism may 
Fig. 790.-Landry's Paralysis. 
Showing acute inflammatory process 
about blood-vessels, with leucocytes in the 
walls. 
1 For an excellent description of the condition in soldiers during the World War, see Casamajor, L., 
Acute ascending paralysis among troops, Arch. Neurol, and Psychiat., 1919, ii, 605. 
2 For further details, see Bailey and Ewing, New York Med. Jour., 1896, Ixiv, 1; Cramer, A., Cen- 
tralbl. f. allg. Path., 1892, iii, 6; and Schmaus, H., Lubarsch-Ostertag, Ergebn. d. allg. Path., 1903, ixl, 
396. 1163 
THE NERVOUS SYSTEM 
occasionally be the same as that found in poliomyelitis is now generally 
believed. 
Inflammation and Degeneration of the Nerves. (Neuritis.) 
In the nerves, as in the brain and cord, degenerative changes commonly accompany 
inflammation, and a distinction is often difficult. The difficulty in sharp differentia- 
tion lies in the fact that degenerative changes in nerves, when intense or long con- 
tinued, often lead to inflammations, and that inflammatory conditions in nerves often 
determine secondary degenerative changes in the nerve fibers. 
Acute Exudative Neuritis.-Acute inflammation of the nerves may 
occur as the result of injury, or it may be secondary to an inflammatory 
process in their vicinity, although, owing to the dense lamellar sheaths 
and the special blood supply, the nerve trunks may escape participation 
even in very severe inflammatory processes in surrounding tissues. The 
inflamed nerve may be red and swollen and infiltrated with serum and 
pus cells. The process may undergo resolution or terminate in destruc- 
tion of the nerve, or it may become chronic and result in the formation 
of new connective tissue. Degeneration and regeneration of the nerve 
fibers, similar to those described as following division of nerve trunks, 
may occur in acute neuritis. 
Multiple Neuritis (Degeneration).-While for convenience of refer- 
ence described under its usual title, this lesion is probably always a degen- 
eration, and would be properly classified under the head of neurone 
degenerations of toxic origin. It is caused by the action of certain min- 
eral poisons, for example, alcohol and lead. It occurs as a complication 
of, or succedaneum to, certain infectious diseases, for example, diph- 
theria, septicemia, measles, smallpox, etc. It is sometimes apparently 
idiopathic. Changes of a degenerative nature are found in the peripheral 
nerves, and are more marked near the peripheral than near the cord. 
Thus the most common nerves affected are the anterior tibial and the 
radial. The most marked changes are in the nerves themselves, there 
being little or no change in the connective tissue. More rarely, espe- 
cially in very acute cases, there are reddening and swelling with some 
inflammatory reaction in the interstitial tissue. The fiber lesion shows 
best in specimens treated with osmic acid and teased in glycerin (Fig. 
791). Here the myelin sheath is seen to be broken up, and instead of a 
continuous envelope of black-stained myelin, the myelin is represented 
by larger or smaller black droplets scattered along a broken or degener- 
ated axis-cylinder. There may be some increase in the connective tissue. 
The sheath of Schwann is usually intact. It is of interest to note that in 
a number of cases (as yet too few to warrant general conclusions) changes 
have been found in the cells of the anterior horn analogous to those 
found after injury to motor nerves. The muscles supplied by the 
affected nerves show various stages of atrophy. The cord and meninges 
usually remain normal. In some cases a spinal meningitis and more or 
less myelitis have been described.1 
1 For bibl., see Kattwinkel, W., and Kerschensteiner, H., Lubarsch-Ostertag, Ergebn. d. allg. Path., 
1903, ix», 1. 1164 
THE NERVOUS SYSTEM 
Chronic Interstitial Neuritis.-This is essentially a chronic interstitial 
inflammation resulting in an increase of the connective tissue in the nerve 
sheaths and intrafascicular bands. As a result of this the nerve fibers 
undergo atrophy from pressure, the medullary sheaths and finally 
Fig. 791.-Degeneration of Nerve Fibers in Multiple Neuritis. 
From a case of alcohol poisoning. Specimen stained with osmic acid. The broken-down medullary 
sheath and fat droplets are stained deep black. 
file axis-cylinders being in many of the fibers partially or completely 
destroyed. The condition is most frequently seen in leprosy. 
Tic Douloureux.-Changes in the peripheral branches of the fifth 
cranial nerve removed from cases of obstinate trifacial neuralgia have 
been reported in a considerable number of cases. These changes consist 
in degeneration of the axis-cylinders and of their medullary sheaths. In 
a smaller number of instances changes have been reported in Gasserian 
ganglia removed from such cases. The changes in the ganglia consist in 
atrophy and disappearance of the nerve cells with increase in the con- 
nective-tissue elements. A peculiar shrunken condition of the cell in 
which the cell retracts to one side of its cell space has been seen; but none 
of these lesions can be considered as necessarily characteristic. 
Chronic Inflammation and Degeneration of the Brain and Cord. 
While this term should be applied only to a primary increase in the 
neuroglia elements at the expense of the parenchymatous, thus making 
the degeneration of the nerve tissue proper entirely secondary, it is 
often difficult to eliminate the possibility of a primary degeneration of 
the nerve cells. Histologically the lesion consists in a proliferation of the 
neuroglia elements. The neuroglia cells increase in number, some of the 
new-formed cells having many processes, others few. In the early cellu- 
lar stage of its formation the proliferative area is soft and gelatinous, 
and tends to increase the size of the part. With further progress of the 
sclerosis, there is a disproportionate development of fibers attached to 
the cells, and finally of fibers independent of cells. With the increase 
of fibers the affected area becomes firmer, making a sort of dense felt- 
work of interlacing fibrils. In this meshwork are found nerve fibers in 
various stages of degeneration. 
Chronic Interstitial Encephalitis-Sclerosis.-This lesion of the brain 
tissue may occur diffusely occupying an entire lobe or more or less of the 
whole brain, or in circumscribed small areas. It consists essentially in 
an increase of the connective-tissue elements, the neuroglia, and an 
atrophy of the nerve elements, particularly the ganglion cells and the 
medullary sheaths of the nerves. With these changes are usually asso- 
ciated the formation of Gluge's corpuscles, corpora amylacea, granular 
and fatty degeneration of the nerve elements, and thickening and pro- THE NERVOUS SYSTEM 
1165 
liferation of cells of the walls of the blood-vessels. The areas of sclerosis 
may be very dense and hard, or gelatinous in consistence. 
The diffuse form of sclerosis is most frequently seen in general pare- 
sis of the insane, and not infrequently in the brains of drunkards. 
A peculiar feature of disseminated sclerosis is that the patches, 
whether in the brain or cord, do not induce the expected secondary 
degeneration. It is, in fact, uncommon to find secondary degeneration 
resulting from even a large patch of sclerosis. This is believed to be due 
to the fact that in nearly all of the patches the axis-cylinders persist even 
after complete destruction of the medullary sheaths. 
The circumscribed form of sclerosis, multiple sclerosis (sclerose en 
plaque), is much more common than the diffuse form, and may occur 
in the brain alone, or more commonly be associated with a similar lesion 
in the spinal cord. The areas of sclerosis vary in size from that of a 
pea to that of an almond. They may be few or numerous, they may 
be white, grayish, or grayish red in color, and are usually but not always 
sharply outlined by the unaltered ' brain tissue. Although in many 
cases the increase in the connective-tissue elements seems to be the 
primary lesion, and the degeneration of the nerve elements secondary 
to this, it is quite possible that in some cases the increase in connective 
tissue may be secondary to a degeneration of the nerve elements from 
loss of nutrition or from other causes. 
There is reason for the belief that multiple sclerosis may sometimes 
be the result of disseminated local necrotic lesions of acute infectious 
diseases-scarlatina, for example-occurring at an early period of life. 
General Diseases of Brain. 
GENERAL PARESIS. (Dementia Paralytica.) 
Paresis1 is peculiarly a disease of modern times, no description of a 
case having been published during the eighteenth century. That it is 
syphilitic in its origin has long been believed; and of late years the very 
constant demonstration of the Wassermann complement fixation reaction 
either in the blood or in the spinal fluid has given additional confirmation 
to this opinion, while the recent demonstration of the Treponema palli- 
dum in the cortex of persons dying of paresis has given a final decision.2 
Nevertheless, there are other factors than syphilis which play a part 
in the disease. One of these is race. The great prevalence of paresis in 
civilized races is in contrast with the practical absence of the disease 
among the negroes of Africa, in whom syphilis is a common occurrence. 
1 The best monograph on paresis is that of Kraepelin, E., translated byMoore as Nervous and Mental 
Disease Monograph Series No. 14, New York, 1913. 
For histological details see Nissl and Alzheimer, Histologische u. histopathologische Arbeiten, 
Jena, 1904, i, 1; also Spielmeyer, W., Lewandowsky, Handb. d. Neurol., 1912, iii, 488; and Macintosh 
and Fildes, Brain, 1914, xxxvii, 178. See also, Mott, F. W., Nature of the condition termed parasyphilis, 
Arch. Neurol, and Psychiat., 1914, vi, 1; Sands, I. J., General paralysis, Neurol. Bull., 1921, iii, 72. 
2 Noguchi, H., and Moore, J. W., Demonstration of T. pallidum in brain in general paralysis, Jour. 
Exper. Med., 1913, xvii, 232; Noguchi, H., New technique for staining T. pallidum, Jour. Am. Med. 
Assn., 1921, Ixxvii, 2052; Stevenson, G. S., Staining spirochetes in nervous tissue, Arch. Neurol, and 
Psychiat., 1922, vii, 349. 1166 
THE NERVOUS SYSTEM 
Nevertheless, when the negro adopts civilized life, he becomes even more 
susceptible to paresis than his white co-inhabitant of large cities. It 
seems very probable that alcohol to excess, mental strain, and heredity 
are important factors in the etiology of paresis, even though syphilis may 
have the decisive role, for of those having the latter disease only a very 
small proportion ever develop paretic symptoms. The symptoms begin, 
as a rule, long after the infection; rarely do they appear within five years 
of the appearance of the chancre. In juvenile forms, the infection is 
congenital. The sex ratio was originally preponderantly masculine, even 
as high as eight to one; now the proportion is three times as many males 
as females. 
There is considerable evidence of recent date pointing to the fact 
that different strains of the specific organism may exist, and that certain 
groups of Treponema pallidum may have a special affinity for the nerv- 
ous system, while other varieties attack the bone or skin by preference; 
but a final decision has not yet been reached on this point. The Wasser- 
mann reaction is present in the blood or in the spinal fluid; and the 
latter also contains an increased number of lymphocytes and excessive 
quantities of globulin, and gives a characteristic reaction when mixed in 
suitable quantities with a colloidal suspension of gold, which in many 
instances differentiates the disease from purely syphilitic conditions with 
similar symptomatology.1 
The tissue lesions are many and complex. There are two simulta- 
neous and independent processes in the brain; one, the destruction of the 
nervous tissue, and the other the disease of the vessel walls with its 
consequences. 
Macroscopically, no characteristic lesion exists. The dura is often 
adherent to the calvarium; pachymeningitis interna hemorrhagica or 
hematoma of the dura is not infrequent; and there may be also more or 
less widespread fresh superficial hemorrhages. The pia is almost always 
cloudy and thickened, the thickening being especially evident along the 
vessels. These alterations of the pia are usually most apparent over the 
anterior and middle portions of the frontal lobes, and in late cases also 
the removal of the pia is often impossible without laceration of the brain 
substance. The posterior portions of the brain rarely show these changes. 
The Pacchionian bodies are frequently much enlarged; and the brain 
in late cases is almost always atrophic; the convolutions are shrunken, 
especially in the anterior two thirds of the brain; and not infrequently 
there are also found irregular depressions, over which the membrane may 
be stretched, with a collection of serum beneath. Occasionally, the 
whole cortex shows a diffuse shrinkage. The ventricles are usually 
dilated, and the ependyma shows more numerous and prominent gran- 
ules than normal. The cortical atrophy is expressed in a great reduction 
in the weight of the brain, which amounts on the average to 100 to 150 
grams. It must, however, be remembered that similar changes, though 
often less extensive, may be seen in senile arteriosclerotic processes, and 
in cases of chronic alcoholism accompanied by a chronic leptomeningitis. 
1 For a discussion of the nature and interpretation of the colloidal gold reaction, see references on 
pages 312 and 1176. THE NERVOUS SYSTEM 
1167 
Extensive and characteristic syphilitic lesions are not extremely frequent 
in the other organs of the body; syphilitic aortitis is, however, frequent 
in paretics, though aneurysm is rare. 
Microscopically, the changes in the brain in paresis are fairly charac- 
teristic, and consist in general of a diffuse inflammatory process with 
degenerative phenomena in the functional portions of the nervous system, 
and more or less extensive changes in the glial material. The inflam- 
matory processes consist chiefly of a diffuse infiltration of the meninges 
and the adventitial lymph-spaces with plasma cells and lymphocytes. 
This infiltration is most extensive in the cerebrum, but is almost always 
present to a limited extent in the cerebellum, central portions of the brain, 
and the spinal cord. In the cerebrum the cortex is the portion which is 
especially attacked by the inflammatory processes. The collection of 
plasma cells in the lymph-sheaths of the more delicate cortical vessels is 
quite characteristic of paresis and is constantly present. Nevertheless 
similar perivascular lesions, either lymphocytic or plasma cell, are also 
seen in syphilitic meningoencephalitis, in carcinomatous and tuberculous 
lesions, in sleeping sickness, cerebral types of poliomyelitis, and rabies. 
The paretic lesion is, however, more diffuse and constant. The plasma 
cells are far more abundant than the lymphocytes. Occasionally, mast 
cells with coarse granules and large phagocytic cells filled with fatty 
material and pigment are seen. The cortex may be involved in cases in 
which the pia is relatively free from inflammatory lesion. The perivas- 
cular adventitial connective tissue may also proliferate and extend out 
into the glia, penetrating the neighboring gray substance in the form of 
long, rod or sausage shaped cells with long, delicate projections. Some of 
these types of cells are, however, unquestionably glial in nature. Endo- 
thelial hyperplasia may lead to extensive new formation of capillaries. 
In sections the vessels seem very numerous as compared with a normal 
brain; but this is partly due to the shrinkage of the brain tissue causing 
an apparent increase. 
The most striking lesion of the functional nervous tissue is the disap- 
pearance of the medullated cortical fibers with atrophy of the supraradial 
reticulum and the tangential fibers in addition, though these lesions are 
not characteristic of paresis, nor indeed are they constant even in fairly 
well marked cases. Another peculiar appearance is produced by the 
local disappearance of the medullated fibers in the cortex, leaving small 
oval or band-like areas in which no medullary material can be made out, 
even with suitable stain. The axis-cylinders may be retained under these 
circumstances. A similar lesion is seen, however, in multiple sclerosis. 
This local destruction of the cortical medullary tissue of the brain may 
attack only a few convolutions, but as the lesion progresses the axis- 
cylinders disappear, as do also the ganglion cells. 
Glial hyperplasia takes place on the free border of the cortex, while 
the tissue below may not show an excess of fibers. As the process be- 
comes more extensive, a thick network of fibers may grow down into the 
substance of the brain, and also grow out in the form of brush-like proc- 
esses towards the pia, thus forming adhesions between this membrane 1168 
THE NERVOUS SYSTEM 
and the cortex. The same hyperplasia of the glia may be found about 
the blood-vessels especially in the deeper layers. The glial overgrowth 
is not directly connected with or proportional to the destruction of the 
nerve cells of the cortex, but the nerve tissue itself seems to be directly 
damaged by the poison of the syphilitic organism. After this has oc- 
curred, the pia may undergo extensive hyperplasia, but occasionally 
such an overgrowth may not occur. These extensively hyperplastic 
changes in the glia cells are especially characteristic of the slowly pro- 
gressive stages of the disease. In paresis with a more rapid course, the 
glia cells more often assume what may be described as the ameboid form 
and apparently act as phagocytic cells in the removal of the fragments 
of the degenerating cortical nerve cells.1 With the continuation of the 
process to the cortical cells, all sorts of degenerative processes occur in 
the bodies of the ganglion cells themselves, which are well demonstrated 
by the Nissl and Bielschowsky stains. Disappearance of the chromatic 
granules, destruction of the nucleus, vacuolar degeneration, atrophy, and 
pigmentation are the most evident changes. This destruction may go 
on to the complete removal of all trace of ganglion cells; it often extends 
only to a particular group; the second cellular layer not infrequently 
remains fairly unaltered in the earlier stages, and even when the disease 
is extensive the process is sclerotic rather than one leading to the com- 
plete destruction of the cells themselves. On the other hand, the process 
may be limited to particular areas, and all the ganglion cells of a small 
portion of the brain may be completely destroyed, so that not only the 
upper and middle layers, but even the deeper layers of the cortex with 
the large pyramidal cells may be completely atrophied. This destruction 
of the large pyramidal cells explains the degenerative changes in the 
pyramidal tract which are found in the cord in cases of this type. 
While in general the lesions of paresis are most constant and best 
marked in the cortical regions, the remainder of the brain rarely escapes 
some change. The cerebellum and the spinal cord, especially the latter, 
show infiltrative and degenerative changes. Alterations in the ganglion 
cells and destruction of the nuclei for the optic muscles explain the defects 
of motility of the eye. In the optic thalamus and the cerebellum the 
degenerative process is chiefly recognizable in the proliferation of the 
neuroglia. In individual cases the process may be especially well devel- 
oped in the cerebellum, and in the later stages of the disease, extensive 
degeneration in the posterior and lateral column of the cord are usually 
met with. In distinction to tabes, the ventral area of Hoche's bundle 
are frequently affected, while the posterior root zones are not so markedly 
altered as in tabes. The lesions of tabes, however, may coexist with 
those of paresis. 
While the symptoms of sleeping sickness are in many ways different 
from those of paresis, there is a striking similarity in the lesions of the 
nervous system in the two diseases.2 
1 For a study of these granular cells, see Schmaus, Lubarsch-Ostertag, Ergebn. d. allg. Path., 1904, 
x\ 350. 
2 See Spielmeyer, W., Die Trypanosomen-Krankheiten, Jena, 1908; also in Lewandowsky, Handb. d. 
Neurol., 1912, iii, 538. THE NERVOUS SYSTEM 
1169 
SENILE DEMENTIA. 
The most constant gross lesion of senile dementia is a diminution in 
the size of the brain, often accompanied by external hydrocephalus. The 
convolutions are shrunken, and the furrows larger than normal, especially 
in the frontal portions. The pia is usually thickened, and the Pacchion- 
ian bodies are prominent. The ventricles may be enlarged and contain 
fluid. The larger vessels, especially those at the base of the brain, may 
show some atherosclerotic changes, but are more frequently normal. 
Microscopically, the thickened pia shows an increase in the fibroblasts, 
lymphoid infiltrations, and fatty and pigmented phagocytes, and the 
vessels are usually thickened. The ganglion cells are extensively pig- 
mented with a bright yellow, granular material which stains with Sudan 
Fig. 791A.-Senile plaques Bielchowsky technique. The preparation is one made by Dr. T. J. 
Sands. 
Ill and blackens with osmic acid. The cell fibrils are pushed to the 
periphery by the pigment accumulation, and the Nissl granules also are 
displaced by the pigment. Similar changes in the ganglion cells are 
present, but less extensively, in extreme old age, in various intoxications, 
especially alcoholic, in paresis, and in atherosclerotic brains. In ad- 
vanced cases of senile dementia, the fibrils are often greatly thickened 
and form a basket-like network about the ganglion cells. The pyramidal 
cells often show large granules in the cytoplasm which do not stain with 
Sudan III, but take a basic stain. Throughout the brain there is exten- 1170 
THE NERVOUS SYSTEM 
sive loss of the ganglion cells; and accompanying this atrophy of the 
ganglion cells there is an atrophy of the nerve sheaths and axis-cylinders 
of the cortical layers. The glia is increased in amount especially on the 
surface of the brain. Many astrocytes and small glia cells with pycnotic 
nuclei appear in the cortical substance. The vessels show, aside from 
occasional atherosclerotic changes, alterations in the endothelium, fatty 
infiltration and atrophy of the muscular layers, and an increase in the 
adventitial connective tissue. A few lymphocytes and degeneration 
products may collect in the perivascular lymph-spaces, but there are no 
extensive collections such as are characteristic of paresis. 
The most characteristic morphological change in senile dementia is 
the appearance in the cortex of the "senile plaques," which are most 
satisfactorily demonstrated by the Bielchowsky stain. While these 
occur occasionally in the brain in old age, in dementia prsecox, and in 
severe general diseases, they are never so abundant as in senile dementia. 
The plaques are formed of a feltwork of fibers composed of axis-cylinders 
and nerve and glia fibrils, surrounding areas in which the products of 
destruction of the nerve tissue have collected. The axis-cylinders fre- 
quently show buds or loops in their continuity. Ganglion cells are rarely 
found in the center of the plaques; occasionally a capillary occupies this 
position. Glia cells are found among the fibers of the plaque and about 
its periphery. 
While the cornu Ammonis is most frequently and most extensively 
involved in senile dementia, similar alterations may be found in the 
cerebellum, the central ganglia, and the pons. Even the cord may show 
atrophy of fibers, growth of glia tissue, fatty and degenerative changes 
in the ganglion cells, and occasionally circumscribed areas of degenera- 
tion; but such changes as a rule are scanty and infrequent. A presenile 
type of dementia with lesions similar to those of the senile group has 
been described by Alzheimer as occurring in persons not over forty years 
of age.1 
It should be remembered that all of the lesions of senile dementia 
enumerated above are merely an exaggeration of what may be called 
physiological senile alterations occurring in a moderate degree in the 
cerebrospinal system of the very aged.2 
PARALYSIS AGITANS. 
This is a chronic, usually progressive disease, characterized by mus- 
cular rigidity, weakness, tremor, and a peculiar attitude of the patient. 
The disease occurs in men twice as frequently as in women, and not in- 
frequently there is a history of heredity. The present view of patholo- 
gists is that the disease is due to an atrophy of the large motor cells of 
the corpus striatum with some secondary thinning of the striohypothal- 
1 Lambert, C. I., Clinical and anatomical features of Alzheimer's disease, Psychiat. Bull., 1916, i, 
413; Sands, I. J., Senile and presenile psychoses, Neurol. Bull., 1918, i, 377. 
2 The most valuable monograph, with bibliography, on the histological changes in the brain in 
senile dementia, is that of Simchowicz, T., Nissl and Alzheimer, Histologische und Histopathologische 
Arbeiten, Jena, 1911, iv, 267. See also Leri, Le cerveau senile, Lille, 1906; McGaffin, C. G., Am. Jour, 
of Insanity, 1910, Ixvi, 649; Southard, E. E., ibid., p. 673; and Tiffany, W. J., ibid., 1914, Ixx. THE NERVOUS SYSTEM 
1171 
amic radiation, the ansa lenticularis, and the ansa peduncularis. The 
small ganglion cells of the cordate nucleus and the putamen are not 
affected. There is also considerable increase in the amount of glia tissue 
in the affected region. 
The fibers of the globus pallidus show atrophy, but no more than may 
be seen in cases of senile dementia. The atrophy of the loops of the 
nucleus caudatus is considerable, and is seen in many cases. The red 
nucleus and the pontine ganglia are not diseased. Numerous small 
hemorrhages have been found in the optic thalami. Changes in Nissl's 
granules and the ganglia cells of the cortex, cerebellum, and spinal cord 
are frequent; but none can be considered as characteristic of paralysis 
agitans. Vascular degenerations of the arteriosclerotic type are often 
present, but are due solely to conditions not connected with the disease. 
Paralysis agitans may, therefore, be considered as due to destruction of 
the large ganglion cells of the corpus striatum. This results in motor 
disturbances due to loss of control of the automatic and association 
activities of the muscles through the connections with the nuclei of the 
hippocampal regions and the extrapyramidal tracts of the spinal cord. 
As this mechanism is infracortical, its activities are unconscious, but as 
it is under the control of the higher cortical centers the tremor may dis- 
appear on voluntary motion.1 
A great many other changes in the central nervous system have been 
described, but these are probably unessential and due merely to the 
accompanying senile and arteriosclerotic processes which occur in many 
persons of advanced years. Among these are extreme fatty degeneration 
of the ganglion cells, especially in the anterior horns of the cervical and 
lumbar cord, the presence of large numbers of corpora amylacea, which 
have been described by a number of observers in the posterior columns 
of the cord, as well as the obliteration of the central canal, none of which 
are characteristic of this disease. When the larynx is affected by the 
tremor, degenerative changes have been found in the vagoglossopharyn- 
geal nucleus.2 
PROGRESSIVE LENTICULAR DEGENERATION. (Wilson's Disease.) 
The characteristics of this disease3 are an atrophic cirrhosis of the 
liver beginning in youth or adolescence and accompanied by degeneration 
in both lenticular nuclei. 
The liver lesion is the usual type of atrophic cirrhosis; the spleen is 
also enlarged though not invariably. In those cases in which death 
occurs early the central nervous system may show no microscopical 
lesions; when, however, the disease has persisted for some time the 
pathological changes in the nucleus may be striking. The softening is 
1 Hunt, J. R., Brain, 1917, xl, 58; Neurol. Bull., 1918, i, 237; and Arch. Int. Med., 1918, xxii, 647. 
2 Foster, E., and Lewy, F. H., Lewandowsky, Handbuch d. Neurologie, 1912, iii, 920 (bibl.); Mendel, 
Paralysis agitans, Berlin, 1911; Gordinier, H. C., Am. Jour. Med. Sc., 1899, cxviii, 648; Dana, C. L., 
ibid., p. 503. 
3 Tilney, F., Neurological Bull., 1918, i, 243; Wilson, S. A. K., Lewandowsky, Handb. d. Neurol., 
1914, v, 951. 1172 
THE NERVOUS SYSTEM 
bilateral involving especially the putamen and varies from a slight dis- 
coloration and a sponginess of the tissues to shrinkage and atrophy 
and, finally, complete disintegration and excavation of the ganglia. 
The caudate nucleus has been described as slightly shrunken but not 
disintegrated. 
Microscopically, there is glial overgrowth which softens afterwards. 
There is often a great increase in the number of glial nuclei; the nerve 
fibers and nerve cells of the normal nucleus disappear. There is a cer- 
tain amount of infiltration with phagocytic wandering cells. The blood- 
vessels show no special change. The pons, medulla, cord, nerves, and 
muscles are also normal. Degeneration secondary to that in the lenticu- 
lar nucleus has been found in the ansa lenticularis and the corpus Luysi. 
The characteristic symptoms of the disease are motor disturbances; 
tremor is marked; spasticity or hypertonicity is also always present. 
Tonic cramps are a late symptom. The mouth is often held open as if 
the patient were laughing. Dysphagia is common, and loss of ability 
to speak. The dysarthria is not severe in the early states of the disease 
but later in children who have learned to speak may become so great 
that they are not able to utter a word. This inability is due to the stiff- 
ness of the muscles of speech. In the later stages muscular weakness 
and emaciation develop and control over the sphincters is lost. Children 
are often simple-minded. 
About 75 per cent, of the cases are familial, though the disease is 
neither congenital nor hereditary. Its cause is unknown, but syphilis 
and alcoholism can be excluded as factors. Similar symptoms are occa- 
sionally noted in illuminating gas poisoning when softening of the len- 
ticular nuclei has occurred.1 
Specific Inflammatory Lesions of the Nervous System. 
Tuberculous inflammation whether of the brain or of the cord is usu- 
ally secondary to tuberculous inflammation in other organs, and is most 
frequent as an extension of tuberculosis of the meninges. In the brain 
substance it usually manifests itself in the formation of circumscribed 
masses of new tissue from 0.5 to 1 centimeter in diameter, or larger. 
These may be single or multiple, are most common in young persons, and 
very frequently occur in the cerebellum (Fig. 792). They are apt to 
occur in connection with tuberculous inflammation of other organs. 
They are frequently solitary tubercles, each consisting of a dense central 
cheesy mass, around which is a grayish zone containing tubercle granula 
and numerous small spheroidal cells, with occasionally larger polyhedral 
cells and giant cells. They do not, as a rule, seem to be formed by an 
aggregation of miliary tubercles, although these may be present at the 
periphery. They sometimes suppurate and break down, and then they 
TUBERCULOUS LESIONS IN THE NERVOUS SYSTEM. 
1 McConnell and Spiller, Jour. Am. Med. Assn., 1912, lix, 2123; and Hill, E., and Semerak, C. B., 
Jour. Am. Med. Assn., 1918, Ixxi, 644. THE NERVOUS SYSTEM 
1173 
simulate simple abscesses. Tubercle bacilli have been found in these 
solitary tubercles. 
Conglomerate and scattered miliary tubercles of the ordinary form 
sometimes occur in the brain, usually in connection with tuberculous 
inflammation of the meninges or ependyma. 
Fig. 792.-Solitary Tubercle of Cerebellum. 
a, a, Miliary tubercles with giant cells; b, b, miliary tubercles without giant cells; c, diffuse tubercle 
tissue; d, central cheesy mass; e, nerve tissue of the cerebellum. 
In the spinal cord solitary nodules may determine extensive second- 
ary degenerations. Multiple tuberculous foci may occur in the cord. 
They are rare and usually secondary to tuberculosis of the spinal meninges. 
Tuberculous inflammation of nerves is rare except at their origins, 
where it is due to an extension from tuberculous meninges. When a 
nerve traverses tuberculous tissues, it may be involved in the inflamma- 
tory process. 
SYPHILITIC LESIONS OF THE NERVOUS SYSTEM.1 
The virus of syphilis may affect the nervous system in two fashions; 
either it may attack the functional epithelium and cause the death of the 
ganglion cells and a growth of glia tissue accompanied by secondary 
degeneration in the ganglia and fiber tracts of the cord, as in tabes and 
general paresis; or it may attack the connective tissue and vascular 
portions of the brain, forming a series of products with which we are 
1 Dunlap, C. B., Anatomical borderline between so-called syphilitic and metasyphilitic disorders in 
brain and spinal cord, Amer. Jour. Insanity, 1912-13, Ixix, 1045. Two important reference books on 
syphilis of the nervous system are, Krause, K., Beitrage zur Pathologischen Anatomie der Hirnsyphilis, 
Jena, 1915; and Gennerich, W., Die Syphilis des Zentralnervensystems, Berlin, 1921. 1174 
THE NERVOUS SYSTEM 
familiar in syphilis of other organs, in other words, gummata and syphi- 
litic granulation tissue. The vascular lesions are similar to those seen 
in other portions of the body. They consist primarily of a swelling of 
the endothelium of the vessels, with the production in the adventitia, 
the media, and the intimal layers of the vessels of new tissue composed 
of spindle cells and loose interstitial connective tissue. In this inter- 
stitial tissue, there are frequently large numbers of lymphocytes or plasma 
cells, and around the periphery of the smaller vessels are collections of 
lymphocytes and occasional plasma cells. As the process continues, the 
Fig. 792B.-Small pial capillary from a case of cerebral syphilis, showing the thickening of the 
vascular wall and the perivascular exudate. The tissue was very gelatinous so that there is consid- 
erable shrinkage. 
newly formed tissue gradually alters into a dense sclerotic fibrous tissue, 
which ultimately destroys the muscular and the elastic laminae of the 
vessels. Occasionally, the process is frankly gummatous in nature, with 
the formation of patches of new connective tissue which break down and 
form necrotic masses, about the periphery of which there may be a few 
giant cells. The lumen of the vessel is greatly reduced in all cases, and 
occasionally may be entirely obliterated. While the process is most THE NERVOUS SYSTEM 
1175 
marked in the larger vessels, it may involve also the veins and the capil- 
laries. In distinction to general paresis, the infiltrate about the capil- 
laries is composed chiefly of lymphocytes rather than plasma cells as in 
the latter disease. While the perivascular lymph-spaces do not, as a 
rule, contain cells from the exudate these may be present; but when the 
disease is extensive and long-continued, the tissue outside of the peri- 
vascular lymph-spaces is infiltrated, and under these circumstances the 
glia also undergoes hyperplasia. Ultimately the changes in the vessels 
lead to degenerative processes due to the lack of nutrition of the brain- 
substance supplied, thus complicating the picture. The ordinary non- 
specific type of arteriosclerosis may also occur in the vessels in the brains 
of those suffering from syphilis, but has nothing to do necessarily with 
the purely leutic process. Small aneurysms may form along the course 
of the larger vessels in both types of disease, the syphilitic and the arterio- 
sclerotic. 
The second type of syphilitic disease of the brain is the gummatous. 
In this, solitary or multiple gummata are formed, which arise solely in 
the elements of the connective tissue; the brain itself is only secondarily 
involved. The gumma is formed of a peripheral mass of granulation 
tissue containing a great variety of cells of the epithelioid variety, with 
lymphocytes, plasma cells, and occasionally mast cells. The plasma 
cells are usually about the vessels. In the interior of the mass there is 
usually an area of cheesy degeneration, about the periphery of which 
may be found a few giant cells. The gumma, if it is small, may ulti- 
mately be replaced by dense connective tissue, and leave little else than 
a scar in the brain substance. The larger gummata may soften in the 
center and ultimately become calcified. The cells of the nervous system 
are involved secondarily; the glia especially undergoes active hyper- 
trophy and many types of glial cells, including the ameboid variety, may 
be observed. Such cells may contain pigment and even become calcified. 
Ganglion cells in the immediate neighborhood of the gumma are fre- 
quently degenerated and stain poorly, and their processes appear very 
sharply demarcated against the edematous brain tissue. The nerve 
fibers also suffer. The medullary sheath may be swollen and the fibers 
broken up, and over small areas completely disappear. Such changes, 
however, are limited to the region of the gumma and do not involve the 
entire brain substance, as do the changes in paresis. 
The most frequent form of cerebral syphilis is a diffuse, basal, gum- 
matous meningitis, beginning in the subarachnoid tissue of the region of 
the chiasm and spreading from this point more or less over the entire 
base of the brain. The newly formed tissue is usually soft and gelatinous 
with areas containing firm connective-tissue strands attached to the basal 
portion of the brain. The gummatous material penetrates the depres- 
sions in the brain substance and covers the region of the cranial nerves. 
The optic nerve and the third nerve especially are frequently diseased, 
which explains the fact that in 40 per cent, of cases of cerebral syphilis 
there are changes in the eye grounds. Hemorrhage and softening are not 
infrequent in the gummatous material. Syphilitic meningitis of the 1176 
THE NERVOUS SYSTEM 
convexity occurs, but is less frequent. With these lesions go constant 
changes in the cerebrospinal fluid. The Wassermann reaction is regu- 
larly positive, the amount of globulin is increased, the cells are usually 
far above the normal, and the alterations in colloidal gold solutions pro- 
duced by the addition of a measured quantity of the spinal fluid are quite 
constant.1 
Syphilitic inflammation in the spinal cord is usually secondary to a 
similar process in the spinal meninges. Gummata, when they occur, are 
modified in size and shape by the anatomical restrictions of the vertebral 
canal. Such masses are significant chiefly because of the more or less 
extensive secondary degenerations which they induce. 
Syphilitic lesions of the nervous system may occur in either the in- 
herited or the acquired type of the disease. In the former, they usually 
show changes early in life, though cases have been reported after puberty. 
More commonly, cerebral syphilis is a manifestation of the acquired dis- 
ease, occurring from ten to twenty years after the initial lesion; but cere- 
bral symptoms may make their appearance within a few months after 
the chancre. Extensive gummatous formation in the brain is rare; 
many of the cases giving clinical symptoms show a relatively slow 
growing vascular or perivascular lesion with very moderate meningeal 
inflammation. 
ACTINOMYCOSIS. 
Actinomycosis of the brain has been described. It is a rare form of 
brain infection, and is usually secondary to actinomycosis of the neck or 
face. The condition is apt to lead to suppuration and abscess formation. 
A case has been reported in which the disease was apparently primary 
in the brain.2 
LEPROUS INFLAMMATION. 
This occurs in the peripheral nerves and consists in the formation 
within the nerves of masses of new-formed tissue somewhat resembling 
granulation tissue. In the cells of this tissue multitudes of characteristic 
bacilli are uniformly found (see page 302). The injuries to the nerve 
fibers explain the clinical symptoms of the variety of leprosy known as 
lepra ansesthetica. 
TUMORS. 
Tumors occurring in the nervous system may be of the types found 
in the other organs or of types peculiar to nervous tissue. They may be 
primary, or secondary to similar growths in other parts of the body. 
Tumors of the Brain.3 
Myxoma, fibroma, lipoma, and osteoma are rare forms of brain tumor. 
1 For a study of the comparative value of various tests, see Hammes, E. M., Am. Jour. Med. Sc., 
1917, cliv, 625. See, also, Vogel, K. M., Arch. Int. Med., 1918, xxii, 496; and Solomon, H. C., Non- 
concomitance of spinal fluid tests, Arch. Neurol, and Psychiat., 1920, iii, 49. 
2 For further details, see Howard, W. T., Jour. Med. Research, 1903, N. S. iv, 301. 
3 For the subject of brain tumors, with bibl., see Oppenheim, Die Geschwiilste des Gehirns, 2d ed., 
Vienna, 1902; and Bruns, Die Geschwiilste des Nervensystems, 2d ed., Berlin, 1908. THE NERVOUS SYSTEM 
1177 
Neuroglioma Ganglionare.-This is a form of tumor probably due to 
disturbances in the development of the brain. It is peculiar to nervous 
tissue and occurs in the form of circumscribed tumors or of diffuse 
enlargements of portions of the brain. The pia mater over these tumors 
is unchanged and the convolutions retain their shape. The tumors 
are formed of neuroglia, with many astrocytes in which are contained 
little groups of ganglion cells. 
Glioma.-This is the most common tumor of the brain, and like the 
preceding is found only in the nervous system or in areas where nerve 
material exists during embryonic life, for example, at the root of the 
nose, and over the sacrum, the anterior and posterior terminations 
of the neural canal. It occurs with special frequency in children and 
young adults. Such tumors occur in all parts of the brain, but are found 
most frequently in the cerebrum. There may be a single tumor, or there 
may be several such tumors in different parts of the brain; some of them 
attain a large size, even more than one-half of a hemisphere may be 
involved. These tumors may be sharply circumscribed or may merge 
imperceptibly into the brain substance. They may be white and hard; 
gray, soft, and gelatinous; infiltrated with small hemorrhages; or partly 
degenerated and softened. The center of a glioma may break down and 
become soft and necrotic or even fluid, and in this way a cyst may be 
formed having a wall of gliomatous tissue. The brain tissue around the 
tumors may be inflamed or necrotic. The tumors arise from the neuro- 
glia, and are composed of neuroglia cells and their delicate interlacing 
processes; the relative quantity of cells and fibrils varies in different 
tumors. If the tissue is of a loose formation with wide meshes between 
the fibers it presents a myxomatous appearance, and has been described 
as a myxoglioma. When the cellular elements are very numerous the 
tumor is often referred to as a gliosarcoma. This term should, however, 
be reserved for tumors in which both connective tissue and glial elements 
are present, in other words, for a mixture of a glioma and a sarcoma. 
Such tumors occur very rarely. The very cellular gliomata, especially 
those containing large multinucleated cells, should be called spongio- 
blastomata rather than gliosarcomata, the spongioblasts being the embry- 
onic ancestors of the glial cells. These spongioblastomata are somewhat 
less frequent than the astrocytic gliomata and are of rather more rapid 
growth, but they do not form metastases and have in general the char- 
acters of all glial tumors, a tendency to softening and to central hemor- 
rhage being well marked. 
In some cases the vascularity of the tumor is such a marked feature 
that the name telangiectatic glioma is applied to it. 
Primary sarcoma occurs in any part of the brain, and is derived 
from the connective tissues of the membranes, or that accompanying 
the blood-vessels. The tumor may be single or multiple. It is com- 
posed usually of round or fusiform cells with more or less basement 
substance. 
Endothelioma is found in the substance of the brain. The tumors 
are of the types described as occurring in the pia mater. 1178 
THE NERVOUS SYSTEM 
Cholesteatoma occurs chiefly in connection with the pia, but the 
tumors may project into the substance of the brain and cause symptoms. 
These tumors are very slow growing and usually originate in deposits of 
squamous epithelial cells left during the closure of the neural groove. 
Grossly the tumors are irregularly spherical, and very hard, and when 
cut across are pearly white and rather loose in structure. Microscopically 
they are composed of flattened epithelial cells mixed in various propor- 
tions with cholesterin crystals. It is sometimes difficult to demonstrate 
the epithelial origin of these growths and the cholesterin crystals may lie 
in a mass of granulation or firm connective tissue, often inclosed in for- 
Fig. 793.-Cholesteatoma of Bpain. 
eign body giant cells (Fig. 793). There is a possibility that a few of these 
tumors do not originate primarily in epithelial remnants; but this ques- 
tion is not yet finally decided.1. 
Angioma occurs in the substance of the brain, and, like the nsevi of the 
skin appears to be congenital. 
Chorionepithelioma of the uterus metastasizes frequently into 
the brain and forms considerable masses, usually very hemorrhagic. 
Indeed, the symptoms of hemorrhage may completely mask those due 
to the tumor, and the sudden death of the- patient may be ascribed to 
apoplexy. 
Carcinoma occurs in the brain, but is almost always secondary to 
carcinoma in some other organ. Owing to the greater blood supply to the 
left hemisphere, the metastases are much more frequent on the left than 
on the right side of the brain.2 • 
1 For a study of cholesteatoma of the brain, see Thomas, J. J., Jour. Med. Research, 1901, N. S. i, 
220 (bibl.). See also Ribbert, Geschwiilstlehre, 2d ed., Bonn, 1914, p. 486 (bibl.). 
2 For an interesting statistical study of metastasis in the central nervous system, see Krasting, K., 
Ztschr. f. Krebsforsch., 1906, iv, 315 (bibl.). 1179 
THE NERVOUS SYSTEM 
Tumors of the Cord. 
In the pia mater of the cord are sometimes found small fibromata, 
osteomata, and lipomata. Multiple fibromata occasionally occur in the 
cord in connection with multiple fibromata of the peripheral nerves. 
Endotheliomata of the types described as existing in the pia mater of 
the brain are much more rarely found in the pia mater of the cord. 
A fatty sarcoma of the pia mater, which infiltrated the cord, formed 
a tumor as large as a filbert, and had for twelve years caused gradually 
increasing paraplegia, has been described.1 
Two curious cases2 of diffuse sarcoma and one of endothelioma of the 
pia mater of the whole length of the cord are recorded. In each case 
the pia mater of the whole length of the cord was diffusely thickened and 
studded with nodules. In two of the cases the growth was composed of 
round cells, in the third case of large endothelial cells arranged in alveoli. 
In two of the cases the clinical symptoms lasted only for about three 
weeks, in the third case for five months. The acuteness of the symptoms 
was such as to indicate the existence of spinal meningitis. 
In the spinal cord itself gliomata, lipomata, fibromata, sarcomata, 
and angiosarcomata occur, but are rare. 
When gliomata do occur in the spinal cord, the new growth is apt to 
extend for some distance lengthwise in the cord and to be attended with 
the formation of a cavity; this condition is usually described under the 
name of syringomyelia. (See p. 1153.) 
An irregular cavity in the gray matter of the spinal cord, lined by a thick layer of gliomatous tissue. 
Fig. 794.-Syringomyelia. 
The tumors of the nerves may be divided into those consisting largely 
of or containing new-formed nerve tissue, true neuromata, and the 
so-called false neuromata, which are for the most part fibromata (Fig. 
221), fibrolipomata or myxomata originating in the connective tissue of 
the nerve (see Neuroma, page 416). Myxosarcomata are less common, 
Tumors of Nerves. 
1 Turner, Trans. London Path. Soc., 1888, xxxix, 25. 
2 Coupland, and Pasteur, Trans. London Path. Soc., 1887, xxxviii, 26. 1180 
NERVOUS SYSTEM 
and primary sarcomata rare (Fig. 795). The nerves may be secondarily 
involved in sarcomata, or in carcinomata through which they pass, though 
Fig. 795.-Neurofibrosarcoma of Musculospibal Nerve. 
not infrequently nerves pass through these tumors without being in the 
least affected. 
HOLES AND CYSTS IN THE BRAIN AND CORD. 
Larger or smaller holes may be found in the brain tissue from dilata- 
tion of the perivascular lymph-spaces, or well-formed cysts may exist 
as a result of hemorrhage, inflammatory softening, hydatids, etc. 
In cases of infection with Bacillus aerogenes capsulatus, gas may 
form in the brain and produce cavities, a condition known as Swiss- 
cheese brain. 
Porencephalus is a term which has had a wide range of application 
to various defects of the brain substance. By some writers the term has 
been used to cover almost any congenital absence of brain tissue. By 
others, brain defects not congenital are included. Its most common 
application is to certain quite well-defined congenital conditions in which 
there is an absence of a considerable portion of one or both hemispheres. 
These may be produced in intrauterine life or post-partum by trauma or 
by chronic inflammation causing necroses.1 The holes may lie deep in 
the substance of the brain. More commonly they come to the surface 
making conical depressions in the cortex, which the dura mater bridges 
over, but into which the pia extends. There may or may not be com- 
munication with the ventricles. This condition may coexist with various 
1 Dahlmann, Ztschr. f. d. ges. Neurol, u. Psychiat., 1910, iii, 223; and Schutte, E., Centralbl. f. allg. 
Path., 1902, xiii, 633 (bibl.); Globus, J. H., Histopathology of porencephalus, Arch. Neurol, and Psychiat., 
1921, vi, 652. 1181 
mental aberrations, spastic hemiplegia, hydrocephalus, etc. Similar 
defects may occur in the cerebellum. 
The form of cavity found in the brain after embalming is of medico- 
legal importance chiefly because of the necessity for distinguishing these 
artefacts from injuries to the organ during life. The pressure of the em- 
balming fluid ruptures the walls of the smaller capillaries which have 
begun to soften as a post-mortem change, and distends the brain tissue 
so as to form spherical, oval, or lenticular cavities. If a microscopic 
section of the wall of one of these cavities is made, it will be found that 
the glia and ganglion cells are perfectly normal in their structure quite 
THE NERVOUS SYSTEM 
Produced post-mortem by injection of embalming fluid. At the upper edge of the cut is the wall 
of a large cavity. A smaller cavity is seen just below. The cells at the edges of the cavities are per- 
fectly preserved. 
Fig. 796.-Traumatic Cavities in Brain. 
to the edge of the cavity (Fig. 796). This is proof that the formation 
of the cyst could not have been ante-mortem, as in this case the nutrition 
of the cells would have been seriously interfered with, even after a few 
hours. The fact that the contents of the cyst are clear and not blood- 
tinged, is an additional proof that the cavity was formed post-mortem.1 
Cysts in the cord may occur as a result of softening or from unknown 
causes. Sometimes very long, narrow canals are found in the spinal 
cord, even reaching nearly its whole length. Some of these are evidently 
the dilated central canal, as they are lined with epithelium. Others, 
however, doubtless originate in hemorrhages (see Hematomyelopore, 
page 1126). 
1 For a case of formation of cysts post-mortem by gas bacilli, see Pick, A., Arch. f. Psychiat.,1890, 
xxi, 910. For other types of post-mortem cyst formation, see Hartmann, Wien. klin. Wchnschr., 
1900, xiii, 963 (bibl.). 1182 
THE NERVOUS SYSTEM 
GLANDULAR APPENDAGES OF THE BRAIN. 
Pineal Gland. (Epiphysis Cerebri.) 
The pineal gland is a small reddish body of a flattened oval shape, 
measuring 5 by 7 millimeters. It is derived from a diverticulum of the 
roof of the third ventricle. Microscopically, it is composed of a number 
of hollow follicles lined with epithelium and separated from each other 
by a vascular connective tissue. There are also a few neuroglia cells, 
ganglion cells, and sympathetic nerve fibers.1 After the sixth or seventh 
year, the gland undergoes an involutionary process, the ganglion cells 
disappearing and the connective-tissue cells increasing and showing some 
hyaline degeneration; the glandular tissue also is diminished in quantity. 
The areas lined by ependyma extend and form small cysts. Much cal- 
careous material is present in the gland in the adult. 
Cysts of the epiphysis are frequently found and are usually con- 
nected with some hypertrophy, and hemorrhages into the substance have 
been noted. The function of the organ is still undetermined. Adiposity, 
early sexual maturity, and cachexia have been seen in connection with 
tumors of the gland, but the possibility that the first two of these condi- 
tions are due to a coincident alteration of the hypophysis must be 
considered.2 
Up to the present time some seventy tumors have been reported. The 
turners are of various types. Teratomata containing epidermis, hair, 
sebaceous glands, cartilage, fat, and smooth muscle have been seen in 
a number of instances, and are due to congenitally displaced fragments 
left during the closure of the medullary plates Other tumors have been 
described as adenoma, sarcoma, glioma, ependymal neuroglioma, and 
primary chorionepithelioma.3 A number of the tumors are endothelial 
in type and are composed of spindle cells arranged in whorl-like masses, 
often inclosing psammomatous particles. The tumors of the gland do 
not, as a rule, form metastases.4 An important secondary symptom is 
hydrocephalus, due to obstruction of the outflow of the cerebrospinal 
fluid. 
This is a small, reddish gray mass, oval in shape, which occupies the 
sella turcica of the sphenoid bone.0 It consists of two lobes, the anterior 
being the larger. This is a prolongation from the buccal cavity and is 
formed of epithelium arranged in trabeculae. It is richly supplied with 
blood-vessels in the form of the sinusoidal capillaries. Three types of 
cell are present: a granular, chromophilic variety staining darkly with 
eosin, and a non-granular basophilic type which stains deeply with meth- 
Pituitary Body. (Hypophysis Cerebri.) 
1 Tilney, F., and Warren, L. F., Morphology and Emotional Significance of the Pineal Body, Phila- 
delphia, 1919. 
2 Goldzieher, fiber ein zirbeldriisengeschwulst, Virchows Arch., 1913, ccxiii, 353. 
3 AsKanazy, Verhandl. d. deutsch. path. Gesellsch., 1906, x, 58; and Rohdenburg, G. L., Proc. New 
York Path. Soc., 1917, xvii, 68. 
4 For a study, with bibl., of tumors of the pineal gland, see Bailey and Jelliffe, Arch. Int. Med., 
1911, viii, 851. See also resume by Dana and Berkeley, Med. Record, 1913, Ixxxiii, 835; and Schuller, 
A Lewandowsky, Handb. d. Neurol., 1913, iv, 337 (bibl.). 
6 Tilney, F„ Contribution to the study of the hypophysis cerebri, with especial reference to its 
comparative histology, Mem. of the Wistar Institute of Anat, and Biol., Philadelphia, 1911, No. 2. THE NERVOUS SYSTEM 
1182a 
ylene blue. The third form does not take either stain deeply. The 
eosinophile cells are increased in acromegaly. 
The posterior lobe is developed as a hollow downgrowth from the third 
ventricle. In adult life in man it is not connected with the ventricle. 
It contains neuroglia cells and nerve fibers. 
Between the two lobes is the pars intermedia, sometimes described as a 
separate lobe, which contains both epithelial cells and neuroglia. Colloid- 
like material may occupy the spaces between the cells in this situation. 
The hypophysis is closely correlated with various diseases of the 
skeleton and organs of the body, among them adiposity, gigantism, 
acromegaly, and some forms of infantilism.1 Regressive changes in the 
gland are frequent; the connective tissue may be increased. Cysts may 
appear in the substance of the gland, and in the condition known as 
struma the colloid material is increased. Lime salts also collect in the 
substance of the gland and form small granules. 
The most frequent tumor of the hypophysis is described as adenoma.2 
Tumors of this type are almost constantly found in connection with 
acromegaly.3 The usual type of adenoma is that derived from the eosin- 
ophile cells, but the basophile cells also may form tumors.4 
Carcinoma (Fig. 797) and sarcoma are seen, though infrequently; 
lipoma and cystic teratoma have been described. The embryological 
connection of the anterior lobe with the pharynx offers an explanation 
Fig. 797.-Carcinoma of Hypophysis. 
for the squamous-cell epitheliomata and carcinomata which occur in the 
hypophysis.5 Cholesteatoma also has been seen. 
Echinococcus and other cysts may occur.6 Gummata and tubercles 
are very rarely seen.7 
1 For further details, see discussion of these diseases in chapters on General Diseases and on Bone. 
See also Cushing, H., The Pituitary Body and its Disorders, Philadelphia, 1912; Wood, F. C., Hypophy- 
sis cerebri, Reference Handbook of the Medical Sciences, 1915, v, 469; Biedl, A., The Internal Secretory 
Organs, New York, 1913; and Falta, Die Erkrankungen der Blutdriisen, Berlin, 1913. 
2 Lowenstein, C., Virchows Arch., 1907, clxxxviii, 44 (bibl.). 
3 Petren, K., Virchows Arch., 1907, cxc, 1 (bibl.). 
4 Erdheim, J., Frankfurt. Ztschr. f. Path., 1910, iv, 70. 
^Bregman, L., and Steinhaus, J., Virchows Arch., 1907, clxxxviii, 360. 
6 For a study of cysts of the hypophysis, see Kanavel, A., Surg., Gynec., and Obst., 1918, xxvi, 61. 
'For a case of gumma of the hypophysis, see Weigert, C., Virchows Arch., 1875, Ixv, 223. 1182b 
THE NERVOUS SYSTEM 
Methods of Preparation of Nerve Tissue for Microscopical Study1 
The general methods of hardening will be found in Part III. For minute study 
there is no one method of staining and mounting upon which we can rely exclusively 
for the study of all lesions. A preliminary examination of areas of inflammatory 
softening, or of the disintegrated tissue in apoplectic clots, or of the new-formed tissue 
in chronic hemorrhagic pachymeningitis interna, may be made by teasing portions 
of the affected tissues in 0.85 per cent, salt solution. Or the tissues in these lesions, 
or in any others in which fatty degeneration is suspected, may be placed for twenty- 
four hours in 1 per cent, aqueous solution of osmic acid, and then washed and teased 
in glycerin. In this way the myelin and the fat will be stained brown or black. 
Secondary and other degenerations of medullated nerves may be studied by soaking 
the nerves for twenty-four hours in 1 per cent, solution of osmic acid, and then staining 
with picrocarmine and teasing and mounting in glycerin. 
To demonstrate the presence of miliary aneurysms in or about apoplectic clots, it 
is usually necessary to macerate the brain tissue in water until the nerve elements 
disintegrate; they may then be washed away under a stream of water, leaving the 
blood-vessels with their aneurysms exposed. Another method is to shake the brain 
tissue in a closed vessel with water.2 
Bielschowsky Method.-This is an exceedingly valuable procedure for demonstrat- 
ing the axis-cylinders, the plaques and incrustations about the ganglion cells of the 
brain, and other pathological structures. 
Tissue, as fresh as possible, is fixed in 4 to 6 per cent, formaldehyde solution, the 
pieces being not over 1 cm. in thickness. Frozen sections stain most satisfactorily; 
but before they are made the tissues should be washed for several hours in running 
water to remove the formaldehyde. After cutting, the sections are transferred with 
a glass needle to a 2 per cent, solution of silver nitrate for twenty-four hours. (Better 
results are sometimes obtained, however, if they are placed first in pyridin for twenty- 
four hours and then thoroughly -washed with distilled water before they are trans- 
ferred to the silver nitrate.) After rapid washing in distilled water, the sections are 
transferred to an ammoniacal silver solution, which must always be freshly prepared 
by mixing 5 c.c. of a 10 per cent, aqueous solution of silver nitrate with 5 drops of a 
40 per cent, solution of sodium hydrate; the precipitate which forms is dissolved.by 
the addition of the least possible amount of ammonia; and the solution is diluted to 
20 c.c. with water. The sections are left in this for fifteen minutes or longer until 
they assume a dark brown color. If 1oo much ammonia is added, the glia and the 
connective-tissue elements also are stained. After the sections become dark, they 
are washed in distilled water and then transferred to an 8 per cent, formaldehyde 
solution for twelve to twenty-four hours, by which the silver in the tissues is reduced. 
Sections of the peripheral nervous system should be transferred first to a solution 
of 5 drops of glacial acetic acid to 20 c.c. of water for a few minutes, so as to prevent 
the connective tissue from taking a deep stain and permit a clearer demonstration 
of the neurofibrils. After reduction, the sections are washed in water, placed in a 
neutral solution of gold chloride, containing 5 drops of 1 per cent, gold chloride solu- 
tion to 10 c.c. of water; in this they remain for about an hour, until the tone of the 
tissue is a reddish violet. They are then washed for thirty seconds in a 5 per cent, 
solution of sodium thiosulphate to remove any unreduced silver, again washed in 
distilled water, passed through graded alcohols, cleared in carbol-xylol, washed m 
xylol, and embedded in neutral dammar. 
When the stain is successful, the axis-cylinders are black, the collagen fibers 
violet or blue, and the medullary sheaths often a reddish color, and the striated muscle 
brownish. The tissues can also be embedded in paraffin, if preferred, but as a rule 
the stain is more specific in frozen sections. 
1 An excellent guide to the latest miscroscopical methods for the examination of the nervous system 
is that of Spielmeyer, W., Technic d. mikroskop. Unterstchung des Nervensystems, 2d ed., Berlin, 1914. 
2 Pick, Berl. klin. Wchnschr., 1919, xlvii, 325, 382. PART III. 
THE METHOD OF MAKING POST-MORTEM EXAMINATIONS: 
AND THE METHODS OF PRESERVING AND 
EXAMINING PATHOLOGICAL TISSUES CHAPTER 1. 
THE METHOD OF MAKING POST-MORTEM 
EXAMINATIONS. 
General Considerations. 
The object in making a post-mortem examination may be to deter- 
mine whether a person has died from violence or poisoning; to account 
for a sudden death; or to study the lesions of disease. In any case the 
examination should include all the important parts of the body, not 
merely a suspected organ, and the results should be recorded at the time 
the examination is made. 
Great care is necessary in endeavoring to ascertain the cause of death 
when the clinical history is imperfect or unknown. Mechanical injuries 
which destroy life by abolishing the function of one of the important 
viscera, are relatively infrequent. Most of the lesions found after death 
are rather the marks of disease than the cause of death. We do not 
know, for example, how great a degree of meningitis, or of pneumonia, 
or of endocarditis, or of cirrhosis, or of nephritis necessarily leads to 
death; but it is certain that one patient may recover with an extent of 
lesion which is sufficient to destroy the life of another. So with acci- 
dents; there is often no evident reason why fractures of the skull or of 
the pelvis should destroy life, yet they usually do. In some of the infec- 
tious diseases, such as typhoid fever, the visible lesions cannot always 
be called the cause of death. Sudden deaths of persons apparently in 
good health are often particularly obscure. In many of them we have 
to acknowledge that we can find no sufficient cause for the death. This 
is of course due to our imperfect knowledge, but it is much better in 
such cases to avow ignorance than to attribute the death to some trifling 
lesion. The brain and the heart are the organs which are especially capa- 
ble of giving symptoms during life, without corresponding lesions after 
death. Very well-marked cardiac or cerebral symptoms may continue 
for days or months, and apparently destroy life, and yet after death 
we find no corresponding anatomical changes.1 But it should be remem- 
bered that recent advances in our knowledge of the cell, which an 
improved technique in hardening and preparation has greatly fostered, 
have already shown that under various abnormal conditions the cells, 
especially of the nervous system, may undergo morphological changes of 
great significance, without perceptible alteration in the gross appearance 
of the affected part, changes which even the microscopical examinations 
of the past have failed to disclose. So that while there often appears to 
1 See Sudden Death, p. 507. 
1185 1186 
MAKING POST-MORTEM EXAMINATIONS 
be a wide discrepancy between symptoms and lesions, with the increase 
of knowledge the scope of this discrepancy is steadily narrowing. It is 
the novice in post-mortem examinations who is particularly apt to mis- 
take for lesions ordinary post-mortem alterations or the effects of 
embalming processes. 
The cause of death is not always to be found in the organ which is 
primarily affected or which shows the most pronounced lesions. Thus 
chronic diffuse nephritis may exist for years with more or less marked 
symptoms of disease. But death may finally be due to a weakened heart 
which was secondarily involved, or occur in uremic convulsions, the 
brain showing no lesions at all. It is desirable, therefore, and in the 
majority of cases possible, to differentiate between obvious lesions and 
the cause of death.1 
External Inspection. 
Before commencing the examination of the internal viscera an inspec- 
tion should be made of the external surface of the body. The minute- 
ness of this inspection will depend upon the character of the case. In 
the case of an unknown person, or of one suspected to have died from 
unnatural causes, it is necessary to search for and record not only all 
contusions, wounds, etc., their size, situation, and condition, but also 
deformities from disease and any physical peculiarities of hair, eyes, 
teeth, moles, etc., by which the person may be identified. In such cases 
it is well, if possible, to photograph, weigh, and measure the body. In 
cases of doubtful identity it is sometimes wise to make a wax or plaster 
cast of the outside of the teeth and jaws. In ordinary examinations we 
note the general nutritive condition of the body, and look for evidences 
of external injury, for skin diseases, ulcers, edema, gouty deposits, 
abscesses, enlarged lymph-nodes, etc. The external organs of generation 
should be searched for syphilitic lesions. 
It is well to weigh the body, since the significance of the weight of 
the individual organs is often closely dependent upon the relationship 
of their weight to that of the entire body. 
Cadaveric Lividity.-It is usual to find certain changes in the exter- 
nal appearances of the body, which are due to the cessation of life and 
the commencement of decomposition. We speak now of bodies which 
have not been buried, but which have been kept in the ordinary way, 
lying on the back, and loosely covered with a shroud or dressed with the 
ordinary clothing. 
After life becomes extinct, and before the blood coagulates, it changes 
its position chiefly in two ways: first, it is driven by their contraction 
out of the arteries into the veins; second, it settles in the veins and 
capillaries of the more dependent parts of the body, inducing usually 
within a few hours after death a mottling of the surface with irregular 
1 It is obvious that lack of space prevents a full presentation of all phases of post-mortem technique; 
for fuller details the reader is referred to Cattell, H. W., Post-mortem Pathology, 3d ed., Philadelphia, 
1906; Wadsworth, W. S., Post-mortem Examinations, Philadelphia, 1915; Busse, O., Das Obduktions- 
protokoll, 2d ed., Berlin, 1903; Nauwerctc, C., Sectionstechnik, 2d ed., Jena, 1894; and the texts on legal 
medicine (see page 481), which contain many hints and procedures of value in the examination of the 
bodies of those who have died under suspicious circumstances. MAKING POST-MORTEM EXAMINATIONS 
1187 
livid patches. These patches may coalesce, forming a uniform dusky 
red color over the back of the trunk, head,'and extremities, and some- 
times over the ears, face, and neck. The same effect is observed on the 
anterior aspect of the body if it has lain on the face. At points of pres- 
sure, from folds in the clothing, or from the weight of the body on the 
table, the red color is absent or less marked. These changes occur 
before putrefaction sets in. This cadaveric lividity or hypostasis should 
not be mistaken for ante-mortem ecchymosis, from which it may usually 
be readily distinguished by its position and extent, by the fact that the 
surface of the skin is not elevated, and by the fact that on incision no 
blood is found free in the interstices of the tissues. Not infrequently 
the subcutaneous tissue in the vicinity of these post-mortem hypostases 
becomes infiltrated with reddish serum. Very soon after death, particu- 
larly in warm weather, the tissues immediately around the subcutaneous 
veins of the neck and thorax, and in other situations, may be stained a 
bluish red color from the decomposition and escape from the vessel of 
the coloring matter of the blood. If the epidermis has been detached at 
any point, the skin beneath soon becomes dry and brown. 
Putrefactive Changes.-Usually in from one to three days, depending 
upon circumstances, a greenish discoloration of the skin appears, at first 
upon the middle of the abdomen, over which it gradually spreads, assum- 
ing a deeper hue and often changing to a greenish purple or brown. 
Greenish patches may now appear on different parts of the body, earliest 
upon those overlying the internal cavities; this discoloration is probably 
produced by the action on the hemoglobin of gases developed by decom- 
position. The eyeballs now become flaccid, and if the eyelids are not 
closed the conjunctiva and cornea become brown and dry. The pressure 
of gases developed by decomposition in the internal cavities not infre- 
quently forces a greater or less quantity of frothy, reddish fluid or mucus 
from the mouth and nostrils, distends the abdomen, and, if excessive, 
may lead to changes of position of the blood in the vessels, and even a 
moderate amount of displacement of the internal organs.1 
After a varying period, sometimes within five or six days, the entire 
surface of the body may be discolored, green or brown. Then the epi- 
dermis may become loosened by the accumulation of gases and fluids 
beneath and the tissues become flaccid. The abdomen may be greatly 
distended and the features distorted from swelling. The rapidity with 
which these changes occur depends upon various conditions. Thus an 
elevated temperature and the presence of air and moisture hasten the 
advent and progress of putrefaction. 
The bodies of infants usually decompose more rapidly than those of 
adults, fat bodies more quickly than lean ones. The infectious diseases, 
intemperance, and the puerperal condition promote rapid decomposition, 
as does also death from suffocating gases. Poisoning by arsenic, alcohol, 
antimony, sulphuric acid, strychnine, and chloroform may retard the 
i With early and marked formation of gas in the tissues and organs, especially in the liver, the 
possibility of infection with Bacillus aerogenes capsulatus should be borne in mind. See p. 321. 1188 
MAKING POST-MORTEM EXAMINATIONS 
progress of decomposition. Burial in dry soil and submersion in water 
also retard the progress of decay.1 
Cooling of the Body.-After death the chemical changes upon which 
the maintenance of the temperature depends rapidly diminish, and the 
body gradually cools to the temperature of the surrounding medium. 
This usually occurs in from about fifteen to twenty hours, but the time 
required depends upon a variety of conditions. Immediately after death 
there is, in nearly all cases, a slight elevation of internal temperature, 
owing to the fact that the metabolic changes in the tissues still continue 
for a time, while the blood ceases to be cooled by passing through the 
lungs and peripheral capillaries. After death from certain diseases- 
yellow fever, cholera, rheumatic fever, and tetanus-a considerable ele- 
vation of internal temperature has been repeatedly observed. The time 
occupied by the cooling of the body may be prolonged after sudden death 
from accidents, acute diseases, apoplexy, and asphyxia. A number of 
cases are recorded in which the body retained its heat for several days, 
without known cause. 
After death from wasting chronic disease, and in some cases after 
severe hemorrhages, the cooling of the body is very rapid, the interior 
temperature being reduced to that of the surrounding air within four or 
five hours. Fat bodies cool less quickly than lean ones, the bodies of 
well-nourished adults less quickly than those of children or old persons. 
The temperature of the surrounding medium, and the degree of protection 
of the body from currents of air, of course, modify the progress of cool- 
ing; and the internal organs naturally retain their heat longer than the 
surface of the body. The rate at which cooling occurs is most rapid, as 
a rule, during the hours immediately following death, notwithstanding 
the post-mortem rise which may ensue. 
It will thus be seen that, if required to pronounce upon the time 
which has elapsed since death in a given case, we can do so only approxi- 
mately. It is necessary to take into account all of the above-mentioned 
conditions which modify the rate of cooling of the body, and then we 
may be able to state only the probabilities of the case. It is furthermore 
unsafe in any case to infer the cause of death from the rate of cooling of 
the body. 
Rigor Mortis.-Death is usually succeeded immediately by a period of 
complete muscular relaxation. The jaw drops and the limbs become 
flaccid. The muscles may retain for two or three hours, however, the 
capacity of contracting, on the application of appropriate stimuli. On 
the average, within six hours the muscles become firm and rigid. This 
post-mortem rigidity is called rigor mortis. On the occurrence of the 
rigor mortis the muscles become fixed in whatever position they may 
have had at the time of its occurrence. It usually begins in the muscles 
of the eyelids, extends to those of the back of the neck and lower jaw, 
1 For a study of bacteria in the blood of the cadaver, see Low, L., Ztschr. f. Heilk., Abth. f. path. 
Anat., 1900, xxi, 47. See also Babes, Ann. d'hyg. pub., 1899, xli, 193. 
Concerning the conversion of the body into adipocere, see Ewina, Peterson and Haines, Text-book 
of Legal Medicine. Philadelphia, 1904, i, 138; see also Ascarelli, Vrtljschr. f. gerichtl. Med., 1906, 
xxxii, 219; Muller, Post-mortem Decomposition, etc., Zurich, 1913; and Ruttan, R. F., and Marshall, 
M. J., Jour. Biol. Chem., 1917, xxix, 319. MAKING POST-MORTEM EXAMINATIONS 
1189 
then to the face and neck, and thence passing downward affects the mus- 
cles of the thorax and lower extremities. It usually disappears in the 
same order. Although commencing on the average six hours after death, 
it may set in at once or be delayed for twenty-four hours or more. It 
may pass off very rapidly, in rare cases in from one to three hours; or 
it may persist for two or three weeks or longer. It may be said in gen- 
eral that the average time of its disappearance is within twenty-four or 
forty-eight hours after its occurrence, depending on temperature, its 
intensity, the mode of death, the period of its advent, etc. Caspar 
states that in fetuses before term he has never observed rigidity, and 
that in young children it is feeble and of short duration. Its occurrence 
and phenomena may be in some cases of the highest medicolegal impor- 
tance; but its careful observation does not, with our present knowledge 
of its significance, appear essentially to further the aims of the practical 
pathologist.1 
Contusions.-It is often important to determine whether violence has 
been inflicted upon a body before death. In regard to this point, we 
must remember, first, that blows and falls of sufficient violence to fracture 
bones and rupture the viscera may leave no marks on the skin, even 
though the person has survived for several days; and, second, that there 
are post-mortem appearances which simulate ante-mortem bruises. A 
severe contusion during life may present, at first, no mark or only a 
general redness. After a short time the injured part becomes swollen 
and of a red color; this color may be succeeded by a dark blue, and this 
in turn fade into a greenish yellow or yellow; these later appearances 
are due to an escape of blood from the vessels and to a subsequent decom- 
position of hemoglobin. If, therefore, we cut into such an ecchymosis 
after death, we find extravasated blood or the coloring matter of the 
blood, in the form of pigment granules, free in the tissues. Post-mortem 
discolorations, on the other hand, although their external appearance 
may resemble that of ante-mortem ecchymosis, are not formed by an 
extravasation of blood, but by a circumscribed congestion of the vessels 
or by an escape of blood-stained serum. If we cut into such discolor- 
ations, therefore, we find no blood outside the vessels. Care should 
be taken not to mistake the lesions of hemorrhagic infection for trau- 
matic ecchymoses. 
Blows on the skin of a body which has been dead for not more than 
about two hours may produce true ecchymoses with extravasation of 
blood, such as can be distinguished with great difficulty or not at all 
from those formed during life. If putrefactive changes be present, the 
difficulty of distinguishing between ante-mortem and post-mortem bruises 
is greatly enhanced. 
Hanging and strangulation are attended with the formation of marks 
on the neck which are described in works on forensic medicine. These 
marks must not be confounded with the natural creases of the skin of 
the neck. Many adults during life have creases of the skin of the neck, 
1 For further details concerning rigor mortis, putrefactive changes, particularly the later stages, 
and the phenomena of cooling of the body, see Tidy, C. M., Legal Medicine, Philadelphia, 1884, vol. 
i, or other works on medical jurisprudence. 1190 
MAKING POST-MORTEM EXAMINATIONS 
one or more in number, running downward from the ear under the chin 
or encircling the neck. After death these creases may be much more 
evident than during life, and may be rendered more decided by the posi- 
tion of the head and the freezing of the body. They usually persist 
until the skin putrefies. 
Wounds.-We should notice the situation, extent, and direction of a 
wound, the condition of its edges and the surrounding tissues. If it be 
a deep, penetrating wound, its course and extent should be ascertained by 
careful dissection rather than by the use of a probe. 
If the edges of a wound be inflamed and suppurating, or commencing 
to cicatrize, it must have been inflicted some time before death. In a 
wound inflicted a short time before death, the edges are usually everted; 
there may be more or less extravasation of blood into the surrounding 
tissues, and the vessels may contain coagula; but sometimes none of these 
changes are observed. The chief characteristics of a wound inflicted 
after death are absence of a considerable amount of bleeding, non- 
retraction of the edges, and the absence of extravasation of blood into the 
tissues. But a wound inflicted within two hours after death may re- 
semble very closely one received during life. In general, unless a wound 
is old enough for its edges to present inflammatory changes, we must 
be very careful in asserting its ante-mortem or post-mortem character. 
Fractures.-It may be important to determine whether a bone was 
fractured before or after death. This point cannot always be decided. 
Fractures inflicted during life are, as a rule, attended with more extrava- 
sation of blood and evidences of reaction in the surrounding tissues; but 
fractures produced within a few hours after death may resemble these 
very closely. Usually a greater degree of force is necessary to fracture 
bones in the dead than in the living body. 
Scars and Tattoo Marks.-The presence and character of cicatrices 
should be noticed. Scars produced by any considerable loss of substance 
may become very much smaller and less conspicuous, but never entirely 
disappear. Slight and superficial wounds, however, leave marks which 
may not be permanent. The discoloration produced by tattooing may, 
although it rarely does, disappear during life. 
Internal Examination.1 
After completing the external inspection of the body, we commence 
the internal examination. In order that this examination may be made 
both thoroughly and rapidly, we should follow a regular method which 
should be such as will enable us to examine the relations of parts to one 
another, without seriously disturbing them, and to remove and inspect 
the organs in such an order and manner as will not interfere with the 
examination of parts which are to follow. In certain cases it may be 
necessary to depart from the regular method;2 but, as a rule, the following 
plan will be found most advantageous. 
J For sizes and weights of various organs, and other data, see Vierordt, Anatom., Physiol., und 
Physikalische Daten u. Tabellen, 3d. ed., 1906. For a study of the weights of the viscera in infancy 
and childhood, see Bovaird and Nicoll, Arch. Pediat., 1906, xxiii, 641. 
2 Sometimes the thoracic or abdominal viscera or both together may wisely be taken out in mass. 
See, for advantages of this method, Heller, G., Vrtljschr. f. gerichtl. Med., 1904, xxvii, 110. MAKING POST-MORTEM EXAMINATIONS 
1191 
It is important to remember the difference between the distribution 
of the blood in the body during life and after death. During life the 
blood is in constant motion and is distributed in a regular way in the 
heart, capillaries, arteries, and veins. Inflammations and obstructions 
to the circulation may disturb this natural distribution and produce con- 
gestion of particular parts of the body. After death the blood ceases to 
circulate; it leaves the left cavities of the heart, the arteries, and capil- 
laries, and collects in the veins and the right cavities of the heart. Ac- 
cording to the character of the disease which causes death, coagulation 
of the blood takes place more or less extensively and at an earlier or 
later period. The local congestions which existed during life often dis- 
appear after death. On the other hand, local congestions are found after 
death which did not exist during life. Thus, after death the scalp often 
contains a large amount of venous blood. The veins of the pia mater 
and the sinuses of the dura mater may be filled with blood. The mucous 
membrane of the larynx and trachea may appear to be deeply congested. 
The lungs are congested if the patient has been comatose for some hours 
before death. All the tissues of the back and the membranes of the 
spinal cord are often gorged with venous blood. The right auricle and 
ventricle of the heart may contain fluid or clotted blood in considerable 
quantity. 
THE HEAD. 
The scalp is divided by an incision across the vertex, from ear to ear. 
The flaps are dissected forward and backward, taking up the temporal 
muscles with the skin and leaving the pericranium attached to the bone. 
The internal surface of the scalp and the pericranium are to be searched 
for ecchymoses and inflammatory lesions. 
A circular incision is now made through the cranium with a saw. 
The incision should, in front, pass through a point about eight to ten 
centimeters above the bridge of the nose; behind, through the occipital 
protuberance. Care should be taken not to cut through the dura mater 
with the saw. When the roof of the cranium is thus entirely loosened, 
a stout hook is introduced under the upper edge of the calvarium, and 
this is wrenched off with a jerk. Some pathologists prefer to make two 
incisions meeting in blunt angles just above and posterior to the external 
auditory canal. The cosmetic effect is then better, as the calvarium is 
more firmly fixed when the body is prepared for burial. 
Sometimes the dura mater is so firmly adherent to the calvarium that 
the latter cannot be torn from it without injury to the brain. In this 
case, and also if the dura mater should have been accidentally cut 
through by the saw in making the circular incision, the dura mater may 
be cut through at the level of the cranial incision, and the brain removed 
with the calvarium and separated afterward. Or, which is better, in 
addition to the circular incision, a longitudinal incision may be made, from 
front to back, about three-quarters of an inch to one side of the median 
line of the skull, and a segment of bone removed. The knife blade may 1192 
MAKING POST-MORTEM EXAMINATIONS 
then be inserted from the open side, and the dura cut away from the 
skull-cap along the line of the longitudinal sinus, where the adhesions are 
apt to be most firm. 
We should notice whether or not the calvarium is symmetrical. The 
cranial bones increase in size by a growth of bone at the edges of the 
sutures. If any suture becomes completely ossified and closed prema- 
turely, the bones will be unequally developed. The thickness and density 
of the cranial bones vary considerably within the limits of health. There 
are often deep depressions on the inner surface of the skull along the 
sagittal suture, caused by the pressure of the Pacchionian bodies, and of 
no pathological significance. We should observe the blood content of 
the bone, determine the existence or absence of fractures, inflammatory 
lesions, exostoses, etc. 
The dura mater is now exposed. It is more or less adherent to the 
calvarium; a moderate amount of adherence, especially in old persons, 
does not denote disease. Very extensive and firm adhesions are usually 
produced by inflammation. Near the median line the Pacchionian bodies 
often project through the dura mater and may produce indentations in 
the internal surface of the calvarium. We must look for clots and for 
tumors and for inflammatory lesions on the external surface of the dura 
mater. The longitudinal sinus should be laid open and its contents 
examined. A circular incision is then made through the dura mater in a 
line corresponding to the cranial incision; the falx is divided between 
the anterior lobes of the brain, and the entire membrane drawm back. 
We should observe the existence of abnormal adhesions of the dura mater 
to the pia mater, bearing in mind that a moderate amount of adhesion 
along the longitudinal fissure is normal. The internal surface of the 
dura mater is to be examined for the products of inflammation and for 
tumors. 
The pia mater covering the convex surface of the brain is now 
exposed. The degree of congestion, and the existence of serum, pus, or 
blood, beneath, within, or upon it, are now to be ascertained before the 
brain is removed. The pia mater in old persons frequently loses its 
transparency and becomes thick and white; this change is most marked 
along the longitudinal fissure and large vessels. Marked and general 
thickening of the pia mater is the result of chronic inflammation. Along 
the longitudinal fissure, and sometimes at a considerable distance from it, 
we usually find small, elevated, whitish nodules, which are the Pacchio- 
nian bodies and are normal in the adult. 
The amount of serum beneath the pia mater varies. A considerable 
amount, especially in cachectic persons, may exist without brain disease. 
Clear serum, raising the pia mater and separating the convolutions of the 
brain, may be simply dropsical or due to chronic meningitis. Turbid 
and purulent serum, beneath and in the pia mater, is due to acute or 
chronic meningitis. The degree of flatness of the surface of the convo- 
lutions should be observed before removing the brain; for, when marked, 
it affords an important indication of pressure, from hemorrhage, inflam- 
matory products, internal fluid effusions, and tumors. The pia mater 
should be carefully examined for miliary tubercles. MAKING POST-MORTEM EXAMINATIONS 
1193 
The Brain.-After examining the convex surface of the brain, the 
anterior lobes of the cerebrum are to be pulled gently backward, the 
nerves, vessels, and tentorium severed, and the medulla cut squarely 
across, as low down as possible. The brain is now removed from the 
cranium by passing the fingers of one hand down, beneath, and behind 
the lobes of the cerebellum, and drawing the brain out, supporting the 
convexity with the other hand. 
The adult brain in the male weighs on the average about 1,400 grams; 
that of the female, about 155 grams less. The average proportional 
weight of the brain to that of the body is about one-forty-fifth, although 
in this, as in the absolute weight, there is considerable variation.1 
Fig. 798.-Side View of the Human Brain, Showing its Fissures and Convolutions. 
The exact situation of any lesion which is apparent externally should 
be described by its relation to the lobes, fissures, convolutions, and sulci 
(Fig. 798). 
The brain is first laid upon its convex surface, and the anterior, mid- 
dle, and posterior cerebral arteries, as well as the basilar and the carotids, 
are first examined for emboli, thrombi, atheroma, and aneurysms. Evi- 
dences of extravasations of blood, tumors, and inflammatory lesions are 
next looked for. The brain is then turned over on to its base. An in- 
cision is made through the pia mater, over the convex surface of the 
cerebrum. The membrane is stripped up, and its adherence to the brain 
and its thickness are noted. 
The more common method of opening the brain is as follows: The 
halves of the cerebrum are separated until the superior surface of the 
corpus callosum is exposed (Fig. 799). A longitudinal incision is made 
through the junction of the corpus callosum and the cerebrum, and 
downward into the ventricle. The incision should be made carefully, so 
1 For a study of the weight of the brain at various ages, see Handmann, E., Arch. f. Anat. u. Physiol., 
Anat. Abth., 1906, Suppl., p. 1. 1194 
MAKING POST-MORTEM EXAMINATIONS 
as not to cut through the ventricle into the ganglia below. The incision 
thus made through the roof of the ventricle is prolonged backward and 
forward in the direction of the cornua, so as to expose the entire ventri- 
cle. A longitudinal incision is then made outward and backward into 
the hemisphere, from the outer edge of the lateral ventricle nearly to 
the pia mater. A second incision is then made through this cut surface 
outward, and this is repeated until the hemisphere is divided into a 
number of long, prism-shaped pieces, held together by the pia mater 
Fig. 799.-Method of Opening the Brain, Showing the Direction of First Incision. 
and a small portion of the cortex. The brain is now turned around so 
as to bring the other hemisphere under the hand, and the operation is 
repeated on the other side. 
The size, shape, and contents of the ventricles should be noticed, and 
the thickness and appearance of the ependyma. 
The fornix and the central portion of the corpus callosum are cut 
across by passing the point of the knife through the foramen of Munro 
and cutting upward. They are then drawn backward, one of the pos- 
terior cornua of the fornix being severed and laid to one side. The MAKING POST-MORTEM EXAMINATIONS 
1195 
velum interpositum and the choroid plexus are now dissected up, the 
blood contents and the general appearance noted, and the third ventricle 
examined. Not infrequently small cysts of the choroid are found, which 
seem to have little or no pathological significance. 
The fourth ventricle is now opened by a longitudinal incision through 
the vermiform process. Each hemisphere of the cerebellum is divided 
first into two parts, by an incision through the upper and inner convex 
border, and then each segment is further divided by incisions in the same 
direction. 
Thin transverse sections are now made through the cerebral ganglia, 
commencing in front (Fig. 800). The ganglia are supported, and the sec- 
Fig. 800.-Method of Opening the Brain, Showing the Unfolded Segments of the Cere- 
brum and Lines of Transverse Incision of the Basal Ganglia and Directions of the Incisions 
of the Cerebellum. 
tions caused to fall apart as they are cut, by carrying the fingers of one 
hand under the brain, and gently lifting the ganglia at points just 
beneath where the sections are made. It is important to observe the 
exact position of any lesions which may be discovered in the cerebral 
ganglia, and the relations of such lesions to the external and internal 
capsule and to the caudate and lenticular nuclei. 
Finally, the segments of the cerebrum and cerebellum are folded up 
together into their original positions, the whole is turned over on to the 
vertex, and thin sections are made through the medulla. Small clots in 
the medulla should not be overlooked. 
In case of the discovery of apoplectic clots, areas of softening, etc., 
either in the hemispheres or in the basal ganglia, after their location and 
extent are determined, they should be carefully searched for lesions of 1196 
MAKING POST-MORTEM EXAMINATIONS 
the blood-vessels, minute aneurysms, areas of degeneration, and rup- 
tures. For this purpose it may be necessary to allow a stream of water 
to run over the affected portion, so as to wash out the brain substance 
and expose the vessels. In some cases the blood-vessels are best exposed 
Fig. 801.-Schematic Picture of Brain, Showing the Method of Dissection from the Base 
(Meynert's method). 
E and F, Temporal lobes turned backward and outward; AB, AC, BD, line of incision to remove basal 
piece. 
by macerating the brain tissue at the seat of the lesion for some hours 
in water, and then either washing out the brain substance under the 
faucet, or removing it by shaking the tissue in water in a closed vessel. 
While the above mode of dissecting the brain gives a very complete 
view of the seat and extent of lesions in 
general, when a more exact localization of 
lesions with a microscopic examination is to 
be made, the following-called Meynert's 
method-is a better method of opening the 
brain: 
After completing the external examina- 
tion, as detailed above, the brain is laid on 
its vertex, the cerebellar end toward the oper- 
ator. The cerebellum is raised by the fingers 
of the left hand, and the pia cut through along 
the sides of the corpora quadrigemina, around 
the crura and along the inner margins of the 
temporal lobes, to the middle cerebral artery 
on both sides (Fig. 801). Then, raising the 
temporal lobes, in turn, by their apices, the pia is cut through along the 
course of the middle cerebral artery into the Sylvian fissure, and along 
the course of its posterior branch to its end. Now, drawing the temporal 
lobes one after the other upward and outward, their junction with the 
Fig. 802.-The Brain Axis 
Separated from the Brain 
Mantle, as Seen from Above 1197 
MAKING POST-MORTEM EXAMINATIONS 
base is cut, the knife being held horizontally so as not to injure the 
basal ganglia until the descending horn is opened. The point of the 
knife being in the descending horn, the incision through the brain sub- 
stance then passes outward and backward well into the posterior horn, 
thus partially severing the lateral surface of the brain, the junction of 
the occipital and temporal lobes. The temporal lobes are then turned 
outward and backward (Fig. 801). 
The operculum is now pulled well outward, completely exposing the 
island of Reil, and a slightly curved transverse incision is made, deep 
enough to pass into the anterior horns of the ventricles, connecting the 
anterior sulci of the island of Reil (-Fig. 801, A, B). 
A, Internal capsule; B, operculum; C, posterior border of corpus callosum; D, descending horn; E, 
cornu Ammonis. 
Fig. 803.-The Brain Mantle, as Seen from Below. 
The cerebellum is now raised, and the point of the knife inserted into 
the ventricle, then with short incisions from within outward, the internal 
capsule on either side from back to front (Fig. 801, CA and DB) is cut 
through, care being taken not to injure the basal ganglia. Then the 
crura of the fornix and the septum lucidum are cut across, the fornix 
being left lying on the corpus callosum. 
The square basal piece (Fig. 802) thus freed-the brain axis-includes 
the island of Reil, the basal ganglia, the crura, pons, medulla, and cere- 
bellum. The remaining portion-the brain mantle-includes the con- 
volutions, corpus callosum, and fornix (Fig. 803). 
The basal piece may be further examined by a series of transverse 
incisions, from one-half to three-quarters of an inch apart, and it may be 1198 
MAKING POST-MORTEM EXAMINATIONS 
hardened either with or without the cerebellum. The convolutions may 
be cut into small pieces by longitudinal and transverse incisions, made 
from within and not reaching quite to the pia mater, which will then serve 
to hold the pieces together in their proper relations to one another.1 
The Base of the Cranium.-We now return to the skull. The re- 
maining sinuses of the dura mater should be opened, and this membrane 
then entirely stripped from the bone. The bones at the base of the skull 
are to be examined for fractures, inflammatory lesions, and tumors. In 
cases of acute purulent meningitis, the temporal and frontal bones should 
be carefully examined, as the inflammatory process is sometimes trans- 
mitted from the internal ear, or mastoid cells, or frontal sinuses. 
The eyes may be removed by breaking the roof of the orbit with a 
hammer, removing the fragments of bone, and dissecting away bone and 
muscles, so as to expose the optic nerve and posterior segment of the 
eye. That portion of the globe which is not covered by conjunctiva can 
now be cut away with scissors and removed with the optic nerve, or, 
when permissible, the whole eye may be cut out. 
The examination of the internal ear may be made by removing its 
entire bony encasement with the saw and chisel, or by the exposure of 
special parts by hammer and chisel, and by suitable opening of the re- 
moved parts with a fine saw. 
Hardening and Preservation of the Tissues for Microscopical Examination. 
For the study of tumors and inflammatory lesions of the bones of the skull and 
ossifications of the dura mater and pia mater, the affected portions should be cut into 
small pieces, fixed in 4 per cent, formaldehyde or in Orth's fluid (see page 1229), and 
decalcified. The dura mater should be stretched on a flat piece of wood or cork with 
pins, before hardening.2 
The pia mater is so delicate that if it is separated from the brain when quite fresh 
its tissues are apt to be injured. The portions of the pia mater which are to be pre- 
served should therefore be removed by cutting off slices of the brain substance about 
half an inch thick, with the membrane still attached, and placing the whole in Orth's 
fluid. After twenty-four hours, the pia mater will have become sufficiently hard to 
permit of its being stripped off without injury, and it is then spread loosely on a flat 
cork with pins, the free surface outward, and the cork floated, specimen side down, in 
80 per cent, alcohol, changing to strong alcohol after twenty-four hours. 
When sections showing the pia in its relationship to the underlying brain tissue 
are required, small blocks of the brain and pia together should be cut out and hard- 
ened in Orth's fluid or in 4 per cent, formaldehyde. 
When the ependyma is to be studied apart from the associated nerve tissue, it may 
be sliced off with a sufficient quantity of underlying brain substance to prevent its 
folding, and hardened in Orth's fluid. The brain may be hardened in Orth's fluid, in 
95 per cent, alcohol, or in 4 per cent, formaldehyde. The pieces of brain tissue should 
not be more than 1 cm. thick; it is better if they are thinner than this. They should 
be suspended in gauze or rest upon a layer of absorbent cotton on the bottom of the 
jar, the pieces, if these are numerous, being held apart by a little cotton. Thus the 
preservative fluid, which should be abundant, is in contact with the surfaces of the 
pieces of tissue. Ordinarily, with a change of fluid on the second day, the fixation by 
formaldehyde or Orth's fluid is complete in a week, when the fixatives are thoroughly 
1 For further details of this method of opening the brain, and a consideration of its advantages, see 
Van Gieson, I., New York Med. Jour., 1889, 1, 57. 
2 For details of the methods of hardening, decalcifying, staining, etc., see p. 1229. MAKING POST-MORTEM EXAMINATIONS 
1199 
washed out and replaced by 50 per cent, alcohol, which, in turn, is replaced after 
forty-eight hours by 80 per cent, or by 95 per cent, alcohol. 
When degeneration in nerves is to be studied, the specimens of nerve tissue may, 
by Marchi's method, be hardened for a week in Muller's fluid, and then transferred to 
the following solution: 
Muller's fluid 2 parts. 
Osmic acid, 1 per cent I part. 
After a week the specimens are washed and transferred to 95 per cent, alcohol. 
In such specimens the fat droplets in the degenerated areas are black, while the myelin 
is yellowish in color. 
Certain lesions, particularly the softenings of the brain, are best studied by teasing, 
when fresh, in 0.5 per cent, solution of sodium chloride, or in frozen sections of the 
fresh tissue. The blood-vessels may be stretched on cork with pins and hardened 
with Orth's fluid or formaldehyde. The eye and portion of the optic nerve, if removed, 
should be fixed by Orth's fluid and the hardening completed by alcohol. 
For many methods of fixation and study which are useful for special purposes, we 
refer to special works on technique. 
THE SPINAL CORD. 
The examination of the spinal cord is usually most conveniently made 
after the removal of the brain. 
The body should be placed face downward, with a block under the 
thorax and the head hanging over the edge of the table. An incision is 
made through the skin and muscles along the entire length of the spine, 
and the soft parts are dissected away on each side so as to expose the 
laminae of the vertebral column. The laminae are then divided, close 
within the articular processes, with the saw. 
The saw should be so directed in severing the laminae that the inci- 
sion shall touch the outer border of the spinal canal, as otherwise the 
laminae and spinous processes are not easily separated. Great care 
should be taken on the one hand not to injure the cord with the saw, 
and on the other completely to loosen the portions of bone to be removed. 
These, which are the spinous processes and laminae, are now torn away 
together, with a stout hook, exposing the cord. 
By means of a long, curved chisel, made for this purpose, the bodies 
of the vertebrae may be removed from the front after the thoracic and 
abdominal viscera are taken out, and the cord thus exposed and re- 
moved. But in this anterior method of removing the cord, as well as by 
the use of chisel and mallet, bone-shears, etc., in the ordinary method, 
there is great liability of injuring the delicate tissues of the cord and 
producing, as Van Gieson has shown,1 mechanical alterations which are 
likely to be mistaken for malformations or the results of disease. 
When the body has lain on the back, the membranes of the cord may 
be found considerably congested, without indicating the pre-existence of 
disease. If the body has lain for some time, especially in warm weather, 
serous fluid may have accumulated within the membranes, as a result of 
post-mortem change. 
Van Gieson, I., New York Med. Jour., 18S2, Ivi, 337, 365, 421. 1200 
MAKING POST-MORTEM EXAMINATIONS 
The roots of the nerves are now to be cut across, as far away as pos- 
sible from the cord, and the cord removed in its membranes, care being 
taken not to press it in any way. It is the safest plan not to grasp the 
cord itself, but with a forceps to seize the dura mater and thus lift it up 
at once as it is freed from its attachments. It is now laid on the table, 
Copies of these outlines may be used for memoranda of the situation of lesions of the spinal cord. 
I, Second cervical; II, fifth cervical; III, eighth cervical; IV, first dorsal; V, eighth dorsal; VI, third 
lumbar; VII, fourth sacral. 
Fig. 804.-Outlines of Sections of the Spinal Cord at Different Levels. 
and the dura mater laid open with scissors on the anterior and posterior 
surfaces over its entire length, and searched for tumors, inflammatory- 
lesions, etc. The finger should be passed gently along the cord as it lies 
on the table, so as to detect any marked softening or sclerosis. The 
weight of the spinal cord is from 30 to 38 grams. It should now be held 
lightly over the fingers, and smooth transverse incisions made, with a MAKING POST-MORTEM EXAMINATIONS 
1201 
very sharp knife or razor, about half an inch apart through its entire sub- 
stance between the segments, leaving these attached to the pia mater. 
The segments of the spinal cord are those parts from which the spi- 
nal nerves arise, and it is convenient for the location and description of 
lesions to number the segments in correspondence with the nerves which 
arise from them, and to indicate on outline diagrams of the cord (Fig. 804) 
the exact seat of small lesions. 
The cut surfaces should be carefully examined for abnormal blood 
contents, hemorrhages, inflammatory lesions, softening, scleroses, and 
pigmentations. Important lesions of the cord may be invisible to the 
naked eye, and hence, if disease be suspected, the organs should be pre- 
served for microscopical examination. The spinal ganglia may now be 
removed and preserved for further examination. After removal of the 
cord, fractures and displacements of the vertebrse are easily recognized. 
Preservation of the Spinal Cord and Its Membranes, and of Peripheral 
Nerves.-After the removal of the spinal dura, the entire cord with its nerve roots- 
the segments into which it has been cut for gross examination being left in place- 
should be laid on a wad of absorbent cotton in a large jar of Orth's fluid or formalde- 
hyde, the segments being slightly separated from each other by a little absorbent 
cotton. Van Gieson recommends the careful rolling of the segmented cord into a 
loose spiral and laying this coil on a wad of absorbent cotton in the fixative. In this 
way the cut ends of the segments are held apart, accessible to the fluid, and harden 
with little distortion. 
The hardening and preservation of the cord may be done by the same methods as 
suggested above for the brain. If the dura mater of the cord alone is to be preserved, 
it should be treated in the manner suggested for the dura mater cerebralis. The pia 
mater spinalis is best studied in sections through the entire cord, the membranes being 
left in situ. 
Peripheral nerves may be hardened in Orth's fluid or in formaldehyde. 
For the hardening of the peripheral nerves, osmic acid is very useful, especially 
when changes in the myelin are to be sought after. As osmic acid does not readily 
penetrate the lamellar sheath so as to come in contact with the nerve fibers, in trunks 
of any considerable size, the following procedure, as suggested by Van Gieson, will be 
found useful: A piece about one-half inch long is cut from the nerve to be examined; one 
end of this segment is held with a forceps, while with another forceps the individual 
nerve fibers, or small clusters of these, are pulled out of the lamellar sheath and put at 
once in a 1 per cent, aqueous solution of osmic acid, in which they remain twenty- 
four hours, and are then washed and transferred to glycerin, to which 25 per cent, 
alcohol is added. In this mixture they may be preserved. Marchi's method is useful 
for the study of degeneration in peripheral nerves. 
THE THORAX AND ABDOMEN. 
The body is replaced on its back, and a single straight incision is 
made from the top of the sternum to the pubes, passing to the left of the 
umbilicus. For this purpose a large knife should be used, held firmly 
in the whole hand, and the movement should be mainly from the shoul- 
der. The first incision should divide everything down to the sternum 
and peritoneum. A short incision should then be made through the 
peritoneum, just below the ensiform cartilage. Into this opening two 
fingers of the left hand are introduced and separated from one another, 
and, the parietes being raised and the sides of the opening being held 1202 
MAKING POST-MORTEM EXAMINATIONS 
apart by the fingers, the peritoneum is divided to the pubes, care being 
taken to hold the knife horizontally so as not to cut the intestines. The 
skin and muscles are then dissected off from the thorax on both sides as 
far back as the false ribs. 
This dissection should be made by long sweeps of the knife, which 
should be made to cut with the full blade and not with the point only; 
and if the skin and muscles be pulled strongly away from the chest with 
the left hand, it may be done very rapidly and with a few strokes of the 
knife. We notice here the amount of subcutaneous fat and the condi- 
tion of the muscles. In order better to expose the abdominal cavity, the 
rectus should be divided transversely beneath the skin just above the 
pubes, and the abdominal flaps may then be turned freely outward. 
General Inspection of the Abdominal Cavity.-We first notice the posi- 
tion and general condition of the viscera. It is best at this stage of the 
examination to note the condition of the vermiform appendix, and to 
look over the peritoneal cavity for serum, inflammatory lesions, evi- 
dences of perforation, and for the existence of invagination, incarcera- 
tion, and hernia of the intestines. A small quantity of reddish serum 
is frequently found in the abdominal cavity, particularly in warm 
weather, as the result of commencing decomposition. 
It should be remarked here that various striking changes in the 
character and appearance of the internal organs are produced by putre- 
faction-changes which are often mistakenly regarded as evidences of 
disease, and much experience is required in judging correctly of their 
significance. These changes are, in general, softening and discoloration, 
both of which may occur as the result of disease. It may be said in 
general that the post-mortem reddening, or hypostases, are most marked 
in the more dependent parts of the organs. Post-mortem softening usu- 
ally affects entire organs, not being limited to a part, as is often the case 
in disease. Gray or grayish-brown post-mortem discolorations are apt 
to appear in those organs or parts of organs which lie in contact with the 
intestinal canal. Parts of internal organs, such as the liver, which have 
been the seat of localized congestion during life, may after death assume 
a dark greenish color. 
The omentum is usually spread over the surface of the small intes- 
tines, but it may be rolled up and displaced in a variety of ways, or may 
be adherent at some point to the small intestines or to the abdominal 
wall. 
The surface of the small intestines should be smooth and shining. 
They may be greatly distended with gas, and thus so completely cover 
the other abdominal viscera that it becomes necessary to let out some of 
the gas by a small puncture. The transverse colon passes across the 
abdomen through the upper part of the umbilical region. It may be 
lower than the umbilicus, or higher up against the liver and diaphragm; 
it may be distended with gas or contracted. 
The liver is situated in the right hypochondriac and epigastric re- 
gions, filling the concavity of the diaphragm. Its upper border reaches, 
in the linea mammillaris, to the fifth intercostal space; in the linea axil- MAKING POST-MORTEM EXAMINATIONS 
1203 
laris, to the seventh intercostal space; close to the vertebral column, to 
the tenth intercostal space. At the median line the upper border of the 
liver corresponds to the lower border of the heart. The left lobe extends 
about three inches to the left of the median line. The lower border of 
the right lobe usually reaches to the free border of the ribs, while the 
left lobe is visible for about an inch below the ensiform cartilage. In 
women the liver is usually lower than in men. 
The position of the liver is affected by changes in the thoracic cav- 
ity, forcing it downward; by changes in the abdominal cavity, forcing 
it upward; by constriction of the waist in tight lacing, forcing it either 
upward or downward; by changes in the size of the organ itself. The 
liver may not only be displaced downward, but dislocated so that its 
convex surface faces the abdominal wall and its posterior edge is turned 
upward against the diaphragm. 
The stomach is situated in the left hypochondriac and epigastric re- 
gions, extending also into the right hypochondrium; it lies in part 
against the anterior wall of the abdomen, in part beneath the liver and 
diaphragm, and above the transverse colon. Its anterior surface, which 
is directed upward and forward, is in contact above with the diaphragm 
and the under surface of the liver, and lower down with the abdominal 
wall opposite to the epigastric region. Its posterior surface is turned 
downward and backward, and rests on the transverse mesocolon, the 
pancreas, and the great vessels. To its lesser curvature or upper border 
are attached the gastrophrenic ligament and the gastrohepatic omen- 
tum. To the greater curvature or lower border is attached the gastro- 
colic omentum. Its cardiac orifice communicates with the esophagus, 
its pyloric end with the duodenum. 
When the stomach is distended the greater curvature is elevated and 
carried forward, the anterior surface is turned upward and the posterior 
surface downward. When distended with food or gas the organ is promi- 
nent; when empty it may hardly be visible below the ribs; when the 
intestines are dilated it may be entirely covered by them. 
Before opening the thorax the hand should be passed up against the 
under surface of the diaphragm on either side, to determine its height. 
According to Quain, the vault of the diaphragm rises, in the dead body, 
on the right side to the level of the junction of the fifth rib and sternum, 
on the left side as high as the sixth rib. Both the relative and the 
absolute height of the diaphragm vary under a variety of pathological 
conditions. 
If the existence of air or gas in the pleural cavities is suspected, the 
abdominal cavity should be filled with water and the diaphragm punc- 
tured below the level of the fluid. If air is present, it will escape in 
bubbles through the water. 
The Thorax. 
We now leave the abdominal viscera and proceed to the examination 
of the thorax. With a costotome or a strong knife the costal cartilages 1204 
MAKING POST-MORTEM EXAMINATIONS 
are divided close to the ribs, the clavicles are disarticulated from the 
sternum, and the latter is removed, care being taken not to wound the 
large veins. We first examine the position of the heart and lungs. 
The Heart.-The upper border of the heart is on a level with the 
third costal cartilage; the lower border extends from 1.3 cm. below the 
lower end of the sternum to the fifth left intercostal space. The left 
boundary of the heart is situated to the left of the junction of the fifth 
rib with its costal cartilage, and behind or to the left of a vertical line 
drawn downward from the left nipple. The right boundary extends 2.5 
cm. to the right of the right edge of the sternum. The portion of the 
heart uncovered by the lungs is of an irregular quadrangular shape. Its 
lateral diameter is from 8.3 cm. to 11.1 cm.; its upper boundary varies 
from the level of the second costal cartilage to that of the fifth, but it is 
usually behind the third or fourth cartilage or fourth space. 
The area of the heart which is found uncovered will, however, vary 
greatly, according to the degree to which the lungs collapse after the 
chest is opened. Any disease which diminishes the size of the lungs, or 
pleuritic adhesions which retract or bind them down, may increase the 
area of exposed heart. On the other hand, emphysema, pneumonia, or 
any disease which increases the size of, or retains the air in, the lungs, may 
diminish the area of exposed heart. The exposed area varies also with 
the size of the heart itself. 
The pericardium is now opened by a slightly oblique incision on its 
anterior surface. The existence of serous, fibrinous, or purulent exu- 
date, and of adhesions, is to be noted. A small quantity of clear serum 
exists normally in the pericardial sac, and this serum may be blood- 
stained from beginning decomposition. White thickenings of the peri- 
cardium on the surfaces of the heart are often seen; they do not indicate 
important disease. 
Now that the pericardial sac is open, the position of the heart can be 
clearly seen. It lies obliquely in the chest, its long axis at an angle of 
about sixty degrees with that of the thorax. The portion of the heart 
which is first seen is the anterior surface of the right ventricle; upward 
and to the right of this is the right auricle, which lies about two-thirds 
on the right of the sternum and about one-third behind it. Its upper 
border usually corresponds to the plane of the middle of the anterior 
end of the second intercostal space on the right side. Its size varies 
with the amount of blood which it contains. The left auricle lies behind 
the root of the pulmonary artery, so that only its appendix is visible. 
The middle of the auricle corresponds to the third costal cartilage. Of 
the left ventricle only a narrow rim is seen, on the left side of the right 
ventricle. The pulmonary valve is usually entirely or in part on the 
left side of the sternum, behind the second space or third costal 
cartilage. 
The aortic valve is usually at the level of the third cartilage or the 
third space, and behind the left two-thirds or half of the sternum. The 
mitral valve is oblique, the upper end to the left. It is on the level of 
the third to the fourth cartilage, near the middle of the sternum. The MAKING POST-MORTEM EXAMINATIONS 
1205 
tricuspid is oblique, its upper end to the left; the upper end is at the 
level of the third cartilage, the third space, or the fourth cartilage. 
The valve is opposite the middle of the sternum. 
The hand should now be passed over the arch of the aorta, to ascer- 
tain whether or not an aneurysm is present. The heart is then grasped 
at the apex, raised out of the pericardium, tilted upward, and removed 
unopened by cutting through the great vessels at its base. It is advisable 
in many cases to remove with the heart the arch of the aorta and as much 
as is practicable of the associated great vessels. In some instances, 
for example when thrombosis of the pulmonary artery is suspected, it is 
well to remove the heart and lungs together.1 
One may gain some knowledge of the sufficiency of the aortic and pul- 
monary valves if the heart is held horizontally by both auricles, so as 
not to pull the valves open, and water is poured into the aortic and pul- 
monary arteries. One observes how well the valves support the column 
of liquid. To ascertain the sufficiency of the mitral and tricuspid valves, 
the auricles are first laid open so as to expose the upper surfaces of the 
valves. A large pipe is passed through the aorta or pulmonary artery 
beyond their valves, and a small stream of water allowed to flow into the 
ventricles. The auriculoventricular valves will be swollen upward, and 
one may observe their degree of sufficiency. The tricuspid valve is 
normally somewhat insufficient. These water tests, however carefully 
applied, are not very reliable, since under the most favorable conditions 
the natural bearings of the valves are not perfectly preserved. 
To ascertain the size of the different valvular openings, we introduce 
the fingers, held fiat with their sides in contact, into each of the orifices, 
and then measure the width of the fingers at the point where they fill the 
orifice. In this way we find that, under normal conditions in the adult, 
the aortic valve measures about 2.5 cm., the mitral about 4.5 cm., the 
pulmonary about 3.1 cm., the tricuspid about 5 cm. 
In order to examine the interior of the heart, one first makes an incision 
through the anterior wall of the left ventricle close by and parallel to 
the septum, and reaching to the apex of the ventricle (Fig. 805). Through 
this opening the blade of the enterotome is passed up into the aorta, the 
pulmonary artery being drawn aside with the fingers, and the ventricle 
and aorta are laid open (Fig. 806). With a little care the incision may be 
made to pass through one of the points of junction of the aortic valves. 
The auricles and ventricles may be empty, or may contain fluid blood 
or the so-called heart clots. These heart clots are of two kinds-those 
which are formed some time before death, and those which are formed 
during the last hours of life and after death. The clots which are formed 
some time before death are usually associated with organic disease of the 
heart, especially with dilatation of the ventricles. They are firm, dry, 
and of whitish color, and may be infiltrated with the salts of lime. They 
lie free in the cavities of the heart, or entangled in the trabeculae, or 
1 The opening of the heart in situ is recommended by many, but we are of the opinion that if care 
be exercised in the removal of the organ from the body and a sufficient portion of the great vessels 
at the base be included there is little risk of premature disturbance of thrombi, etc., on the valves, while 
the examination of the interior may be much more thoroughly, conveniently, and safely done. 1206 
MAKING POST-MORTEM EXAMINATIONS 
firmly adherent to the endocardium, and are usually composed of coagu- 
lated fibrin, blood platelets, leucocytes, and red blood cells, and often 
lamellated. The clots which are formed during the last hours of life 
and after death are red, yellow, or white. They may be soft or succu- 
lent or quite firm, and may be free in the heart cavities, or be adherent 
Fig. 805.-Heart Showing Lines for Incision in Opening. 
to the trabeculae, or extend into the large vessels. They are usually most 
constant and of largest size in the right auricle and ventricle. Such 
clots may be formed within two hours after death. Clots of this char- 
acter are common. If, then, the blood coagulates in the heart within 
twenty-four hours before death, this coagulum may not be distinguish- 
able from the ordinary post-mortem clots. If it is supposed, therefore, 
that a person dies from heart clot developed a few hours before death, MAKING POST-MORTEM EXAMINATIONS 
1207 
the proof of this must be derived largely from the clinical symptoms, and 
not from the autopsy. 
The condition of the aortic valves and of the endocardium, and the 
thickness and appearance of the walls of the left ventricle, papillary 
muscles, chordae tendineae, etc., are now noticed. 
The right ventricle is now opened by an incision through its anterior 
wall, close to the septum (Fig. 805), and examined in the same way. 
The endocardium of the upper part of the left ventricle is sometimes 
Fig. 806.-Heart Opened, Exposing the Aortic Valves. 
thick and white, without the existence of valvular lesions or clinical 
history of disease. The endocardium and valves are often stained red, 
particularly in warm weather, by imbibition of coloring matter of the 
blood, set free by decomposition. This discoloration is especially 
marked in cases of infection with Bacillus aerogenes capsulatus. 
To complete the examination of the cavities the enterotome is passed 
into each auricle, and carried down into the corresponding ventricle, and 
an incision made along the outer border of both auricle and ventricle to 
the apex of the latter. In this way the auriculoventricular valves are 
completely exposed. The coronary arteries should be opened through 1208 
MAKING POST-MORTEM EXAMINATIONS 
all their main trunks, with fine probe-pointed scissors, and carefully- 
examined for marks of inflammation, emboli, thrombi, etc. 
In cases of Stokes-Adams disease or cardiac arrhythmias where injury 
of the conducting system of the heart is suspected, that organ should be 
opened according to the lines shown in the appended sketch (Fig. 807).1 
The superior vena cava should be cut high up, at least an inch from its 
auricular mouth, and as much as possible of the vessel should be spared 
in detaching the heart from the lungs on the right side. The vessels 
should then be tied, and the entire heart injected with 4 per cent, formal- 
AORTA 
PULM. ART. 
SUP. VENA CAVA 
d-EFT VENT. 
KT. 
AUR. 
RT. 
VENT. 
INF VENA CAVA 
Fig. 807.-Special Incision for Opening Heart, in Order to avoid Injury to Conducting 
System. 
dehyde, the organ being placed in a large quantity of the same fluid. 
The incisions should be made after the heart has hardened for two or 
three days; or, if preferred, the openings can be made while the heart is 
fresh and the fixation carried out on the opened organ. The first cut 
should be made with scissors along the opening of the inferior vena cava, 
the right auricular wall being cut parallel with and close to the auriculo- 
ventricular groove and the incision extended to the apex of the auricular 
appendix. This permits the inspection of the auricle and tricuspid valve. 
The scissors should then be inserted into the inferior vena cava and a cut 
made along the right border of the ventricle to its apex. A third incision 
should be made from the apex of the right ventricle up through the pul- 
monary artery, the scissors being kept well over to the left so as to pass 
between the left anterior and posterior cusps of the pulmonary valve. 
1 Oppenheimer, B. S., Jour. Amer. Med. Assn., 1912, lix, 937. 1209 
MAKING POST-MORTEM EXAMINATIONS 
The anterior papillary muscle should be avoided in this incision as the 
right branch of the auriculoventricular system passes directly from the 
interventricular septum to this muscle. On the left side an incision 
should be made through the orifices of the pulmonary veins, and then 
the left ventricle should be opened by a cut between the two papillary 
muscles to the apex; from the apex an incision into the artery parallel 
with the interventricular septum should be made. After formaldehyde 
fixation the heart should be hardened in 70 per cent, alcohol until suitable 
portions are embedded for cutting. 
After removing the blood, the heart should be finally weighed. The 
normal average weight of the heart in adults is, according to an estimate 
of H. D. Arnold,1 in males about 290 grams; in females about 260 grams. 
The weight of the heart relative to that of the body is in males about 
1 : 158 to 178; in females, about 1 : 149 to 176. According to Buhl, the 
average thickness of the wall of the left ventricle at about the middle of 
the cavity is from 1.6 cm. to 1.7 cm.; of the right ventricle, from 0.4 to 
0.6 cm. 
The size of the heart, speaking generally, corresponds to the size and 
the development of the individual. In judging of an increase or de- 
crease in its size we must consider the weight of the organ and the thick- 
ness of its walls. If the person dies while the heart is contracted, the 
walls of the ventricles will appear thicker, their cavities smaller than 
usual.2 If he dies of some exhausting disease like typhoid fever, or if 
decomposition has commenced, the heart walls will usually be flabby 
and the cavities will appear larger than usual. 
Preservation of Specimens.-Parenchymatous and fatty degeneration of the 
heart may be studied microscopically by teasing the fresh muscle in 0.85 per cent, 
salt solution, or by examining in the same solution fresh sections made with the 
freezing microtome, or by hardening small pieces of the muscle in 1 per cent, osmic 
acid and teasing in equal parts of glycerin and water. 
When lesions of the conducting system are to be studied the whole heart should 
be fixed for forty-eight hours in warm Orth's fluid or 4 per cent, formaldehyde. 
When the presence of bacteria is suspected, cultures should be made and the tissues 
should be preserved in strong alcohol. 
The pleural cavities are next examined. The hand is passed into 
each, and the existence of serous or fibrinous exudation or of old adhe- 
sions ascertained. The method of detecting the presence of air has been 
given above. After the commencement of putrefaction reddish serum 
may accumulate in the pleural cavities. This should not be mistaken 
for the result of disease. 
The Lungs.-Each lung is lifted up in turn, the vessels, etc., at its base 
are divided, and the organ is removed. If the pleura is very adherent it 
is better to strip off the costal pleura with the lung. After the external 
surface of the lung is inspected, and its size, shape, color, and consistence 
and the condition of the bronchial lymph-nodes are observed, the bronchi 
1 Arnold, Observations on the Weight of the Normal Heart in Adults, in Two Hundred and Sixteen 
Cases, Reports of the Boston City Hospital, 1899, x, 83. 
2 For method of determining hypertrophy of the heart, see Muller, W., Die Massenverhaltnisse 
des mensch. Herzens. 1883. 1210 
MAKING POST-MORTEM EXAMINATIONS 
are opened with scissors having long, narrow, blunt-pointed blades, one 
blade a little longer than the other. The lung is held in the left hand 
with its base upward, the large bronchi which run on the inner side of 
the lower lobe being first opened, afterward those of the upper lobe. 
Each bronchus should be followed to its smaller ramifications. 
We should observe the contents of the bronchi and the appearance of 
their walls. In the larger and medium-size bronchi the cartilages in 
their walls do not form complete rings, but appear shining through the 
mucous membrane like irregular white patches. This appearance should 
not be mistaken for a pathological change. In bodies which have been 
dead for some time, especially in cold weather, the bronchial mucous 
membrane may be red and swollen as a post-mortem change. The 
contents of the stomach are sometimes forced, after death, into the 
pharynx, and thence find their way into the trachea and bronchi, giving 
them a peculiar reddish and even gangrenous appearance. Bronchitis 
does not always leave lesions which can be seen after death. The large 
vessels should now be examined for thrombi, emboli, or other lesions. 
After the examination of the bronchi the lung is turned over, the 
vessels, etc., at its root, are grasped with the left hand, and a long, deep in- 
cision is made from apex to base. We observe the appearance and tex- 
ture of the lungs, whether the air vesicles are dilated (emphysematous) or 
filled with serum, blood, or inflammatory exudation. Fluid can be 
pressed out of the air vesicles without breaking down the lung tissue. 
Solid inflammatory exudation, on the other hand, renders the lung more 
resistant and easily broken down. Attention should be paid to the ooz- 
ing of purulent or other fluid from the smaller bronchi when the lung 
is squeezed near the cut surface. It is the rule to find the lower lobes 
more congested than the upper. 
Preservation of the Lungs and Bronchi.-If the lungs have been cut, small 
pieces from the affected portions of lung tissue or bronchi should be hardened in Orth's 
fluid, care being taken not to squeeze or handle them unnecessarily. It is better, 
when the microscopical examination is more important than the macroscopical, not to 
open the lungs at once, but to fill the air spaces with preservative fluid by means of a 
funnel attached to a short rubber tube and cannula, which is tied into the main bron- 
chus. In this way not only are the minute structures better preserved, but the air 
vesicles are filled out and hardened in an approximately natural condition. Care 
should be taken not to have too great a pressure from the inflowing fluid, since then 
exudations might be displaced or the lung distorted or ruptured. While the lung is 
being filled it should be immersed in a vessel of the same preservative fluid, in which, 
after closing the cannula or ligating the bronchus, it lies for twenty-four hours. It is 
then cut into small pieces and the hardening completed. For the display of certain 
gross lesions, such as tuberculous and other cavities of the lungs and bronchi, tumors, 
etc., the lungs filled in this way are opened by an incision along the posterior surface 
from apex to base and hung in jars. For this purpose 4 per cent, formaldehyde solu- 
tion may be used for both fixation and preservation in the jars. A variety of harden- 
ing agents may be used: Orth's fluid and 4 per cent, formaldehyde are on the whole the 
best. If, however, the lung is commencing to decay, strong alcohol will stop the proc- 
ess most quickly and give as good results as are possible under the circumstances. 
Alcohol should be used when the lungs are to be examined for bacteria. 
It is often desirable, and particularly in cases in which the topography of lesions is 
to be studied, as in acute miliary tuberculosis, acute and chronic phthisis, infarctions, 
etc., to inject the blood-vessels with colored gelatin. The lung should, after the injec- 
tion, be hardened in alcohol. MAKING POST-MORTEM EXAMINATIONS 
1211 
The Pharynx, Larynx, Esophagus, and Thyroid Gland.-For the re- 
moval of these parts the incision through the skin should be carried 
upward as far as practicable-when permissible, to a point 1 inch be- 
low the chin, the head being allowed to hang backward over the edge of 
the table. 
The soft parts are dissected from the larynx, care being taken not to 
cut the thyroid body, and an incision is made through the floor of the 
mouth, following the internal surface of the inferior maxilla. Through 
this incision the fingers are introduced into the mouth, the tongue is 
drawn down, the posterior wall of the pharynx is divided above the tonsils, 
and the tongue, pharynx, and larynx are drawn out together. These 
organs are then pulled downward, and with the aid of the knife the trachea 
and esophagus are removed entire, the esophagus being cut just above 
the stomach. If the contents of the stomach are to be preserved, as in 
cases of suspected poisoning, a ligature is put around the esophagus just 
below the point at which it is to be cut off. 
With the enterotome the pharynx and esophagus are now slit open 
upon their posterior surfaces. The mucous membrane thus exposed is 
examined for evidences of caustic poisons, of inflammation, tumors, 
strictures, varices, etc. The enterotome is next introduced into the 
larynx, and this organ and the trachea are laid open along the poste- 
rior wall. Here we look for edema of the arytenoepiglottidean folds 
(edema of the glottis), for evidences of catarrhal, croupous, ulcerative, 
and syphilitic inflammation, and for tumors and lesions of the laryngeal 
cartilages. Edema and redness of the larynx may result from post-mor- 
tem changes, especially in bodies which have been kept for several days 
in cold weather. A well-marked edema glottidis during life may leave 
no trace after death. Putrefactive changes usually commence early in 
the larynx and trachea. 
The thyroid gland is dissected off and examined. Its weight varies 
considerably, being, according to Krause, somewhat over 30 grams. 
Preservation of the Pharynx, Larynx, Trachea, Etc.-These structures are 
freed from superfluous tissue and suspended entire by a thread in a large quantity of 
Orth's fluid or Flemming's osmic-acid mixture, after which the hardening is completed 
in the usual way. Four per cent, formaldehyde is now widely used. The esophagus 
should be stretched loosely on sheet cork with pins, and hardened in either of the 
above fluids. The thyroid may be cut into small pieces and similarly hardened. 
The Abdomen. 
Returning now to the abdominal cavity, we first dissect off the omen- 
tum. Tubercles of the peritoneum may be best seen in the omentum. 
The colon is then raised and dissected free, to the cecum on one side and 
to the rectum on the other. The colon and small intestines are then 
drawn first to the right and then to the left side, so as to expose in turn 
the right and left kidneys. As each kidney is brought into view an in- 
cision is made through the peritoneum over the track of the ureter. The 
ureter is followed through its entire length and its condition ascertained. 
Sometimes one, more rarely all, of the abdominal viscera are un- 1212 
MAKING POST-MORTEM EXAMINATIONS 
usually movable, owing to a relaxation of their ligamentous or other sup- 
ports. This condition-enteroptosis-is common in the liver, more fre- 
quent in the spleen, and especially so in the kidneys. It has been 
occasionally described in the stomach and intestines. 
The Kidneys.-These organs are now removed, the peritoneum and 
fat being separated from them with the hand, and the vessels being di- 
vided with the knife. The adrenals, at the upper end of each kidney, 
are removed at the same time. The kidneys may be softened by putre- 
faction, or the surface may have a greenish gray color, caused by the 
post-mortem action of putrefactive gases on the hemoglobin. 
An incision is made through the capsule along the convex border of 
the kidney, and the membrane stripped off. We notice the degree of 
adherence of the capsule to the kidney, and also the surface of the latter, 
whether smooth or roughened, pale, congested, or mottled; an incision 
is made along the convex surface down to the pelvis, so that the organ 
is divided into halves. We observe the relative thickness of the cortical 
and pyramidal portions, as well as the size of the entire organ. To as- 
certain the latter point, it is well to weigh each kidney; the normal 
weight is from 130 to 150 grams The left kidney is, according to Orth, 
from five to seven grams heavier than the right. At from twenty to 
thirty-five years of age, according to Thoma, the weight of the heart is to 
the weight of both kidneys as 1 : 1.1. The weight of the kidneys of adults 
is given by Vierordt in general as about 0.48 per cent, of that of the entire 
body. 
It is necessary to remember that in a kidney which is much atrophied 
there may be an increase of fat in the pelvis, which gives the organ 
nearly its normal size and weight, while the kidney tissue proper may 
have in great measure disappeared. 
We now inspect the kidney tissue more closely, especially the cortical 
portion. The pyramids consist largely of tubes running in nearly 
straight lines from the apex to the base of each pyramid. These straight 
tubes pass from the pyramids into the cortex in bundles, called medul- 
lary rays, many of them retaining their straight course until they nearly 
reach the surface of the kidney. These straight tubules send off branches 
on all sides of the rays, which become convoluted, form Henle's loops, 
and finally terminate in the Malpighian bodies. In this way the cortex 
of the kidney, as seen in section, is divided into alternate bands of straight 
tubes, and convoluted tubes, with glomeruli; both sets of bands being 
perpendicular to the surface of the kidney, and called respectively medul- 
lary rays and labyrinths. About the convoluted tubules and glomeruli 
is a rich venous plexus; and since after death the blood usually remains 
in this plexus and in the glomeruli, the bands containing the convoluted 
tubules, i.e., the labyrinths, usually appear red, while the medullary rays 
are grayish white. In a normal kidney, therefore, the cortex should be 
regularly striped in narrow alternating red and whitish bands. For a 
further description of the finer anatomy of the tubules, see page 849. 
The average thickness of the cortex of the kidney is 4.8 mm. 
If there be extensive congestion, the entire cortex is red. If the epi- MAKING POST-MORTEM EXAMINATIONS 
1213 
thelium of the tubules degenerates and fills them up, or if there are con- 
siderable changes in the interstitial tissue, the regular bands are lost and 
the cortex is irregularly mottled. If the tubular epithelium becomes 
filled with fat globules, this is indicated by an opaque yellow color of the 
affected parts; in many cases, therefore, the existence of a kidney lesion 
•can be recognized with the naked eye. 
If waxy degeneration be present to a marked extent, it may be mani- 
fest by a peculiar translucent appearance of the affected parts, but in 
most cases it is necessary to apply reagents to demonstrate it satisfac- 
torily. The cut surface of the kidney is washed with water, to free it 
from blood, and repeatedly brushed with an aqueous solution of iodine 
(iodine 1 part, potassium iodide 3 parts, water 100 parts). The glo- 
meruli and the blood-vessels are most frequently affected, and, if so, they 
may appear as mahogany-colored dots and lines on a yellow ground. 
But this reaction is not constant, and, for accurate detection of amy- 
loid substance, recourse should be had to other reagents applied to sec- 
tions of the hardened tissues (see page 59). 
The pelvis of the kidney should be examined for inflammatory lesions 
and calculi. Sometimes a whitish fluid is seen in the pelvis and can be 
squeezed from the papillae; this is produced by a post-mortem desqua- 
mation of the epithelium, but is likely to be mistaken for pus. 
Preservation of the Kidney.-If the kidney is not opened, the blood-vessels 
may be injected through the renal artery, slowly and under a low pressure, with Orth's 
fluid or Flemming's osmic-acid mixture. After the vessels are filled with either of the 
above fluids, they are tied, and the entire organ is placed in a large quantity of the 
injecting fluid for twenty-four hours. The kidney is then cut into small pieces, and 
the hardening is completed in the usual way. 
In most cases, however, the kidneys will have been opened for inspection at the 
autopsy. Then small pieces are removed from the various regions and hardened in 
one of the above fluids or in 4 per cent, formaldehyde. 
Kidneys which are to be examined for the presence of bacteria should be cut into 
small pieces and placed at once in strong alcohol, which should be changed once or 
twice; in this they are permanently preserved. 
The Adrenals-Suprarenal Capsules.-These are, in the fetus, of an 
ovoidal, in the adult, of a triangular shape. They are situated at the 
upper and inner border of the kidney, to which they are loosely attached 
by connective tissue. On the anterior surface is an irregular fissure, 
called the hilus, from which the veins emerge. The size of the adrenals 
varies considerably, but in the adult the average vertical diameter is from 
3.2 cm. to 4.5 cm., the transverse diameter about 3.2 cm., and they are 
from 4.2 mm. to 6.4 mm. in thickness. They weigh in the adult from 4 
to 8 grams. They are relatively larger in children than in adults. They 
are composed of a cortical and a medullary portion, the cortex forming a 
yellowish shell around the dark red or brown medulla. They are en- 
closed in a connective-tissue capsule, from which fibrous processes extend 
inward, dividing the gland into a series of irregular chambers. Those in 
the cortex are mostly elongated, giving this portion a striated appear- 
ance, while those in the medulla are polyhedral. It is in these spaces 
that the parenchyma cells lie. The adrenals readily decompose; the 
inner layer of the cortex may soften and break down, so that the outer 1214 
MAKING POST-MORTEM EXAMINATIONS 
zone forms a sort of cyst filled with reddish brown broken-down sub- 
stance. Hypertrophy, tuberculosis, and cheesy degeneration, fatty de- 
generation, and tumors are to be looked for. 
Preservation.-The adrenals should be hardened in Orth's fluid or in strong 
alcohol. Four per cent, formaldehyde is also useful, especially if frozen sections are 
to be made for study of anisotropic fats. 
The Spleen.-This organ has, when removed from the body, the gen- 
eral shape of a flattened ellipsoid, most curved on its external and pos- 
terior surface. It is situated in an oblique position on the left side of 
the stomach, and between its cardiac end and the diaphragm. The 
vessels are given off from its inner surface, which is crossed by a more 
or less well-marked vertical ridge. The point of emergence of the vessels 
is called the hilus. Its long diameter extends from the seventh inter- 
costal space to the eleventh rib. Its upper portion is separated from the 
ribs by the lungs; its lower portion, by the diaphragm. 
It is, according to Vierordt, on the average, from 12 to 13 cm. long; 
from 7 to 8 cm. broad, and about 3 cm. thick. Its average weight is 
about 171 grams. The dimensions of the spleen as given by Krause are 
somewhat greater than the above; but its measurement and weight 
vary considerably within the limits of health. It is in these respects 
the most variable organ in the body. In old age the average weight 
gradually diminishes. 
The spleen is inclosed in a fibrous capsule covered with peritoneum. 
The parenchyma is formed of blood-vessels and fibrillar connective tissue, 
and of a soft, dark red pulp in which are embedded whitish spheroidal 
or elongated bodies, the glomeruli, or Malpighian bodies. In the normal 
human spleen the glomeruli are usually hardly perceptible to the naked 
eye, but sometimes they are very plain. Sometimes the fibrous stroma 
is very apparent, sometimes not. 
The size, consistence, and color of the organ vary a good deal within 
normal limits; it may soften in decomposition. Thickenings of the capsule 
and abnormal adhesions are very common, and often occur without any 
clinical history indicating disease. We should look for changes in size, 
color, and hardness; for pigmentation, hyperplasia of the connective 
tissue, amyloid degeneration, tubercles, and infarctions. 
Not infrequently one or more spheroidal or flattened so-called acces- 
sory spleens are found in the vicinity of the spleen; they vary in size 
from that of a pea to that of a walnut. 
Preservation.-In certain diseases of the pulp, anemia, leukemia, malaria, etc., 
smears or impressions of the tissue should be made, and examined by the staining 
methods described under the lesions of the blood. For general purposes small pieces 
of the organ are hardened in Orth's fluid, in Flemming's osmic-acid mixture, or in 
alcohol. Helly's fluid or carefully neutralized 4 per cent, formaldehyde are employed 
for finer cytological studies. 
The Intestines.-The rectum is divided, the intestine is seized with the 
left hand, and, being kept stretched, is separated from its attachments 
by repeated incisions through the mesentery close to the gut, until the 
duodenum is reached, where the intestine is again cut off. The operation 1215 
is more cleanly if, before dividing the gut, ligatures are placed around 
it at either end. The entire length of the gut is now laid open with the 
enterotome along the mesenteric attachment; the mucous membrane 
is cleaned with a stream of water and then examined. 
In cases of suspected poisoning, a ligature should be placed around 
the rectal end of the gut and two around the duodenal end, and it should 
then be cut off below the former and between the latter ligatures. The 
gut is now opened and the contents are emptied into a clean glass jar for 
delivery to the chemist, care being taken that they are not allowed to 
touch anything but the inner surface of the jar. After washing the in- 
testine in pure, fresh water and examining it, it should be placed entire 
in another clean jar and the jar sealed. 
Cadaveric lividities are very common in the intestines, and are 
usually most marked in the dependent portions. They are apt to occur 
in patches, but may be diffuse and very extensive. If the wall of the 
gut be stretched, they are often seen to be discontinuous, owing to the 
pressure of the blood from the parts which are squeezed by folds. Small 
patches of arborescent or diffuse red staining are often seen, formed by 
the imbibition from the vessels of decomposing hemoglobin. In the 
more advanced stages of decomposition the mucosa may be softened and 
loosened. A dark purple or brownish discoloration of the entire intes- 
tinal wall is frequently seen, either diffuse or in patches. Much experi- 
ence and careful observation are requisite in forming a correct judgment 
regarding the significance of changes of color in the intestines. Caution 
is necessary in distinguishing normal digestive hyperemia from abnormal 
congestion. A very considerable congestion may exist without disease. 
The lesions ordinarily to be looked for are catarrhal, croupous, and 
ulcerative inflammations, perforations, hemorrhages, strictures, tumors, 
amyloid degeneration, swelling and ulceration of the solitary follicles 
and Peyer's patches, and pigmentation. For the detection of amyloid 
degeneration of the mucosa this structure should be carefully washed, 
and brushed with a solution of iodine. 
Preservation.-For the general purposes of microscopic study, portions of the 
gut should be gently stretched on cork (the mucosa side free) and hardened in Orth's 
fluid or in Flemming's osmic-acid mixture. 
For obvious reasons the mucous membrane should be handled as little as possible, 
for, in the majority of cases, decomposition and softening have already set in at the 
time of the autopsy, and, even under the most favorable conditions, the epithelium 
is very easily rubbed off. 
In cases in which the most perfect preservation of the topographical features, as 
well as the minute structure of the intestinal mucosa, is desired, even at the expense of 
an inspection of the fresh tissue, another mode of procedure is to be recommended. 
Selected segments of the gut are, after removal from the body, allowed to remain 
unopened on the table while ligatures are tied around the ends. The isolated seg- 
ments, or the whole gut, may now be moderately filled-not distended-with one of 
the above fluids by means of a syringe with a needle cannula; or one end of the seg- 
ment may be tied and the fixative introduced through a funnel at the other, which 
end is then ligated.. The segments to be preserved should now be placed unopened in 
the fixative solution. After twenty-four hours they may be opened with scissors or a 
sharp knife, cut into suitable pieces, and kept permanently in 80 per cent, alcohol. 
The Stomach and Duodenum.-We now introduce the enterotome into 
the duodenum at its transverse portion, and open it on the convex border. 
MAKING POST-MORTEM EXAMINATIONS 1216 
MAKING POST-MORTEM EXAMINATIONS 
When the pylorus is reached the incision is carried obliquely over to 
the greater curvature of the stomach, along which it is extended as far as 
the esophageal opening, and the organ examined in situ; or, if a more 
careful examination of the stomach is called for, after ascertaining 
whether or not the bile duct is pervious (see below), the duodenum and 
stomach may be removed together, and the stomach opened and exam- 
ined on the table. Alterations in size and form, the presence of tumors, 
ulcers, etc., may now be sought for. 
If poisoning be suspected, a ligature should have been placed, earlier 
in the examination (see above), around the lower end of the esophagus 
and the duodenum. The stomach and duodenum are now removed to- 
gether unopened. They are to be opened in a carefully cleansed glass 
jar, and after an inspection of the mucous membrane and the contents 
with the naked eye and a hand lens, stomach, duodenum, and contents 
are to be sealed in the jar for the chemist. 
We now look for the orifice of the bile-duct, which will be found 
about the middle of the descending portion of the duodenum on its con- 
cave border. Pressure on the gall-bladder or on the common duct will 
usually cause the bile to flow into the intestine if the ducts are pervious. 
But a sufficient degree of stoppage may exist in the ducts to give rise to 
marked symptoms of disease, without preventing the flow of bile under 
these conditions, even with a moderate pressure. A long director is now 
passed into the gall-duct, which is laid completely open; ulcerations, 
cicatrices, gall-stones, inflammatory lesions, and tumors are looked for. 
In stricture of the gall-duct the mucous membrane above will often be 
found bile-stained, while below it is colorless. At this point, should 
there be any special reason for doing so, the portal vein, which lies close 
behind the ductus choledochus, should be opened and examined for peri- 
phlebitis, phlebitis, and thrombosis. The mucous membranes of the 
duodenum and stomach are now examined. Acute inflammation from 
caustic poisons, chronic catarrhal inflammations, hemorrhages, ulcers, 
erosions, swelling of the solitary follicles (lymph-nodules), and tumors 
are lesions most frequently seen. We sometimes find a diffuse congestion 
of the stomach, similar to that produced by irritant poisons, as a result 
of doses of croton oil given just before death. 
Preservation.-The same methods should be used as for the intestines (see 
above). Tumors should be cut into small pieces and hardened in Orth's fluid or 
4 per cent, formaldehyde. 
The Liver.-To remove the liver, the diaphragm is first divided on 
one side of the suspensory ligament as far back as the spine; the suspen- 
sory ligament is then divided; then the right and left lobes being in turn 
raised, the lateral ligaments are severed. Then, the left lobe being seized, 
the organ is dragged obliquely downward into the abdominal cavity, the 
remaining attachments being dissected away. The liver is first laid on 
its superior surface and the gall-bladder and its contents are examined. 
The character of the gall is to be determined, and gall-stones, inflam- 
matory lesions, and tumors are to be sought for. To determine the 
actual size of the organ, it should be both measured and weighed. Its MAKING POST-MORTEM EXAMINATIONS 
1217 
size varies greatly in different healthy individuals, but in general it may 
be said that it measures from 25 to 30 cm. transversely, from 15.3 to 18 
cm. anteroposteriorly, and from 9 to 12 cm. at its thickest part; its or- 
dinary weight is between 1,550 and 1,860 grams. In children its weight 
relative to that of the body is greater than in adults. The liver is 
increased in size and weight during digestion and by congestion from 
any cause. 
The convex surface of the right lobe of the liver not infrequently 
shows several grooves running from front to back, approximately par- 
allel with the suspensory ligament of the liver. These grooves, which 
may be found in persons of all ages, are believed by some to be usually 
congenital, by others to be the result of pressure of the diaphragm and 
the abdominal muscles on a relaxed atrophic liver. They seem in any 
event to be of no practical importance. On the other hand, a transverse 
groove running at right angles to the axis of the body is a not infrequent 
result of tight lacing, and is usually associated with local connective- 
tissue thickening of the capsule and underlying tissue of the liver. In 
this way the liver may become much distorted and the gall-bladder com- 
promised. 
The capsule of the liver is now examined; the organ is then laid on its 
lower surface and several deep incisions are made from above downward. 
The color and consistence of the liver tissue should be noticed, also the 
distinctness with which the lobular outlines can be seen; whether or not 
the centers of the lobules are congested or their peripheries lighter in 
color than usual; the presence of tumors, tubercles, abscesses, ecchinococ- 
cus, new connective tissue, and pigmentation. Suspected amyloid de- 
generation should be tested for by iodine solution. 
We often find the surface of the liver of a greenish or very dark 
brown color; less frequently the same color extends into the substance of 
the organ. This discoloration, which is entirely post-mortem, is, like 
the similar discoloration of other internal organs, produced by the action 
of the gases of putrefaction on the coloring matter of the blood. 
Preservation.-For the study of parenchymatous degeneration, sections of the 
fresh frozen tissue or small teased fragments should be examined in 0.85 per cent, salt 
solution. For general purposes small pieces should be hardened in Orth's fluid, in 
4 per cent, formaldehyde, or in alcohol. Tumors should be treated in the same way. 
The Pancreas.-This organ, of a light yellowish red color, is elon- 
gated, irregularly prismatic in shape, and flattened anteroposteriorly; 
the right end, called the head, is broader than the rest and lies in the 
concavity of the duodenum. The remainder of the organ, the body and 
tail, are usually tapering and lie transversely in the abdominal cavity, 
the tail reaching to the spleen. Its size and weight vary considerably; 
its usual length is from 15.3 to 23 cm.; its breadth about 3.8 to 4.5 cm.; 
its thickness about 1.3 to 3.8 cm.; its weight is usually from 70 to 108 
grams. The organ may be rounded instead of flattened; the head and 
tail may be disproportionately large; the tail may be unusually long or 
may be divided or curved. The superior mesenteric artery and vein, 1218 
MAKING POST-MORTEM EXAMINATIONS 
which pass behind the gland, are usually partly embedded in it, but are 
sometimes completely inclosed. 
A longitudinal incision should be made through the whole gland, 
and its substance and duct should be searched for calculi, tumors, mal- 
formations, and evidences of acute and chronic inflammation, fat necro- 
sis, and amyloid degeneration of. the blood-vessels. The pancreas is 
frequently of a dark red color from post-mortem staining. 
Preservation.-Portions of this organ should be hardened in strong alcohol, 
Orth's fluid, or Flemming's osmic-acid mixture. 
The examination of the thoracic duct, which lies to the right and 
posterior to the aorta, may now be made. Among the most important 
of its lesions is tuberculosis, since it has been shown that from a tuber- 
culous lesion here the generalization of bacilli not infrequently oc- 
curs. Inflammatory lesions, carcinoma, and partial or total occlusion 
from pressure may be found. 
The solar plexus, which surrounds the origin of the celiac axis and the 
superior mesenteric artery and lies between the adrenals, may now be 
sought. Lesions of the semilunar and other ganglia are to be noted- 
atrophy, pigmentation, and degenerations. 
The condition of the hemolymph-nodes in the prevertebral fat should 
be ascertained (see page 546). 
The Aorta.-The size of the lumen of this vessel should be determined. 
The average circumference of the ascending aorta in the adult may be 
taken in general as about 69 mm.1 Either in situ or after removal the 
aorta should be opened by an incision extending its whole length and 
continued into its larger branches. 
The Genitourinary Organs. 
The Male Organs.-If the urine is to be examined it may be drawn off 
with a catheter; or a vertical incision may be made into the bladder just 
above the symphysis pubis, and some of the urine dipped out. The cut 
end of the rectum should now be grasped with the left hand and raised 
up, and this and the bladder, prostate gland, etc., dissected away from 
the pelvis, the knife being carried close to the bone. The bladder is 
now drawn backward and the loose tissue close under the symphysis 
pubis cut. The body of the penis is then shoved backward within the 
skin and dissected away from behind, beneath the symphysis, and finally 
cut off just behind the glans penis. The penis and bladder are now 
drawn backward and upward, and the pelvic organs removed together. 
Or, the penis may be removed by sawing awTay the bones above the pubic 
arch, and then dissecting away the penis, whose root is thus exposed. 
The pelvic organs are then laid on the table, the bladder uppermost; 
a long director is passed into the urethra, which is opened on its upper 
surface through its entire length, and the bladder widely opened. In 
the urethra the presence of strictures, diverticula, ulcers, inflammatory 
1 See Vierordt's Tables; also v. RitodK, Ztschr. f. klin. Med., 1907, Ixi, 36. MAKING POST-MORTEM EXAMINATIONS 
1219 
lesions, is to be noticed; in the bladder inflammatory lesions, hypertro- 
phies, congestion and ecchymosis of the mucous membrane, hyperplasia 
and ulcers of the lymph-nodules, and tumors. The organs are now 
turned over; the rectum is opened and examined for varicose veins, hem- 
orrhages, ulcers, strictures, and tumors. The prostate gland is then cut 
into and the presence of calculi, inflammatory lesions, hypertrophies, 
and tumors sought for. Lastly, the vesiculce seminales are examined, in 
which, though rarely, we may find evidences of tuberculous inflamma- 
tion and dilatation. 
The testicles may be removed, when necessary, without cutting the 
scrotum, by enlarging the inguinal canals from within and crowding the 
glands through them and cutting them off. The average weight of the 
adult testicle with its epididymis is, according to Krause, from 15 to 
24.5 grams. Inflammatory lesions, tuberculosis, abscesses, and tumors 
are the most frequent lesions. 
Preservation.-The urethral canal and bladder may be pinned open and hard- 
ened in Orth's fluid or in Flemming's osmic-acid mixture. The prostate, vesiculae 
seminales, testicles, and tumors may be hardened in the same fluids or formaldehyde. 
The Female Organs.-The position and general condition of the pelvic 
organs should first be determined by inspection. Abnormal adhesions 
of the ovaries, broad ligaments, Fallopian tubes, and uterus; malposi- 
tions of the uterus; subserous tumors of the uterus, and ovarian tumors, 
are frequently observed. Hemorrhage into the posterior cul-de-sac is 
sometimes found. The urine should be collected, if necessary, as above 
directed; the organs should be dissected away laterally, as in the male, 
care being taken not to injure the ovaries and Fallopian tubes. The 
bladder is then drawn strongly backward and upward, and dissected 
away from the symphysis and the pubic arch, and, the point of the knife 
being carried forward and downward, the vagina is cut off in its lower 
third, the rectum severed just above the anus, the remaining attachments 
cut, and the pelvic organs are taken out together. If it is necessary to 
remove the external generative organs, after freeing the lateral surfaces 
of the internal organs and the bladder, the legs are widely separated and 
the vulva and anus circumscribed by a deep incision. The tissues close 
beneath the pubic arch are now dissected away from below, and the 
vulva is thrust back beneath the symphysis; it is now seized above the 
bone, and together with the anus dissected away and removed with the 
other organs. 
The bladder is first opened and examined. The vulva may now be 
examined for hypertrophies, inflammatory lesions, ulcers, cicatrices, 
cysts, and tumors. The vagina is opened along the anterior surface; its 
more common lesions are inflammations, fistulse, ulcers, tumors, and 
rarely cysts. 
The Uterus.-Before opening this organ its size and shape should be 
determined. The adult virgin uterus is a pear-shaped body, flattened 
anteroposteriorly; the upper portion, or body, is directed upward and 
forward, while the lower portion, the cervix, is directed downward and 
backward. It is covered anteriorly by peritoneum to a point a little 1220 
MAKING POST-MORTEM EXAMINATIONS 
below the level of the os internum; posteriorly, to a point a little below 
the level of its junction with the vagina. The peritoneal investment 
separates from the organ at the sides to form the broad ligaments. The 
uterus is held in position by the broad and round ligaments and by its 
attachments to the bladder and rectum and vagina. The upper end, 
the fundus, does not extend above the level of the brim of the pelvis. 
Its average length is about 7.6 cm.; its breadth about 5.1 cm.; its thick- 
ness about 2.5 cm.; its average weight is about 31 to 46 grams. During 
menstruation the uterus is slightly enlarged, the mucous membrane 
of the body becomes thicker, softer, and its vessels are engorged with 
blood; while its inner surface is more or less thickly covered with blood 
and cell detritus. A description of the complicated changes in the 
uterus which pregnancy entails may be found in the works on obstetrics. 
After pregnancy the uterus does not return to its original size, but 
remains somewhat larger; the os is wider and frequently fissured. 
We not infrequently find in the mucous membrane of the lower part 
of the cervix small, transparent, spheroidal structures, called ovula 
Nabothi; these are small retention cysts caused by the closure of the 
orifices of the mucous glands. The more common lesions observed in 
the uterus are malpositions, malformations, lacerations, ulcerations of 
the cervix, acute and chronic inflammation of the mucous membrane or 
muscularis, or both, thrombosis and inflammation of the veins, and 
tumors. 
In the infant the uterus is small, the body flattened, the cervix dis- 
proportionately large. During childhood the organ increases in size, 
but the body remains small in proportion to the cervix. At puberty, the 
shape changes, and the body becomes larger. 
The ovaries are flattened, ovoidal bodies, situated one on each side, 
and lying nearly horizontally at the back of the broad ligament of the 
uterus. Their size is variable, and they are usually largest in the virgin 
state. They measure about 3.8 cm. in length, 1.9 cm. in breadth, and 
nearly 1.3 cm. in thickness. Their average weight is from 3.9 to 6.5 
grams. The sides of the ovary and its posterior border are free; it is 
attached along the anterior border; to its end is attached the ovarian 
ligament, to its outer extremity one of the fimbriae of the Fallopian tube. 
The ovary is covered on its free surface by cylindrical epithelium, and 
its surface is less glistening than the general peritoneum. The surface 
of the ovary is smooth in the young, but becomes rougher and depressed 
in spots as the process of ovulation goes on. In adult females we 
usually find corpora lutea in their various stages. We should seek for 
evidences of acute and chronic inflammation, for tumors and cysts. 
The Fallopian tubes, lying in the upper margin of the broad liga- 
ments, are from 7.6 to 10 cm. in length. The length often differs con- 
siderably on the two sides. They commence at the upper angles of the 
uterus as small perforated cords, which become larger farther outward, 
and bend backward and downward toward the ovary. They terminate 
in an expanded fimbriated extremity about 2.5 cm. beyond the ovary. 
They are covered by peritoneum, and the mucous membrane lining MAKING POST-MORTEM EXAMINATIONS 
1221 
them, continuous with that of the uterus, is thrown into longitudinal 
folds. Malpositions by adhesions, closure, inflammations, and cysts 
are the more common lesions. The possibility of tubal pregnancy should 
be borne in mind. 
Preservation.-All of these organs and their tumors may be hardened in Orth's 
fluid or in 4 per cent, formaldehyde. The vagina should be stretched flat on cork, 
and the cavity of the uterus laid wide open. Great care should be taken not to 
touch either the internal surface of the uterus or the external surfaces of the ovaries, 
since in both the epithelium is very easily rubbed off. 
It is better, after opening them by a transverse incision, to suspend the ovaries by 
a thread in a j ar of the preservative fluid than to let them lie on the bottom, since the 
epithelium is thus less likely to be rubbed off. Larger cysts of the ovary for exhibition 
purposes should be distended with preservative fluid. 
The Closure of the Body after the Post-mortem Examination. 
At the end of the autopsy the body should be restored as nearly as 
possible to its natural external appearance. 
Fluids should be removed, vacant spaces filled with absorbent mate- 
rial, such as cotton, jute, or sawdust, and the incisions closed by sutures. 
Bacterial Examination of Post-mortem Specimens. 
It is often important to make a thorough post-mortem examination 
by cultures as well as morphologically of the blood and of all the viscera. 
This is important not only in those cases which during life gave clinical 
evidence of general infection, but also in many forms of disease whose 
nature is still wholly obscure. 
In the interpretation of the result of all such examinations, however, 
it should be borne in mind that after death a new distribution of germs 
may occur, and that from the gastrointestinal canal and from other sur- 
faces or cavities of the body microorganisms may, as decomposition 
progresses, penetrate the tissues and the viscera. 
A careful consideration of the general conditions under which the 
body has been kept and its state of decomposition is of special importance 
in the interpretation of the significance of the Bacillus coli communis, 
which is always present in such enormous numbers in the intestinal canal, 
and which is not only apt to effect wide distribution in the body after 
death, but as a result of careless manipulation is likely to be accidentally 
brought in contact with other viscera after the opening of the gut. The 
preparation of cover-slips for staining and the making of cultures is, as 
a rule, best done at the autopsy table. 
It is well as each organ is exposed-commencing with the heart-to 
sear the surface of the organ to be examined with a broad-bladed knife 
heated over a flame, and then, making an incision through the seared 
surface with a sterilized scalpel, to press a sterilized cotton swab into 
the opening and absorb the juices which exude, or to pick out a small 
fragment of the solid tissue from the depths of the opening, or to secure 
some of the blood or fluid on a sterilized platinum loop; and then with 
the material thus procured to make the required cultures and afterward 
the cover-slip smears for staining. 1222 
MAKING POST-MORTEM EXAMINATIONS 
If it be necessary to transport the material to the laboratory before 
making cultures, it is well to reserve the unopened organs, or large por- 
tions of these in the case of the solid viscera, and to wrap each separately 
in a cloth saturated with sublimate solution, or to put each in a separate 
sterile receptacle for transportation. 
It is well to remember that in the last hours of life the safeguards 
of the body against the entrance and growth of microorganisms may 
be ineffective, so that the determination of the significance of bacteria 
in the tissues a short time after death requires care and experience.1 
While every autopsy should be ma.de as carefully and completely 
as circumstances permit, it should be always borne in mind that in 
examinations which may have medicolegal bearings it is of the highest 
importance to examine thoroughly both macroscopically and micro- 
scopically every part of the body from which light may be derived as to 
the cause of death, for in medicolegal cases it is not infrequently as 
important to be able by a complete examination to declare the absence 
of lesions which could cause death, as to determine the presence of those 
upon which the opinion as to the actual cause of death in a particular 
case rests. Bearing this in mind, the technique of autopsy-making is 
essentially the same whatever the ends which the facts elicited may be 
destined to serve. 
Autopsies in Medicolegal Cases. 
Autopsies in Cases of Suspected Poisoning. 
In cases of suspected poisoning which may possibly have a medico- 
legal bearing, the examination should be made with extreme care and 
thoroughness. The inspection of the body and the examination of all 
the viscera should be thorough and detailed. Every appearance should 
be noted at the time, and nothing left to the memory. It is well to have 
an assistant record the observations as they are made. The disposition 
of the parts and organs in jars should be also noted at the same time. 
It is important to remember that many poisons destroy life without 
producing appreciable lesions, and also that many cases of sudden death 
occur, not due to poisons, and without any discoverable cause. 
In bodies which are exhumed for examination, the tissues may be so 
changed by decomposition that it is impossible to say whether lesions 
have or have not existed. In such cases the careful and separate preser- 
vation of the viscera and other parts for chemical examination, is often 
all that can be done. 
It is always best, in cases of suspected poisoning, to preserve for the 
chemist not only the stomach and intestines, but the entire liver and 
brain; or, if only portions of these can be saved, these portions should 
be carefully weighed, as well as the entire organs, and the relative 
amount of tissue reserved carefully noted at the time. It is even well, 
particularly in cases in which the administration of the readily diffusible 
1 For details of bacterial flora of the human body see pp. 175 and 226. MAKING POST-MORTEM EXAMINATIONS 
1223 
poisons, such as arsenic, strychnia, etc., is suspected, to preserve the 
whole of all the internal organs, together with a large piece of muscle 
and bone; since with large quantities of tissue the results of the chemical 
analysis depend less upon calculations, and are hence more compre- 
hensible to the average jury. In all such cases jars should, if possible, 
be procured which have never been used before, and these should be 
carefully washed and rinsed with distilled water. They should have 
glass stoppers and be sealed at once and carefully labelled before leaving 
the hands of the operator. If they can be delivered to the chemist with- 
out much delay, no preservative fluid should be added. If they are to 
be kept for a considerable time, pending the action of a coroner's jury 
or for some other reason, a small quantity of pure strong alcohol may 
be poured over them. The operator should be particular to preserve a 
quantity, at least half a pint, of the specimen of alcohol used, in a clean, 
sealed, and labelled bottle, so that this may be tested by the chemist 
and be proved to be free from the poison. It is better in all cases, how- 
ever, to avoid, if possible, the use of alcohol. In all autopsies which 
may have medicolegal importance full notes should be taken by an 
assistant as the operation proceeds, carefully read over immediately 
afterward and dated, and kept by the operator for future reference. 
The labelling and disposition of the jars should be recorded in the notes. 
The specimens should not for a moment be out of the sight of the opera- 
tor until they are placed under lock and key and seal, or are delivered 
to some authorized person, so that there may be no question of their 
identity should the case come into court. 
Examination of the Bodies of New-born Children.1 
In examining the bodies of new-t>orn children, we may have to determine, besides 
the ordinary lesions of disease, the age of the child, whether it was born alive, how long 
it has been dead, what was the cause of death. 
Size, Age, and Characters of the New-born Child.-The fresh corpse of a new- 
born child at term no longer resembles that of] the immature fetus. The skin is firm 
and pale, like that of an adult. The lanugo has disappeared except on the shoulders. 
In the majority of cases the hair on the head is 1.5 to 2 cm. long. The great fonta- 
nelle is, on the average, 2 to 3 cm. long. As determined by an analysis of 661 cases, 
the average length is 50 cm., the weight 3,256 grams. The nails are hard and reach 
to the tips of the fingers, but not to those of the toes. The cartilages of the ears and 
nose are hard. The labia are more nearly closed. An ossification center in the lower 
epiphysis of the femur should be sought for, as its presence is one of the most reliable 
signs of the maturity of the fetus. If it is absent, the fetus is, as a rule, not more 
than thirty-seven weeks old; but in rare cases it may be absent at term. A center of 
ossification 1 mm. in diameter indicates an age of thirty-seven to thirty-eight weeks, 
if the child was born dead or died soon after birth. Rarely it is no larger than this 
at term. A diameter, at birth, of 1.5 to 9 mm. indicates an age of 40 weeks. A 
diameter of more than 9 mm. indicates, as a rule, that the child has lived some time 
after its birth; a less diameter than 7 mm., however, does not prove the contrary. 
Twenty-four hours after the birth of the child the skin is firmer and paler. The 
umbilical cord is somewhat shrivelled, although still soft and bluish in color. From 
1 The human embryo, according to the estimate of His, measures in length approximately at 4 
weeks from 7-8 mm.; at 5 weeks 13 mm.; at the end of the second month 25-28 mm. Schroder estimates 
the approximate length of the fetus at later lunar months as follows: 3d, 70-90 mm.; 4th, 100-170 mm.; 
5th, 180-270 mm.; 6th, 280-340 mm.; 7th, 350-380 mm.; 8th, 425 mm.; 9th, 467 mm.; 10th, 490-500 
mm. Consult for further data McMurrich, The Development of the Human Body, 1903, p. 108 (bib].), 
and Keibel and Mall, Manual of Human Embryology, Philadelphia, 1910. 1224 
MAKING POST-MORTEM EXAMINATIONS 
the second to the third day the skin has a yellowish tinge and the cuticle sometimes 
appears cracked. The umbilical cord is brown and dry. From the third to the fourth 
day the skin is yellower, and the cuticle is apt to separate from the skin. The umbil- 
ical cord is of a brownish red color, flattened, semi-transparent, and twisted. The 
skin around its insertion is red and congested. 
General Inspection.-The head should be examined for the marks of injuries. 
Very commonly some portion of the scalp will be found swollen and infiltrated with 
blood and serum. This may be the caput succedaneum formed during delivery. The 
mouth and nose should be examined for the presence of foreign bodies which might 
have caused suffocation. 
The neck should be examined for marks of strangulation. The umbilical cord may 
be twisted around the child's neck and strangle it. The mark left by the cord is usu- 
ally continuous, broad, not excoriated, sometimes accompanied by ecchymoses in the 
skin. 
The surface of the body should be examined for the presence of vernix caseosa, 
blood, marks of injury, and the existence of putrefaction. It should be remembered 
that putrefaction is apt to commence earlier in the bodies of young children than in 
those of adults. 
The umbilical cord may be cut or torn. It usually separates by the fifth day, some- 
times not until the tenth. If the umbilicus is cicatrized and healed, the child has 
probably lived for three weeks. A zone of redness around the insertion of the cord 
may exist previous to birth. Redness and swelling (which may disappear after death) 
with suppuration can be found only in a child which has lived for several days. The 
drying and mummification of the cord may take place as well in dead as in living 
children. It is possible for a child to die by hemorrhage from a cut or torn cord, 
either before or after it has breathed. The umbilical vessels should be examined, as 
they may be the seat of umbilical infection. 
The extremities may exhibit fracture of the bones. These may occur during intra- 
uterine life from injuries to the mother or from unknown causes; or may be produced 
by violence in delivery, or by injuries after birth. 
Internal Examination.-The Head.-The fontanelles and sutures should first be 
examined as to their size and for penetrating wounds. An incision should then be 
made through the scalp across the vertex, and the flaps turned backward and forward 
as in the adult. With a small knife the edges of the bones should be separated from 
the membranous sutures and the dura mater, beginning low down in the frontal and 
going back into the lambdoidal suture on either side. The bones are then drawn out- 
ward and cut through around the skull with strong scissors. The brain is removed 
and examined as in the adult.1 
Effusions of blood-cephalhematoma-may be formed, soon after birth, between 
the pericranium and bone, or, more rarely, between the dura and bone. Clots are 
also found between the dura mater and skull; between the dura and pia mater; more 
rarely in the substance of the brain, as the result of protracted or instrumental 
deliveries, or of injuries after birth. 
The cranial bones may be malformed, or exhibit the lesions of rickets or caries, or 
be indented, fissured, or fractured. These latter lesions may be produced during 
intrauterine life by injuries to the mother, by unknown agencies, by difficult deliveries, 
or by direct violence after birth. 
In cases of chronic internal hydrocephalus in young children, in which the ventri- 
cles are much dilated and the brain substance is thinned over the vertex, the brain is 
very apt to be torn in removal, and the amount of dilatation thus becomes difficult of 
determination. It is, therefore, better in such cases to place a pail of water beneath 
the head, or even immerse the latter in it, and remove the brain in the water. In this 
way it floats after removal, supported on all sides. It may now be opened in the 
water and the extent of the lesion determined at once, and parts saved for microscop- 
ical examination. 
If it be desired to preserve the brain for demonstration of the lesion or for a 
museum specimen, it should be transferred unopened to a large jar containing 4 per 
cent, formaldehyde. A portion of the ventricular fluid should now be removed with 
1 Or an incision through the bones with a fine saw may be made as in the adult. MAKING POST-MORTEM EXAMINATIONS 
1225 
a syringe provided with a small cannula, and replaced by formaldehyde. This may 
be done by puncturing the ventricles from below. The fluid in the jar, as well as in 
the ventricles, should be changed in forty-eight hours. The brain may then be cut 
transversely across, when the degree of dilatation of the ventricles, etc., will be 
revealed. The weight of the brain, according to Bischoff, is 380 grams. 
It is normally much softer and pinker than in the adult, the pia more delicate; both 
may be much congested or anemic without known cause. The ventricles contain 
very little serum. Malformations, apoplexies, hydrocephalus, simple and tuberculous 
inflammatory lesions, are to be looked for. 
The Spinal Cord.-Extravasations of blood between the membranes of the cord 
may occur from the same causes as those in the brain. Spina bifida is the most fre- 
quent malformation. 
The Thorax and Abdomen.-These are opened as in the adult. The peritoneal 
cavity contains a very little clear serum A red fluid may be produced by decompo- 
sition. The peritoneum is often the seat of intra-uterine inflammation. 
The Diaphragm.-In still-born infants its convexity reaches to the fourth or fifth 
rib. After respiration it reaches a point between the fourth and seventh ribs. Its 
position is, however, so variable that it is of little diagnostic importance. 
The Thorax.-The thymus gland, at this period very large, occupies the upper por- 
tion of the anterior mediastinum, covering the trachea and large vessels. Its average 
weight is about 13 grams. It is usually about 5 cm. long, 3.8 cm. wide at its lower 
part, and about 0.63 to 0.85 cm. in thickness. It may be hypertrophied and compress 
the large vessels, or be inflamed and suppurating. 
The heart lies more nearly in the median line than in the adult. It weighs from 
20 to 24 grams. The ventricular walls are of nearly equal thickness. The pericar- 
dium contains very little serum. A considerable quantity of red fluid may accumu- 
late here as a result of decomposition. There may be small extravasations of blood 
beneath the pericardium in still-born children and in those born alive. Pericarditis 
with effusion of serum and fibrin, and endocarditis with consequent changes in the 
valves, may exist before birth. Malformations and malpositions of the heart and 
large vessels are not infrequent. Small soft reddish nodules may be present on the 
edges of the valves, which are remnants of the fetal mucous tissue but may be mis- 
taken for the marks of endocarditis. The time of closure of the foramen ovale and 
the ductus arteriosus varies very widely in different cases. 
The pleural cavities contain very little serum, but decomposition may lead to the 
accumulation of a considerable quantity of red fluid. Small extravasations of blood 
in the subpleural tissue may be found in children who have died before birth and after 
protracted labors. Inflammation, with exudation of serum, fibrin, and pus, may 
exist before birth. 
The lungs in a still-born child are small, do not cover the heart, are situated in the 
upper and posterior portions of the thorax, are of a dark red color and of firm, liver- 
like consistence, and do not crepitate. In a child born alive, which has respired 
freely, the lungs fill the thoracic cavity, but do not cover the heart as much as in the 
adult; they are of a light red or pink color, and crepitate on pressure. If respiration 
has been incompletely performed, we find various intermediate conditions between 
the fetal and inflated states. 
If any doubt exists as to respiration having taken place, it is customary to employ 
the hydrostatic test. This is done by placing the lungs, first together, then separately, 
and afterward cut into small pieces, in water. It is commonly said that if they sink 
the child has not breathed; if they float it has. This test is not, however, a certain 
one.1 
The lesions of inflammation, and vesicular and subpleural emphysema, may be 
found in the lungs of new-born children. 
The pharynx should be opened and examined for foreign bodies. 
The larynx and trachea should be examined for the lesions of inflammation and for 
injuries to the cartilages. 
The thyroid gland weighs about 12 grams. It may be so enlarged as to interfere 
with respiration. 
1 See works on medical jurisprudence. 1226 
MAKING POST-MORTEM EXAMINATIONS 
The Abdomen.-The kidneys are lobulated and proportionately larger than in the 
adult. Thoma estimates the average weight of both organs together as 23.6 grams. 
There may be ecchymoses on their surface; inflammation; deposits of uric acid and 
urates in the tubules of the pyramids; cystic dilatation of the tubules, sometimes 
reaching an enormous size. There may be absence or retarded development of one 
kidney. Malformations and malpositions of the kidneys are of frequent occurrence. 
The adrenals are large. They may be dilated into large cysts filled with blood. 
The spleen is large and firm. Its average weight is about 11 grams. It may be 
abnormally enlarged, and its surface is sometimes covered with fresh inflammatory 
exudations. 
The Intestines.-In the small intestines, inflammation and swelling and pigmenta- 
tion of the solitary and agminated follicles (lymph-nodules) are sometimes found. 
The large intestine usually contains meconium, but this may be evacuated before or 
during birth. The sigmoid flexure is not so marked as in the adult. 
The formation of gas in the stomach and intestines does not usually take place 
until respiration is established. If decomposition has commenced, however, gas may 
be formed as a part of the process. 
The liver is of a dark red color, is large, and contains much blood. Its size dimin- 
ishes after respiration is established. Its average weight is 118 grams. The size is so 
variable, before and after respiration, that it gives little information as to the age of 
the child. Large extravasations of blood are sometimes found beneath the capsule of 
the liver without known cause. A variety of pathological conditions, fatty and waxy 
degeneration, gummy tumors, etc., may be found. 
The bladder may be full or empty, both in still-born children and in those which 
have breathed. Dilatation and hypertrophy may exist during intrauterine life. 
Generative Organs.-The external generative organs in both males and females are 
more prominent than in adults. The ovaries are high up in the pelvis and large; the 
cervix uteri is long; the body small and lax, resting forward against the bladder. 
Phimosis in the males is the normal condition. Malpositions and retarded develop- 
ment of the testicles should be noticed. It should be observed whether the anus is 
perforate. 
The bones, in suspected cases, should be examined for the lesions of inflammation, 
rickets, and syphilis. 
Preservation.-The various fetal tissues may be preserved by the same methods 
as are employed for those of the adult; but as they are very delicate they should be 
handled with great care and the preservative fluids changed with sufficient frequency. CHAPTER II. 
GENERAL METHODS OF PRESERVING PATHOLOGICAL SPECI- 
MENS AND PREPARING THEM FOR STUDY. 
It is not our purpose in this section to give a complete account of 
the technical procedures required in the study of pathological specimens. 
We wish simply to furnish a few brief hints as to the most useful methods 
for ordinary purposes. Additional suggestions will be found in parts of 
the book dealing with special tissues and organs.1 
The Study of Fresh Tissues. 
Although for the most part the conditions for the minute study of 
tissues are more favorable after these have been fixed and hardened by 
a suitable chemical agent, it is yet in many cases very important to 
examine them in the fresh state. 
In this condition many of the degenerative changes in cells are more 
clearly seen than after fixation, while the study of living cells in indif- 
ferent fluids with various stains may throw much light upon vital phe- 
nomena and the changes which supervene when life ceases and the cell 
falls under the sway of the simple physical and chemical forces. 
Fresh tissues may be teased apart, mounted and studied in 0.85 per 
cent, sodium chloride solution, but it is usually much more satisfactory to 
cut frozen sections of the tissue to be examined. 
The study of living cells is often facilitated by the addition to the 
physiological salt solution of small amounts of either neutral red, methy- 
lene blue, thionin, Janus green, or trypan blue. These dyes stain the 
nuclei or other portions of the cell, and often give very satisfactory 
pictures.2 
In the method of Arnold3 the cells are protected from pressure of the 
cover-glass and the study facilitated by the use of thin sections of dried 
elder pith dipped in the fluid containing the living cells and tinged with 
the coloring agent. 
For the methods of studying the circulation on the curarized frog 
see page 127. 
Rapid Fixation and Frozen Sections. 
A rapid fixation and development of detail in structural elements in 
fluids may be secured by allowing a drop of formaldehyde to run under 
1 For the technical details of many complex methods which are invaluable for special purposes, 
one may consult Lee, Microtomist's Vade-Mecum, 7th edition, Philadelphia, 1913; Mallory and Wright, 
Pathological Technique, 7th edition, Philadelphia, 1918; and Schmorl, Die pathologisch-histologischen 
Untersuchungsmethoden 7th edition, Leipzig, 1914. The special technique of the blood will be found 
in Schriddle and Naegeli, Hamatologische Technik, 1910; Wood, Chemical and Microscopical Diag- 
nosis, 3d edition, New York, 1917; and Gilbert and Weinberg, Traits du sang, Paris, 1913. 
2 Consult for theory of vital staining, Ruzicka, Ztschr. f. wissensch. Mikros., 1905, xxii, 91 and 
548. For colorability of living cells, see Coco, A. M., Centralbl. f. allg. Path., 1902, xiii, 604. 
3 Arnold, J , Munch, med. Wchnschr., 1906, liii, 585. 
1227 1228 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
the cover-glass and mingle with the salt solution, the flow being directed 
by a bit of filter paper put close to the edge of the cover-glass on the side 
opposite to that on which the fixative is added. The formaldehyde may 
be washed out by saline and the latter replaced by a dilute aqueous 
solution of thionin to stain the nuclei. 
When an immediate diagnosis of a solid tissue is required, useful 
results may be obtained by a combination of the freezing method with 
the use of formaldehyde as a fixative.1 Any form of freezing microtome 
and either ether, ethyl chloride, or liquid carbonic acid may be used. 
Many tissues can be frozen immediately after their removal from the 
body, cut, floated on to a slide with salt solution, and then stained with 
a saturated aqueous solution of thionin blue, toluidin blue, Unna's poly- 
chrome methylene blue, or other basic dyes. They can be mounted in 
the saline or preferably in Bruns'2 glucose medium, in which they keep 
for a few hours. 
An excellent stain for frozen sections is that recommended by Good- 
pasture.3 For its preparation 1 gm. of methylene blue and 1 gm. of 
potassium carbonate are dissolved, in 400 c.c. of distilled water, and the 
whole is boiled in a flask for thirty minutes. When the solution has 
cooled, 3 c.c. of glacial acetic acid are added, and the mixture is shaken 
thoroughly until the precipitate is dissolved and then concentrated by 
gentle boiling to a volume of 200 c.c. The solution is cooled under the 
tap and is ready for use immediately. The nuclei are stained a deep 
purple and the connective tissue a bright rose red. 
When the tissues are gelatinous or contain considerable fat, they can 
be fixed in hot 4 per cent, formaldehyde (50° C.) or even boiled for a few 
minutes in the same solution. This will permit of an immediate exami- 
nation. Such fixation is very imperfect, however, and portions of the 
tissue should always be reserved for regular fixation, and sectioned after 
embedding. 
If an immediate examination is not of great importance Wright's 
method is the best to use. This is as follows: 
1. Fix pieces of tissue in 4 per cent, aqueous formaldehyde, for fifteen 
to twenty-four hours. 
2. Cut the tissue into slices not over 5 mm. thick, and after rinsing in 
water, freeze and section. 
3. Float the sections off the knife into water; select a suitable one; 
and spread it smoothly on a slide by passing the slide into the water 
under the section and drawing the latter gradually up on the glass. 
4. Drain off the water. 
5. Blot the section with smooth blotting paper. It will then adhere 
to the slide. If it contains much mucoid material cover the section with 
absolute alcohol for a few seconds before blotting it. 
6. Pour over the section a small quantity of absolute alcohol, allowing 
it to stay on for five seconds. 
1 Cullen, Bull. Johns Hopkins Hosp., 1895, vi, 67. 
2 Bruns' glucose medium is made up as follows: Distilled water, 140 c.c.; glucose, 40 gm.; glycerin, 
10 gm. About 5 c.c. of 40 per cent, formaldehyde should be added to prevent decomposition and 
to fix the tissues. 
3 Goodpasture, E. W., Jour. Am. Med. Assn., 1917, Ixix, 998. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1229 
7. Cover the slide with a thin solution of celloidin; drain off; allow the 
film to become firm by waving the slide in the air for a few seconds, and 
then place the slide in water. 
8. The section can be stained by any of the usual methods, as it is 
held permanently to the slide by the celloidin, unless the absolute alcohol 
used in dehydration is left on too long. 
Fixation, Hardening, and Preservation. 
Alcohol is a useful fixative for tissues in which bacteria or glycogen 
are to be demonstrated, either 95 per cent, or absolute ethyl alcohol 
being employed. The pieces of tissue should be small, as penetration is 
not satisfactory when the bulk is more than 1 or 2 c.c. The quantity 
of alcohol used should be 40 to 50 times the volume of the tissue to be 
hardened. A little absorbent cotton may be placed in the bottle to keep 
the blocks of tissue from sticking to the bottom. After twenty-four 
hours the alcohol should be renewed. On the third day the tissue is 
transferred to strong or to absolute alcohol for completion of the hard- 
ening, which will usually be finished within five or six days. 
While for many purposes other and more delicate methods of harden- 
ing tissues are to be recommended, alcohol is most useful for solid tissues 
in which bacteria are to be sought, for such specimens as are not quite 
fresh and in which the process of decay is to be immediately checked, 
and in general for tissues in which the determination of topographical 
features for diagnostic or other purposes is the chief end in view. 
Formaldehyde, which is obtainable in a 35 to 37 per cent, aqueous 
solution, is now most generally employed for routine fixation. Formalin, 
formol, etc., are merely trade names for formaldehyde of this strength 
as prepared by different chemical houses. For fixation, the formalde- 
hyde is used in a 4 per cent, solution, made by adding 1 part of the com- 
mercial preparation to 8 parts of water. The fresh tissues, in small 
pieces, are put into this solution for forty-eight hours, the fluid being 
renewed at the end of twenty-four hours. They are then transferred 
to 60 per cent, alcohol for twenty-four hours, and the hardening is 
completed with strong alcohol. 
Muller's fluid, which has been much used as a hardening agent, 
has the following composition: 
Potassium bichromate 2.5 parts. 
Sodium sulphate 1.0 part. 
Water 100.0 parts. 
Muller'g fluid is now most often used in combination with other 
fixatives. 
Thus Orth's fluid, which is Muller's fluid to 90 parts of which 10 parts 
of 37 per cent, formaldehyde are added, is a most valuable agent for fix- 
ing and hardening delicate cells. The mixture should be made at the 
time of using because it soon changes. The pieces of tissue should be 
small, the fluid largely exceeding the tissue in bulk. The hardening is 1230 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
completed in three or four days, when the specimens should be thoroughly 
washed in water and preserved in 80 per cent, alcohol. 
Osmic acid is of great value, especially in combination, for the 
hardening of small portions of delicate tissues, since it serves to fix the 
elements in a nearly normal condition and stains them brown or black. 
Osmic acid stains most forms of fat black and on this account is a valuable 
agent for the detection of this substance in the tissues. It is generally 
used in 1 per cent, aqueous solution, the tissues, in very small pieces 
and when quite fresh, being placed in it and allowed to remain for twenty- 
four hours. They are then washed thoroughly in water and may be 
preserved in 80 per cent, alcohol. 
Flemming's Osmic Acid Mixture.-For the purpose of fixing delicate 
tissue elements to show minute structural detail, such as mitotic figures, 
this mixture is of great value. It is made of 
1 per cent, chromic acid 15 parts. 
2 per cent, osmic acid 4 parts. 
Hydric acetate, glacial 1 part. 
This mixture does not keep well, and hence should be made up in small 
quantities. Small portions of tissue should soak in the mixture for 
twenty-four hours, then, after thorough washing in water, they are put 
for twenty-four hours in 70 per cent, alcohol, and next in strong alcohol, 
in which they are kept. 
Corrosive Sublimate.-This is a most excellent fixative for the minute 
cytological study of tissues; but unless the material is preserved within 
an hour after its removal from the body post-mortem changes will nullify 
its advantages. 
Mercuric chloride 5 gm. 
Sodium chloride 6 gm. 
Hydric acetate, glacial 5 c.c. 
Water 100 c.c. 
The tissues should remain in sublimate solution, as a rule, not longer 
than from one to three hours. 
Specimens fixed in sublimate develop a mercurial precipitate, do not 
stain well, and become brittle unless the excess of sublimate is removed. 
This can be largely done by prolonged washing in running water; but 
it is much more easily and certainly accomplished by the chemical action 
of dilute iodine solution. The specimen is removed from the sublimate 
mixture and put at once into 70 per cent, alcohol. To this is added 
from time to time a sufficient quantity of saturated alcoholic solution of 
iodine (or tincture of iodine) to give the alcohol a moderately deep yellow 
color. At first this color gradually disappears, and the iodine solution 
should be repeatedly added until the color persists. The specimens 
are now transferred to 70 per cent, alcohol, and, after twenty-four hours, 
to strong alcohol. 
Zenker's fluid is a good fixative and acts rapidly. It is a combina- 
tion of Muller's fluid and corrosive sublimate with acetic acid. Its 
formula is: METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1231 
Potassium bichromate 2.5 parts. 
Sodium sulphate 1 part. 
Mercuric chloride 5 parts. 
Hydric acetate, glacial 5 parts. 
Water 100 parts. 
The acetic acid should be added at the time of using, since the com- 
plete mixture readily decomposes. Small pieces of tissue may be hard- 
ened in this solution in from four to twenty-four hours. They should 
be thoroughly washed in running water and preserved in 80 per cent, 
alcohol. 
Hellos Fluid.-As acetic acid destroys certain types of cell granules, 
a neutral preserving fluid must be employed in the study of the finer 
details of the bone-marrow, spleen, and other hematopoietic organs. A 
useful mixture is Helly's fluid, the formula for which is as follows: 
Potassium bichromate 2.5 parts. 
Sodium sulphate 1 part. 
Mercuric chloride; 5 parts. 
Neutral, 37 per cent, formaldehyde 5 parts. 
Water ! . . . . 100 parts. 
Very thin slices of tissue are fixed for four to five hours, then washed 
thoroughly in water, and hardened in ascending strengths of alcohol. 
The use of iodine is not necessary. The formaldehyde can be neutral- 
ized by shaking with an excess of calcium carbonate. 
Dominions Solution.-This is valuable as a fixative for the hemato- 
poietic organs. It is made up as follows: 
Saturated solution of mercuric chloride 100 c.c. 
37 per cent, formaldehyde 15 c.c. 
Saturated aqueous solution of picric acid 15c.c. 
To the above, tincture of iodine is added drop by drop until the solution 
is very faintly yellow. Specimens are fixed for twenty minutes to five 
hours, depending upon their thickness, which should not be in excess of 
3 mm. The material is not washed in water, but is transferred directly 
to alcohol, unless the fixation has been very prolonged. Crystals of 
mercuric compounds can be removed by treating the sections with 
iodine, and then washing them in alcohol until all the iodine is removed. 
Pathological specimens which occur, or are isolated, in the form of 
membranes, should be stretched with pins on a piece of wood or flat 
cork before being immersed in the preservative fluids. Minute struc- 
tures, such as occur in exudates from the mucous membranes and in 
cyst fluids, renal casts, etc., may be hardened in Flemming's osmic-acid 
mixture or in formaldehyde followed by alcohol. Under these conditions 
renewals or changes of the fluids may be effected in tubes by the use of 
the centrifugal machine. The specimens may finally be preserved in 
80 per cent, alcohol. 
Decalcifying. 
Bones which are the seat of lesions, and calcified tissues, must be 
freed from lime salts before thin sections can be made. 1232 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
Tissues which are to be decalcified should be in small pieces and first 
well hardened in alcohol, formaldehyde, or Orth's fluid. Zenker's fluid 
and sublimate are not satisfactory. 
The best method for the rapid decalcification of tissues is by means of 
a solution of nitric acid containing 5 parts by weight of the acid to 95 parts 
of water. The strong nitric acid of commerce has a specific gravity of 
1.414 and contains 68 per cent, of acid; approximately 7.5 c.c. of acid, 
therefore, are to be used with 92.5 c.c. of water. The amount of fluid 
used should be large, and it should be frequently shaken, or. preferably, 
kept turning with one of the small water motors used in chemical labora- 
tories. The fragments of tissue should be tested repeatedly by pricking 
them with a fine steel needle. When no grating is felt along the needle 
it may be assumed that the lime has disappeared. The fragments are 
then transferred to a 5 per cent, solution of sodium sulphate for twelve 
to twenty-four hours, and then washed for forty-eight hours in running 
water. The tissue can then be cut on a freezing microtome, or embedded 
in celloidin or paraffin. 
A saturated aqueous solution of sulphurous acid is less destructive to 
the tissues, but decalcifies more slowly than does nitric acid. 
Embedding and Section Cutting. 
Some dense tissues, after being well hardened, are sufficiently solid to 
permit the making of thin sections without further preparation; but in 
most cases very thin sections cannot be prepared unless the interstices 
of the tissue are filled with some embedding material, which gives it 
greater consistence and holds the elements firmly in their natural rela- 
tions to one another, while the section is being made. Celloidin and 
paraffin are the most generally useful materials for this purpose. 
Celloidin, a non-explosive, purified form of gun-cotton, is best 
obtained in the form of thin shavings, since in this form it is most easily 
dissolved. A 6 per cent, solution is made in equal parts of sulphuric 
ether and strong alcohol. Small pieces of the tissue are soaked for 
twelve hours in this celloidin solution diluted with an equal amount of 
the mixture of alcohol and. ether, then for twelve hours in the 6 per 
cent, celloidin solution. If the specimen be small and require but little 
support, it may now be laid directly on the end of a small block of wood 
or cube of glass or vulcanite, and a few drops of celloidin poured around 
it. In most cases, however, it is better to make a small paper box, in 
which the. specimen is placed in a proper position, and the celloidin 
poured in around it so as completely to inclose it. In either case a con- 
siderable quantity of celloidin should be poured around the specimen, 
since the celloidin shrinks considerably in hardening. The paper box 
may be made by winding a strip of thin paper around the end of the 
supporting block, allowing it to project for a sufficient distance beyond 
the end. The paper is held in place by a rubber band. We have thus 
a cylindrical box with a solid bottom projecting below it by which the 
whole can be held in the clamp of the microtome. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1233 
After the specimen, either free on the end of the block or in its box, 
is surrounded by celloidin, it should be allowed to stand for a short time 
exposed to the air, so that the celloidin may harden on the outside by the 
evaporation of the ether. If the temperature be high, the too rapid 
evaporation of the ether will cause bubbles to appear in the mass. This 
should be avoided by covering the specimen with a bell-jar. After the 
celloidin mass has acquired sufficient hardness on the outside to keep its 
shape, the whole should be placed in 80 per cent, alcohol, in which 
the celloidin will harden and acquire a sufficient consistence for cutting 
in a few hours. When this is accomplished the paper may be stripped 
off, and the specimen is ready for sectioning. 
After the sections have been cut they may be stained in the usual way 
(see below) and mounted in glycerin or balsam. If mounted in balsam, 
the oil of origanum cretici is used for clearing. 
The uncut portion of tissue may be preserved, embedded in celloidin, 
by keeping it in 80 per cent, alcohol. It is better, in permanent pres- 
ervation of uncut celloidin-embedded specimens in bulk, to cut them 
off from the wooden blocks, since alcohol extracts from these a dark 
resinous material which colors the specimen and interferes with the 
staining of sections. If glass or vulcanite blocks be used, the whole may 
be kept in alcohol. 
Stepanow has devised a more rapid procedure in celloidin embedding, 
The celloidin solution is made by the following formula, a few days being 
required for dissolving: 
Celloidin 15 gm. 
Oil of cloves 50 c.c. 
Ether 200 c.c. 
Absolute alcohol 10 c.c. 
The hardened specimen is transferred from strong alcohol to a small 
portion of the solution in a closed bottle. In from three to six hours a 
small piece of ordinary tissue is usually impregnated. It is then put in 
position on the mounting block and placed in pure chloroform. In this 
the proper consistency for section cutting is secured in from two to three 
hours, after which the whole is transferred to 80 per cent, alcohol. If 
the specimen remaining after sections have been secured is to be kept, it 
should be removed from the block and placed in chloroform. 
For further details of this method see the original description.1 
Paraffin.-For routine purposes, and also when extremely thin sec- 
tions are required, paraffin embedding is more convenient than celloidin. 
If the specimen has been properly hardened and suitably embedded, 
sections measuring 2 by 4 cm. can be made without difficulty. The 
technique of embedding is as follows: 
Specimens from formaldehyde or picric acid fixation are passed directly 
into 50 per cent, alcohol; those from sublimate are washed in water 
before being transferred to 50 per cent, alcohol. The blocks remain in 
alcohol of this strength for several hours, and are then transferred to 
70, 80, and 95 per cent, alcohols, remaining in each for several hours, 
1 Stepanow, Ztschr. f. wissensch. Mikros., 1900, xvii, 185. 1234 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
the length of time depending upon the thickness of the blocks and upon 
the number in the container. The final transfer is to absolute alcohol, 
of which at least two changes must be provided in order to remove every 
trace of water, as otherwise the tissue will be irretrievably ruined in the 
later stages of the process. 
When the specimen is thoroughly dehydrated by absolute alcohol, it 
should be put into a mixture of carbon disulphide and alcohol, equal 
parts; then into pure carbon disulphide; then into carbon disulphide 
saturated with paraffin at room temperature; and, finally, into carbon 
disulphide saturated with paraffin at 37° C. If the block is thin, it 
must remain in each of these mixtures for from three to four hours. If 
it is large, the time must be proportionately longer. The specimen is 
then transferred to a dish of melted paraffin, and, after one hour, to a 
second dish of melted paraffin for one hour. Paraffin with a melting 
point of 52° C. is usually employed. At the end of two hours the tissue 
is removed and embedded in fresh paraffin. 
A small paper box considerably larger than the specimen itself is 
filled with melted paraffin, and with a warm needle or forceps the speci- 
men is transferred to the paper box and set in its proper position in the 
bottom, so that the surface to be cut lies against the bottom of the box. 
In order to avoid the slow cooling of the paraffin around the specimen in 
successive layers, which prevents the formation of a homogeneous mass, 
the paper box with its contents is quickly cooled by being put into cold 
water, even iced water. When the paraffin block is hard, it is fastened 
with paraffin to one of the various discs belonging to the paraffin 
microtome, trimmed so as to have a rectangular cutting surface, and 
sections are cut with a dry knife. 
After the tissues are embedded, sections can be cut with a chisel 
knife on one of the simpler freezing microtomes, though much better 
results can be obtained by using a more elaborate type. 
Celloidin sections are best cut on a machine of the Thoma or Schanze 
type, which permits the use of a long knife set obliquely. During the 
process of cutting the knife should be flooded with 80 per cent, alcohol. 
Paraffin sections are usually cut in ribbons on an automatic feed 
rotating microtome of the Minot type. Excellent paraffin sections can 
be cut, however, on the sliding form, though not so conveniently or so 
speedily. 
In order to stain these sections, the paraffin must be removed from 
the interstices; this may be done with xylol. But when the supporting 
paraffin is removed from the sections they are liable to fall to pieces 
during the further staining and other manipulations. The only practi- 
cal plan, therefore, is to affix them to a slide and carry them in this way 
through the various staining and mounting procedures. 
The best way of affixing delicate paraffin sections to a slide is by 
means of a thin film of albumen. Equal parts of white of egg and 
glycerin are thoroughly stirred together, and filtered through paper, and a 
small amount of carbolic acid is added to prevent the growth of micro- 
organisms. A very small drop of this albumen mixture is placed on one METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1235 
end of the slide, and with the ball of the finger or a fold of cloth it is 
spread over the rest of the slide in as thin a film as possible. The sec- 
tions as they are cut are floated on warm distilled water at a temperature 
three or four degrees below the melting point of the paraffin. On this 
they flatten out and lose any wrinkles which may have formed in the 
cutting. The slide is then inserted under the section in the water and 
gently raised, the sections being steadied with a camel's hair brush. As 
soon as the sections are in proper position on the slide, the water is 
drained off, the sections being held in place with the brush, and the slide 
is set aside in a dust-free place to dry. After it has dried, the paraffin 
is melted by passage of the slide cautiously high over a Bunsen flame or, 
what is better, by standing for a few minutes in a paraffin oven. Any 
excess of heat, either while the section is being flattened on the water or 
after the paraffin has dried, will ruin the tissues for staining purposes. 
While the slide is still warm, it is plunged into a jar of xylol, oscillated to 
and fro a few seconds, then placed in a jar of absolute alcohol, then 
passed through a series of jars containing different strengths of alcohol- 
95 per cent., 70 per cent., and 50 per cent., remaining a few minutes in 
each, and finally into water. Now the sections upon the slide may be 
stained in whatever way desired, carried up through the graded alcohols 
to absolute alcohol, then cleared in xylol or other clearing media, and 
mounted in balsam. 
Tightly covered cylindrical jars-the Coplin jar is excellent-or wide- 
mouthed bottles are used for the better manipulation of paraffin sections, 
the whole slide being dropped into the receptacle for staining as well as 
for the dehydration and clearing. 
Methods of Staining. 
Sections of hardened tissues may be stained for microscopical study 
in a variety of ways, but for routine work the double staining with hema- 
toxylin and eosin is most generally useful, and is applicable to nearly 
all cases. 
Hematoxylin solution (Delafield's) is prepared as follows: To 100 
c.c. of saturated solution of ammonia alum add 1 gram of hematoxylin 
crystals dissolved in 6 c.c. of 95 per cent, alcohol. This solution is ex- 
posed to the light for a week, during which time the color changes from 
a dirty red to a deep bluish-purple.1 Then 25 c.c. each of glycerin and 
wood naphtha are added. This mixture is allowed to stand for a day 
or two and is then filtered, and the filtration is repeated at intervals until 
a sediment no longer forms. 
The solution is now ready for staining, the best results being obtained 
by diluting the fluid with from ten to twenty times its bulk of water. 
The sections are immersed in the fluid, and allowed to remain until they 
have acquired a distinct purple color which persists after rinsing in 
water. They are now placed for a moment in a dilute alcoholic solution 
1 The time required for this "ripening" of the solution may be spared by the use of hematin in the 
place of hematoxylin. 1236 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
of eosin, and then mounted in glycerin which has been colored lightly 
with an alcoholic solution of eosin. In this way the nuclei of the cells 
will be stained a purple color, while the cell bodies, and to a certain 
extent the intercellular substance, will be colored a light rose red. 
If specimens are to be mounted in Canada balsam, they are stained 
with hematoxylin as before, and the eosin staining is done by tinging 
with a saturated alcoholic solution of eosin, the alcohol with which the 
final dehydration of the specimen is accomplished. A similar result 
may be obtained by tinging the oil of cloves or origanum with which the 
clearing of the sections is effected. 
Iron Hematoxylin (Heidenhain's).-Sections, preferably fixed to the 
slide, are soaked for three to six hours in a 2.5 per cent, solution of ferric 
ammonium alum. They are then stained for twenty-four hours in a 
mixture of hematoxylin, 1 gram; absolute alcohol, 10 c.c.; water 90 c.c. 
After washing in tap water, the sections are differentiated in the alum 
solution, 2.5 per cent, or weaker, depending upon the desired rate of 
decoloration. The preparations should be watched carefully under the 
microscope to determine when the desired depth of standing is reached. 
This method is especially valuable for the study of nuclear struc- 
tures, the color of these ranging from blue to black, depending upon the 
length of time of immersion in the stain and the grade of differentiation. 
Picro-acid Fuchsin (Van Gieson's Stain).-This double stain, first 
suggested by Van Gieson especially for the nerve tissue, has wide appli- 
cations in both normal and pathological histology, and is most useful 
when following a deep hematoxylin stain. 
It colors the fibrillated connective-tissue fibers and the neuroglia in 
general a bright or garnet red, and also the axis-cylinders and ganglion 
cells. Myelin, muscle fibers, and certain other cells are stained yellow, 
while the nuclei after the hematoxylin stain are brownish red in color. 
Van Gieson's stain is also of value, although its limitations in this 
particular are not yet fully determined, as a coloring-agent for hyalin, 
amyloid, colloid, and mucin in the tissues. As a differential stain for 
fibrillated connective-tissue fibers it is of value in the study of various 
tumors and especially of the sarcomata. 
It is commonly prepared in two strengths, the stronger for use espe- 
cially in nerve-tissue staining, the weaker for general purposes. The 
formulae and method of using as suggested by Freeborn1 are as follows: 
Piero-acid Fuchsin. 
Stronger solution- 
1 per cent, aqueous solution acid fuchsin 15 c.c. 
Saturated aqueous solution picric acid and water, each 50 c.c. 
Weaker solution- 
1 per cent, aqueous acid fuchsin 5 c.c. 
Saturated aqueous solution picric acid 100 c.c. 
The tissues may be hardened either in alcohol, or in Orth's fluid, or 
in formaldehyde. . 
Sections are first stained deeply with hematoxylin, washed in water, 
and put into the staining fluid, in which they remain for varying periods, 
1 Freeborn, Proc. New York Path. Soc., 1893, p. 73. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1237 
depending upon the tissue and the strength of the stain, but in general 
from one to five minutes. The sections are then rapidly dehydrated by 
alcohol, cleared with oil of origanum, and mounted in balsam. 
Mallory's Anilin-blue Stain.-This stain is especially useful in 
bringing out in blue the fibrillae and reticulum of connective tissue, 
though various hyaline substances are similarly colored. The nuclei, 
protoplasm, elastic fibers, axis-cylinders, neuroglia fibers, and fibrin are 
stained red; while red blood-cells and myelin sheaths are yellow. 
The details of the method are as follows:1 
1. Fix in Zenker's fluid. 
2. Embed in celloidin or paraffin. 
3. Stain sections in a 0.2 per cent, aqueous solution of acid fuchsin 
for five minutes or longer: 
4. Transfer directly to the following solution for twenty minutes or 
longer: 
Anilin blue soluble in water (Griibler) 0.5 
Orange G. (Griibler) 2.0 
1 per cent, aqueous solution of phosphomolybdic acid 100. 
5. Wash and dehydrate in several changes of 95 per cent, alcohol. 
6. Clear in xylol or in oil of origanum. 
7. Xylol balsam. 
Methylene blue combined with eosin is a very valuable stain for 
preparations fixed in any of the sublimate mixtures.2 
Dominici's Stain.-Another procedure giving very beautiful pic- 
tures is the toluidin blue-eosin-orange stain of Dominici. This requires 
a 1 per cent, aqueous solution of toluidin blue, or methylene blue, if 
preferred, and a mixture containing 1 gram each of water-soluble eosin, 
orange G, and tannin, dissolved in 100 c.c. of distilled water. The sec- 
tions are immersed for several minutes or less in the eosin-orange stain, 
and then washed in water. They are next stained for several minutes 
in the toluidin blue solution, washed rapidly in water, and differentiated 
in 90 per cent, alcohol containing 1 per cent, of glacial acetic acid. After 
a few seconds in the acid alcohol the sections are transferred to absolute 
alcohol which is changed until they are washed free from acid. The 
sections are then cleared in xylol and mounted in neutral dammar. 
Giemsa's3 Stain for Blood and Tissues.-The stain is prepared as 
follows: 
Azur II-Eosin 3.0 gm. 
Azur II 0.8 gm. 
Glycerin c. p 250.0 c.c. 
Methyl alcohol c. p 250.0 c.c. 
The dyes are thoroughly dried over H2SO4, finely pulverized, and sifted through a 
fine-meshed silk sieve; then dissolved by shaking in the glycerin heated to 60° C. To 
this glycerin solution is added the methyl alcohol also heated to 60° C., the whole 
thoroughly shaken and allowed to stand for twenty-four hours and then filtered. 
The stain is prepared for the market ready for use by Griibler. 
1 See Mallory and Wright, Pathological Technique, 7th edition, Philadelphia, 1918. 
2 For details of the procedure, see Mallory and Wright, Pathological Technique, 7th edition, Phila- 
delphia, 1918, p. 111. 
3 Giemsa, Centralbl. f. Bakteriol., Orig. I, 1904, xxxvii, 308. 1238 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
For Staining Blood.-1. Air-dried blood smears are fixed for two 
to three minutes in methyl alcohol and dried off with filter paper. 
2. The dye is diluted with water (1 drop of the dye to about 1 c.c. 
of distilled water). The water may to advantage be warmed to 30° 
to 40° C. 
3. Pour the freshly diluted dye over the smear and stain for ten to 
fifteen minutes. 
4. Wash off in water jet. 
5. Dry partially with blotting paper and then in the air. Mount in 
balsam. 
For Staining Tissues.-For staining tissues the following method 
of Schridde1 may be useful. 
1. Five micra paraffin sections are stained for twenty minutes in a 
mixture of two drops of Giemsa's solution and 1 c.c. of water. 
2. Washed carefully in water. 
3. Dried off with blotting paper. 
4. Transferred immediately to anhydrous chemically pure neutral 
acetone. 
5. Transferred to xylol. Mounted in neutral dammar. 
Unna's Polychrome Methylene-blue Stain.-This is prepared 
for the market by Griibler. The formula for its use given by Mallory 
and Wright is as follows: 
1. Stain paraffin or celloidin sections hardened in alcohol in poly- 
chrome methylene-blue five to ten minutes or longer. 
2. Wash in acidulated water. 
3. Fix in 10 per cent, solution of bichromate of potassium half a 
minute. 
4. Wash in water. 
5. Dry on slide with filter-paper. 
6. Decolorize in anilin plus 1 per cent, hydrochloric acid (a few 
seconds only). 
7. Wash off with oil of bergamot. 
8. Balsam. 
Thionin.-Thionin is especially useful as a stain for mucin. In the 
following-Hoyer's formula-the mucin is colored red, the remaining 
tissue blue. 
1. Harden in corrosive sublimate, followed by alcohol. 
2. Paraffin sections are passed through xylol or chloroform to free 
them from paraffin, then 95 per cent, alcohol and, after washing in water, 
are placed in a 5 per cent, aqueous solution of corrosive sublimate for 
three to five minutes. 
3. Stain in a dilute solution of thionin for ten to fifteen minutes. 
4. Alcohol. 
5. Clear in a mixture of oils of cloves and thyme. 
6. Turpentine oil or oil of cedar. 
7. Balsam. 
1 Schridde, Centralbl. f. allg. Path., 1905, xvi, 769. 1239 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
The sublimate should not be removed from the tissues by iodine, as is 
usual as a preliminary to staining. 
Thionin is useful for the staining of exudates, frozen sections, etc. It 
may be kept in a stock saturated aqueous solution to be variously diluted 
as used. 
Best's Method for Staining Glycogen.-The tissues are hardened 
in alcohol; 10 per cent, trichloracetic acid, formaldehyde and sublimate 
are less satisfactory. Washing in water must be avoided, the prepara- 
tions being transferred directly to alcohol. The material is then em- 
bedded in celloidin, and cut. Paraffin sections must be flooded with a 
thin celloidin solution after the paraffin has been removed, and should 
be flattened on warm alcohol instead of on warm water. 
The stain is made up as follows: 
Carmine, 2 gm. 
Potassium carbonate, 1 gm. 
Potassium chloride, 5 gm. 
Distilled water, 60 c.c. 
The mixture is boiled, and 20 c.c. of strong liquor ammoniac are added. 
It is then ready for use and keeps for some three weeks. The technique 
is as follows: g 
1. Stain deeply with Delafield's hematoxylin; differentiate in acid 
alcohol. 
2. Wash in water. 
3. Stain in carmine solution, 2 parts; strong liquor ammoniae, 3 parts; 
methyl alcohol, 3 parts. 
4. Transfer to a mixture of methyl alcohol, 40 c.c.; absolute alcohol, 
80 c.c.; distilled water, 100 c.c. The sections are allowed to remain in 
this mixture for one to five minutes. 
5. Wash in 80 per cent, alcohol; transfer to absolute alcohol; clear 
in xylol or oil of origanum; and mount in dammar. 
The glycogen granules stain red; the nuclei are blue. The stain colors 
all of the glycogen and also certain secreting cells of the stomach, corpora 
amylacea of the nervous system, fibrin, and occasionally mucus and the 
granules of mast cells; it also colors calcified bone. 
Bielschowsky Silver Stain for Connective Tissue.1-The tissues 
should be obtained as soon as possible after death and the blocks, which 
should not exceed 1 cm. in thickness, be fixed in a 10 to 15 per cent, solu- 
tion of formaldehyde, and embedded in paraffin. Thin sections are cut, 
mounted on slides, and allowed to dry in an incubator at 37° C. for twelve 
hours or longer. The paraffin is then removed, and the sections brought 
down to 50 per cent, alcohol. They are then stained as follows: 
1. Place the sections for one to six hours, at ordinary room tempera- 
ture, in a solution made up of 10 c.c. of 10 per cent, watery solution of 
silver nitrate and 40 c.c. of 50 per cent, alcohol. 
1 Bielschowsky, M., Jour. f. Psychol, u. Neurol., 1904-05, iv, 227. The method given has been 
slightly modified from the original by Samuel Lowenthal, technician at the George Crocker Special 
Research Fund, Columbia University, and has proved very satisfactory. 1240 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
2. Dip sections once in 40 per cent, alcohol, and transfer to the follow- 
ing silver ammonium hydroxide solution for twenty minutes to one hour. 
To 10 c.c. of 10 per cent, silver nitrate, add 3 drops of 40 per cent, sodium hydrate, 
and then add ammonia drop by drop until the precipitate is dissolved; it is advisable 
to stop adding the ammonia while there are still a few granules of the precipitate in 
the container. The solution is then filtered into a Coplin jar, and 40 c.c. of 50 per 
cent, alcohol are added. 
8. Remove sections from the silver ammonium hydroxide solution, 
and dip them into a Coplin jar containing 40 per cent, alcohol to which 
1 drop of 37 per cent, formaldehyde has been added. 
The connective-tissue origin of the tumor is evident from the interpenetrating strands demonstrated 
by the Bielschowsky method. 
Fig. 808.-Sarcoma of Neck. 
9. Wash sections in 40 per cent, alcohol, and place them for a few 
minutes in a toning bath made up by adding 5 drops of 1 per cent, gold 
chloride and 2 drops of glacial acetic acid to 40 c.c. of 40 per cent, alcohol. 
10. Wash sections in 40 per cent, alcohol for one minute. 
11. Dip in a mixture of 40 c.c. of 40 per cent, alcohol and 10 c.c. of 
5 per cent, solution of hyposulphite of soda, for a few seconds only. 
12. Place in 50 per cent, alcohol; then in 95 per cent, alcohol, and 
then in absolute alcohol. 
13. Clear in xylol, and mount in dammar or balsam. 
The chief value of this stain, aside from its use in the study of the METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1241 
nervous system, is in the demonstration of the finer connective-tissue 
fibrils in tissues. In sarcomata (iFig. 808), with the exception of lympho- 
sarcoma and myeloma, such fibrils run between the cells, whereas in the 
carcinomata (Fig. 809) the fibrous tissue runs only about the alveoli. 
The stain thus often makes possible a diagnosis in tumors whose classi- 
fication is otherwise doubtful. 
The alveolar structure, however, is demonstrated by the Bielschowsky method. 
Fig. 809.-Spindle-cell Tumor of Neck, Resembling Sarcoma. 
Methods of Preserving Specimens for Gross Demonstration and for 
Museums. 
When specimens of abnormal tissues or organs are to be preserved 
entire for exhibition in jars in a museum, the superfluous parts are first 
removed and the requisite dissections made. Then they are carefully 
placed in the position and form which it is wished to preserve, by stuff- 
ing with horsehair or absorbent cotton and by the use of thread. When 
thus carefully adjusted they are either suspended or laid on a wad of 
absorbent cotton in 60 to 80 per cent, alcohol or in 4 per cent, formalde- 
hyde solution. In this they usually become hard, and finally, after the 
removal of the temporary stuffing and braces, are transferred for per- 
manent exhibition to fresh, clear, 80 per cent, alcohol, or, in case of 
formaldehyde hardening, to a fresh solution of the formaldehyde, to 
which, if the jar is likely to be exposed to cold, a little glycerin is added 
to prevent freezing. This description applies especially to such speci- 
mens as have cavities to distend or display. 1242 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
The more simple specimens, such as the solid viscera, tumors, etc., 
may be washed and hardened in 60 per cent, alcohol or in 4 per cent, 
formaldehyde solution.1 
In many cases an excellent hardening is obtained by injecting the 
preservative fluid through the blood-vessels. The lungs are well hard- 
ened by pouring the fluid through the trachea into the air spaces. 
Firm-walled cysts of various kinds are well preserved in a condition 
of distention by drawing off the natural contents through a fine cannula 
and refilling with, and immersing in, formalin solution. Delicate cysts, 
such as echinococcus cysts, small embryos in their membranes, cystic kid- 
neys, etc., may be preserved in a nearly natural conditon in formaldehyde.2 
Kaiserling's Method of Fixing Natural Colors in Museum Specimens.3 
1. Fixation for one to five days in: 
Formaldehyde 200 c.c. 
Water 1000 c.c. 
Nitrate of potassium 15 gm. 
Acetate of potassium 30 gm. 
Change the position of the specimen frequently. The time of fixation 
varies with the tissue or organ and size of the specimen. 
2. Drain and place in 80 per cent, alcohol one to six hours, and 
then in 95 per cent, alcohol for one to two hours, to restore the color, 
which is somewhat affected in the fixing solution. 
3. Preserve in: 
Acetate of potassium 200 gm. 
Glycerin 400 c.c. 
Water 2000 c.c. 
Since exposure to light reduces the color contrasts, the specimen 
should be prepared and kept in the dark. 
The Importance of Careful Fixation and Preservation. 
We would most urgently commend to the reader the importance of 
putting pathological specimens which are to be hardened and subse- 
quently examined microscopically, at the earliest possible moment into 
the preservative fluids, which should always be abundant. Furthermore, 
when specimens are large it is very desirable to cut them open, so that 
the fluids may come into direct contact with the tissues. It should be 
borne in mind that immediately after death or the removal of parts from 
the body, especially in warm weather, changes commence in the tissues 
and progress very rapidly, so that in some cases a few hours ' or even a 
1 For a method of preparing thick serial sections of brain for permanent preservation in formalde- 
hyde and gelatin, see Mannowsity, A., Centralbl. f. allg. Path., 1906, xvii, 467. Also, for the method 
of preserving sections and whole structures for exhibition in gelatin, see Watters, Med. Rec., 1906, Ixx, 
985. 
2 For the technique of the clearing method by potassium hydroxide in the demonstration of ossifica- 
tion centers, distribution of blood-vessels, etc., see Hill, Bull. Johns Hopkins Hosp., 1906, xvii, 11. 
8 See Mallory and Wright, Pathological Technique, 7th edition, Philadelphia, 1918. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1243 
few moments ' delay will not only render subsequent microscopical exam- 
inations difficult and unsatisfactory, but may lead to serious errors. 
Alcohol and 4 per cent, formaldehyde are the most generally useful agents. 
Carbolic acid and glycerin should not be used, even for the temporary preser- 
vation of fresh tissue. They not only do not harden and preserve the 
tissue elements, but they-especially glycerin-render them almost use- 
less for microscopic examination. 
The not uncommon practice of wrapping a specimen in a cloth soaked 
in alcohol or carbolic acid, and permitting it to remain in this for hours 
or days, is of no use whatever in preserving specimens of which micro- 
scopic examinations are to be made. Almost equally useless is the too 
common practice of placing a specimen in a bottle which it nearly fills, 
and pouring a little preservative fluid around it. Not only should the 
proper fluids be used, but these should be abundant, and the specimen 
so prepared and arranged that they may come into direct contact with it. INDEX 
Abbott and Gilder sleeve, on acid-fast 
bacteria, ref., 300 
Abderhalden, E., on ferments in diagnosis, 
ref., 218; on physiological chemistry, 
ref., 4 
Abderhalden reaction, 218 
Abdomen, examination, post-mortem, of, 
1201, 1211, 1225, 1226 
Abel, J. J., and Davis, W. S., on skin 
pigment, ref., 66 
Abel, K., on gynecology, ref., 909; 
on nature of adrenal secretion, ref., 599; 
on suprarenal body, ref., 491 
Abramow, on blood-vessel changes in 
syphilis, ref., 308; on peritonitis, ref., 
791 
Abricossoff, on rhabdomyoma, ref., 422 
Abrin poisoning, 178, ref., 232 
Abscess, 105, 229 
metastatic, 233 
of bone, 1057, 1063, 1065 
brain, 1155 
gall-ducts, 843 
heart, 616 
kidney, 864 
liver, 822 
lung, 696 
mamma, 991 
mediastinum, 723 
muscle, 1038 
spleen, 572 
vagina, 915 
repair of, 232 
retropharyngeal, 738 
tropical, of liver, 822 
Absorption, 30 
from peritoneum, ref., 127 
studies of, 127 
Acardiacus acephalus, 363 
acormus, 363 
amorphus, 363 
anceps, 363 
Acarus scabiei, 156 
Acetanilide poisoning, 478 
Achondroplasia, 1043 
Achorion Schbnleinii, 172 
Achromatic figure in mitosis, 79 
Acid, arsenious, 474 
beta-oxybutyric, 483 
carbolic, 477 
hydrochloric, 472 
hydrocyanic, 477 
nitric, 471 
osmic, as fixative, 1230 
oxalic, 472 
oxybutyric, 483 
picric, 477 
sulphuric, 471 
tartaric, 472 
Aconite poisoning, 481 
Acrania, 359, 1110 
Acromegaly, 496, 1045 
Actinomyces bovis, 262 
in lung, 696 
Actinomycosis, 261 
of brain, 1176 
Fallopian tubes, 981 
intestine, 775 
mamma, 994 
ovary, 960 
testicle, 1021 
tongue, 736 
Adamantinoma, 448 
Adami, J. G., on arteriosclerosis, ref., 
645; on cell regeneration, ref., 94; 
on conditions of disease, ref., 21; 
on dissecting aneurysm, ref., 651; 
on endothelioma, ref., 442; on giant- 
cell sarcoma, ref., 436; on heman- 
gioma, ref., 424; on hypertrophy, ref., 
74; on infection, ref., 176; on inflamma- 
tion, ref., 126; on inflammation and 
fibrosis, ref., 112; on malignant rhab- 
domyoma in trout, ref., 422; on meta- 
plasia, ref., 75; on mitosis, ref., 81; 
on myelinic substances in cells, ref., 
49; on myelins, ref., 860; on neuroma, 
ref., 418; on origin of tumors, ref., 385; 
on perirenal lipomata, ref., 794; on 
reversion, ref., 75; on teratoma of 
testicle, ref., 1024 
Adaptation, 8 
1245 1246 
INDEX 
Adaptation, of animals to alien sub- 
stances, 224 
Addison's disease, 490 
adrenals in, 491 
Addnie, 556 
Adenitis, 549 
Adenocarcinoma of stomach, 757 
of uterus, 945 
Adenochondroma of salivary glands, 801 
Adenoids, 664, 738, 739, 741 
Adenoma, 450 
fetal, of thyroid, 451, 586 
hydradenoides, 913 
malignant, 452 
of uterus, 945 
of adrenals, 591 
Bartholin's glands, 913 
bladder, urinary, 903 
bronchi, 675 
esophagus, 744 
gall-ducts, 846 
hypophysis, 1182 
kidney, 891 
larynx, 668 
liver, 836 
lung, 722 
mamma, 1004 
pancreas, 806 
pineal gland, 1182 
prostate, 1028 
stomach, 755 
testicle, 1022 
thyroid, 586 
structure of, 392 
Adenomyoma of intestine, 782, 784 
of vagina, 916 
uterus, 941 
Adenomyxosarcoma of mamma, 1004 
Adenosarcoma, 440 
Adipositas dolorosa, ref., 401 
Adiposity, hypophyseal, 497 
Adler, on diagnosis of malignant tumors 
of lung, ref.,723;on emigration of leuco- 
cytes, ref., 102; on gumma of heart, ref., 
619; on malignant growths of lung, ref., 
722; on malignant growths of lungs and 
bronchi, ref., 468 
Adler and Meltzer, on lymph-vessels, 
ref., 658 
Adrenaline, degeneration of heart muscle 
after injections of, ref., 617 
in paraganglioma, 413 
Adrenals, 588 
Adrenals, absence of, 588 
accessory, 588 
atrophy of, 588, 589 
degeneration of, 589 
examination, post-mortem, of, 1213, 
1226 
fat infiltration of, 589 
function of, 588 
ganglioneuroma of, 412 
glioma of, 408 
hemorrhage of, 590 
hyperplasia of, 591 
hypertrophy of, 74 
in Addison's disease, 491 
inflammation of, 590 
malformations of, 588 
neuroblastoma of, 409 
paraganglioma of, 413 
pigmentation of, 589 
position of, 1213 
preservation of, 1214 
"sarcoma" of, 410 
secretion of, 588 
internal, of, in Addison's disease, 
491 
size of, 1213 
syphilis of, 590 
thrombosis of, 590 
tuberculosis of, 490, 590 
tumors of, 591 
weight of, 1213 
Aerobes, facultative, 162 
obligate, 162 
Afanassieff, on granulation tissue, ref., 
177 
Age, cancer, 453 
relation of, to disease, 20 
to etiology of cancer, 388 
Agenesia, 356 
Agglutination, 206 
group, 206 
test, technique of, 222 
use of, 207 
Agglutinins, 206 
in typhoid fever, 276 
tests for, 531 
Aggressins, 178 
Agnathia, 356 
"Ague cake," 572 
Air, compressed, disease, 18 
emboli, 42 
in blood, 532 
in caisson disease, 19 INDEX 
1247 
Air, in pericardium, 595 
microorganisms in, ref., 175 
supply, relation of, to disease, 9 
Akerland, on membranous enteritis, ref., 
774 
Albert, H., on chordoma, ref., 403, 404; 
on Trichinella spiralis, ref., 154 
Albrecht, E., on albuminous degenera- 
tion, ref., 49; on chorionepithelioma of 
liver, ref., 839; on fatty degeneration, 
ref., 49; on hemangioma, ref., 424; on 
myelinic substances in cells, ref., 49; 
on necrosis, ref., 67; on origin of tumors, 
ref., 385 
Albrecht and Arzt, on intestinal diver- 
ticula, ref., 759 
Albrecht, H., and Logothetopulos, K., on 
endometritis, ref., 930 
Albumin film for fixing sections to slide, 
1234 
Albuminous degeneration (see Degenera- 
tion, albuminous), 48 
Albuminuria, 855 
orthostatic, 855 
postural, 855 
Alcock, on mosquitoes, ref., 349 
Alcohol as tissue fixative, 1229 
poisoning, 478 
Alderson, H. E., on Hodgkin's disease, 
ref., 557 
Aleuronat exudates, 223 
Alexander, on adrenals and nervous sys- 
tem, ref., 588 
Alexin, 125, 187, 197, 199 
Allergy, 215 
Aloes poisoning, 476 
Altmann, on mitochondria, ref., 77 
Altmann's granules, 77 
Alveoli, 439, 445 
Alzheimer, A., on neuroglia, ref., 1133 
Amann, J. A., on gynecology, ref., 909; 
on sarcoma of vagina, ref., 916 
Amastia, 987 
Ambard, on classification of nephritis, 
ref., 881; on excretion of kidney, ref., 
882 
Ambard coefficient, 881 
Amboceptor, 203 
Amenomiya, R., on regeneration of mu- 
cous membranes, ref., 85 
Amidobenzol poisoning, 478 
Amitosis, 81 
Ammonia poisoning, 473 
Amoeba dysenteriae, 133 
in colitis, 768 
liver abscess, 823 
Amputation neuroma, 419 
Amyelia, 1111 
Amyloid, 56 
degeneration (see Degeneration, 
amyloid), 57 
stain for, 59 
tests for, 59, 1212 
tumors of larynx, 668 
pharynx, 740 
tongue, 668, 735 
Anaerobes, facultative, 162 
obligate, 162 
Anaphylaxis, 178, 215 
in status lymphaticus, 500 
theories of, 216 
Anaplasia, 384 
in tumors, 374, 384 
Anasarca, 29 
Anchylostoma duodenale, 151 
anemia due to, 534 
Anderson, J. F., on modes of infection 
with typhoid bacillus, ref., 275; on 
snake venoms, ref., 480; on tubercle 
bacilli in blood, ref., 296 
Anderson and Goldberger, on infective 
agent in typhus fever, ref., 334 
Andres, on tuberculosis of heart, ref.s 
619 
Andrews, on desmoid of muscle, ref., 1041 
Anemia, 23, 26, 517, 533 
aplastic, 538 
in tumors, malignant, 379 
Banti's, 544 
bone-marrow in, 1071 
chlorotic, 533 
infantum pseudoleukemica, 543 
in tumors, malignant, 379 
local, 26 
of brain, 1119 
kidney, 853 
liver, 809 
lung, 676 
spleen, 569 
pernicious, 536 
secondary, 534 
spleen in, 578 
splenic, 544 
Von Jaksch, 543 
Anencephalia, 360, 1110 
Aneurysm, 648 1248 
INDEX 
Aneurysm, cirsoid, 651 
conditions leading to, 648 
cylindrical, 650 
dissecting, 651 
false, 651 
fusiform, 650 
miliary, 652 
multiple, 649 
mycotic, 649 
of aorta, 648, 651 
brain, 1122 
coronary arteries, 652 
heart, 606 
valves, 607 
hepatic artery, 811 
pulmonary arteries, 652 
sacculated, 650 
spurious, 651 
syphilis and, 649 
varicose, 651 
Aneurysmal varix, 651 
Angina (see Pharyngitis), 737 
diphtheroid, 242 
membranous, 242 
pectoris, 618 
Vincent's, 326 
Angioma, 422 
capillary, 423 
cavernosum, 423 
of heart, 634 
spleen, 580 
differential diagnosis of, 425 
hem-, 423 
lymph-, 424 
of arteries, 653 
bladder, urinary, 903 
bone, 1081 
brain, 1174 
choroid plexus, 1109 
ependyma, 1109 
esophagus, 744 
kidney, 890 
larynx, 668 
liver, 835 
mamma, 1005 
mouth, 733 
muscle, 1041 
ovary, 961 
penis, 1013 
peritoneum, 794 
pharynx, 741 
salivary glands, 801 
stomach, 754 
Angioma of thymus, 582 
thyroid, 585 
tongue, 735 
umbilical cord, 797 
vulva, 912 
simplex, 423 
hypertrophicum, 424 
telangiectoides, 423 
Angiolipoma, 402 
Angiosarcoma, 438 
of liver, 839 
mamma, 1006 
spinal cord, 1175 
uterus, 942 
Anhydremia, 516 
Anilin-blue stain, 1237 
poisoning, 478 
Animal, cancer in, 387, 388 
infectious diseases of, ref., 183 
parasites, 130 
species, relationships of, blood test 
in, 198, 208 
venom, 479 
Anitschkow, N. N., on degeneration of 
muscle fibers of heart, ref., 616; on 
fibromyomata of esophagus, ref., 744; 
on leiomyoma, ref., 1040; on malposi- 
tion of kidney, ref., 853; on myomata 
of esophagus, ref., 744 
Anomalies, hereditary, 21 
Anopheles in malaria, 346 
Anthracosis of lung, 703 
Anthrax, 258 
bacillus, 259 
of intestine, 775 
Antibodies, 201, 202 
formation of, effect of x-ray on, 
204 
Anticytolysins, 201 
Anticytotoxins, 201 
Antiformin in sputum examinations, 291 
Antigen, 201 
Antiprecipitin, 209 
Antiprothrombin, 515 
Antithrombin, 515 
Antitoxin, 189 
B. aerogenes capsulatus, 191 
definition of, 194 
diphtheria, 190, 316 
unit of, ref., 190 
formation of, 191 
tetanus, 190, 318 
unit, ref., 190 INDEX 
1249 
Antivenin, 479 
Anus, atresia of, 759 
Aorta, aneurysm of, 648, 651 
examination, post-mortem, of, 1218 
hypoplasia of, 635 
malformations of, 600 
rupture of, 635 
stenosis of, 600, 630, 653 
syphilis of, 647 
tuberculosis of, 646 
Aortitis, syphilitic, 647 
Aphthae, 731 
Aplasia, 356 
Apolant, on carcinosarcoma, ref., 389; 
on carcinosarcoma in mice, ref., 440 
Apoplectic foci in brain, 1121 
Apoplexy, 28 
cerebral, 1120 
of brain, 1120 
placental, 953 
serous, of brain, 1120 
spinal, 1125 
Appendicitis, 777 
oxyuris, in, 151 
Appendix vermiformis, 777 
absence of, 759 
bacteria in, 782 
concretions in, 781 
cysts of, 781, 787 
dilatation of, 781 
diverticula of, 760 
eosinophilia in, 781 
foreign bodies in, 781 
gangrene of, 778 
in typhoid fever, 778 
inflammation of, 777 
necrosis of, 777 
obliteration of lumen of, 779 
parasites in, 782 
strictures of, 779 
tuberculosis of, 778 
tumors of, 785 
Arachnoid (see Pia mater), 1094 
Arey, L. B., on osteoclasts, ref., 72 
Argyria, 67 
pigmentation of kidney in, 861 
of liver in, 822 
Arken, on syphilitic ulcers of intestine, 
ref., 767 
Arloing, on bactericidal action of mucus, 
ref., 175 
Arnaud, on hemorrhage in adrenals, ref., 
590 
Arndt, G., on Hodgkin's disease, ref., 557 
Arnheim, on spirochetes, ref., 138 
Arnold, on fibrin formation, ref., 102; on 
iron pigment in cells, ref., 703; on lac- 
tating mamma, ref., 986; on lymph- 
nodes, ref., 546; on plasmosomes, ref., 
77; on sarcoma of liver, ref., 839; on 
technique, ref., 1227; on weight of 
heart, ref., 1209 
Arnsperger, on dermoid cysts of ovary, 
ref., 973 
Arnstein, on lymphosarcoma of lung, ref., 
722 
Arrhenius, on Ehrlich's "side-chain" hy- 
pothesis, ref., 195 
Arrowsmith, on hyperkeratosis linguae, 
ref., 735 
Arsenic poisoning, 474 
tolerance to, 470 
Artefacts of nervous system, 1112, 1199 
Arteries, aneurysm of, 648, 651 
atheroma of, 640 
calcification of, 637, 641 
cerebral, aneurysm of, 1122 
embolism of, 38, 1126 
examination, post-mortem, of, 
1193 
structure of, 1118 
thrombosis of, 1126 
coronary, aneurysm of, 615, 652 
distribution of, ref., 614 
embolism of, 615 
endarteritis of, 614 
examination, post-mortem, of, 
1207 
infarction of, 615 
lesions of, 614 
nodules on, 598 
sclerosis of, 614 
thrombosis of, 614 
cysts, atheromatous, of, 640 
degeneration of, 635 
emboli, tumor, in, 653 
hepatic, lesions of, 811 
inflammation of (see Arteritis), 637 
pulmonary, aneurysm of, 652 
embolism and thrombosis of, 679 
infarction of, 679 
malformations of, 602 
renal, embolism and thrombosis of, 
854 
rupture of, 635 
sclerosis of, 639 1250 
INDEX 
Arteries, syphilis of, 647 
terminal, embolism of, 36 
tuberculosis of, 646 
tumor emboli in, 653 
tumors of, 653 
wounds of, 635 
Arteriosclerosis, 639 
classification of, 645 
conditions leading to, 644 
relation of, to heart hypertrophy, 
632 
Arteritis, acute, 637 
chronic, 639 
embolic, 637 
end-, 637 
obliterative, 639 
peri-, 637 
nodosa, 646 
syphilitic, 647 
thrombo-, 637 
proliferans, 638 
tuberculous, 646 
Arthritis, 1083 
chronic, 1084 
deformans, 1084 
exudative, 1083 
gonococcal, 1083 
gouty, 1085 
neuropathic, 1086 
pneumococcic, ref., 1083 
rheumatic, 1084 
serofibrinous, 1083 
serous, 1083 
streptococcic, ref., 1084 
suppurative, 1083 
syphilitic, 1086 
tuberculous, 1085 
uratica, 1085 
Arthropathy, hypertrophic pulmonary, 
1046 
Arthropoda, 156 
Ascarelli, on adipocere, ref., 1188 
Ascaris in bladder, urinary, 905 
lumbricoides, 150 
in liver, 841 
megalocephala, chromosomes in, 79 
Asch, on elimination of bacteria in body, 
ref., 176; on excretion of bacteria by 
kidney, ref., 864 
Ascheim, S., on dysmenorrhea, ref., 926 
Aschoff, L., on appendicitis, ref., 782; 
on arteriosclerosis, ref., 645; on Aschoff 
bodies, ref., 619; on carcinoid tumors, 
appendix, ref., 786; on cell regenera- 
tion, ref., 94; on compensatory hyper- 
trophy, ref., 73; on contracted kidney, 
ref., 880; on cysts, ref., 396; on emboli, 
ref., 36; on immunity, ref., 224; 
on malformations of female generative 
organs, ref., 909; on nephritis, ref., 862; 
on neuroma, ref., 418; on Oxyuris 
vermicularis in appendix, ref., 151; 
on thrombosis, ref., 32, 39, 40; on 
tumors, ref., 467 
Aschoff and Bacmeister, on carcinoma of 
gall-bladder, ref., 846; on formation of 
gall-stones, ref., 848 
Aschoff, de la Camp, ion Beek, and Kronig, 
on thrombosis, ref., 680 
Aschoff nodules, ref., 351 
in myocardium, ref., 616, 619 
Ascites, 30, 789 
chyliform, 789 
chylous, 789 
in cirrhosis of liver, 828 
Ascoli, on regeneration of mucous mem- 
branes, ref., 85 
Ashford, B. K., on Monilia albicans, ref., 
171 
Asiatic cholera, 278 
Askanazy, M., on Balantidium coli, ref., 
140; on chorionepithelioma of epiphy- 
sis, ref., 1182a; on dermoid cysts of 
ovary, ref., 973; on pigment, ref., 64; 
on regeneration of blood, ref., 92; on 
Strongyloides stercoralis, ref., 155 
Aspergillus, ref., 172 
Asphyxia, 9, 503 
Assmann, H., on osteosclerosis, ref., 1062 
Astrocytes, 406 
Ataxia, cerebellar, 1154 
Friedreich's, 1154 
hereditary, 1154 
locomotor, 1145 
Atelectasis of lung, 680 
Atelomyelia, 1111 
Athelia, 987 
Atheroma, 394, 640 
Atlassoff, on B. typhosus, ref., 265 
Atresia ani, 759 
Atrophia musculorum lipomatosa, 1035 
Atrophy, 45 
acute yellow, of liver, 816 
experimental, 818 
brown, 47 
of heart, 606 INDEX 
1251 
Atrophy, degenerative, 46 
disuse, 47 
general, from malnutrition, 47 
neurotic, 48 
of adrenals, 588, 589 
blood-vessels, 635 
bone, 1050 
brain, 1117 
heart, 606 
kidney, 853, 878 
liver, 814, 816 
lymph-nodes, 547 
muscle, 1032, 1035 
pancreas, 801 
prostate, 1024 
spleen, 567 
stomach, 747 
testicle, 1016 
uterus, 924 
pigment, 45 
pressure, 47 
progressive spinal muscular, 1143 
senile, 47 
simple, 45 
Auer and Lewis, on anaphylaxis, ref., 217 
Auerbach, on B. influenzae, ref., 246 
Aufrecht, on portals of entry of B. tuber- 
culosis, ref., 297 
Auriculoventricular node, 627 
Austin, J. H., on nephritis, ref., 862 
Austrian, C. R., and Hamman, L., on 
tubercle bacilli in blood, ref., 
296 
Autenrieth, on poisons, ref., 481 
Autoagglutination, 206 
Autocytotoxins, 200 
Autointoxication, 179, 469, 482 
dyscrasic, 483 
retention, 483 
Autolysins, 202 
Autolysis, 71, 114, 122 
in lung exudates, 690 
Autopsies (see Post-mortem examina- 
tion), 1185 
Autosite, 367 
Auto toxins in fever, 502 
Autotransplantation of tissue, 388, 389 
Avery, O. T., on acute lobar pneumonia, 
ref., 248 
Avery, Chickering, Cole, and Dochez, on 
acute lobar pneumonia, ref., 248 
Avery and Lyall, on concurrent infection 
in tuberculosis, ref., 718 
Axenfeld, on xerosis bacillus, ref., 317 
Axis-cylinder process, nature of, 1131 
Axone, degenerations in, 1133, 1141 
nature of, 1131 
Ayer, on cyst of intestine, ref., 785 
Baastrup, on sarcoma of tongue, ref., 735 
Babes, V., on bacteria in blood of cadaver, 
ref., 1188; on hemorrhagic infections, 
ref., 321; on Madura foot, ref., 262; on 
rhinoscleroma, ref., 313 
Babesia bigemina, 143 
Bacillus, 159 
acid-fast, 300 
aerogenes capsulatus, 321 
anthracis, 260 
immunization to, 260 
botulinus, 324 
cholerae gallinarum, 321 
coli communis, 243, 276 
coniunctivitidis, 265 
diphtheriae, 315 
action of, in animals, 316 
antitoxin, 316 
carriers, 317 
communicability of, 316 
pseudo-, 317 
diplo-, 160 
Ducrey's, 258 
dysenteriae, 278, 769 
edematis maligni, 323 
enteritidis, 323 
Friedlander, 245 
in lobar pneumonia, 692 
fusiform, 326 
gas, 321 
grass, 300 
haemorrhagicus, 321 
septicus, 321 
velenosus, 321 
hay, 300 
hoffmanni, 317 
icteroides, ref., 335 
influenzae, 263 
Koch-Weeks, 265' 
leprae, 303 
mallei, 256, 257 
mucosus capsulatus, 245 
paratyphoid, 277, 
perfringens, 321 
pestis, 320 
plague, 320 
proteus group of, 245 
vulgaris, 246 1252 
INDEX 
Bacillus, pseudodiphtheriae, 317 
pseudoinfluenzae, 265 
pseudotetanicus, 319 
pseudotuberculosis, 258 
liquefaciens, 258 
pyocyaneus, 244 
rhinoscleromatis, 313 
Shiga's, 277 
smegma, 300 
strepto-, 160 
suisepticus, 321 
tetani, 317, 318 
toxins of, 318 
tuberculosis, 282, 289 
antiformin in examination of, 291 
bovine type, ref., 299 
in cervical nodes, 740 
branching forms of, ref., 289 
differentiation of, 300 
distribution of, 297 
methods of staining, 290 
number of, in lesions, 295 
portals of entry, 297, 704 
sources of, 298 
toxic products of, 292 
varieties of, 291 
typhi murium, 321 
typhosus, 265 
agglutination of, 276 
carriers, 275 
differentiation of, 276 
distribution of, in body, 274 
methods of staining, 276 
modes of infection with, 275 
toxins of, 265 
welchii, 321 
whooping-cough, 350 
x, 335 
xerosis, 317 
Bacteria, 158 
action of alexins on, 187 
of germicides on, 163 
light on, 162 
temperature on, 162 
in body, 177 
adaptation of, ref., 186 
aerobic, 162 
aerogenic, 164 
agglutination of, 206 
aggregations of, 160 
aggressins of, 178 
anaerobic, 162 
as disease-excitants, 227 
Bacteria, chemotaxis of, 162 
chromogenic, 164 
classification of, 168 
Clostridium forms, 159 
cultures of, 168 
denitrifying, 166 
disposal of, in body, 176 
distribution of, 166 
elimination of, by secretions, 176 
emboli of, 104 
endotoxins of, 165 
enzymes of, 164 
examination of specimens, post-mor 
tern, for, 1221 
fermentation and, 164 
forms of, 159 
functional characters of, 167 
growth of, conditions of, 162 
hemolysins of, ref., 179 
higher, 160 
in bladder, urinary, 901 
blood, ref., 176, 533, 1221 
gall-bladder, 844 
gall-ducts, 843 
inflammation, 104 
intestine, 768, 770, 773 
kidney, 864, 865, 871, 883 
liver, 823 
lung, 684, 691, 696, 697 
mouth, ref., 736 
spleen, 581 
stomach, ref., 750 
uterus, 936 
vagina, 915, 918 
water, 166 
infective nature of, proofs of, 179 
involution forms, 159 
life of, conditions of, 162 
messmates, 167 
metabolism of, 163 
metachromatic granules in, 159 
monomorphism in, 161 
motility of, 162 
multiplication of, 162 
nitrifying, 166 
parasitic, 167 
phagocytosis of, 209 
photogenic, 164 
pleomorphism in, 161 
poisons of, 177 
polymorphous, 160 
portals of entry of, 176 
products of, in body, 177 INDEX 
1253 
Bacteria, protection of body against, 176 
ptomaines of, 164 
pyogenic, 234, 246 
relationships of, 167 
reproduction of, 159 
rod-like, 159 
role of, in nature, 165 
saprophytic, 167 
species of, 167 
spheroidal, 159 
spiral, 159 
spores in, 161 
symbiosis of, 167 
thermophilic, 163 
toxins of, 164, 177 
ultramicroscopic, ref., 159 
variations in, 159, 161 
varieties of, 167 
zymogenic, 164 
Bacteriemia, 232 
in tuberculosis, pulmonary, 718 
Bacteriolysis, 196, 200 
Bacterio-opsonins, 211 
Bacterioprotein, 177 
Bacterio tropic substances, 211 
Baehr, G., on experimental nephritis, 
ref., 880; on glomerular nephritis, ref., 
864 
Baehr and Plotz, on typhus fever, ref., 333 
Baer, J. W., on typhoid ulcers, ref., 270 
Baeslack, F. W., on meningococcus, ref., 
255 
Baginsky and Sommerfeld, on pseudo- 
membranous inflammation, ref., 
241 
Bail, on disposal of bacteria in blood, ref., 
176 
Bail and Weil, on aggressins, ref., 178 
Bailey, on pseudomyxoma peritonei, ref., 
797 
Bailey, C. H., on experimental arterio- 
sclerosis, ref., 645; on experimental 
nephritis, ref., 880; on foreign bodies 
in heart, ref., 604 
Bailey, F. R., on lesions in hydrophobia, 
ref., 326 
Bailey and Ewing, on Landry's paralysis, 
ref., 1160 
Bailey and Jelliffe, on tumors of pineal 
gland, ref., 1179 
Baitsell, G. A., on connective tissue 
regeneration, ref., 89; on fibrin in re- 
pair of wounds, ref., 112 
Balanitis, 1012 
Balantidium coli, 140 
Baldwin, E. R., on allergy and reinfection 
in tuberculosis, ref., 294 
Baldwin, F. A., on anemic infarcts of 
liver, ref., 811 
Baldwin, J. F., on dermoid of kidney, 
ref., 888; on carcinoma of pancreas, 
ref., 806 
Baldy, J. M., and Williams, H. L., on 
kraurosis of vulva, ref., 911 
Balfour and Wildner, on paraganglioma 
of carotid, ref., 413 
Ballantyne, on antenatal pathology, ref., 
176; on malformations, ref., 355; on 
malformations of female generative 
organs, ref., 909 
Ballowitz, on malformations of kidney, 
ref., 851 
Bancroft, F. W., on transplantation of 
periosteum, ref., 93 
Bang, on lipoids, ref., 53 
Banti, on splenic anemia, ref., 544 
Banti's anemia, 544 
Banzhaf and Famulener, on anaphylaxis, 
ref., 217 
Bardeen, C. R., on visceral changes 
following burns, ref., 11 * 
Barenberg, L. H., on vaccines in whoop- 
ing-cough, ref., 351 
Barfurth, on regeneration, ref., 83 
Barger, on adrenal secretions, ref., 491; 
on chemistry of ptomaine poisoning; 
ref., 481; on the simpler natural bases, 
ref., 164 
Barile, on neuroma, ref., 418 
Barker, L. F., on nervous system, ref., 
1089, 1129, 1136; on regeneration of 
nerve tissue, ref., 1139 
Barney, J. D., on hydronephrosis, ref., 885 
Barratt, on mitochondria, ref., 77 
Barrie, G., on giant-cell sarcoma, ref., 
436, 1080 
Barrie and Hillman, on giant-cell sar- 
coma, ref., 436 
Bartel and Bauer, on status lymphaticus, 
ref., 500 
Bartel and Spieler, on experimental 
tuberculosis, ref., 297 
Bartholin's glands, tumors of, 913 
Bartholow, on pellagra, ref., 496 
Bartlett and Ozaki, on phagocytic cells, 
ref., 121 1254 
INDEX 
Basch, on benign growths of stomach, 
ref., 755 
Basedow's disease, 488 
Bashford, on age and cancer, ref., 388; 
on cancer statistics, ref., 453; on cell 
proliferation, ref., 377; on chronic 
irritation and neoplasms, ref., 387; 
on civilization and cancer, ref., 387; 
on tumor origin, ref., 384 
Bashford and Murray, on age distribution 
of sarcoma, ref., 427; on cancer, ref., 
468; on cancer statistics, ref., 453; 
on heterotypical mitoses in cancer, 
ref., 382 
Bashford, Murray, and Cramer, on 
tumor metastases, ref., 378 
Bashford, Murray, and Haaland, on 
tumor transplantation, ref., 93 
Basophile cells, 522 
Bass, C. C., on cultivation of malarial 
parasite, ref., 344 
Bass, C. C., and Johns, F. M., on alveo- 
dental pyorrhea, ref., 135 
Bassoe, on pathogenic blastomycetes, 
ref., 171 
Bateson, W., on heredity, ref., 21 
Batten, on nerve lesions in diphtheria, 
• ref., 314 
Bauereisen, on pyelonephritis with cysti- 
tis, ref., 884 
Baumgarten, on coronary arteries, ref., 
614; on portals of entry of B. tubercu- 
losis, ref., 297; on tissue formation by 
endothelium, ref., 87; on tuberculous 
and syphilitic orchitis, ref., 1020; 
on urogenital tuberculosis, ref., 882 
Bayer, G., on adrenal secretions, ref., 491; 
on regeneration of lymph-nodes, ref., 
91, 546 
Bayliss, W. M., on chemotaxis, ref., 102; 
on general physiology, ref., 4; on 
nature of enzyme action, ref., 164 
Bazy, L., on hemorrhage in Fallopian 
tubes, ref., 977 
" Beaker, cells," 55 
Beattie, J., on acute rheumatism, ref., 351 
Bechhold, H., on colloids, ref., 4 
Becht and Leuckhart, on antibody forma- 
tion, ref., 201 
Becker, on rhabdomyoma of testis, ref., 
1021 
Beckey, on keratin in melanoma, ref., 433; 
on melanocarcinoma, ref., 467 
Beckton, on mitochondria, ref., 77 
Beer, on adrenals in liver, ref., 588; on 
adrenal remnants in liver, ref., 836; 
on false diverticula of intestine, ref., 
760; on glomerular cysts, ref., 879 
Behla, on carcinoma, ref., 467 
Behrenroth, on Balantidium coli, ref., 140 
Beifeld, A. F., on lesions of Hodgkin's 
disease, ref., 563 
Beitzke, H., on cervical and bronchial 
lymph-nodes, ref., 676; on metastatic 
carcinomata of adrenal, ref., 592; on 
mode of infection in pulmonary tuber- 
culosis, ref., 297; on tuberculous peri- 
tonitis, ref., 793 
Bell, E. T., on identification of types of 
fat, ref., 53 
Bence-Jones' albumose, 1073, 1074 
Benda, C., on dwarfism, ref., 1043; on 
endothelium and mesothelium, ref., 
442; on mitochondria, ref., 77; on 
origin of miliary tuberculosis, ref., 
708; on sarcoma of aorta, ref., 653; 
on syphilitic arteritis, ref., 647 
" Bends," the, 18 
Benedict, on chyle cysts of mesentery, 
ref., 795 
Benedict, F. G., on inanition, ref., 9 
Beneke, on adenosarcoma, ref., 440; on 
neuroma, ref., 418 
Beneke, R., and Banning, F., on fatty 
infiltration of heart, ref., 612 
Benignancy of tumors, 376 
Bennecke, on angioma of intestine, ref., 
782; on angioma of stomach, ref., 755 
Benzol in leukemia, 528 
Berard and Alamartine, on tumors of 
parathyroid, ref., 588 
Berblinger, on gumma of heart, ref., 619 
Beriberi, 496 
Bering, F., on effect of light on organism, 
ref., 17 
Berka, on cystadenoma of mamma, ref., 
997; on fibroadenoma of mamma, ref., 
1004; on fibrocystadenoma, ref., 452 
Berkeley and Beebe, on parathyroids, ref.( 
588 
Berkeley, C., and Bonney, V., on esthi- 
omene of vulva, ref., 912 
Bernard, on mesothelioma of pleura, ref., 
729 
Berner, on cysts in kidney, ref., 886 
Bernheim, on blood transfusion, ref., 531 1255 
INDEX 
Bernheim and Gruber, on mixed infections, 
ref., 183 
Berry, on appendicitis, ref., 782; on 
sarcoma of tonsil, ref., 741 
Bertarelli, on animal inoculations in 
syphilis, ref., 308 
Besredka, on anaphylaxis, ref., 216 
Besredka and Steinhardt, on anaphylaxis, 
ref., 216 
Best's stain for glycogen, 1239 
Beta-oxybutyric acid, 483 
Betel-nut cancer, 387 
Bettmann, A., on bronchitis, ref., 672 
de Beurmann and Gougerot, on sporo- 
trichosis, ref., 173, 263 
v. Beust, on adenoma of pancreas, ref., 806 
Beuttenmuller, H., on hyperplastic peri- 
ostitis, ref., 1046 
Bezancon and Labbe, on germicidal action 
of lymph-nodes, ref., 176 
Bidone, on fibroma of muscle, ref., 1041 
Biedl, A., on internal secretory organs, 
ref., 483, 491, 1045; on physiology and 
pathology of hypophysis, ref., 497; 
on pituitary body, ref., 1179 
Biedl and Kraus, on bacteria in kidney, 
ref., 871; on elimination of bacteria in 
secretions, ref., 176 
Bielchowsky, M., on connective tissue 
stain, ref., 1239 
Bielchowsky's stain for connective tissue, 
1239 
Bierring and Egdahl, on splenectomy in 
splenic anemia, ref., 544 
Biggs, G. P., on aortic aneurysm, ref., 
652 
Biland, J., on cysts of placenta, ref., 957 
Bile-ducts, lesions of (see Gall-ducts), 842 
Bilharzia haematobia, 145, 387 
Bilirubin, 65 
Billings, F., on infective endocarditis, 
ref., 622 
Billings and Capps, on myelogenous 
leukemia, ref., 541 
Billings and Rosenow, on vaccine in 
Hodgkin's disease, ref., 563 
Binder, on round-cell sarcoma of heart, 
ref., 635 
Binder, A., on congenital liver cirrhosis, 
ref., 831 
Bing, on amaurotic family idiocy, ref., 
1115; on brain and spinal cord, ref., 
1089 
Binnie, on sarcoma of thyroid, ref., 587 
Biondi, on fibroadenoma of pancreas, ref., 
806 
Bircher, E., on cretinism, ref., 1045; on 
thyroid hyperplasia, ref., 584 
Birch-Hirschfeld, on intestine as portal of 
entry for bacteria, ref., 791 
Birt and Lamb, on Malta fever, ref., 320 
Bismuth subnitrate poisoning, 473 
Bissell, W. W., on fat in blood, ref., 532 
Bizzozero, on tissue regeneration, 76 
Black death, 320 
leg, 323 
Black, Rosenberg, and McBride, on tests 
for syphilitic aortitis, ref., 648 
Blackfan, on anaphylaxis, ref., 217 
Bladder, gall- (see Gall-bladder), 842 
urinary, 896 
abscess of, 899, 900 
absence of, 896 
bacteria in, 901 
calculi in, 905 
circulation in, study of, 127 
cysts of, 904 
dilatation of, 897 
diverticula of, 896, 897 
examination, post-mortem, of, 
1219, 1226 
extroversion of, 896 
foreign bodies in, 905 
hemorrhage of, 898 
hernia of, 897 
hyperemia of, 898 
hyperplasia of epithelium of, 900 
hypertrophy of, 897 
inflammation of (see Cystitis), 
898 
malformations of, 896 
malpositions of, 897 
mucosa, repair of, ref., 85 
parasites in, 905 
perforation of, 898 
polyp of, 445 
preservation of, 1219 
rupture of, 898 
study of inflammation in, 99 
syphilis of, 901 
tuberculosis of, 901 
tumors of, 903 
in aniline workers, 386 
wounds of, 897 
Blanchard, on Dipylidium caninum, ref., 
149 1256 
INDEX 
Bland-Sutton, on adrenal function, ref., 
589; on ganglioneuroma of mesentery, 
ref., 795; on giant-cell sarcoma, ref., 
436; on odontomata of man and ani- 
mals, ref., 406; on pigmentation of in- 
testine, ref., 789; on sacral tumors and 
cysts, ref., 1112; on tumors innocent 
and malignant, ref., 468 
Blastomycetes, 158, 169 
in ependyma, 1109 
Blastomycosis, 171 
Blau, on cavernous angiomata of phar- 
ynx, ref., 741 
" Bleeders," 29 
Blennorrhea, 228 
Blessing, on tumors of mouth, ref., 733 
Block and Hall, on dermoid cysts of blad- 
der, ref., 904 
Blocq, P., and Marinescu, G., on heredi- 
tary ataxia, ref., 1153 
Blood, 514 
abnormal, leucocytes of, 523 
agglutinins of, 206, 531 
air in, 42, 532 
amount of, determination of, 518 
anemia, 26, 517 
aplastic, 538 
Banti's, 544 
infantum pseudoleukemica, 543 
pernicious, 536 
secondary, 534 
splenic, 544 
von Jaksch, 543 
anhydremia, 516 
bacteria in, ref., 176, 533 
capillaries, lesions of, 658 
cells, red, 518 
agglutination of, test for, 222 
alterations in, 518, 520 
altitude, effect of, on, ref., 521 
diminution of, 518 
formation of, defective, 519 
fragility of, in jaundice, 576 
gigantoblasts, 521 
lysis of, 197 
megaloblasts, 521 
megalocytes, 520 
microcytes, 520 
morphology of, 520 
normoblasts, 521 
nucleated, 521 
number of, 518 
poikilocytes, 520 
Blood cells, red, regeneration of, 91 
staining reactions of, ref., 520 
white (see Leucocytes), 521 
chloroma, 542 
chlorosis, 533 
circulation of, after injury, 99 
changes in, 22 
post-mortem, 1191 
study of, in living animals, 127 
clots, forms of, 514 
coagulability of, 514 
color index, 537 
composition of, 514 
"crises," 521 
diseases of, 533 
examination of, 349, 529 
fat in, 532 
stain for, 531 
ferments of, 523 
foreign bodies in, 532 
forming organs, lesions of, 533 
gas in, 42 
Giemsa's stain for, 1237 
hematogenesis, defective of, 519 
hemoglobin, free in. 516 
hemoglobin index, 537 
hemolysins of, 531 
hydremia, 516 
hypostasis, post-mortem, 1187 
in malaria, 342, 349 
laking of, 197 
leucocytes of, 521, 523 
leucocytosis, 525 
leukemia, 538 
melanemia, 533 
normal, leucocytes of, 521 
oligocythemia, 517, 518 
parasites in, 533 
pigment, 63, 533 
test for, ref., 64 
plates, 527 
plethora, 518 
polychromatophilia, 537 
polycythemia, 517 
precipitin test for, 208 
reaction of, 515 
regeneration of, 91 
relationships, 198, 208 
serum, 102 
stains for, 349, 530, 1237 
transfusion of, 531 
transudation of, 29 
uric acid in, 861 INDEX 
1257 
Blood-vessels, aneurysm of, 651 
atrophy of, 635 
changes in walls of, 22 
embolism of, 35 
formation of, 89 
hypertrophy of, 635 
hypoplasia of, 635 
lesions of, in tuberculosis, pul- 
monary, 716 
in typhoid fever, 273 
sclerosis of, 639 
thrombosis of, 35 
tumors of, 422, 438, 441, 653, 657 
water in, 516 
Bloodgood, J. C., on adenoma of thyroid, 
ref., 489, 586; on cystadenoma of 
mamma, ref., 993; on cysts of bone, 
ref., 1081; on cysts of mamma, ref., 
1010; on cysts of thyroid, ref., 586; 
on giant-cell sarcoma, ref., 434 
Bloomfield, A., on metabolism in per- 
nicious anemia, ref., 538 
Blum, V., on enlargement of penis, ref., 
1012 
Blumberg, on malignant adenoma of liver, 
ref., 837 
Blumenthal, on reaction of body in 
infection, ref., 181 
Blumer, G., on bacteriology of lobular 
pneumonia, ref., 697; on myoma of 
round ligament, ref., 941; on tubercu- 
lous aortitis, ref., 646 
Blumer and Laird, on hemorrhagic septi- 
cemia, ref., 323 
Blumer and MacFarlane, on noma,ref., 910 
Blythe, on poisons, ref., 481 
Bockenheimer, P., on bone cysts, ref., 
1081; on leontiasis ossea, ref., 1046 
Body, cooling of, as predisposing to 
infection, ref., 698 
post-mortem, 1188 
fluids in inflammation, 124 
nature of living, 3 
Boer, on anthracosis of lung, ref., 704 
Boerner, on concretions in joints, ref., 
1087 
Boils (see Furuncle), 228 
Boldt, H. J., on carcinoma of uterus, ref., 
943; on sarcoma of vagina, ref., 916 
Bolduan and Koopman, on immunity, 
ref., 225 
Boldyreff, on ferments in diagnosis, ref., 
218 
Bone, 1042 
abscess of, 1057, 1063, 1065 
achondroplasia, 1043 
acromegaly, 1045 
atrophy of, 1050 
caries of, 1069 
cells of, 1042 
cysts of, 1081 
decalcification of, 1051, 1231 
dwarfism, 1042 
enostoses, 1076 
examination, post-mortem, of, 1224, 
1226 
exostoses, 1076 
formation, new, 1057 
in dura mater cerebralis, 1092 
spinalis, 1104 
muscle, 1040 
pia mater cerebralis, 1103 
spinalis, 1105 
fractures of, 1051 
healing of, 1070 
general considerations, 1042 
gigantism, 1045 
healing of, 1070 
hemorrhage in, 1056 
hyperemia of, 1056 • 
hyperostosis, 1076 
inflammation of (see Osteitis and 
Periostitis), 1056 
leontiasis ossea, 1046 
-marrow in leukemia and anemia, 
1071 
metastasis in, 379 
pigmentation of, 1056 
regeneration of, 91 
necrosis of, 1067 
osteomalacia, 1051 
osteophytes of, 1057, 1076 
periostitis, hyperplastic, 1046 
phosphorus necrosis of, 1069 
rachitis, 1052 
regeneration of, 90, 1070 
rickets, 1052 
rider's, 404 
sclerosis of, 1060, 1062 
sequestrum in, 1068 
softening of, 1051 
syphilis of, 1059, 1066 
differential diagnosis of, 1048 
transplantation of, 93 
tuberculosis of 1059, 1065 
differential diagnosis of, 1049 1258 
INDEX 
Bone, tumors of, 404, 1073, 1074 
ulceration of, 1069 
Bonnet, on teratoma of testicle, ref., 1023 
Bonney, V., on esthiomene of vulva, ref., 
912 
Bonney and Ellis, on odontoma, ref., 406 
Bor chard, on hemangioma of muscle, ref., 
1041 
Bordet, on hemolysins, 197; on immunity, 
ref., 224 
Bordet and Gengou, on bacillus of whoop- 
ing-cough, ref., 350; on fixation of 
complement, ref., 214 
Borrel, A., on Demodex folliculorum, 
ref., 157 
Borrmann, R., on carcinoma of stomach, 
ref., 468, 758; on corium carcinoma, 
ref., 465; on hemangioma, ref., 423; 
on malignancy in tumors, ref., 378; 
on metastasis of tumors, ref., 379; 
on sarcoma of penis, ref., 1013 
Borst, on adamantinoma, ref., 448; 
on endotheliomata, ref., 443; on 
neuroma, ref., 418; on pathological 
organization, ref., 126; on sacral tumors 
and cysts, ref., 1112; on squamous-cell 
• carcinoma of stomach, ref., 758; 
on tumors, ref., 467; on tumors of 
sacral region, ref., 393; on tumors of 
veins, ref., 657 
Borth, on concretions in joints, ref., 1087 
Boschowsky, on sarcoma of lung, ref., 721 
Bostroem, E., on tumors of pia mater, ref., 
1101; on dermoid cysts of ventricles, 
ref., 1109 
Bothriocephalus cordatus, 149 
cristatus, 149 
latus, 149 
anemia due to, 534 
Bottomley, on operative treatment of 
tuberculous peritonitis, ref., 793 
Botulism, 324 
Bouchard, Ch., and Roger, G. H., on gen- 
eral pathology, ref., 7, 21 
Boughton, on anaphylaxis, ref., 217 
Bovaird, D., on human and bovine tuber- 
culosis, ref., 299; on lesions of bron- 
chial lymph-nodes, ref., 676; on 
primary splenomegaly, ref., 578 
Bovaird and Nicoll, on weight of viscera 
in infancy, ref., 1190 
Boveri, on mitosis, ref., 81; on origin of 
tumors, ref., 382 
Bowers, on tumors of mesentery, ref., 794 
Boycott, Damant, and Haldane, on caisson 
disease, ref., 18 
Boyd, on sarcoma of pancreas, ref., 806 
Braasch, W. F., on hematuria, ref., 856 
Braasch, W. F., and Thomas, G. J., on 
functional tests in nephritis, 
ref., 882 
Bradley, on cysts of thyroid, ref., 586 
Brain, 1110 
abscess of, 1155 
absence of, 1110 
actinomycosis of, 1176 
anemia of, 1119 
anencephalia, 1110 
aneurysm, miliary, of, 1122 
apoplectic foci in, 1121 
apoplexy of, 1120 
serous, of, 1120 
arteries of, 1118 
atrophy of, 1117 
axis, 1197 
blood-vessels of, 1119 
lesions of, 1128 
cephalocele, 1110 
circulatory changes in, 1118 
congenital diseases of, 1114 
cyclopia, 1110 
cysts of, 1181 
degeneration of, 1127, 1128, 1129 
neurone, 1133 
primary, 1143 
secondary, 1141 
dementia paralytica, 1165 
senile, 1169 
diseases, general, of, 1165 
dissection of, 1193, 1196 
edema of, 1120 
embolism of, 1126 
encephalocele, 1110 
examination, post-mortem, of, 1191, 
1193, 1198 
gas cysts in, 1181 
gumma in, 1171 
hemorrhage in, 1120 
hernia of, 1110 
holes in, 1181 
hydrencephalocele, 1110 
hydrocephalus, 1110 
hydromeningocele, 1110 
hypertrophy of, 1161 
idiocy, amaurotic family, 1115 
Mongolian, 1114 INDEX 
1259 
Brain, inflammation of (see Encephalitis), 
1155, 1157, 1164 
injuries of, 1115 
lesions of, in Asiatic cholera, 279 
in shell shock, 1121 
in sunstroke, 495 
malformations of, 1110 
mantle, 1197 
membranes, nature and lesions of, 
1089 
method of opening, 1193, 1196 
microcephalia, 1110 
morphology of, 1129 
paresis, general, 1165 
pigmentation of, 1118 
porencephalus, 1181 
preservation of, 1225 
removal, post-mortem, of, 1191, 1193 
in hydrocephalus, 1224 
sand, 1091, 1094, 1101, 1109 
sclerosis of, 1165 
tuberous, of, 1114a 
senile plaques in, 1170 
softening of, 1126, 1155 
structure of, 1129 
Swiss-cheese, 1181 
syphilis of, 1173 
Tay-Sachs disease, 1115 
thrombosis of, 1126 
tuberculosis of, 1092, 1099, 1106, 
1172 
tumors of, 1092, 1101, 1109, 1176 
vascular changes in, 1118 
ventricles, nature and lesions of, 1105 
tumors of, 1109 
weight of, 1193 
in new-born, 1225 
Bramwell, B., on familial cirrhosis of 
liver, ref., 830; on myasthenia gravis, 
ref., 1035 
Branchial fistulae and cysts, 736 
Brasche, on metastasis of tumors, ref., 378 
Braun and Thiry, on diphtheritic septi- 
cemia, ref., 315 
Braunwarth, C., on cystic kidney, ref., 888 
Brauer, Schroder, and Blumenfeld, on tu- 
berculosis, ref., 301 
Breast (see Mamma), 986 
hyperplasia, senile parenchymatous, 
of, 452 
inflammation of, 452 
Bregman, I., and Steinhaus, J., on tumors 
of hypophysis, ref., 1180 
Breitzke, H., on cervical and bronchial 
lymph-nodes in tuberculous in- 
fection, ref., 740 
Brem, W. V., on blood transfusion, ref., 
531 
Bremer, J., on absorption in large intes- 
tine, ref., 774 
Brenner, on myxoma of heart, ref., 634 
Breus, on cysts of uterus, ref., 940 
Brewer, G. E., on infection of kidney after 
injury, ref., 176; on suppurative ne- 
phritis, ref., 864 
Brewis, on lipoma of heart, ref., 634 
Brickner, on congenital lipomata, ref., 402 
Brieger and Ehrlich, on degenerations in 
spinal cord, ref., 1136 
Bright's disease (see Nephritis), 865 
Brigidi and Piccoli, on persistent thymus 
and Hodgkin's disease, ref., 581 
Brill and Libman, on B. pyocyaneus in 
blood, ref., 244; on calcification of liver, 
ref., 822 
Brill and Mandlebaum, on primary sple- 
nomegaly, ref., 578 
Brill, Mandlebaum, and Libman, on pri- 
mary splenomegaly, ref., 578 
Brill's disease, 334 
Brinckerhoff, on leprosy in the United 
States, ref., 304 
Brinckerhoff and Tyzzer, on experimental 
smallpox in monkeys, ref., 339 
Brissaud, on cystadenoma of mamma, 
ref., 993 
Broman, on malformations, ref., 355; on 
malformations of heart, ref., 600 
Bronchi, 669 
calcification of, 674 
casts of, 672 
dilatation of, 672 
examination, post-mortem, of, 1210 
hemorrhage of, 669 
inflammation of (see Bronchitis), 669 
lung stones in, 674 
occlusion of, 673 
preservation of, 1210 
syphilis of, 672 
tuberculosis of, 672, 674 
tumors of, 675 
Bronchiectasia, 672 
Bronchiolitis exudativa, 672 
Bronchitis, 669 
bacteria in, 671 
capillary, 670 1260 
INDEX 
Bronchitis, catarrhal, acute, 669 
chronic, 671 
croupous, 671 
fibrinous, chronic, 672 
pseudomembranous, 671 
purulent, 670 
syphilitic, 672 
tuberculous, 672 
Bronchopneumonia, 692, 693 
excitants of, 696, 697 
exudate in, 693 
persistent, 695 
resolution in, 694 
streptococcal, 694 
streptothrix in, 696 
tuberculous, 711 
Bronfenbrenner, on Abderhalden reaction, 
ref., 218 
Bronson, E', on osteomalacia, ref., 1044 
" Bronze skin," 65 
4'Bronzed diabetes," 830 
Brooks, H., on acromegaly, ref., 497; on 
caisson disease, ref., 18; on myocar- 
ditis, ref., 616 
Brooks, P. B., on oysters and typhoid 
fever, ref., 275 
Brosch, on esophageal diverticula, ref., 
743; on trauma and formation of 
malignant tumors, ref., 386 
Brouardel, on sudden death, ref., 509 
Broun, L., on carcinoma of vagina, ref., 
917 
Brown, on snake poisons, ref., 479 
Brown, L., Heise, F. H., and Petroff, S. A., 
on concurrent infection in tuberculosis, 
ref., 300 
Brown, P. K., and Cummins, IT. T., on 
coccidioidal granuloma, ref., 169 
Brown, T. R., on Trichinella spiralis, ref., 
154 
Brown, W. H., on blood-plates, ref., 529 
Brown and Simpson, on anthrax, ref., 260 
Bruce, on Trypanosoma brucei, ref., 136 
Bruce and Dawson, on neuroma, ref., 418 
Brumpt, on animal parasites, ref., 132 
Bruning and Schwalbe, on cancer sta- 
tistics, ref., 453; on carcinoma of 
stomach in children, ref., 756 
Brunn, M., on peritonitis, ref., 793 
v. Brunn, on appendicitis, ref., 782 
Brunner, on retropharyngeal tumors, 
ref., 740 
Bruns, on brain tumors, ref., 1176 
Bruns and Kayser, on agglutinative reac- 
tions of colon-typhoid group, ref., 276 
Bryce, T. H., on malformations of the 
heart, ref., 600 
Bubo, 305, 550 
of penis, 1013 
Bubonic plague, 320 
Buchbinder, on intestine as portal of entry 
for bacteria, ref., 791 
Buday, K., on bacteria in gangrene of 
lung, ref., 684; on cystic adenoma of 
mamma, ref., 1004 
Buerger, L., on pneumococci, ref., 249; 
on tumors of bladder, ref., 445; on 
thromboangiitis obliterans, ref., 639 
Buerger and Lautman, on mixed tumors of 
kidney, ref., 891 
Bulkley, on tumors of undescended 
testicle, ref., 1015 
Bull and Pritchett, on antiserum for B. 
aerogenes capsulatus, ref., 322 
Bullock and Rohdenburg, on epithelial 
proliferation, ref., 95; on sarcoma of 
liver in rats, ref., 388 
Bundschuh, E., on carcinoma and tuber- 
culosis, ref., 723; on rhabdomyoma, 
ref., 422; on tuberculosis of mamma, 
ref., 994; on tuberous cerebral sclerosis, 
ref., 1114a 
Bunting, on carcinoid tumors of intestine, 
ref., 784; on sarcoma of spleen, ref., 580 
Bunting and Yates, on organism of Hodg- 
kin's disease, ref., 563 
Burge, W. E., on action of ultraviolet light 
on tissue proteins, ref., 17 
Burgess, on chloroma, ref., 542; on malig- 
nant rhabdomyoma in man, ref., 422 
Burns, death from, 10 
degrees of. 10 
Burns, Slack, Castleman, and Bailey, on 
complement fixation in tuberculosis, 
ref., 293 
Burri, on staining Treponema pallidum, 
ref., 311 
Bursae, 1087 
Buschke, A., on yeasts and moulds in 
disease, ref., 173 
Busse, O., on occurrence of duodenal 
ulcers after severe burns, ref., 11; 
on duodenal ulcers, ref., 767; on post- 
mortem examinations, ref., 1186; on 
renal growths, ref., 892; on tumors of 
muscle, ref., 1040 INDEX 
1261 
Butler, on abnormalities of thoracic duct, 
ref., 659 
Butler, G. R., on membranous enteritis, 
ref., 774 
Butlin, H. T., on epithelioma of scrotum, 
ref., 1014 
Butt, on tumors of undescended testicle, 
ref., 1015 
Buttner, 0., on endometritis, ref., 930; 
on peritonitis, ref., 791 
Buxton, on giant cells, ref., 119 
Buxton and Shaffer, ferments, ref., 376 
Buxton and Torrey, on absorption from 
peritoneum, ref., 115, 792; on disposal 
of bacteria in blood, ref., 176 
Byam, on trench fever, ref., 352 
Cabot, on clinical examination of blood, 
ref., 533 
Cachexia in tumors, 380 
strumipriva, 485 
Cadwallader, R., on Hirschsprung's dis- 
ease, ref., 763 
Caisson disease, 18 
Calcareous infiltration, 60 
Calcification, 60 
of arteries, 637 
heart, 612 
kidney, 857, 860 
liver, 822 
lung, 674, 726 
muscle, 1038 
penis, 1013 
placenta, 953 
pleura, 726 
veins, 655 
Calcium bilirubinate in gall-stones, 847 
carbonate in gall-stones, 847 
salts in gall-stones, 847 
Calculi, ref., 63, 905 
biliary, 847 
composition of, 847 
of bladder, urinary, 905 
composition of, 905 
gall-bladder and -ducts, 847 
composition of, 847 
kidney, 890 
prepuce, 1013 
tonsil, ref., 739 
vesical, 905 
Calkins, G. N., on growth of parame- 
cinm, ref., 96; on protozoa, ref., 133; 
on spirochetes, ref., 138; on vaccine 
bodies, ref., 339 
Callison and Mackenty, on paraganglioma 
of carotid, ref., 413 
Callus, 1070 
Calmette, on entrance of bacteria through 
intestine, ref., 792; on intestinal origin 
of pulmonary tuberculosis, ref., 297 
Calmette and Guerin, on intestinal origin 
of pulmonary tuberculosis, ref., 
297 
Cammidge, P. J., on intestinal bacteria, 
ref., 774 
Camp, W. E., and Baumgartner, E. A., 
on leukocytosis, ref., 52 
Campbell, on leptothrix, ref., 263 
Cancer (see Carcinoma), 453 
age, 453 
cages, 389 
cell, 456 
chimney sweeps, 1014 
colloid, 467 
communicability of, 385 
"cures," 457 
Demodex folliculorum in, 157 
families, 388 
houses, 385 
of animals, 387, 388 
osteoid, 1079 
streets, 385 
villages, 385 
x-ray, 386 
Cancer a deux, 385 
Cancer en cuirasse, 1009 
Cancroid, 376, 460 
Cannon, on bodily changes, ref., 20, 589 
Canon, on bacteriology of blood, ref., 533 
Cantharides poisoning, 476 
Capillaries, lesions of, 658 
Capps, J., on aneurysm of coronary 
arteries, ref., 615, 652 
Caput medusae, 654, 828 
obstipum, 1039 
succedaneum, 1224 
Carbolic acid poisoning, 477 
Carbonic monoxide poisoning, 480 
oxide poisoning, 480 
Carbuncle, 229, 258 
Carcinoid tumors of appendix vermi- 
formis, 786 
of intestine, 783, 786 
Carcinoma, 453 
adenogenous, 464 1262 
INDEX 
Carcinoma and goiter, 586 
mixed tumors, 457 
pregnancy, 948 
tuberculosis, 723, 948 
ulcers of stomach, 753 
basal-cell, 462 
differential diagnosis of, 465 
calcification of, 457 
cells, small round, infiltration of, in, 
392 
colloid, of peritoneum, 797 
connective tissue stain for, 1241 
corium, 465 
cure, spontaneous, of, 454 
cylindrical-cell, 459, 465 
of appendix vermiformis, 786 
degeneration of, 457 
differential diagnosis of, 439 
durum, 459 
encephaloid, 459 
epidermal, 459 
flat-cell, 459 
following x-ray burns, 14 
forms of, 459 
gelatinous, 460, 467 
of peritoneum, 797 
glandular, 459 
growth of, 459 
incidence of, 453, 454 
in hypertrophy of prostate, 1026, 
1029 
lymphatic permeation in, 454 
medullary, 459 
melano-, 460, 467 
metastasis of, 454 
mitotic figures in, 457 
molle, 459 
muciparous, of peritoneum, 797 
mucoid, of peritoneum, 797 
multiple, 454 
myxomatodes, 467 
of adrenals, 592 
arteries, 653 
Bartholin's glands, 913 
bladder, urinary, 904 
bone, 1081 
brain, 1174 
bronchi, 675 
dura mater spinalis, 1104 
epiglottis, 669 
esophagus, 744 
Fallopian tubes, 981 
gall-bladder and -ducts, 846 
Carcinoma of hypophysis, 1180 
intestine, 785 
kidney, 893 
larynx, 668 
liver, 837 
lung, 722 
mamma, 1006 
male, 1030 
mouth, 734 
nose, 662 
ovary, 969, 974 
pancreas, 806 
penis, 1013 
peritoneum, 796 
pharynx, 741 
pleura, 729 
prostate, 1026, 1029 
salivary glands, 801 
seminal vesicles, 1024 
spleen, 580 
stomach, 755 
statistics of, 755 
testicle, 1022 
thyroid, 586 
thymus, 582 
tongue, 735 
tonsil, 741 
urachus, 897 
ureter, ref., 904 
urethra, 908 
uterus, 943 
vagina, 917 
vulva, 913 
parenchyma and stroma of, relation 
between, 459 
cells of, 455 
scirrhous, 459 
simplex, 459, 465 
spontaneous cure of, 454 
squamous-cell, 459 
statistics of, 453, 755 
structure of, 392 
telangiectoides, 459 
transformation of, to sarcoma, 389 
tricho-, 464 
Carcinosarcoma, 440, 444 
of esophagus, 744 
mamma, 1006 
thyroid, 587 
uterus, 942 
Caries of bone, 1069 
Carl, on hypernephroma of adrenal in 
frog, ref., 591 INDEX 
1263 
Carlisle, on relapsing fever, ref., 324 
Carotid gland, 592 
paraganglioma of, 413 
tumors of, 594 
Carrel, on technique of tissue culture, ref., 
96; on transplantation of organs, ref., 
93 
Carriers, cholera, 280 
typhoid, 275 
Carroll, on mosquito in yellow fever, ref., 
335; on polyps of intestine, ref., 783 
Carter, on elimination of pigment by kid- 
ney, ref., 864; on mosquito in yellow 
fever, ref., 335 
Cartilage in muscle, 1040 
pia mater spinalis, 1105 
tonsil, 741 
loose, in joints, 1087 
regeneration of, 90 
tumors of, 402 
Caruncle, urethral, 907, 913 
Cary, E. G., on cartilage and bone in 
tonsil, ref., 741 
Caryochromes, 1129 
Caseation, 70 
Cassirer, R., on intermittent limping, ref., 
639 
Castle, on carcinoma of liver in children, 
ref., 837 
Castle, W. E., on heredity, ref., 21 
Casts of kidney, 856 
Catarrh, dry, 671 
nasal (see Rhinitis), 661 
purulent, 228 
Cattell, H. W., on post-mortem technique, 
ref., 1186 
Cave, E. J., on pneumococcic arthritis, 
ref., 1083 
Cavernoma of liver, 835 
Cecil, R. L., on adenoma of islands of 
Langerhans, ref., 803; on adenoma of 
pancreas, ref., 806; on hypertrophy of 
islands of Langerhans, ref., 803; on re- 
lation of pancreas to diabetes, ref., 492 
Cecil and Bulkley, on Oxyuris vermicu- 
laris in appendix, ref., 151; on parasites 
in appendix, ref., 782 
Cecil and Soper, on meningococcus endo- 
carditis, ref., 622 
Cecum, 775 
inflammation of, 775 
Ceelen, W., on calcification of liver, ref., 
822 
Cell anarchy in tumors, 372 
Celler, H. L., and Thdlhimer, W., on gas- 
tric and duodenal ulcer, ref., 752 
Celloidin embedding, 1232 
Cells, atrophy of, 44, 45 
"beaker," 55 
blood (see Blood cells and leuco- 
cytes). 
degeneration of, 45 
division of, 76 
amitotic, 81 
direct, 81 
indirect, 78 
mitotic, 78 
giant, 118 
"heart failure," 64 
hypertrophy of, 44 
infiltration of, 45 
mast, 109 
naevus, 447 
necrobiosis, 45 
necrosis of, 45 
plasma, 109 
regeneration of, 82 
impulse to, 94 
relationship of, to organs, 5 
serous infiltration of, 54 
significance of, 4 
"slumbering," 382 
structure of, 76 
Cephalhematoma, 1224 
Cephalin, 515 
Cephalocele, 1110 
Cercomonas hominis, 140 
Cerebellum, atrophy of, 1153 
Cerebrospinal fluid, nature of, 1107 
Cerenville and Tavel, on necrotic colitis, 
ref., 774 
Cervix uteri, erosions of, 932 
inflammation of, 932 
syphilis of, 933 
tuberculosis of, 933 
tumors of, 940 
Cestoda, 146 
Chalatow, on metastasis of tumors in 
spleen, ref., 379 
Chalazion, 394 
Chalicosis of lung, 703 
Chalk-stones, 494 
Chancre, 305 
soft, 258 
Chancroid, 258 
Chantemesse and Podwyssotsky, on fever, 1264 
INDEX 
ref., 502; on inflammation, ref., 123; 
on regeneration, ref., 94 
Chapin, C. V., on diphtheria carriers, ref., 
317; on meningococcus carriers, ref., 
256; on microorganisms in air, ref., 
175; on sources and modes of infec- 
tion, ref., 176; on typhoid carriers, 
ref., 275 
Chapman, on kidney lesions, ref., 340 
Charbon, 258 
symptomatique, 323 
Charcot-Leyden crystals, 672, 1071 
Chauffard, A., and Troisier, J., on icterus 
in infectious disease, ref., 576 
Cheesman, T. M., and Meltzer, S. J., on 
local predisposition in infection, ref., 
176; on suppurative nephritis, ref., 864 
Cheesy degeneration, 70 
Cheloid, 398 
Chemistry, biological, 3, 7 
Chemotaxis, 101, 112, 121, 124, 162, 210, 
227, 840 
negative, 102 
Chevassu, on tumors of testicle, ref., 1022 
Chiari, H., on auto-digestion of pancreas, 
ref., 802; on congenital malformations 
of liver, ref., 808; on death from phle- 
bitis of hepatic vein, ref., 814; on 
syphilitic arteritis, ref., 647; on typhoid 
fever, ref., 273 
Chibret, on adamantinoma, ref., 448 
Chilblains, 11 
Child, C. M., on body changes, ref., 45; 
on general biological methods, ref., 7 
Chimney-sweeps cancer, 1014 
Chittenden and Albro, on skin pigment, 
ref., 66 
Chittenden and Underhill, on experimental 
production of pellagra, ref., 496 
Chlamydozoa, 141, 341 
Chloral hydrate poisoning, 479 
Chlorine gas poisoning, 472 
Chloroform, liver degeneration after use 
of, 816, 818, 831 
poisoning, 478 
lesions of liver in, 816, 818, 831 
Chloroma, 542, 1073 
of dura mater cerebralis, 1093 
mamma, 1006 
Chlorosis, 533 
Cholangitis, 842, 843 
Cholecystitis, 842, 843 
Cholelithiasis, 847 
Cholera, Asiatic, 278 
carriers, 280 
communicability of, 280 
• preventive inoculation in, 281 
spirillum of, 279 
reproduction of, ref., 160 
chicken, bacillus of, 321 
Cholesteatoma of brain, 1173 
hypophysis, 1180 
mamma, 1006 
pia mater cerebralis, 1101 
Cholesterin in gall-stones, 847 
tissue, 53 
tumors, 425 
Chondrioconts, 77 
Chondriomes, 77 
Chondriomites, 77 
Chondriosomes, 77 
Chondrodystrophia fetalis, 1043 
Chondrolipoma of muscle, 1041 
Chondroma (see also Enchondroma), 402 
of bone, 1077 
bronchi, 675 
choroid plexus, 1109 
clitoris, 913 
dura mater cerebralis, 1092 
spinalis, 1103 
lymph-nodes, 564 
mamma, 1005 
muscle, 1041 
ovary, 961 
pancreas, 806 
peritoneum, 794 
pia mater cerebralis, 1101 
salivary glands, 798 
spleen, 580 
testicle, 1021 
osteoid, 1077 
Chondro-osteosarcoma, 440 
Chondrosarcoma, 440 
of mamma, 1006 
uterus, 942 
Chorda dorsalis, embryology of, ref., 
403 
Chordoma, 403 
Chorioma, 948 
Chorionepithelioma of brain, 1174 
of Fallopian tubes, 982 
liver, 839 
pineal gland, 1179 
pregnancy, 948 
testicle, 952, 1024 
vulva, 913 INDEX 
1265 
Chorionepithelioma of brain, with 
teratoma, 952 
Chorionic villi, 949 
wandering cells, 950 
Choroid plexus, 1105 
brain sand in, 1109 
cysts of, 1109 
inflammation of, 1106 
tumors of, 1109 
Christian, H. A., on diet in nephritis, ref., 
882; on functional tests in nephritis, 
ref., 882; on multiple myeloma, ref., 
431, 1073; on pneumonic exudates, 
ref., 689 
Christian, Frothingham, O'Hare, and 
Woods, on functional tests in nephritis, 
ref., 882 
Christian and O'Hare, on experimental 
nephritis, ref., 880 
Christie, C. D., and Stewart, G. N., on 
diabetes insipidus, ref., 493 
Chromaffin tumor, 413 
Chromatic figure in mitosis, 79 
Chromatoblast in naevus, 447 
Chromatolysis, 1135, 1137, 1138, 1146 
Chromatophore in naevus, 447 
Chromatophoroma, 432 
Chromophilic bodies, 1130, 1135, 1137 
Chromosome equilibrium, 382 
Chromosomes, 78 
division of, in tumors, 384 
Chyluria, 898 
Cicatricial tissue, 109 
Cicatrix, 110 
Ciechanowski, on hypertrophy of prostate, 
ref., 1026 
Ciliata, 140 
Circle of Willis, 1118 
Circulation, collateral, 25 
disturbances of, experimental study 
of, 42 
Circulatory system, 595 
Cirrhosis of liver, 825 
Citron, on immunity, ref., 191 
Cladothrix, 161 
Clairmont, P., on action of saliva on 
bacteria, ref., 175 
Clasmatocytes, 109 
Clitoris, chondroma of, 913 
malformations of, 909 
Cloacae, 760 
Clonorchis sinensis, 144 
in gall-ducts, 841 
Clots, heart, 608 
Cloudy swelling (see Degeneration, albu- 
minous), 48 
Clough, M. C., on tubercle bacilli in 
blood, ref., 296 
Clough and Richter, on autoagglutination, 
ref., 206 
Club-foot, 361 
-hand, 361 
Clunet, on malignant tumors, ref., 468 
Coagulation necrosis, 69, 71 
of blood, 514 
Cobb, on sarcoma of omentum, ref., 
794 
Cobbett, C., on tuberculosis, ref., 301 
Cobbett and Melsome, on granulation 
tissue in infection, ref., 177 
Cocci, 159 
diplo-, 160 
strep to-, 160 
Cnccidiidea, 142 
Coccidioidal granuloma, 169 
Coccidiodes immitis, 169 
Coccidium oviforme, 142 
in liver, 812 
Coco, A. M., on colorability of living cells, 
ref., 1227 
Cohn, on changes in myocardium, ref., 
614 
Cohnheim, on origin of tumors, ref., 
383 
Cohnheim's fields, 1031 
hypothesis of origin of tumors, 
383 
Colchicum poisoning, 476 
Cold, action of, 11 
Cole, R., on acute rheumatism, ref., 351; 
on pneumonia, ref., 205; on toxic 
products of pneumococcus, ref., 249; 
on typhoid meningitis, ref., 273 
Cole and MacCallum, on streptococcal 
bronchopneumonia, ref., 694 
Coleman and Buxton, on typhoid bacil- 
lus, in blood, ref., 274 
Colitis, 767 
acute catarrhal, 767 
infectious, 768 
amebic, 768 
bacterial, 769 
chronic, 774 
croupous, 771 
excitants of, 768, 770, 773 
experimental, ref., 770 
membranous, 774 1266 
INDEX 
Colitis, mucous, 774 
necrotic, 773 
nodular, 771 
pseudomembranous, 771 
tropical, 768 
Collagen in fibroma, 397 
in tumors, 437 
Collins, on pneumococci, ref., 249 
Collodion sacs, ref., 353 
Colloid degeneration, 54, 56 
Colloidal gold reaction, 312, 1163 
Colmers, F., on endothelioma, ref., 442; 
on sarcoma of penis, ref., 1013 
Colocynth poisoning, 476 
Colon bacillus (see B. coli communis), 
243 
group, 244 
Colon, dilatation of, 763 
Hirschsprung's disease, 763 
inflammation of (see Colitis), 767 
Colwell, H. A., and Russ, 8., on radium, 
z-rays and the living cell, ref., 
12 
Comedones, 394 
Commensals, 167 
Complement, 204 
fixation, 214 
in echinococcus infection, 148 
gonorrhea, 253 
tuberculosis, 293 
Concretions in appendix vermiformis, 
781 
in intestine, 781 
pancreatic ducts, 807 
prostate, 1029 
seminal vesicles, 1024 
Condyloma, 306 
of penis, 1012, 1013 
pointed, of vulva, 911 
Condylomata acuminata, 911 
Cone, on chronic gastritis, ref., 748; 
on tuberculous esophagitis, ref., 744 
Conforti, on tumors of omentum, ref., 
794 
Congestion (see Hyperemia), 23 
chronic, 26 
hypostatic, 26, 677, 696 
post-mortem, 1186 
venous, 23, 24 
Conium poisoning, 481 
Conklin, E. G., on amitosis, ref., 81; 
on heredity and environment, ref., 
Connective tissue, Bielschowsky silver 
stain for, 1239 
regeneration of, 87 
tumors of, benign, 396 
malignant, 427 
Connell, on edema of lungs, ref., 678; 
on fat embolism, ref., 42 
Conorhinus megistus, 137 
Conradi and Bierast, on B. coli, ref., 243 
Constantini, on sarcoma of pancreas ref., 
806 
Constitutio lymphatica, 500 
Contagion in cancer, 389 
Contagium, ref., 185 
Contamin, on cancer, ref., 467 
Contrecoup, injury by, 1115 
Contusions, post-mortem, 1189 
Cooke, on chorionepithelioma of testis, 
ref., 1024 
Cooper, on hematoma of umbilical cord, 
ref., 797 
Copper poisoning, 476 
Coplin, W. L., on branchial cysts, ref., 
736; on pulmonary edema, ref., 678; 
on tumors of esophagus, ref., 744 
Cord, umbilical, tumors of, 797 
Cordes, on carcinoma of nose, ref., 662 
Corner and Fairbanks, on sarcoma of 
stomach, ref., 755 
Cornet, on tuberculosis, ref., 301 
Cornil, on tumors of breast, ref., 468; 
on tumors of mamma, ref., 1005 
Cornil and Carnot, on regeneration of 
mucous membranes, ref., 85 
Corning, E., on cysts of appendix, ref., 
781; on diverticula of appendix, ref., 
760 
Cornu humanum, 445 
Corpora aliena articulorum, 1087 
amylacea, 60 
in brain, 1127 
ependyma, 1109 
nerve tissue, 1149, 1156, 1162, 
1167 
prostate, 1026, 1029 
stain for, 1239 
cavernosa penis, inflammation of, 
1012 
plates, fibrous, in, 1012 
Corpus luteum cysts, 963 
Corpuscles, Gluge's, 1127, 1159 
Corrosive sublimate as fixative, 1230 
for blood, 530 INDEX 
1267 
Corrosive sublimate, poisoning, 63, 475 
kidney in, 63, 860, 863 
Corynebacterium granulomatis maligni, 
563 
Councilman, W. T., on arteriosclerosis, 
ref., 646; on cerebrospinal meningitis, 
ref., 255; on excitant of smallpox, ref , 
339; on gonorrheal myocarditis, ref., 
616; on interstitial nephritis, ref., 869; 
on lung lobule, ref., 685; on sudden 
deaths due to heart, ref., 605 
Councilman and Lafleur, on Amoeba dys- 
enteriae, 133 
Councilman, Mallory, and Pearce, on 
bacteriology and pathology of 
diphtheria, ref., 314 
Councilman, Mallory, and Wright, on 
cerebrospinal meningitis, ref., 
256 
Coupland and Pasteur, on tumors of spinal 
cord, ref., 1175 
Courmont and Duffau, on spleen in infec- 
tion, ref., 177, 572 
Cowdry, E. V., on mitochondria, ref., 77 
Cowie, on differentiation of smegma and 
tubercle bacillus, ref., 300 
Cowper's glands, lesions of, 1029 
Coy on, on bacteria in stomach, ref., 750 
Cozzolino, on melanosarcoma of nose, ref., 
662 
Cragin, E. B., and Hull, E. T., on chloro- 
form poisoning, ref., 479 
Craig, C. F., on ameba, ref., 134; on 
complement fixation in tuberculosis, 
ref., 293; on Wassermann test, ref., 312 
Craig, C. F., and Nichols, H. J., on Wasser- 
mann reaction, ref., 312 
Cramer, A., on Landry's paralysis, ref., 
1160; on sunstroke, ref., 495 
Craniopagus, 365 
parasitic, 367 
Craniorrhachischisis totalis, 359 
Cranioschisis, 359 
Craniotabes, 1053 
Craw, on agglutination of typhoid bacilli, 
ref., 276 
Creite, on fibroma of mamma, ref., 995 
Crenothrix, 161 
Cretinism, 486, 1044 
Crile and Lower, on effects of fatigue on 
neurones, ref., 1138 
Croton oil poisoning, 476 
Crotti, on thyroid and thymus, ref., 587 
Crouse, on tumors of appendix, ref., 785 
Crowder, on tuberculous lymphadenitis, 
ref., 553 
Crowder and Crowder, on angioneurotic 
edema, ref., 21 
Cryptococcus dermatidis, 170 
Cryptorchismus, 1015 
Culex in malaria, 346 
Cullen, E. K., on calcification of heart 
muscle, ref., 617 
Cullen, T. S., on calcification of muscle 
fibers of heart, ref., 613; on cancer of 
uterus, ref., 468, 943; on cysts of 
Bartholin's glands, ref., 913; on cysts 
of vagina, ref., 918; on diseases of 
umbilicus, ref., 759, 897, 941; on endo- 
metritis, ref., 930; on frozen sections, 
ref., 1228; on hydrosalpinx, ref., 976; 
on myoma of round ligament, ref., 941; 
on myoma of uterus, ref., 941; on 
peritonitis, ref., 791; on sarcomatous 
changes in myoma, ref., 941; on 
tumors of umbilicus, ref., 797 
Cummins, W. T., and Sanders, J., on 
coccidioidal granuloma, ref., 169 
Cumston, C. G., on sarcoma of prostate, 
ref., 1028 
Cunningham, R. H., on death from 
electric currents, ref., 12; on experi- 
mental thyroidism, ref., 485 
Curare, use of, ref., 42 
Curschmann, H., on excitants of cystitis, 
ref., 901; on typhoid cystitis, ref., 274 
Curschmann's spirals, 672 
Cushing, H., on calculus formation, ref., 
848; on gall-bladder infections, ref., 
844; on gonococcus peritonitis, ref., 
791; on the pituitary body, ref., 95, 
493, 497, 1182a; on tumors of auditory 
nerves, ref., 416 
Cushing, H., Weed, L. H., and Wegefarth, 
P., on relation of cerebrospinal 
fluid and hydrocephalus, ref., 
1109 
Cushny, A. R., on experimental cirrhosis 
of liver, ref., 831; on secretion of urine, 
850 
Cutis anserina, 505 
Cutler, E. C., and Morton, J. J., on pul- 
monary embolism, ref., 40 
Cyanide of potassium poisoning, 477 
Cyclopia, 360, 1110 
Cyclops strenuus, 149 INDEX 
1268 
Cylindroma, 448 
Cystadenoma, 451 
adamantinum, 448 
of mamma, 993, 997 
male, 1030 
ovary, 963 
papillary, 451 
Cysticercus cellulosse, 146 
in ependyma, 1109 
heart, 635 
kidney, 893 
muscle, 1041 
peritoneum, 797 
pia mater cerebralis, 1103 
spinalis, 1105 
teenise mediocanellatse, 147 
Cystite en plaque, 901 
Cystitis, acute catarrhal, 898 
chronic, 899 
cystica, 900 
emphysematous, 901 
excitants of, 901 
exudative, 898 
membranous, 901 
necrotic, 899 
nodular, 900 
suppurative, 900 
tuberculous, 901 
with pyelonephritis, 884 
Cystocele, vaginal, 897, 914 
Cystomata, ovarian, 395 
Cystosarcoma, 440 
of mamma, male, 1030 
Cysts, 394 
adenomatous, of ovary, 963 
apoplectic, of pancreas, 807 
atheromatous, 640 
branchial, 734, 736 
butter, of mamma, 1010 
colloid, of ovary, 966 
congenital, 395 
corpus luteum, 963 
dermoid, 393 
of bladder, urinary, 904 
intestine, 785 
kidney, 888 
lungs, 723 
mouth, 734 
nose, 662 
ovary, 971 
spleen, 580 
ventricles, 1109 
echinococcus, 147 
Cysts, echinococcus, of pancreas, 807 
endopancreatic, 807 
epidermoid, 395 
follicular, of ovary, 962 
foreign-body, 395 
formed by softening and disintegra 
tion of tissue, 395 
gas, of brain, 1181 
intestine, 785 
hydatid, 147 
lutein, of ovary, 963 
milk, 394 
of appendix vermiformis, 781, 787 
bladder, urinary, 904 
bone, 1081 
brain,' 1181 
choroid plexus, 1109 
esophagus, 745 
Fallopian tubes, 982 
hypophysis cerebri, 1182a 
intestine, 785 
jaw, 1082 
kidney, 886 
larynx, 669 
liver, 839 
mamma, 997, 1010 
male, 1030 
mesentery, 795 
mouth, 734 
neck, 736 
omentum, 795 
ovary, 959, 962, 971 
pancreas, 807 
parovarium, 976 
pericardium, 599 
peritoneum, 795, 797 
pia mater cerebralis, 1103 
pineal gland, 1182 
placenta. 957 
pleura, 729 
prostate, 1029 
scrotum, 1014 
spleen, 580 
stomach, 758 
thyroid, 586 
tongue, 735 
urachus, 896 
urethra, 908 
vagina, 918 
vulva, 913 
peripancreatic 807 
proliferative, of pancreas, 807 
pseudo-, of pancreas, 807 INDEX 
1269 
Cysts, pseudomucinous, of appendix ver- 
miformis, 787 
retention, 394 
of Cowper's glands, 1030 
larynx, 668 
mamma, 1010 
ovary, 962 
pancreas, 807 
sacral, 1112 
sebaceous, of penis, 1013 
serous, 394 
transudation, 395 
Cytase, 205 
Cytolysins, 200 
anti-, 201 
Cytolysis, 197, 200 
Ehrlich's hypothesis, application of, 
to, 202 
phagocytosis in, 204 
Cytolytic substances, 197 
Cytomicrosomes, 77 
Cytoryctes vaccinae, 338 
Cytotoxins, 200 
anti-, 201 
auto-, 201 
specific, 200 
DaCosta, on blood, ref., 514; on tumors of 
parathyroid, ref., 588 
Da Fano, C., on immunity reaction in 
tumors, ref., 120; on tumor transplan- 
tation, ref., 93 
Dagonet, on tumors of dura mater, ref., 
1092 
Dahlmann, on porencephalus, ref., 1181 
Dahms, on differentiation of smegma and 
tubercle bacillus, ref., 300 
Dana, C. L., on paralysis agitans, ref., 
1171 
Dana and Berkeley, on tumors of pineal 
gland, ref., 1182a 
Dandy, W. E., and Blackfan, K. D., on 
hydrocephalus, ref., 1107 
Dar ger, W., on kraurosis of vulva, ref., 
911 
Davenport, C E., on chemotaxis, ref., 102; 
on heredity, ref., 21 
Davidsohn, W., on amyloid degeneration, 
ref., 59; on hyaline degeneration, ref., 
57 
Davis, on B. influenza, ref., 264; on Buyo 
cheek cancer, ref., 387; on carcinoma 
of bronchi, ref., 675; on diabetic gan- 
grene, ref., 491; on diseased tonsils, ref., 
739; on diverticula of duodenum, ref., 
759; on Ducrey's bacillus, ref., 258; on 
leptothrix, ref., 263; on meningococcus 
in blood, ref., 255; on pathology of ad- 
renals, ref., 590; on streptococcus arth- 
ritis, ref., 1084; on tumors of adrenal, 
ref., 592 
Dawson, B., Hume, H. E., and Bedson, 
S. P., on infective jaundice, ref., 352; 
on spirochetes, ref., 139 
Dayton, H., on hemolymph-nodes, ref., 
547 
Death, black, 320 
sudden, 507 
and persistent thymus, ref., 500 
from pulmonary embolism, 39 
time of, determination of, post mor- 
tem, 1188 
violent, 503 
Deaver, J. B., and McFarland, J., on 
diseases of breast, ref., 989 
Debernardi, on tumors of testis, ref., 1021 
Decalcification of tissue, 1231 
Decidual reaction in tubal pregnancy, 986 
Decomposition, post-mortem, 1187 
Dederer, on transplantation, ref., 93 
Deficiency, mental, 1114 
Degeneration, 48 
acute, 48 
albuminous, 48 
of heart, 610 
kidney, 858 
liver, 816 
muscle, 1036 
pancreas, 802 
stomach, 747 
amyloid, 57 
of adrenals, 589 
arteries, 637 
heart, 612 
intestine, 764 
kidney, 860, 863 
liver, 820 
lymph-nodes, 548 
muscle, 1037 
pancreas, 803 
spleen, 567 
stomach, 747 
thyroid, 583 
uterus, 925 
ascending, of nervous system, 1143 
cancerous, 459 INDEX 
1270 
Degeneration, cheesy, 70 
chronic, of brain, 1161 
of spinal cord, 1161 
colloid, 54, 56 
of thyroid, 583 
combined system, 1150 
descending, of nervous system, 1141 
fatty, 49, 50 
of arteries, 636 
endocardium, 612 
heart muscle, 611 
joints, 1083 
kidney, 859 
liver, 820 
muscle, 1036 
pancreas, 802 
placenta, 953 
prostate, 1024 
stomach, 747 
uterus, 925 
veins, 655 
glycogenic, 53 
of kidney, 860 
liver, 821 
granular, 48 
hyaline, 57 
of arteries, 637 
heart, 612 
lymph-nodes, 548 
muscle, 1037 
pancreas, 803 
prostate, 1024 
thyroid, 583 
uterus, 925 
hydropic, 54 
in tumors, 376 
lardaceous, 57 
lipoid, 52 
mucous, 54 
neurone, 1133, 1143 
toxic, 1163 
of dendrites, 1134 
fibromyoma of uterus, 940 
nerves, 1163 
nervous system, 1133 
parenchymatous, (see Degeneration 
albuminous), 48 
of ganglion cells, ref., 1156 
kidney, 858 
liver, 816 
primary, of nervous system, 1143 
progressive lenticular, 1171 
secondary, of nervous system, 1141 
Degeneration, sarcomatous, of fibroids, 
942 
waxy, 57 
of muscle, 1037 
Dejerine, on nervous system, ref., 1129 
De Jong and Muskens, on Hirschsprung's 
disease, ref., 763 
Delafield, on colitis, ref., 767 
Delafield's hematoxylin solution, 1235 
Delamare, on syphilitic nephritis, ref., 883 
Delamare and Lecene, on giant cells in 
carcinoma, ref., 455 
Delhi boil, 139 
Dementia paralytica, 1165 
senile, 1169 
Demodex folliculorum, 157 
in cancer, 157 
De Nancrede, C. B. G., and Butterfield, 
E. E., on ileocecal tuberculosis, 
ref., 776 
Dendrites, 1130 
degeneration of, 1134 
Denis, W., on splenectomy in anemia, 
ref., 538 
Dercum's disease, ref., 401 
Dermatitis, blastomycotic, 171 
x-ray, 13 
Dermatomyositis, 1039 
Dermoid cysts, 393 
tumors of penis, 1013 
Dermoids, 368 
Desmoid, 399 
of muscle, 1041 
Deutsch, K., on syphilis of mamma, ref., 
994 
Dewey, on tuberculosis of stomach, ref., 
750 
de Vecchi, on tuberculosis of adrenals, 
ref., 490 
DeWitt, L. M., on dysmenorrhea, ref., 
926; on islands of Langerhans, ref., 803; 
on myositis ossificans, ref., 1039 
Diabetes, bronzed, 492, 830 
insipidus, 492 
mellitus, 491 
secretions, internal in, 492 
metabolism in, ref., 491 
phloridzin, ref., 492 
Diapedesis, 102 
hemorrhage by, 27 
Diaphragm, eventration of, 789 
examination, post-mortem of, 1203, 
1225 INDEX 
1271 
Diaphragm, height of, 1203 
malpositions of, 789 
Diaptomus gracilis, 149 
Diastematomyelia, 1111 
Diaster phase of mitosis, 79 
Diathesis, hemorrhagic, 29 
Dicephalus, 366 
tetrabrachius, 366 
tribrachius, 366 
Dichlorodiethylsulphide, 472 
Dick, on fusiform bacilli, ref., 326 
Dickson, E. C., on botulism, ref., 324 
Dickson, W. E. C., on periarteritis no- 
dosa, ref., 645 
Diet in etiology of tumors, 385 
Dieterle, T., on cretinism, ref., 1045 
Dietrich, on carcinoid tumors of intestine, 
ref., 783 
Dieudonne and Otio, on B. pestis, ref., 320 
Digestive system, 730 
Digitalis poisoning, 481 
Dimples, postanal, 1114 
Dioxydiamido-arsenobenzol, 138 
Diphtheria, 313 
antitoxin, 190 
theory of, 190 
bacteriology of, 315 
carriers of, 317 
communicability of, 316 
concurrent infections in, 315 
immunization, artificial, in, ref., 
337 
lesions in, 314 
of larynx, 666 
pharynx, 738 
pseudo-, 241 
Schick test in, 317 
susceptibility to, 317 
toxin, 190, 316 
Diplobacillus, 160 
Diplococci, 160 
Diplococcus intracellularis meningitidis, 
254, 255 
pneumonire, 246 
in lobar pneumonia, 687, 691 
types of, 248 
Diplomyelia, 1111 
Diprosopus, 366 
diophthalmus, 366 
distomus, 366 
tetraophthalmus, 366 
triophthalmus, 366 
Dipygi, 365 
Dipylidium caninum, 149 
Disease, adaptation in, 8 
characters of, 4 
communicable, 184, 226 
conditions of, 8 
external, 9 
internal, 19 
contagious, 184 
disposition to, 8 
endemic, 185 
epidemic, 185 
excitants of, 6 
bacterial, 227 
general, 485 
infectious, 226 
classification of, 226 
communicable, 184 
general considerations, 226 
non-communicable, 184 
occupational, 9 
pandemic, 185 
relation of age to, 20 
of air supply to, 9 
heredity to, 21 
race to, 20 
sex to, 20 
"specific," 226 
Disposition to disease, 8 
Distoma buski, 144 
haematobium, 145 
hepaticum, 144 
lanceolatum, 144 
pulmonale, 144 
siense, 144 
Diverticula, acquired, of intestine, 759 
false, of intestine, 759 
Meckel's, 358, 759 
of appendix vermiformis, 760 
bladder, urinary, 896, 897 
esophagus, ref., 743 
and empyema, ref., 726 
intestine, 759 
pharynx, 736 
urethra, 906 
Dmochowski and Janowski, on cysts of 
liver, ref., 839; on pyogenic powers of 
typhoid bacillus, ref., 274 
Dobrowolski, Z., on lymph-nodules of 
tonsils, ref., 738 
Dochez, A. R., on blood cultures in pneu- 
monia, ref., 690; on D. pneumoniae in 
blood, ref., 247; on factors in recovery 
from pneumonic infection, ref., 250 1272 
INDEX 
Dochez and Avery, on communicability of 
pneumonia, ref., 690 
Dock, G., on chloroma, ref., 542; on sar- 
coma of stomach, ref., 755; on tri- 
chomonas, ref., 140 
Dock and Warthin, on chloroma, ref., 542 
Doepfner, K., on intestinal diverticula, 
ref., 759 
Doerr, on anaphylaxis, ref., 216 
Doerr and Russ, on anaphylaxis, ref., 216 
Doflein, on protozoa, ref., 133; on Tre- 
ponema pallidum, ref., 309 
Dohle bodies in scarlatina, 340 
Doinikow, B., on regeneration of nerve 
fibers, ref., 1136 
Dolley, D. H., on effects of fatigue on 
neurones, ref., 1138 
v. Domarus, on pseudoleukemic lympho- 
mata, ref., 556; on regeneration of 
blood, ref., 92 
Dominici's solution, 1231 
stain, 1237 
Donath, on sarcoma of esophagus, ref., 
744 
Donath and Landsteiner, on paroxysmal 
hemoglobinuria, ref., 519 
Donovan, C., on Leishmania donovani, 
ref., 139 
Doran, A., on carcinoma of Fallopian 
tubes, ref., 981 
Doty, on quarantine in yellow fever, ref., 
335 
Douglas, J., and Eisenbrey, A. B., on tu- 
berculosis of spleen with polycythemia, 
ref., 575 
Douglas and LeWald, on concretions in 
appendix, ref., 781 
Douglass, on sarcoma of intestine, ref., 
784 
Dowd, C. N., on angioma of spleen, ref., 
580; on cervical tuberculous lymph- 
nodes, ref., 552; on cysts of mesentery, 
ref., 795 
Dracunculus medinensis, 154 
Dragendorff, on poisons, ref., 481 
Dragstedt, L. R., Moorhead, J. J., and 
Burcky, F. W., on autointoxica- 
tion, ref., 483 
Draper, J. W., on autointoxication, ref., 
483 
Draper and Hanford, on experimental 
scarlatina, ref., 340 
Dropsy, 29, 595 
Drosophila, chromosomes of, 79 
Drowning, death from, 504 
Drummond, on diet and tumor growth, 
ref., 373 
Drysdale, on round-cell sarcoma of heart, 
ref., 635 
Ducrey's bacillus, 258 
Duct, thoracic, obstruction of, 658 
Wirsung's, obstruction of, 807 
Wharton's dilatation of, 798 
Duesberg, on plasmosomes, ref., 77 
Duke, W. W., on purpura, ref., 500 
Dum-dum fever, 139 
Dunbar, L. O., on typhoid fever, ref., 274 
v. Dungern, on immunity, ref., 224 
Dunn, on diabetes insipidus, ref., 493 
Dunn, J. S., on adenoma of kidney in 
children, ref., 891; on ganglioneuroma, 
ref., 412; on ganglioneuroma of mes- 
entery, ref., 795; on hypernephroma, 
ref., 892 
Dura mater cerebralis, 1089 
bone in, 1092 
examination, post-mortem, of, 
1192, 1198 
hemorrhage in, 1089 
inflammation of (see Pachymen- 
ingitis), 1090 
structure of, 1089 
syphilis of, 1092 
thrombosis of, 1089 
tuberculosis of, 1092 
tumors of, 1092 
psammoma of, 442 
spinalis, 1103 
bone in, 1104 
hemorrhage of, 1103 
inflammation of (see Pachymen- 
ingitis), 1103 
parasites of, 1104 
tuberculosis of, 1103 
tumors of, 1103 
Durante, on neuroma, ref., 418 
Durham, on mosquito in yellow fever, 
ref., 335 
Dutton and Todd, on tick fever in 
monkeys, ref., 325 
Duval, C. IF., on excitants of scarlatina, 
ref., 340 
Duval and Lewis, on pneumococci, ref., 
249 
Dwarfism, 499, 1042 
Dyrenfurth, F., on rachitis, ref., 1052 INDEX 
1273 
Dysentery (see Colitis), 767 
bacillary, 277 
bacilli of, 278, 770 
Entamoeba histolytica in, 134 
Dysmenorrhea, membranous, 926 
Dyspnea, 9 
Dysthyreosis, 489 
Dystrophia, adiposogenitalis, 497 
Dystrophy, muscular, progressive, 1033 
Ear, internal, examination, post-mortem, 
of, 1198 
middle, relation of, to meningitis, 
ref., 1098 
Eber, A., on animal tuberculosis, ref., 292 
Ebstein, P., on hyperplastic periostitis, 
ref., 1046 
Ecchondroses, 403 
Ecchymoses, 28 
Echinococcus, 147 
cysts, 147 
exogena, 148 
in bladder, urinary, 905 
bone, 1082 
dura mater spinalis, 1104 
ependyma, 1109 
Fallopian tubes, 981 
heart, 635 
hypophysis, 1182a 
jaw, 1082 
kidney, 893 
liver, 840 
muscle, 1041 
pancreas, 807 
peritoneum, 797 
pleura, 729 
prostate, 1029 
spleen, 580 
testicle, 1024 
thyroid, 587 
uterus, 953 
veins, 657 
multilocularis, 148 
scolecipariens, 148 
Eckersdorff, on sarcoma of lung, ref., 721 
Eclampsia, lesions of liver in, 816, 818 
Ecoffey, on benign tumors of veins, ref., 
657 
Ectoparasites, 130 
Ectopia cardis, 358 
Ectopic pregnancy, 982 
Edema, 29 
in nephritis, 30 
Edema, malignant, 323 
of brain, 1120 
glottis, 664 
larynx, 664 
lung, 678 
lymph-nodes, 548 
pia mater cerebralis, 1094 
vulva, 909 
purulent, 229 
Eden, T. W., on placenta, ref., 953 
Eden and Lockyer, on displacements of 
uterus, ref., 922; on gynecology, ref., 
909 
Eder, on action of light, ref., 17 
Edinger, on nervous system, ref., 1129 
Edsall and Ghriskey, on communicability 
of pneumonia, ref., 249 
Eggel, on carcinoma of liver with cirrhosis, 
ref., 837; on malignant adenoma, ref., 
452 
Ehrlich, on carcinosarcoma in mice, ref., 
440; on immunity, ref., 224; side-chain 
hypothesis of, 191 
Ehrlich and Apolant, on transplantation 
of tumors, ref., 389 
Ehrlich and Lazarus, on anemia, ref., 
533 
Ehrlich's hypothesis, application of, to 
cytolysis, 202 
Ehrmann, S., on effect of light on the 
organism, ref., 17 
Eimeria stiedse, 142 
von Eiselsberg, on carcinomata of thyroid, 
ref., 587; on tumors of thyroid, ref., 
587 
Eisenbrey, on lymphosarcoma of in- 
testine, ref., 784 
Eisendrath, D. N., on hydronephrosis, 
ref., 885; on malformation of kidney, 
ref., 851 
Eisendrath and Schultz, on pyelonephritis 
with cystitis, ref., 884 
Eising, on leiomyoma of gastrointestinal 
canal, ref., 421 
Elaterium poisoning, 476 
Elbe, on sublimate poisoning, ref., 475, 
860 
Electosomes, 77 
Electricity, death from, 12 
Elephantiasis neuromatosa, 414 
of penis, 1013 
scrotum, 1013 
vulva, 912 1274 
INDEX 
Eliason, E. L., on foreign bodies in stom- 
ach, ref., 759 
Elliott, C. A., and Kanavel, A. B., on 
hemolytic icterus, ref., 575 
Ellis, A. G., on lipoma of uterus, ref., 
936 
Ellis, E. G., on aneurysms of cerebral 
vessels, ref., 1122 
Elser, on cerebrospinal meningitis, ref., 
256 
Elser and Huntoon, on meningococcus, 
ref., 256; on meningococcus in blood, 
ref., 255 
Elsesser, O. J., on Abderhalden reaction, 
ref., 218 
Elting, on gonorrhea, ref., 251 
Embedding tissues, 1232 
Emboli, 35 
air, 42 
fat, 41, 532 
in lungs, 678 
liver-cell, ref., 36 
parenchyma-cell, ref., 36 
placental-cell, ref., 36 
sources of, 40 
tumor-cell, 42 
Embolism, 35 
effects of, 36 
of brain, 1126 
cerebral arteries, 38 
kidney, 854 
liver, 811 
lung, 679 
muscle, 1038 
spinal cord, 1128 
spleen, 570 
paradoxical, 40 
post-operative, 40 
pulmonary, 38 
retrograde, 40 
Embryomata, cystic, 392, 3-93 
of ovary, 971 
solid, 393 
Emerson, H., on experimental nephritis, 
ref., 880; on pneumothorax, ref., 724; 
on status lymphaticus, ref., 500 
Emery, W. D., on nature and causation of 
tumors, ref., 385 
Emphysema of lung, 681, 683 
interstitial, 683 
senile, 683 
vesicular, 681 
subcutaneous, 321 
Empyema, 228, 725, 726 
Encephalitis, acute, 1155 
chronic, 1163 
interstitial, 1164 
disseminated, 1156 
epidemic, 1157 
hemorrhagic, non-suppurative, 1156 
parenchymatous, ref., 1156 
suppurative, 1156 
Encephalocele, 1110 
Encephalomeningocele, 360 
Enchondroma (see also Chondroma), 403 
of larynx, 668 
lung, 721 
mouth, 733 
pleura, 728 
Endarteritis, 637 
obliterating, 614, 640 
of coronary arteries, 614 
Endemic disease, 185 
Enderlen, on extroversion of bladder, ref., 
896; on regeneration of bone marrow, 
ref., 91 
Endocarditis, 620 
acute, 620 
bacteria in, 622 
chronic, 625 
gonorrheal, ref., 622 
infective, ref., 622 
malignant, 621 
mycotic, 621 
pneumococcus, 622 
stenosis of valves in, 626 
thrombi in, 624 
tuberculous, 626 
ulcerative, acute, 621 
chronic, 626 
malignant, 621 
vegetations in, 621, 624 
verrucous, 621 
Endocardium, 620 
degeneration of, 612 
inflammation of, 620 
Endocervicitis, acute, 932 
chronic, 932 
Endocrine glands, abnormal function of, 
in muscular dystrophy, 1034 
in myasthenia gravis, 1035 
Endometritis, 925 
acute catarrhal, 925 
chronic, 926 
dissecans, 930 
exfoliative, 926 INDEX 
1275 
Endometritis, fungosa, 929 
membranous, 930 
subacute, 930 
syphilitic, 930 
tuberculous, 930 
Endometrium, inflammation of (see 
Endometritis), 925 
menstrual changes in, 926 
polypoid, 929 
Endoparasites, 130 
Endophlebitis, 656 
chronic, 657 
in liver, 814 
Endothelioma, 441 
of bone, 1081 
brain, 1173 
dura mater cerebralis, 1092 
spinalis, 1103 
lymph-nodes, 564 
ovary, 962 
peritoneum, 795 
pia mater cerebralis, 1101 
spinalis, 1105 
pleura, 729 
spinal cord, 1179 
vagina, 917 
Endothelium, ref., 107 
regeneration of, 89 
Endotoxin, 177 
bacterial, 165 
in fever, 502 
Engelhorn, E., on tuberculous salpingitis, 
ref., 980 
Engelken, H., on adenoma of kidney in 
children, ref., 891 
Englander, 8., on diverticula of urethra, 
ref., 906 
Englemann, on sacral tumors and cysts, 
ref., 1112 
Enostoses, 405, 1076 
Entamoeba histolytica, 133 
in colitis, 768 
tetragena, 134 
Enteritis, 764 
acute catarrhal, 764 
chronic catarrhal, 764 
exudative, 765 
follicular, 764 
nodular, 764 
phlegmonous, ref., 765 
pseudomembranous, 765 
streptococcus, ref., 774 
suppurative, 765 
Enteritis, syphilitic, 767 
tuberculous, 765 
Enteroliths, 788 
Enzymes, bacterial, 164 
proteolytic, in disposal of foreign 
bodies, 117, 121 
Eosin-hematoxylin stain for nerve tissue, 
1181 
Eosinophile cells, 522 
Eosinophilia in appendix, 781 
Ependyma, 1105 
cysts of, 1109 
examination of, method of harden- 
ing, 1198 
inflammation of, 1106 
lesions of, 1106 
parasites of, 1109 
tumors of, 1109 
Ependymitis, 1106 
Epicardial nodules, 598 
Epidemic disease, 185 
Epididymis, inflammation of, 1017 
Epididymitis, 1017 
Epiglottis, tumors of, 669 
Epignathus, 367 
Epilepsy, 1114a 
Epiphysis cerebri, lesions of, 1182a 
Epispadias, 359, 1011 
Epistaxis, 28, 661 
Epithelial bodies, 588 
tumors in ventricles, 1109 
Epithelioma, 459, 460 
adamantinum, 448 
differentiation of, from ulcers, 462 
of bronchi, 675 
scrotum, 1014 
squamous-cell, of salivary glands, 
801 
Epithelium, ciliated, of respiratory pas- 
sages, ref., 670 
proliferation of, 95 
regeneration of, 85 
squamous, in other than skin tumors, 
461 
Eppinger, H., on spleen, ref., 566 
Epulides, 1075 
Epulis, 436, 733 
Erb, on thromboangiitis obliterans, ref., 
639 
Erdheim, on histology of thyroid, ref., 584 
Erdheim, J., on tumors of hypophysis, 
ref., 1182 
Erdman, on caisson disease, ref., 19 1276 
INDEX 
van Ermengem, on intestinal bacteria, ref., 
774 
Ernst, P., on cartilaginous tumors, ref., 
402; on malformations of central 
nervous system, ref., 1110; on metas- 
tases in chondromata, ref., 403; on 
psammoma, ref., 1094; on tumors of 
bronchi, ref., 675 
Erysipelas, 240 
of penis, 1013 
vulva, 910 
Erythremia, 518 
Erythroblastoma, 1074 
Erythrocytes (see Blood-cells, red), 518 
Erythrocytoma, 1074 
Erythrocyto-opsonins, 211 
Escher, on rachitis, ref., 1052 
Esophagitis, 743 
catarrhal, 743 
pseudomembranous, 743 
syphilitic, 744 
toxic, 744 
tuberculous, 744 
Esophagus, 742 
abscesses in, 744 
absence of, 742 
cysts of, 745 
dilatation of, 742 
diverticula of, ref., 743 
examination, post-mortem, of, 1211 
foreign bodies in, 743, 744 
hemorrhage in, 742 
inflammation of (see Esophagitis), 
743 
malformations of, 742 
perforation of, 742 
rupture of, 742 
stenosis of, 743, 744 
tuberculosis of, 744 
tumors of, 744 
ulcer of, 744 
varices of, 742 
Esser, J., on circulatory changes in lungs, 
ref., 678 
Esthiomene, 912 
ft tat mamelonne, 748 
Ether poisoning, 479 
Etienne, on tuberculous endocarditis, ref., 
626 
Eustrongyhis gigas in kidney, 896 
visceralis, 151 
Evans, G. H., on chronic peritonitis, ref., 
793 
Evans, Bowman, and Winternitz, on 
tuberculosis, ref., 285 
Eve, on lesions of pancreas, ref., 805 
Ewing, J., on adipocere, ref., 1188; on 
bacteria in smallpox, ref., 337; on 
eclampsia, ref., 818; on epithelial cell 
changes in measles, ref., 342; on gan- 
glion cells, ref., 273, 1136; on hypoleu - 
cocytosis, ref., 527; on lesions of goiter, 
ref., 489; on lymphatic constitution, 
ref., 500, 509; on malarial nephritis, 
ref., 871; on metastasis of tumors, ref., 
381; on sudden death, ref., 509; on 
thymoma, ref., 376; on tumors of testis, 
ref., 1021; on vaccine bodies, ref., 338; 
on bone tumors, ref., 1080 
Ewing and Strauss, on precipitin test for 
blood, ref., 208 
Examination, post-mortem, 1185 
Exner, A., on gonococcal inflammation of 
rectum, ref., 776 
Exophthalmic goiter, 488 
Exophthalmos, 488 
Exostoses, 405, 1076 
Exudates, 30, 103, 228 
in inflammation, 103 
role of, 124 
sterile, method of securing, 223 
Exudation, study of, on frog, 127 
Eye, examination, post-mortem, of, 1198 
glioma of, 408 
Eyre, J. 17. H., on Malta fever, ref., 320 
Eyre and Leathern, on pneumococci, ref., 
249 
Eysell, A., on malaria, ref., 349 
Faber, on arteriosclerosis, ref., 644 
Faber, H. K., on experimental nephritis, 
ref., 880 
Face, lines of embryonic union of, 730 
malformations of, 730 
Falk, on ganglioneuroma, ref., 412 
v. Falkowski, on angioma, ref., 835 
Fallopian tubes, 976 
absence of, 976 
accessory, 976 
actinomycosis of, 981 
closure of, 976 
cysts of, 977, 982 
dilatation of, 976 
ectopic pregnancy, 982 
decidual reaction of, 986 INDEX 
1277 
Fallopian tubes, examination, post-mor- 
tem, of, 1220 
hemorrhage of, 977 
hydrosalpinx, 976 
inflammation of (see Salpingitis), 
977 
malformations of, 976 
malpositions of, 976 
parasites in, 981 
preservation of, 1221 
pyosalpinx, 978 
rupture of, 984 
syphilis of, 981 
tuberculosis of, 980 
tumors of, 981 
Falta, W., on diseases of ductless glands, 
ref., 1045; on ductless glandular dis- 
eases, ref., 483; on pituitary body, ref., 
1179; on senile gangrene, ref., 69 
Faltin, on bacteria of urinary passages, 
ref., 901 
Famine fever, 324 
da Fano, on nervous system, ref., 1136 
F antham, Stephens, and Theobald, on ani- 
mal parasites, ref., 132 
Farcin de boeuf, 262 
Farcy, 256 
Farmer, C. J., on making coilodium sacs, 
ref., 353 
Farmer, Moore, and Walker, on hetero- 
typicalmitoses incancer,ref., 382 
Farrant, R., on thyroid hyperplasia, ref., 
584 
Fasciola hepatica, 144 
in gall-ducts, 841 
veins, 657 
Fasciolopsis buski, 144 
Fat-acid crystals, technique of staining, 
ref., 53 
emboli, 41 
in blood, 532 
stain for, 531 
liver, 819 
muscle, 1035 
necrosis, 71 
-tissue, regeneration of, 91 
tumors of, 401 
Fatigue, effect of, on neurones, 1138 
Fatty degeneration (see Degeneration, 
fatty), 49, 50 
infiltration (see Infiltration, fatty), 
49, 52 
Favus, 172 
Faykiss, on formation of blood-vessels, 
ref., 90 
Federmann, A., on orchitis, ref., 1018 
Fehling, H., on osteomalacia, ref., 1051 
Feldmann, on chordoma of sacrum, ref., 
404 
Felix, W., on malformations of female 
generative organs, ref., 909 
Fenwick, on hair balls in stomach, ref., 
759; on sarcoma of stomach, ref., 755 
Fermentation, bacteria in, 164 
microorganisms in, ref., 169 
Ferments, bacterial, 164 
in leucocytes, 523 
Fetal inclusions, 368 
in tumors, 393 
Fetus acardiacus, 363 
malformations of, 355 
size of, at various periods, 1223 
Fetus infetu, 973 
Fever, 501 
catarrhal, epidemic, 263 
famine, 324 
hospital, 333 
inflammatory, ref., 233 
jail, 333 
Malta, 319 
puerperal, ref., 233, 933 
rat-bite, organism of, 138 
relapsing, 324 
scarlet, 339 
seven-day, 324 
ship, 333 
spirillum, 324 
splenic, 258 
spotted, 333 
Rocky Mountain, 334 
suppurative, ref., 233 
surgical, ref., 233 
tick, 325, 334 
traumatic, ref., 233 
trench, 351 
typhoid, 265 
typhus, 333 
yellow, 334 
Fibrin, 102 
in repair of wounds, ref., 112 
Fibroadenoma, 451 
intracanalicular, 451 
of mamma, 1004 
male, 1030 
pancreas, 806 
pericanalicular, 452 1278 
INDEX 
Fibroblasts, 88, 108 
Fibrocarcinoma, 459 
Fibrochondroma of pharynx, 740 
Fibrocystadenoma of breast, 452 
Fibroglia, ref., 396 
Fibroids, degeneration, sarcomatous, of, 
942 
edematous, 401 
of uterus, 420 
"recurrent," 429 
wandering, 938 
Fibroleiomyoma of veins, 657 
Fibrolipoma, 402 
of pharynx, 740 
Fibroma, 396 
degeneration, mucoid, in, 400 
differential diagnosis of, 398, 421 
durum, 396 
hard, 396 
intracanalicular, of mamma, 995 
metaplasia of, 399 
molle, 396 
molluscum, 398 
multiple, of skin, 398 
of appendix vermiformis, 785 
bladder, urinary, 903 
bone, 1075 
brain, 1176 
bronchi, 675 
dura mater, cerebralis, 1092 
spinalis, 1103 
ependyma, 1109 
esophagus, 744 
Fallopian tubes, 981 
gall-bladder and -ducts, 846 
heart, 634 
intestine, 782 
joints, 1087 
kidney, 890 
larynx, 668 
liver, 836 
lung, 721 
lymph-nodes, 564 
mamma, 995 
male, 1030 
mouth, 733 
muscle, 1041 
nerves, 1180 
ovary, 960 
pancreas, 806 
penis, 1013 
pericardium, 599 
peritoneum, 794 
Fibroma of pharynx, 740 
pia mater cerebralis, 1101 
spinalis, 1105 
pleura, 728 
salivary glands, 798 
scrotum, 1014 
skin, 398 
spinal cord, 1179 
spleen, 580 
stomach, 754 
testicle, 1021 
thyroid, 587 
tongue, 735 
vagina, 916 
vulva, 912 
pericanalicular, of mamma, 997 
soft, 396 
Fibromata nervorum, 414 
Fibromyoma, 419 
differential diagnosis of, 421 
of esophagus, 744 
Fallopian tubes, 981 
uterus, 936, 937 
vagina, 916 
Fibromyxoma of bladder, urinary, 903 
Fibroneuroma of liver, 836 
Fibrosarcoma, 428, 437 
of peritoneum, 795 
salivary glands, 798 
vulva, 912 
ovarii mucucellulare, 971 
Fibrosis, 112 
testis, 1018 
Fick, on endotheliomata, ref., 443 
Ficker, on flies and typhoid fever, ref., 275 
Fiebach, on dermoid cysts of ovary, ref., 
973 
Field, C. W., on excitants of scarlatina, 
ref., 340 
Filaria bancrofti, 154 
in bladder, urinary, 905 
kidney, 893 
lymph-nodes, 565 
medinensis, 154 
sanguinis hominis, 154 
Filarial lymphatic varix, ref., 155 
Findel, on tubercle bacilli, ref., 296 
Finney and Friedenwald, on polypoid 
tumors of stomach, ref., 754 
Finsen, N., on action of ultraviolet light, 
ref., 17 
Finsterer, J., on sarcoma of mamma, ref., 
1006 INDEX 
1279 
Firth, on microorganisms in air, ref., 175 
Fischer, on acromegaly, ref., 1045; on 
adamantinoma of tibia, ref., 448; on 
chorionepithelioma of liver, ref., 839 
Fischer, B., on acromegaly, ref., 497 
Fischer, E., on Mendelian heredity, ref., 
21; on false diverticula of intestine, ref., 
760; on tumors, ref., 467; on tumors of 
bladder, ref., 903 
Fischer and Hooker, on fats and fatty de- 
generation, ref., 49 
Fischer and Zieler, on hemangioma, ref., 
424; on lymphangioma, ref., 424 
Fischl, on fetal infection, ref., 183 
Fischler, on experimental cirrhosis of 
liver, ref., 831 
Fistula, 106 
branchial, 736 
rectovaginal, 915 
vesicovaginal, 914 
Fitz, R. H., on cysts of pancreas, ref., 807; 
on dilatation of colon, ref., 763; on 
lesions of pancreas, ref., 805; on Paget's 
disease of bone, ref., 1050 
Fixateur, 205, ref., 210 
Fixation of complement, 214 
of immune substance, 199 
tissues, 1229 
rapid, 1228 
Flagella, 158 
Flea, rat, 157 
Flebbe, on sarcoma of stomach, ref., 755 
Flechsig, P., on tabes dorsalis, ref., 1150 
Fleischer and Loeb, on experimental myo- 
carditis, ref., 616 
Flemming's osmic acid mixture, 1230 
Flesch and Winternitz, on teratoid tumors 
of thyroid, ref., 587 
Fletcher, H. M., on tuberculous cavities in 
liver, ref., 834 
Flexner, S., on abrin and ricin intoxica- 
tion, ref., 232; on action of light, ref., 
17; on autolysis, ref., 122; on chronic 
interstitial myocarditis, ref., 617; on 
communicability of poliomyelitis, ref., 
333; on connective tissue in cirrhosis of 
liver, ref., 827; on dysentery, ref., 770; 
on dysentery bacillus, ref., 278; on 
endarteritis in cerebrospinal menin- 
gitis, ref., 638; on epidemic meningitis, 
ref., 256; on experimental meningitis, 
ref., 255; on experimental pancreatitis, 
ref., 805; on fatty degeneration of 
heart, ref., 612; on focal necrosis of 
liver, ref., 815; on focal necroses in 
typhoid fever, ref., 271; on lesions of 
plague, ref., 320; on peritonitis, ref., 
791; on pneumonia of bubonic plague, 
ref., 696; on serum therapy in menin- 
gitis, ref., 256; on specific therapy of in- 
fections, ref., 225; on terminal infec- 
tion, ref., 183; on thrombi, ref., 33; on 
toxalbumin intoxication, ref., 179, 232; 
on tuberculous esophagitis, ref., 744; on 
typhoid bacilli in heart, ref., 274 
Flexner and Amoss, on anterior polio- 
myelitis, ref., 332 
Flexner and Anderson, on diphtheria 
bacilli in lungs, ref., 315 
Flexner and Jobling, on serum therapy in 
meningitis, ref., 256 
Flexner and Lewis, on anterior polio- 
myelitis, ref., 331 
Flexner and Noguchi, on anterior polio- 
myelitis, ref., 332; on snake venom, 
ref., 480 
Flexner, Noguchi, and Amoss, on anterior 
poliomyelitis, ref., 332 
Flexner and Pearce, on experimental pan- 
creatitis, ref., 805 
Flexner and Sweet, on experimental 
colitis, ref., 770 
Flies, as carriers of typhoid, ref., 275 
Flockemann, on pulmonary syphilis, ref., 
721 
Flugge, on distribution of tubercle bacilli, 
ref., 298 
Flukes, 144 
Fluss, K., on polyps of urethra, ref., 908 
Focal necrosis, 69, 232 
in liver in typhoid fever, 271 
Fontaine, Hasse, and Mitchell, on blasto- 
mycosis, ref., 171 
Food poisoning, 324, 481 
Ford, on bacteria of body surfaces, ref., 
175; on intestinal bacteria, ref., 774 
Fordyce, J. A., on pathology of syphilis, 
ref., 648 
Foreign-body tubercles, 118 
Foreign bodies, injuries from, 18 
substances, disposal of, in body, 114 
experimental study of, 126 
Formaldehyde as tissue fixative, 1229 
Forman and Warren, on myeloma, ref., 
431 
Forni, on fibroma of pericardium, ref., 599 1280 
INDEX 
Forssner, H., on carcinosarcoma of uterus, 
ref., 942 
Forsyth, on Haffkine method in plague, 
ref., 321 
Foster, E. and Lewy, F. H., on paralysis 
agitans, ref., 1168 
Foster, L. S., on senile changes in aorta, 
ref., 644 
Fothergill, W. E., on endometritis, ref., 
930 
Fowler, H. A., on renal calculi, ref., 890; 
on syphilis of bladder, ref., 903 
Fractures, post-mortem, 1190 
Fraenkel, E., on Aschoff bodies, ref., 619; 
on diagnosis of malignant tumors of 
lung, ref., 723; on giant-cell sarcoma of 
heart, ref., 635; on osteotabesinfantum, 
ref., 1055; on pseudomyxoma peritonei, 
ref., 797; on tumors of pleura, ref., 
729 
Fragilitas ossium, 1043 
Fraikin, on lipoma of muscle, ref., 1041 
Framboesia tropica, 326 
Franckel, on melanosarcoma of thyroid, 
ref., 587 
Frank, A., on plasmocytoma, ref., 431; on 
tumors of testis, ref., 1022 
Frank, R. T., on chorionepithelioma, ref., 
949, 952, 956; on chorionepithelioma of 
testis, ref., 1024; on placental extracts, 
ref., 95; on thyroid tissue in ovary, ref., 
973; on gynecological pathology, ref., 
909 
Frankel, B., on carcinoma of larynx, ref., 
666; on pulmonary embolism, ref., 40 
Frankl, O., on myoma of uterus, ref., 937 
v. Franque, O., on uterine polyps, ref., 937 
Fraser, A., on hypernephroma, ref., 892; 
on liver in chloroform anesthesia, ref., 
816 
Fraser, J., on human and bovine tuber- 
culosis of bone, ref., 1065; on tubercu- 
lous osteitis, ref., 1065; on types of B. 
tuberculosis, ref., 299 
Frazier, on cysts of mesentery, ref., 795 
Freeborn, on picro-acid-fuchsin stain, ref., 
1236 
Freeman, R. G., on focal necrosis in 
measles, ref., 342; on fatty infiltration 
of liver in children, ref., 820; on oysters 
and typhoid fever, ref., 275; on vac- 
cination, ref., 339 
Freifeld, on neuroblastoma, ref., 409 
French and Boycott, on Trichocephalus 
dispar, ref., 153 
Freund, on ganglioneuroma, ref., 411 
Frieberger and Frohner, on infectious dis- 
eases of animals, ref., 353 
Friedemann, on anaphylaxis, ref., 216 
Friedenwald, J., on chronic ulcers of 
stomach, ref., 753 
Friedlander bacillus, 245, 692 
Friedman, G. A., and Katz, E., on hemo- 
lytic icterus, ref., 575 
Friedmann, F., on tonsils as portals of 
entry for tubercle bacilli, ref., 
740 
Friedreich's ataxia, 1154 
Friedreich, N., on hereditary ataxia, ref., 
1154 
Friend, on chyle cysts of mesentery, ref., 
795 
Frissell, on acute rheumatism, ref., 351 
Frog, circulation of, 42 
study of inflammation in, 127 
Frost, on anterior poliomyelitis, ref., 
333 
Frost-bite, degrees of, 11 
Frothingham, on demonstration of Negri 
bodies, ref., 329 
Frothingham, C., on arterial lesions, ref., 
638; on arteriosclerosis, ref., 645 
Frozen sections of tissues, method of 
making, 1227 
stains for, 1228 
Fuerst, on giant cells, ref., 119 
Fujinami, A., on regeneration of cartilage 
and bone, ref., 91; on rhabdomyoma, 
ref., 422; on tumors of muscle, ref., 
1041 
Fulleborn, on filaria, ref., 155 
Fullerton, on pathogenic blastomycetes, 
ref., 171 
Fungus, favus, 172 
fission, 158 
mould, 158, 171 
poisoning, 477 
ray, 262 
yeast, 158, 169 
Funk, on cysts of mesentery, ref., 795; on 
vitamines, ref., 496 
v. Furth, O., on physiological chemistry, 
ref., 4 
Furuncle, 228 
Futaki, Takaki, Taniguchi, and Osumi, on 
rat-bite fever, ref., 138 INDEX 
1281 
Futh, on epulis, ref., 733 
Fiitterer, on squamous-cell carcinoma of 
stomach, ref., 758 
Gabell, James, and Payne, on odontoma, 
ref., 406 
Gade, on multiple carcinomata, ref., 454 
Gage and Hunt, on ileocecal tuberculosis, 
ref., 776 
Gallaverdin, L., on stricture of intestine, 
ref., 763 
Gall-bladder, bacteria in, 844 
calculi of, 847 
dilatation of, 846 
examination, post-mortem, of, 1216 
inflammation of, 842, 843 
lesions of, 842 
perforation of, 842 
rupture of, 842 
tuberculosis of, 844 
tumors of, 846 
Gall-ducts, abscess of, 843, 844 
bacteria in, 843 
calculi of, 847 
constriction of, 845 
dilatation of, 845 
examination, post-mortem, of, 1216 
inflammation of, 842, 843 
lesions of, 842 
new-formed, in cirrhosis of liver, 
827 
occlusion of, 842, 845 
tuberculosis of, 844 
tumors, of, 846 
Gall-stones, 847 
composition of, 847 
in pancreatic duct, 807 
role of microorganisms in, 848 
Gamboge poisoning, 476 
Ganglia, 1087 
Ganglioma of uterus, 942 
Ganglioglioneuroma, 412 
Ganglioneuroma, 411, 418 
of peritoneum, 795 
Gangrene, 68 
dry, 69 
emphysematous, 322 
hospital, 910 
in arteritis, 639, 642 
moist, 69 
of appendix vermiformis, 778 
lung, 683 
Gangrene of pancreas, 805 
vagina, 916 
vulva, 910 
senile, ref., 69 
Gappisch, on actinomyces-like structures 
in tonsillar crypts, ref., 739 
Garrod, A. E., on metabolism, ref., 21 
Gas bacillus, 321 
chlorine, 472 
cysts in brain, 1177 
intestine, 785 
formation, B. aerogenes in, 322 
post-mortem, 1187 
in bladder, urinary, 901 
blood, 42 
pericardium, 595 
mustard, 472 
poisoning, 472, 480 
illuminating, degeneration of nerv- 
ous system in, 1169 
Gaskell, J. F., on changes in glomeruli and 
arteries, ref., 872; on hemorrhagic focal 
glomerulo-nephritis, ref., 867 
Gasserian ganglion, tumor of, 409,1164 
Gastritis, 747 
acute catarrhal, 747 
chronic, 748 
croupous, 749 
diphtheritic, 749 
exudative, 749 
membranous, 749 
phlegmonous, 749 
suppurative, 749 
syphilitic, 750 
toxic, 750 
tuberculous, 750 
Gaucher's splenomegaly, 544, 576 
Gay, on artificial immunization, ref., 220; 
on complement fixation, ref., 209; on 
typhoid carriers, ref., 275; on typhoid 
fever, ref., 274. 277 
Gay and Southard, on anaphylaxis, ref., 
216 
Gaylord, H. R., on giant-cell sarcoma, ref., 
434; on fibrin in pleurisy, ref., 725 
Gebhard, C , on chondrosarcoma of uterus, 
ref., 942; on gynecology, ref., 909 
Geisse, on staphylococci, ref., 237 
Geissler, on tuberculosis of arteries, ref., 
646 
Gellhorn, G., on hypernephroma of 
vagina, ref., 917 
Gemmules, 1131 1282 
INDEX 
Genitourinary organs, examination, post- 
mortem, of, female, 1219, 
1226 
male, 1218, 1226 
female, 909 
male, 1011 
Geographic tongue, 732 
Germicides, 163 
Gerulanos, on dermoid tumor of penis, 
ref., 1013 
Gettler, A. O., andSt.George, A. V., on wood 
alcohol poisoning, ref., 478 
Ghon and Hintz, on leiomyoma of gas- 
trointestinal canal, ref., 421; on tumors 
of muscle, ref., 1040 
Ghon and Sachs, on B. aerogenes capsula- 
tus, ref., 323 
Giannettasio, on umbilical tumors, ref., 759 
Giant cells, 118 
foreign body, 434 
in carcinoma, 456 
in sarcoma, 434 
stellate bodies in, 119 
Gibson, R. B., on fever, ref., 502 
Giemsa, G., on stain for blood, ref., 350; 
on stain for blood and tissues, ref., 
1237 
Giemsa's stain for blood and tissues, 1237 
von Gierke, E., on carcinoma of thyroid, 
ref., 586; on glycogen infiltration, ref., 
53; on oxidase reaction in muscle fibers, 
ref., 1031 
Giffin, H. Z., on hemolytic icterus, ref., 
575 
Gigantism, 498, 1045 
Gigantoblasts, 521 
Gilbert and Lippmann, on gall-bladder 
infections, ref.. 844 
Gilbert and Villaret, on dilatation of veins 
of abdominal wall, ref., 828 
Gilbert and Weinberg, on blood examina- 
tion, ref., 1227 
Gilchrist, on blastomycotic dermatitis, 
ref., 171; on multiple fibromata, ref., 
398 
Gilchrist and Stokes, on Cryptococcus 
dermatidis, ref., 170 
Gilman, on dermoid tumors of mouth, 
ref., 734 
Glaister and Logan, on carbon monoxide 
poisoning, ref., 480 
Gland, pineal, lesions of, 1182 
structure of, 1182 
Glanders, 256 
diagnosis of, 258 
of testicle, 1021 
Glands, Cowper's, lesions of, 1029 
mammary, regeneration of, 86 
salivary, regeneration of, 86 
Glas, on abnormalities of larynx, ref., 664; 
on cysts of larynx, ref., 669 
Glegg, on hay fever, ref., 662 
Glia, structure of, 406 
Glinski, on mixed tumors of esophagus, 
ref., 744 
Glioma, 406 
malignant, 440 
of brain, 1177 
ependyma, 1109 
pineal gland, 1182a 
spinal cord, 1179 
telangiectatic, of brain, 1173 
Gliosarcoma, 440 
of brain, 1173 
Glockner, on endothelioma of pleura, ref., 
729 
Glomeruli, lesions of, in nephritis, 866 
Glomerulonephritis, 867 
Glomset, on Dbhle bodies in scarlatina, 
ref., 340 
Glossina morsitans, 136, 137 
palpalis, 137 
Glossitis, 735 
Glottis, edema of, 664 
Gluge's corpuscles, 1127, 1157 
Glycogen, infiltration, 53 
in rhabdomyoma, 421 
paraganglioma, 413 
stains for, 53, 1239 
Glycosuria, 491, ref., 492 
Glynn, E. E., on adrenal function, ref., 
589; on hypernephroma, ref., 892 
Goebel, C., on lipomata of pharynx and 
larynx, ref., 740; on tumors and cysts 
of jaw, ref., 1082 
Goetsch, E., on atrophy of uterus, ref., 
924 
Goetsch, W., on rachitis, ref., 1052 
Goetze, on multiple carcinomata, ref., 454 
Goiter (see Struma), 584 
and carcinoma, 586 
exophthalmic, 488 
metabolism in, ref., 489 
Goldberger, on mosquito in yellow' fever, 
ref., 335; on pellagra, ref., 496 
"Golden" coccus, 235 INDEX 
1283 
Goldmann, E. E., on transplantation of 
tumors into spleen, ref., 580 
Goldzieher and v. Bokay, on carcinoma of 
liver, ref., 837 
Gonorrhea, 251 
complement fixation test in, 253 
in vulva, 910 
Gonococcus (see Micrococcus gonor- 
rhoeae), 251 
peritonitis, ref., 791 
Goodpasture, E. W., on mitochondria in 
tumors, ref., 380; on stain for frozen 
sections, ref., 1228 
Goodridge, M., on air embolism, ref., 42 
Goodwin, G. M., on corrosive sublimate 
poisoning, ref., 863 
Goodwin and v. Sholly, on meningococcus, 
ref., 256 
Goose-skin, 505 
Gordinier, H. C., on paralysis agitans, ref., 
1168 
Goto, S., on myositis ossificans, ref., 1039 
Gottstein, A., on microorganisms in air, 
ref., 175 
Gougerot, H., on yeasts and moulds in dis- 
ease, ref., 173 
Gout, 493 
joint lesions in, 1085 
Gowers, tract of, 1141 
Graef, on trauma and formation of malig- 
nant tumors, ref., 386 
Graf, on traumatic cysts of pancreas, ref., 
807 
Graf, E., on periarteritis nodosa, ref., 646 
Grafenberg, E., on chorionepithelioma of 
vulva, 913 
Graham, E. A., on acute yellow atrophy 
of liver in children, ref., 818; on dis- 
placements of liver, ref., 808; on hem- 
orrhagic disease, ref., 29; on tumors of 
Bartholin's glands, ref., 913 
Graham-Smith, on flies and typhoid fever, 
ref., 275; on flies in relation to disease, 
ref., 176; on precipitin test for blood, 
ref., 208; on xerosis bacillus, ref., 317 
Grandhomme, on tumors of mediastinum, 
ref., 376 
Granulation tissue, 108 
in wound infection, ref., 177 
Granulations, 108 
exuberant, 111 
Granuloma, coccidioidal, 169 
infectious, ref., 282, 396 
Gramuloma, infectious, differential diag- 
nosis of, 391 
of tongue, 736 
Graves' disease, 488 
Graves, S., on Wassermann reaction, ref., 
312 
Grawitz, P., on hypernephroma, ref., 892 
Greeff, on trachoma, ref., 341 
Greenough, R. B., on malignancy in tu- 
mors, ref., 380; on metastasis of tumors, 
ref., 381 
Greenough, R. B., and Hartwell, H. F., on 
cystadenoma of mamma, ref., 993; on 
fibrocystadenoma, ref., 452 
Greenough and Simmons, on hemorrhage 
from nipple, ref., 990 
Gregarinida, 142 
Griffith, on aneurysm of coronary arteries, 
ref., 652; on carcinoma of liver in chil- 
dren, ref., 837; on glioma, ref., 408 
Griffith, A. S., on human and bovine tu- 
berculosis of bone, ref., 1065 
Griffith, J. P. C., on dilatation of colon, 
ref.. 763; on Meckel's diverticulum, 
ref., 759 
Grober, on infection of pleura, ref., 727; 
on pleura as portal of entry for bac- 
teria, ref., 698 
Grondahl, N. B., on fat emboli of brain, 
ref., 42 
Gronemann, on paraganglioma of carotid, 
ref., 413 
Grosser, on fissures in cervical region, ref., 
736 
Ground itch, 152 
Grover, A. L., on experimental cirrhosis of 
liver, ref., 831 
Gruber, on bone formation in muscle, ref., 
1040; on duodenal ulcers, ref., 767; on 
syphilitic arteritis, ref., 647 
Grvlee, on angioma of parotid in children, 
ref., 801 
Grunert, on atrophy of bones, ref.. 1051 
Guarnieri, on smallpox, 338 
Guillain, G., and Barre, J. A., on shell 
shock, ref., 1121 
Guinea worm, 154 
Guiteras, on mosquito in yellow fever, ref., 
335 
Guldner, E., on periarteritis nodosa, ref., 
646 
Gull and Sutton, on arteriosclerosis, ref., 
639 1284 
INDEX 
Gumma, 306 
in brain, 1171 
dura mater cerebralis, 1092 
heart, 619 
liver, 831 
pia mater cerebralis, 1101 
vulva, 911 
Gums, tumors of, 436 
Gunn, L. G., on carcinoma of prostate, 
ref., 1029 
Gurd, F. B., on gonorrheal salpingitis, ref., 
978 
Gussio, on tumors of parathyroid, ref., 
588 
Guyer, on cell division, ref., 80 
Guyot, G., on formation of lymph-vessels 
in pleurisy, ref., 727 
Gwyn, on typhoid bacillus, ref., 274 
Gynecomastia, 987, 988 
Haaland, on carcinosarcoma, ref., 389; on 
carcinosarcoma in mice, ref., 440 
Haasler, on regeneration of bone-marrow, 
ref., 91 
v. Haberer, H., on angioma of salivary 
glands, ref., 801; on osteitis fibrosa, 
ref., 1049 
v. Hacker, on sarcoma of esophagus, ref., 
744 
Hada, on melanin, ref., 432 
Hadley, on chyle cysts of mesentery, ref., 
795 
Haemosporidia. 143 
Haffkine, on preventive inoculation in 
cholera, 281; on preventive inoculation 
in plague, 321 
Hagedorn, on cardiac tumors, ref., 634; 
on tumors of the heart, ref., 634 
Hagen, W., on sacral tumors and cysts, 
ref., 1112 
Haldsz, on sarcoma of pancreas, ref., 806 
Halberstaedter, on radium, ref., 13 
Halberstaedter and v. Prowazek, on tra- 
choma, ref., 341 
Haldane and Smith, on determination of 
amount of blood in body, ref., 
518 
Halisteresis, 1050, 1051 
Hall, on fibromyomata of esophagus, ref., 
744 
Hall, J. N., on lesions of bronchial lymph- 
nodes, ref., 676 
Hall, M. E., on metastatic carcinoma of 
ovary, ref., 971 
Halle, N., and Motz, B., on tuberculosis 
of prostate, ref., 1028 
Halstead, A. E., and Le Count, E. R., on 
tuberculous inflammation of 
mamma, ref., 993 
Halsted, W. S., on compensatory hyper- 
trophy, ref., 74; on regeneration of thy- 
roid gland, ref., 86 
Hamartoma, 424 
Hamburger, W. W., on sporotrichosis, ref., 
173 
Hamilton, A., on poisoning by nitric acid 
fumes, ref., 471; on tetrachlorethane 
poisoning, ref., 479; on trinitrotoluene 
poisoning, ref., 477 
Hamilton, A. S., on rupture of heart, ref., 
604 
Hamilton and Horton, on pseudodiph- 
theria bacilli, ref., 317 
Hammer, J., on accessory lung, ref., 676 
Hammarsten, on physiological chemistry, 
ref., 4 
Hammerschlag, R., on regeneration of 
lymph-nodes, ref., 546; on regeneration 
of lymph-nodes and lymph-vessels, ref., 
91 
Hammes, E. M., on tests in cerebral syphi- 
lis, ref., 1176 
Hand, on tuberculosis of lymph-nodes, 
ref., 676 
Handley, IF. S., on cancer of mamma, 
ref., 1008; on lymphatic permeation in 
cancer, ref., 454; on Paget's disease of 
nipple, ref., 1010 
Handmann, E., on weight of brain, ref., 
1193 
Hanging, death from, 504 
Hansell, on glioma, ref., 408 
v. Hansemann, on acute diverticulitis, 
ref., 760; on anaplasia, ref., 374; on 
blastomycetes in brain cysts, ref., 1109; 
on civilization and cancer, ref., 387; on 
cystite en plaque, ref., 901; on function 
of tumor cells, ref., 373; on malignant 
adenoma, ref., 452; on malignant 
adenoma of liver, ref., 837; on malig- 
nant tumors, ref., 468; on metastasis of 
tumors in spleen, ref., 379; on mitoses 
in tumor cells, ref., 384; on mixed 
tumors of salivary glands, ref., 801; 
on multiple carcinomata, ref., 454; INDEX 
1285 
on perithelial sarcoma, ref., 438; on 
tumor origin, ref., 384 
v. Hansemann's hypothesis of origin of 
tumors, 384 
Hansen, on lepra bacilli, ref., 303 
Hanser, on echinococcus cysts of pan- 
creas, ref., 807; on myxoma of heart, 
ref., 634 
Hanssen, on amyloid degeneration, ref., 
59 
Hanusa, on spermatocele, ref., 1016 
Hanzlik and Karsner, on salicylate poi- 
soning, ref., 857 
Haptines, ref., 195 
Haptophorous group, 193 
Harberer, on bone cysts, ref., 1081 
Harbitz, on lesions of bronchial lymph- 
nodes, ref., 676; on neurofibromatosis, 
ref., 414; on paraganglioma, ref., 413; 
on tuberculosis of lymph-nodes, ref., 
298; on tuberculous lymph-nodes in 
children, ref., 553; on tumors of para- 
thyroid, ref., 588 
Harbitz and Grbndahl, on actinomycosis of 
intestine, ref., 775 
Harbitz and Platou, on age distribution of 
sarcoma, ref., 427 
Hare, H. A., on air embolism, ref., 42; 
on tumors of mediastinum, ref., 723 
Hare and Beardsley, on medical compli- 
cations of typhoid fever, ref., 274 
Harelip, 356 
Harrigan, on lipoma of intestine, ref., 782 
Harris, on cysts of ureter, ref., 890 
Harris, F. I. and Hoyt, H. S., on toxic 
action of ultraviolet rays on living cells, 
ref., 18 
Harrison, Lambert, and Burrows, on 
technique of tissue culture, ref., 96 
Hart, on epithelial tumors of ependyma, 
ref., 1109 
Hartmann, on post-mortem cyst forma- 
tion, ref., 1178 
Hartz, on sarcoma of stomach, ref., 755 
Hasenfeld, on hypertrophy of heart, ref., 
633 
Hassel, on dermoid tumors, ref., 734 
Hassin, on meningeal carcinoma, ref., 
1092 
Hasslauer, on bacteria of nose, ref., 662; 
on tumors of nasal septum, ref., 664 
Hastings, Halpin, and Beach, on avian 
tuberculosis, ref., 292 
Hauser, G., on carcinoma of stomach, ref., 
758; on chronic ulcers of stomach, ref., 
753; on fibrin formation, ref., 102; on 
growth of cancer, ref., 457; on malig- 
nant polyps, ref., 445; on tumor origin, 
ref., 384; on tumors of intestine, ref., 
783 
Hauser's hypothesis of origin of tumors, 
384 
Hausmann,, W., on sensibility to light of 
animals and plants, ref., 17 
Haussling and Martland, on giant-cell 
sarcoma, ref., 436 
Hawk, P. B., on polycythemia, ref., 
517 
Hay bacillus, 300 
fever, 661, ref., 662 
Hayem's solution, formula for, 530 
Hay thorn, S. R., on pulmonary anthra- 
cosis, ref., 703; on tuberculous aortitis, 
ref., 646 - 
Head and Ham, on regeneration of nerve 
fibers, ref., 1136 
Head, examination, post-mortem, of, 
1191, 1224 
louse, 156 
Healing by first intention, 98 
second intention, 110 
of wounds, 107 
Heart, 600 
abnormalities of, 600, 603 
abscess of, 616 
absence of, 602 
action, irregular, 627 
aneurysm of, 606, ref., 652 
angina pectoris, 618 
aorta, malformations of, 600 
atrophy of, 606 
auriculoventricular node, 627 
beat, cause of, 626 
block, 626 
calcification of, 612 
clots, 608, 1205 
conducting system, 627 
degeneration of, 610 
dilatation of, 628, 633 
displacement of, 603 
embolism of, 615 
endocardium, degeneration of, 612 
inflammation of (see Endocardi- 
tis), 620 
examination, post-mortem, of, 1204, 
1225 1286 
INDEX 
Heart, hyperplasia of, fibrous, 618 
replacement, 617 
hypertrophy of, 628, 632, 633 
hypoplasia of, 603 
infarction of, 38 
infiltration, fatty, of, 613 
inflammation of (see Myocarditis 
and Endocarditis), 615, 620 
insufficiency of, 631 
malformations of, 600 
malpositions of, 600, 603 
muscle, fatty degeneration of, 611 
relation of, to circulation, 22 
myocardium, inflammation of (see 
Myocarditis), 615 
segmentation and fragmentation 
of, 613 
parasites in, 635 
pigment in, 606 
polypi, 608 
position of, 1204 
preservation of, 1209 
reptilian, 600 
rupture of, 604 
sinoauricular node, 627 
stenosis of, 631 
Stokes-Adams disease, 628 
sudden death in lesions of, ref., 605 
syphilis of, 619 
thrombosis of, 608 
tuberculosis of, 619, 626 
tumors of, 634 
valves, aneurysm of, 607 
aortic, insufficiency of, 630 
stenosis of, 631 
changes in, 22 
insufficiency of, 630, 631 
lesions of, 630 
malformations of, 600 
mitral, insufficiency of, 631 
stenosis of, 631 
pulmonary, lesions of, 631 
size of, 1205 
stenosis of, 630, 631 
sufficiency of, test, post-mortem, 
of, 1205 
tricuspid, lesions of, 631 
vegetations, 608 
ventricles, left, hypertrophy of, 632, 
633 
right, hypertrophy of, 632, 633 
weight of, 1209 
in new-born, 1225 
Heart, wounds of, 603 
"Heart failure" cells, 64 
Heat, damage from, 10 
exhaustion, 494 
Heazlit, L., on hair balls in stomach, ref., 
759; on osteosarcoma and Paget's dis- 
ease, ref., 437 
Hecht, on bronchopneumonia, ref., 693 
Hedinger, on sarcoma of thyroid, ref., 
587 
Hedren, G., on mixed tumors of kidney, 
ref., 891 
Heiberg, on cysts of pancreas, ref., 807; 
on tumors of pancreas, ref., 806 
Heidenhain, on mitosis, ref., 78; on 
structure of muscle fiber, ref., 1031 
Heidenhain's iron hematoxylin, 1236 
Heineke, A., on sublimate poisoning, ref., 
857 
Heineke, on lesions of salivary glands, 
ref., 798 
Heine-Medin's disease, 1159 
Heinz, R., on inflammation, ref., 126; 
on origin of fibrin in pleurisy, ref., 725; 
on phagocytic power of liver endothe- 
lium, ref., 822; on physiology of blood- 
vessels, ref., 643; on physiology of heart, 
ref., 628; on physiology of lungs, ref., 
687 
Heist, Solis-Cohen, and Kolmer, on ante- 
rior poliomyelitis, ref., 333 
Hektoen, L., on antibody formation, 201; 
on aortic aneurysm, ref., 652; on 
bacteriology of measles, ref., 342; 
on cardiac anomalies, ref., 602; on 
changes in myocardium, ref., 614; 
on endarteritis in tuberculosis, ref., 
638; on factors in recovery from 
pneumonic infection, ref., 250; on 
giant cells, ref., 119; on hemophago- 
cytosis, ref., 223; on immunity, ref., 
225; on infectious diseases of unknown 
origin, ref., 353; on opsonins, ref., 
211, 213; on phagocytosis of anthrax 
bacilli, ref., 260; on precipitin test for 
blood, ref., 208 
Hektoen and Curtis, on antibody forma- 
tion, ref., 201 
Hektoen and Herrick, on secondary sar- 
coma of liver, ref., 839 
Hektoen, L., and Perkins, C. F., on sporo- 
trichosis, ref., 173; on yeasts and moulds 
in disease, ref., 173 INDEX 
1287 
Hektoen, Mathers, and Jackson, on ante- 
rior poliomyelitis, ref., 332 
Held, H., on neurogliocytes, ref., 409 
Hellebore poisoning, 476 
Hellendall, on retropharyngeal tumors, 
ref., 740 
Heller, on colloid tumors of tongue, ref., 
735; on Hirschsprung's disease, ref., 
763; on pleural lymph-nodes, ref., 
685 
Heller, G., on removal of viscera, post- 
mortem, ref., 1190 
Heller and Lepere, on B. pyocyaneus, ref., 
244 
Hellman, A. M., on fibroma of ovary, 
ref., 960 
Helly, on exudate cells, ref., 105; on 
blood-forming organs, ref., 533 
Helly's fluid, 1231 
Helmholtz, on adenoma of pancreas, ref., 
806 
Hemagglutinins, 206 
Hemangioendothelioma, 443 
Hemangioma, 423 
differential diagnosis of, 425 
of dura mater cerebralis, 1092 
heart, 634 
intestine, 782 
pericardium, 599 
spleen, 580 
Hematemesis, 28, 746 
Hematocele, 1016 
Hematogenesis, defective, 519 
Hematoidin, 64, 519 
Hematolysis, 519 
Hematoma, 28 
of pia mater cerebralis, 1101 
umbilical cord, 797 
Hematometra, 920 
Hematomyelia, 1125, 1126 
Hematomyelopore, 1126 
Hematoporphyrin, effect of, 17 
Hematoxylin stains, 1235, 1236 
Hematozoon of Texas fever, 143 
Hematuria, 28, 855 
essential, 855 
Hemicephalia, 359 
Hemochromatosis, 65, 830 
Hemoglobin index, 537 
Hemoglobinemia, 516, 519 
Hemoglobinuria, 519 
of cattle, 143 
Hemolymph-nodes, 546 
Hemolymph-nodes, compensatory hyper- 
trophy of, ref. 87 
examination, post-mortem, of, 1218 
Hemolysins, 197 
bacterial, ref., 179 
tests for, 531 
Hemolysis, 64, 198 
test, technique of, 222 
Hemopericardium, 595 
Hemophagocytosis, 223 
Hemophilia, 29 
Hem opsonins, 211 
Hemoptysis, 28 
Hemorrhage, 27 
by diapedesis, 27 
rhexis, 27 
capillary, in brain, 1120 
forms of, 28 
in new-born, 29 
Hemorrhagic diathesis, 29 
infarction, 28 
septicemia, 321 
Hemorrhoids, 654, 777 
urethral, 908 
vesical, 898 
Hemosiderin, 64, 519 
Hemosporidia of malaria, 344 
Hemothorax, 724 
Hemotoxins, 197 
Henderson, Y., on carbon monoxide 
poisoning, ref., 480; on reaction of 
blood, ref., 516 
Henke, on neuroma, ref., 419; on tumors, 
ref., 468 
Henkel, M., on gynecology, ref., 909 
Henle, loop of, 850 
Henrid, on malignant growths of lung, 
ref., 722 
Hepatitis, 822 
acute exudative, 822 
interstitial, chronic (see Liver, cir- 
rhosis of), 825 
peri-, 834 
purulent, 822 
syphilitic, 831 
tuberculous, 832 
Hepatization, gray, of lung, 689 
red, of lung, 687 
Hepatoma, 376 
atypical hemorrhagic malignant, of 
liver, 839 
Herb, I. C., on acute parotitis, ref., 
798 1288 
INDEX 
Heredity in etiology of cancer, 387 
relation of, to disease, 21 
Hermann, on tuberculosis and carci- 
noma of lung, ref., 723; on squamous- 
cell cancer of lung, ref., 722 
Hermaphroditism, 1011 
pseudo-, 1011 
true, 1011 
Hernia intestinovaginalis, 914 
of bladder, urinary, 897 
brain, 1110 
intestine, 762 
ovary, 957 
uterine, 923 
Herpes of prepuce, 1013 
tonsurans, 172 
Herrick, on Ascaris lumbricoides, ref., 150 
Herrick, F. C., on portal pressure in 
cirrhosis, ref., 828 
Herrick, W. W., and Janeway, T. C., on 
Trichinella spiralis, ref., 153 
Herring, P. T., on glomeruli, ref., 866 
Herrmann, on lipoid substance in adrenal, 
ref., 589 
Herter, C. A., on endogenous poisons, 
ref., 482; on infantilism, ref., 1043 
Hertwig, O., on radium biology and 
therapy, ref., 13 
Herweg, on tumors of umbilical cord, ref., 
797 
Herzheimer, G., on adenocarcinoma of 
liver, ref., 837; on adrenal tumors, ref., 
591; on carcinoma of gall-bladder, 
ref., 846; on carcinoma of liver, ref., 
837; on carcinoma of pancreas, ref., 
806; on carcinosarcoma, ref., 440; 
on carcinosarcoma of esophagus, ref., 
744; on malformations of heart, ref., 
600; on neuroblastoma, ref., 409; on 
paraganglioma, ref., 413; on squamous 
epithelium, ref., 462; on syphilis, ref., 
308; on syphilitic ulceration of rectum, 
ref., 776; on tuberculosis, ref., 284 
Herzheimer and Reinke, on tumors, ref., 
467 
Herzheimer and Roth, on tuberculosis, 
ref., 284 
Herzheimer and Schmidt, on Dercum's 
disease, ref., 401; on lymphangioma, 
ref., 424 
Herz, on acute myelogenous leukemia, 
ref., 540 
Herzog, on carcinosarcoma of esophagus, 
ref., 744; on insects as plague carriers, 
ref., 321; on mesothelioma of peri- 
toneum, ref., 795 
Hess, A., on obliteration of gall-ducts, 
ref., 801 
Hess, A. F., on lesions of hepatic veins, 
ref., 828 
Hess, O., on regeneration of liver, ref., 86; 
on cysts, ref., 396 
Hesse, O., on carcinoma following x-ray 
burns, ref., 14 
Heterotopia, 404, 1111 
false, 1112 
Heterotransplantation of tissues, 388 
Hetsch, on inoculation against Asiatic 
cholera, ref., 281 
Hetzel, on melanosarcoma of liver, ref., 
839 
Heubner, O., on osteotabes infantum, ref., 
1055 
Hewitt, on necrosis of renal epithelium, 
ref., 857 
Heymann, on tumors of trachea, ref., 669 
Higbee, W. S., and Ellis, A. G., on Paget's 
disease of bone, ref., 1050 
Higgins, W. H., on poisoning by bismuth 
subnitrate, ref., 473 
Hill, on caisson sickness, ref., 18; on 
potassium hydroxid clearing method, 
ref., 1242 
Hill, E., and Semerak, C. B., on softening 
of lenticular nuclei, ref., 1169 
Hill, L. W., on albuminuria in children, 
ref., 855 
Himmelberger, on avian tuberculosis, ref., 
292 
Hinman, F., on functional tests in 
nephritis, ref., 882 
Hinselmann, H., on melanosarcoma of 
vulva, ref., 912 
Hintze and Lubarsch, on elimination of 
bacteria in secretions, ref., 176 
Hirsch, on hypertrophy of heart, ref., 
633; on streptococcus enteritidis, ref., 
774 
Hirsch, K., on sarcoma of ependyma, ref., 
1109 
Hirschberg, on melanosarcoma, ref., 432 
Hirschfeld, on polycythemia, ref., 518; on 
pseudoleukemic lymphomata, ref., 556 
Hirschler, on adrenal remnants in liver, 
ref., 836 
Hirschsprung's disease, 763 INDEX 
1289 
Hirsuties, 589 
His, bundle of, 627 
Hiss, P. H., on B. coli communis, ref., * 
244; on B. typhosus, ref., 266; on 
capsule stain for streptococcus pyo- 
genes, ref., 238; on cultivation of 
typhoid bacilli, ref., 276; on dysentery 
bacillus, ref., 278; on pneumococci, 
ref., 249; on staining encapsulated 
pneumococci, ref., 250 
Hiss, P. H., and Atkinson, J. P., on anti- 
toxic immunity, ref., 190 
Hiss and Russell, on B. typhosus, ref., 
244, 276; on dysentery bacillus, ref., 
278 
Hiss and Zinsser, on bacteria in meat 
poisoning, ref., 324; on bacteriology, 
ref., 158; on infectious diseases, ref., 
354; on leucocyte extract, ref., 214; 
on stain for tubercle bacilli, ref., 296; 
on technique of agglutination tests, 
ref., 222; on tuberculin preparations, 
ref., 294; on vaccines, ref., 212 
Hitschmann and Adler, on chronic endo- 
metritis, ref., 930 
Hober, R., on physical chemistry, ref., 4 
Hodenpyl, E., on absence of spleen, ref., 
566; on actinomycosis of lung, ref., 
261; on etiology of appendicitis, ref., 
782; on lung pigment, ref., 704; on 
tonsillitis, ref., 738; on tuberculosis of 
pleura, ref., 729 
Hodge, on effects of fatigue on neurones, 
ref., 1138 
Hodgkin's disease, 556 
bacillus of, 562 
lesions of liver in, 835 
spleen in, 578 
Hoen, A. G., on amyloid degeneration of 
muscles, ref., 1038; on uvula in ab- 
normal conditions, ref., 738 
Hoevels, K., on leiomyoma of uterus, ref., 
421; on malignant myoma of uterus, 
ref., 941 
Hoffman, on cancer statistics, ref., 453; 
on dusty trades and consumption, ref., 
704; on multiple myeloma, ref., 431 
Hofmann, on carbon monoxide poisoning, 
ref., 481 
Hofmann, M., on gigantism, ref., 1045 
Hofmeister, F., on bone formation, ref., 
1042 
Holt, L. E., on pyloric stenosis, ref., 745 
Holt and Ratterman, on sarcoma of lung, 
ref., 721 
Homen, on streptococcus toxin, ref., 240 
Homeotransplantation of tissues, 388 
Honl, I., on hemorrhagic infections, ref., 
500 
Honsell, on benign metastasizing goiters, 
ref., 586; on chondroma of muscle, ref., 
1041; on malignant tumors of tonsil, 
ref., 741 
Hookworm, 151 
disease, 152 
Hooper, C. W., and Whipple, G. H., on 
icterus, ref., 20, 65 
Hopkins, J. G., on chloral hydrate poi- 
soning, ref., 479; on phagocytosis of 
red blood-cells, ref., 211 
Hopkins, J. G., and Lang, A., on strep- 
tococci, ref., 238 
Hormones, ref., 492 
Horn, cutaneous, 445 
Horseshoe kidney, 360 
Hort, E. C., and Penfold, W. J., on fever, 
ref., 502 
Hospital fever, 333 
Housemaid's knee, 1088 
Howard, on actinomycosis of brain, ref., 
1172; on B. mucosus capsulatus, ref., 
245; on cardiac hypertrophy, ref., 633; 
on economic loss by insects, ref., 176; 
on extra-intestinal lesions induced by 
typhoid bacillus, ref., 272; on flies and 
typhoid fever, ref., 275; on hemorrhagic 
septicemia, ref., 323 
Howard, Dyar, and Knab, on mosquitoes, 
ref., 349; on mosquito in yellow 
fever, ref., 335 
Howard and Hoover, on tropical abscess of 
liver, ref., 823 
Howard and Ingersoll, on bacteria in 
nasal inflammation, ref., 662 
Howard-and Wolbach, on obliteration of 
bile-ducts, ref., 845 
Howe, on arachnoid tumors, ref., 1103 
Howell, on coagulation of blood, ref., 515 
Howell, W. H., on heart beat, ref., 628 
Howell-Evans, on ulcers of tongue, ref., 
735 
Howland, J., and Richards, A. M., on liver 
in chloroform anesthesia, ref., 816 
Howship's lacunae, 1061 
Hubbard, on dilatation of colon, ref., 763 
Huber, on chorda dorsalis, ref., 403 1290 
INDEX 
Huebschmann, P., on fatty infiltration of 
heart, ref., 612 
Hueck, W., on skin pigments, ref., 66 
Hueter, C., on dwarfism, ref., 1043; on 
pseudomyxoma peritonei, ref., 797 
Hueter and Karrenstein, on osteoid sar- 
coma of mamma, ref., 1006 
Huffman, 0. V., on tubal pregnancy, ref., 
982 
Huguenin, on bacteria in smallpox, ref., 
337 
Hulisch, on structure of sarcoma, ref., 427 
Hunnicutt, J. A., on compensatory hyper- 
trophy, ref., 74; on regeneration of 
thyroid gland, ref., 86 
Hunt, on wood alcohol poisoning, ref., 478 
Hunt, E. L., on medicolegal value of 
precipitin test, ref., 208 
Hunt, J. R., on paralysis agitans, ref., 
1171 
Hunter, on cancer statistics, ref., 388 
Huntington, G. S., on malformation of 
kidney, ref., 852 
Huntington, Schulte, and Car malt, on 
anatomy of salivary glands, ref., 801 
Hunziker, H., on uterine polyps, ref., 937 
Hurwitz and Drinker, on aplastic anemia, 
ref., 538; on benzol anemia, ref., 528 
Hutchinson, on vulnerability of apex of 
lung, ref., 718 
Hutyra, on hemorrhagic infection, ref., 321 
Hyaline degeneration (see Degeneration, 
hyaline), 57 
substances, 56 
Hydatid mole, 954 
Hydatids, 147 
Hyde and Lo Brasso, on exposure of the 
body to the sun's rays, 18 
Hydrarthrosis, 30 
Hydremia, 516 
Hydrencephalocele, 1110 
Hydroa aestivale, 17 
Hydrocele, 30, 1015 
Hydrocephalus, 29, 1105, 1110 
acute, 1100 
brain, removal of, in, 1224 
chronic, 1107 
congenital, 1107 
externa, 1110 
interna, 1110 
primary in adults, 1108 
secondary, 1108 
Hydrochloric acid, 472 
Hydrocyanic acid poisoning, 477 
Hydromeningocele, 1110 
Hydrometra, 920 
Hydromyelia, 1111 
Hydronephrosis, 885 
experimental, 885 
Hydropericardium, 29, 595 
Hydroperitoneum, 30 
Hydrophobia, 326 
animal inoculations in, 327 
diagnosis of, 330 
excitant of, 327 
immunization, artificial, in, ref., 337 
Negri bodies in, 328 
preventive inoculation in, 330 
virus of, 327 
Hydropic degeneration, 54 
Hydropneumothorax, 724 
Hydrops cystidis felleae, 846 
spurius, 787 
Hydrorrhachis, 1111 
Hydrosalpinx, 976 
Hydrostatic test, 1225 
Hydrothorax, 29, 724 
Hygroma, cystic, 425 
Hyman, C. H., and Leary, T., on anthrax, 
ref., 260 
Hymen, malformations of, 909 
Hymenolepis diminuta, 149 
nana, 149 
Hyperemia, 23 
active, 23, 24 
of bladder, urinary, 898 
bone, 1056 
brain, 1119 
kidney, 854 
liver, 809 
lung, 677 
ovary, 957 
pia mater cerebralis, 1095 
spleen, 569 
thyroid, 583 
uterus, 923 
passive, 23, 24 
Hyperglycemia, 491 
Hyperkeratosis linguae, 735 
Hypernephroma, 375 
metastatic, of larynx, 669 
of adrenals, 591 
kidney, 893 
liver, 836 
vagina, 917 
vulva, 913 INDEX 
1291 
Hyperostosis, 1076 
Hyperplasia, 73, 112 
endothelial, 455 
of lymph-nodes, 549 
spleen, 576 
nodular, of intestine, 770, ref., 764 
of bladder epithelium, 900 
heart, 617, 618 
liver, 835 
lymph-nodes, 554 
spleen, 571 
thymus, 581 
thyroid, 584 
replacement, 73, 112 
of heart, 617 
muscle, 1039 
neuroglia, 1139 
senile parenchymatous, of breast, 
452 
Hyperthyreosis, 489 
Hypertrophy, 73 
compensatory, 73 
of heart, 633 
functional, 73 
of bladder, urinary, 897 
blood-vessels, 635 
brain, 1116 
heart, 73, 628 
kidney, 74, 853 
liver, 74, 829 
mamma, 988 
muscle, 74, 1035 
prostate, 1024 
spleen, 74 
thymus, 581 
thyroid, 74 
tongue, 735 
tonsils, 736 
pseudo-, 73 
simple, 73 
Hyphae, 171 
Hyphomycetes, 158, 171 
Hypoleucocytosis, 526, 527 
Hypophysis cerebri, lesions of, 1182 
structure of, 1182 
lesions of, in acromegalia, 497 
in diabetes insipidus, 493 
dwarfism, 499 
gigantism, 499 
hypophyseal adiposity, 497 
Hypoplasia, 356 
Hypospadias, 359, 1011 
Hypostasis, post-mortem, 1187 
Ibrahim, J., on pyloric stenosis, ref., 745 
Ichoremia, ref., 233 
Ichthyosis, 732 
Icterus, 65 
gravis, 816 
hemolytic, 575 
infective, 352 
spirochetes in, 139 
Idiocy, amaurotic family, 1115 
Mongolian, 1114 
Ileocecal tuberculosis, hyperplastic, 775 
Illig, on myomata of esophagus, ref., 744 
Immune body, 199, 201, ref., 204 
substance, 197, 199, 201, ref., 204 
fixation of, 199 
Immunity, acquired, 186 
active, 188 
antibacterial, 187, 196 
antimicrobic, 187 
artificial, to streptococcus, 240 
antitoxic, 187, 189 
bactericidal, 196 
bacteriolytic, 187, 196 
bibliography of, 224 
definition of, 186 
hereditary, 186 
natural, 186 
nature and forms of, 185 
passive, 189 
Immunization, artificial, 186, 187 
specific character of, 220 
natural, 186 
of animals to alien substances, 224 
processes involved in, 221 
Inada, Ido, Hoki, Kaneko, and Ito, on 
Spirochaeta, ref., 139 
Inada, R., on serum treatment in in- 
fective jaundice, ref., 352 
Inclusions, fetal, 368 
Incubation period of infection, 182 
Index, opsonic, 213 
Infantile paralysis, 331, 1159 
Infantilism, 1042 
Infarction, 36 
hemorrhagic, 28 
atrophic, of liver, 813 
of heart, 38 
intestine, 38 
kidney, 38, 854 
liver, 37, 811, 812, 813 
lung, 38, 679 
muscle, 1038 
placenta, 953 1292 
INDEX 
Infarction of spleen, 38, 570 
Infarcts, 36 
absorption of, 37 
anemic, 37 
hemorrhagic, 37 
location of, 37 
uric acid, in kidney, 861 
white, 37 
Infection, 175, 179 
and immunity, 181 
condition of body in, 180 
of microorganisms in, 181 
concurrent, 182 
congenital, 183 
definition of, 181, 185 
forms of, 182 
granulation tissue in, ref., 177 
hemorrhagic, ref., 500 
incubation period in, 182 
mixed, 182 
nature of, 181 
purulent, ref., 233 
spleen in, ref., 177 
terminal, 183 
theory of, ref., 179 
Infectious diseases, 181, 226 
bibliography of, 353 
communicability of, 184 
definition of, 181, 185 
of animals, 353 
of unknown origin, 353 
granulomata, ref., 282 
Infiltration, calcareous, 60 
fat, of adrenals, 589 
fatty, 49, 52 
of heart, 613 
liver, 819 
muscle, 1036 
pancreas, 802 
glycogenic, 53 
hydropic, of muscle, 1038 
leukemic, differential diagnosis of, 
430 
lymphocytic, differential diagnosis 
of, 430 
purulent, 106 
serous, 54 
Inflammation, 97 
bacteria in, 104 
body fluids in, 124 
catarrhal, 113 
characterization of, 126 
definition of, 126 
Inflammation, degeneration in, J13 
experimental study of, 126 
exudative, 103, 105, 113 
practical study of, 12 
fibrinous, 113 
foreign bodies in, 115 
general survey of, 123 
hemorrhagic, 113 
in non-vascular tissue, 98 
vascular tissue, 99 
interstitial, 112, 114 
leucocytes in, 124 
microorganisms in, 104 
mucopurulent, 113 
mucous, 113 
necrotic, 113 
of mucous membranes, 241 
parenchymatous, 114 
phagocytes in, 115 
practical study of, 127 
productive, 113 
pseudomembranous, 113 
purulent, 113 
regenerative, 113 
reparative, 113 
resolution in, 106 
resorption in, experimental study of, 
126 
scrofulous, of lymph-nodes, 552 
seropurulent, 113 
serous, 113 
significance of, 123 
special phases of, 113 
suppurative, 113, 227 
in typhoid fever, 273 
symptoms, cardinal of, 103 
tuberculous, 282 
diffuse, 287 
Influenza, 263 
Infusoria, 140 
Ingier, A., on hyperplasia of mamma, 
ref., 993 
Injury, inflammatory reaction to, 98 
Insects as carriers of infection, 176 
method of study of, 157 
Insolation, 494 
Intermediary body, 203 
substance, 203 
Intestine, 759 
absorption in, ref., 774 
actinomycosis of, 775 
ameba in, 768 
anthrax in, 775 INDEX 
1293 
Intestine, bacteria in, 768, 770, 773 
cloacae, 760 
concretions in, 788 
cysts of, 785 
degeneration of, 764 
dilatation of, 763 
diverticula of, 759 
dysentery, 767 
embolism of, 763 
examination, post-mortem, of, 1202, 
1214, 1226 
hemorrhage of, 763 
hemorrhoids, 777 
hernia of, 762 
Hirschsprung's disease, 763 
hyperemia of, 763 
hyperplasia nodular, of, 764, 770 
incarceration of, 760 
infarction of, 38, 763 
inflammation of (see Enteritis and 
Colitis), 764, 767, 775, 776, 
777 
intussusception of, 761 
invagination of, 761 
lesions of, in Asiatic cholera, 279 
in typhoid fever, 266, 272 
malformations of, 759 
malpositions of, 759 
melanosis of, 788 
mycosis of, 775 
parasites in, 775 
permeability of wall of, for bacteria, 
ref., 774 
pigmentation of, 788 
polyps of, 445, 782 
preservation of, 1215 
ruptures of, 763 
sand in, 788 
strictures of, 763 
syphilis of, 767, 776 
thrombosis of, 763 
transposition of, 759 
tuberculosis of, 765, 775 
tumors of, 782 
ulcers of, 767, 769, 775 
volvulus of, 760 
wounds of, 763 
Intoxication, auto-, 179 
septic, 178 
Intoxications, 182 
Intussusception of intestine, 761 
Inversio vesicae, 359 
Iodine content of thyroid, 489 
Ipsen, J., on hypernephroma, ref., 892; 
on intestinal tuberculosis, ref., 766 
Iron hematoxylin stain, 1236 
"masked," ref., 64 
reactions for, ref., 64 
Irons and Graham, on pathogenic blasto- 
mycetes, ref., 171 
Irritation, chronic, in etiology of tumors, 
386 
Ischemia, 26 
Ishida, M., on pigmentation of atrophied 
muscle fibers, ref., 1033 
Isolysins, 202 
Ischiopagus, 365 
parasitic, 367 
Itch, ground, 152 
insect, 156 
Ito and Matsuzaki, on Spirochaeta ictero- 
haemorrhagise, ref., 139 
Jackson, on sarcoma of lung, ref., 721 
Jackson, Porter, and Quinby, on throm- 
bosis of mesenteric veins, ref., 763 
Jacob, on carcinoma of stomach, ref., 758; 
on glioma, ref., 407; on secondary car- 
cinoma of liver, ref., 837 
Jacobi, on congenital lipomata, ref., 
402 
Jacob's ulcer, 463 
Jacobson, N., on hair balls in stomach, 
ref., 759 
Jacobson, V. C., and Goodpasture, E. W., 
on hypernephroma, ref., 892; on ob- 
struction of hepatic veins, ref., 814 
Jacobsthal, on infantile scorbutus, ref., 
496 
Jadassohn, on leprosy, ref., 304 
Jaeger, on cerebrospinal meningitis, ref., 
256 
Jail fever, 333 
Jakob, A., on lesions of central nervous 
system, ref., 1121 
Von Jaksch's anemia, 543 
Jalap poisoning, 476 
James, on lesions of stomach as portals 
of entry for bacteria, ref., 750; on 
pneumopericardium, ref., 596 
James and Sappington, on fibroma of 
intestine, ref., 782; on leiomyomata of 
stomach, ref., 754 
Jamin and Merkel, on coronary arteries, 
, ref., 614 1294 
INDEX 
Janeway, H. H., Barringer, B. S., and 
Failla, G., on radium therapy in cancer, 
ref., 12 
Janeway, T. C., on functional tests in 
nephritis, ref., 882; on hyperplastic 
periostitis, ref., 1046; on nephritic 
hypertension, ref., 874 
Janiceps, 365 
Janicki and Rosen, on Bothriocephalus 
latus, ref., 149 
Janney, N. IF, Goodhart, S. P., and 
Isaacson, F. I., on muscle dystrophy, 
ref., 1034 
Janowski, on suppurative inflammation, 
ief., 231 
Janus, 365 
Jaundice (see Icterus), 65 
Jaw, cysts and tumors of, 1082 
tumors of, 406, 436, 448 
Jaworski and Korolewicz, on occult 
hemorrhage in gastrointestinal canal, 
ref., 746 
Jeanneret, on albuminuria in children, 
ref., 855 
Jehle, on albuminuria in children, ref., 
855 
Jellett, H., on endothelioma of vagina, 
ref., 917 
Jelliffe, on death from electric currents, 
ref., 12 
Jelliffe and Larkin, on chordoma in 
brain, ref , 404 
Jendrassik, on muscular dystrophy, ref., 
1035 
Jenner stain for blood, 530 
Jensen, on tumor metastases, ref., 378 
Jepson, on dermoid cysts of intestine, 
ref., 785 
Josionek, A., on effect of light on the 
organism, ref., 17 
Jessup, D. S. D., on carcinoid tumors of 
appendix, ref., 786; on Hodgkin's 
disease, ref., 557; on myoma of recto- 
vaginal septum, ref., 941; on plasmocy- 
toma, ref., 431 
Jewett, on teratomata of tonsil, ref., 741 
Jobling, J. IF., and Petersen, IF. F., on 
Abderhalden reaction, ref., 218; on 
active immunity, ref., 189; on casea- 
tion, ref., 71; on epidemiology of pel- 
lagra, ref., 496 
Jobling, Petersen, and Eggstein, on serum 
ferments in pneumonia, ref., 250 
Jochmann, G., on bacteriemia in pul- 
monary tuberculosis, ref., 718; on 
phagocytes, ref., 121; on serum therapy 
in meningitis, ref., 256 
Johnston, on lepra bacilli, ref., 303 
Joints, 1082 
cartilage, loose, in, 1087 
degeneration of, 1082 
"false," 1070 
inflammation of (see Arthritis), 1083 
syphilis of, 1086 
tuberculosis of, 1085 
tumors of, 1086 
Jona, J. L., on fever, ref., 502 
Jones, on cysts of mesentery, ref., 795; 
on sarcoma of appendix, ref., 785 
Jones, W. A., on myasthenia gravis with 
thymoma, ref., 1035 
Jopson, J. H., and Speese, J., on Paget's 
disease of nipple, ref., 1009 
Jopson and White, on sarcoma of large 
intestine, ref.. 784 
Jordan, on acute osteomyelitis, ref., 1064 
Jordan, Russell, and Zeit, on typhoid 
bacillus in water, ref., 275 
Jores, I., on lead poisoning, ref., 476 
Jores, L., on arteriosclerosis, ref., 640 
Jorgenson, on microorganisms and fer- 
mentation, ref., 169 
Joslin, on diabetes mellitus, ref., 492 
Josue, O., Lewis, T., and Mackenzie, J., 
on muscular system of heart and 
its relation to disease, ref., 627 
Judd, E. S., on carcinoma of prostate, 
ref., 1029; on hypertrophy of prostate, 
ref., 1027 
Jump, H. D., Beates, H., and Babcock, 
IF. IF., on adrenal function, ref., 
589 
Jung, P., on kraurosis of vulva, ref., 911; 
on tuberculous salpingitis, ref., 980 
Jurgeliinas, A., on granulation tissue in 
infection, ref., 177 
Kaempfer, on odontoma, ref., 406 
v. Kahlden, C., on cysts of ovary, ref., 
963; on periarteritis nodosa, ref., 646 
Kahn, M., on functional tests in neph- 
ritis, ref., 882; on renal calculi, ref., 
890 
Kaiserling's fluid, 1242 
Kakeis, on sarcoma of pancreas, ref., 806 
Kala-azar, 139 INDEX 
1295 
Kalble, on bacteria in normal lymph- 
nodes, ref., 546 
Kanavel, A., on cysts of hypophysis, ref., 
1182a 
Kaneko and Okuda, on serum treatment 
in infective jaundice, ref., 352 
Kangri basket cancer, 387 
Kanoky, J. P., on carcinoma in bones, 
ref., 1081; on thyroid tumors of bones, 
ref., 586 
Kappis, on urogenital tuberculosis, ref., 
882 
Karakascheff, on pathology of adrenals, 
ref., 590 
Karcher, on bacteria in bronchitis, ref., 
671 
Karsner, H. T., on blood transfusion, ref., 
531; on chemical pneumonia, ref., 698; 
on functional tests in nephritis, ref., 
882; on poisoning by tartaric acid, ref., 
472 
Karsner and Ash, on infarction of lung, 
ref., 679 
Karsner and Meyers, on lobular pneu- 
monia, ref., 696 
Kartulis, on amebic colitis, ref., 769 
Karyokinesis, 78, 80 
Karyolysis, 68 
Karyomitosis, 80 
Karyorrhexis, 68 
Kataplasia, 75 
Katase, A., on fat embolism, ref., 42; 
on teratoma of lungs, ref., 721 
Kattwinkel, W., and Kerschensteiner, H., 
on multiple neuritis, ref., 1161 
Kaufmann, E., on achondroplasia, ref., 
1043; on adenoma of testis, ref., 
1022; on carcinoma of urethra, ref., 
908; on cysts of pericardium, ref.,599; 
on endothelioma of peritoneum, ref., 
795; on malignant hypernephromata 
of adrenal, ref., 592; on malformations 
of penis, ref., 1011; on tumors of 
pancreas, ref., 806; on tumors of 
testicle, ref., 1022 
Kawamura, on cholesterin in kidney, ref., 
860; on lipoids, ref., 53; on rhabdo- 
myoma, ref., 422; on ulcer of stomach, 
ref., 751 
Kaye, G. W. C., on x-rays, ref., 12 
Kayser, on cysts of mesentery, ref., 795; 
on malformation of mamma, ref., 987 
Keays, F. L., on caisson disease, 18 
Kedrowsky, W. J., on emphysematous 
cystitis, ref., 901 
Keen, on surgical complications of 
typhoid fever, ref., 274; on thrombosis 
of pulmonary artery, ref., 680 
Keen and Coplin, on sacral tumors and 
cysts, ref., 1112 
Keen and Funke, on paraganglioma of 
carotid, ref., 413 
Keibel and Mall, on size of human 
embryo, ref., 1223 
Keilty, on tumors of pleura, ref., 729 
Keith, on bone formation, ref., 1042; on 
malformations of female generative 
organs, ref., 909; on malformations of 
heart, ref., 600 
Kelly, A. O. J., on cause of calculus for- 
mation, ref., 848; on chronic peritonitis, 
ref., 793; on cirrhosis of liver, ref., 825; 
on lymphatic leukemia, ref., 539; on 
tumors of appendix, ref., 785 
Kelly and Cullen, on myoma of uterus, 
ref., 937 
Kelly and Hurdon, on vermiform appen- 
dix, ref., 782 
Keloid, 398 
Kelynack, on pathology of vermiform ap- 
pendix, ref., 782; on renal growths, ref., 
892 
Kendall, A. I., on intestinal bacteria, ref., 
774 
Kennedy, on regeneration of nerve fibers, 
ref., 1136 
Keratin in carcinoma, 463 
in melanocarcinoma, 467 
melanoma, 433 
Kermauner, F., on malformations of fe- 
male generative organs, ref., 909; on 
malformations of male generative or- 
gans, ref., 1011 
Kerr, on statistics of lobar pneumonia, 
ref., 690 
Kettle, on fibrosarcoma, ref., 398; on 
hemangioma of kidney, ref., 423; on 
metastasis of tumors in spleen, ref., 
379; on tumors, ref., 468 
Keyes, on snake poisons, ref., 480 
Kidner, F. C., on myositis ossificans, ref., 
1039 
Kidney, 849 
abscess of, 864 
absence of, 851 
albuminuria, 855 1296 
INDEX 
Kidney, anatomy of, 849 
and atrophy of liver, 857 
anemia of, 853 
arteriosclerotic contracted, 872 
atrophy of, 851, 853, 878 
bacteria in, 864, 865, 871, 883 
calcification of, 857, 860 
calculi of, 890 
casts in, 855 
congestion of, 854 
contracted, secondary, 876 
true, 873 
cortical substance, 850 
cysts of, 886 
degeneration of, 858, 861 
disease of, classification of, 861 
elimination by, 851, 855 
embolism of, 854 
examination, post-mortem, of, 1212, 
1226 
excretion of bacteria by, 864 
pigment by, ref., 864 
excretory functions, 851, 855 
function, tests of, 880 
glomeruli, alterations in, 866 
granular, 878 
hematuria, 855 
hemorrhage in, 855 
horseshoe, 360, 851 
hydronephrosis, 885 
hyperemia of, 854 
hypertrophy of, 74, 853 
infarction of, 38, 854 
• infarcts, uric acid, in, 861 
infection, ascending, of, 864 
embolic, of, 864 
after injury, ref., 177 
infiltration of, 859 
inflammation of (see Nephritis), 861 
lesions of, in poisonings, 857, 863 
lobulated, 361 
lobulation, fetal, of, 852 
malarial parasite in, 871 
malformations of, 851 
malpositions of, 852 
medullary substance, 850 
movable, 853 
necrosis of, 857 
nephroses, 861, 862 
parasites in, 893 
parenchymatous, chronic, 876 
pelvis, lesions of, 885 
perinephritic suppuration, 886 
Kidney, pigmentation of, 861 
preservation of, 1213 
primary contracted, 872 
pyelitis, 883 
red, large, 877 
regeneration of, 86, 853 
surgical, 865 
syphilis of, 883 
thrombosis of, 854 
tuberculosis of, 882 
tubules, 850 
lesions of, 867 
tumors of, 890 
in cerebral sclerosis, 1114 
uric acid deposits in, 861 
wandering, 853 
weight of, 1212 
in new-born, 1226 
white, large, 876 
King, on benign tumors of intestine, ref., 
782 
Kinnicutt, F., on orchitis in typhoid fever, 
ref., 273; on phlegmonous gastrftis, ref., 
750 
Kirchheim, L., on hypertrophy of mamma, 
ref., 988 
Kirpicznik, J., on tuberous cerebral scle- 
rosis, ref., 1114 
Kisskalt, on cooling of body and infection, 
ref., 698; on natural immunity, ref., 186 
Kitt, on infectious diseases of animals, 
ref., 353 
Klebs, on malformations of male genera- 
tive organs, ref., 1011 
v. Klecki, on bacteria in kidney, ref., 871 
Kleine and Mollers, on inherited immu- 
nity, ref., 186 
Kleinhaus, F., on adenomyoma of vagina, 
ref., 916 
Kleinschmidt, 0., on renal calculi, ref., 
890 
Klemensiewicz, on abnormal mitoses, ref., 
80 
Klemperer, on tubercle bacilli in blood, 
ref., 296 
Klestadt, W., on osteitis fibrosa, ref., 1049 
Klimenko, on permeability of intestinal 
wall for bacteria, ref., 774 
Klopstock, on enlargement of spleen in 
cirrhosis of liver, ref., 828 
Klopstock and Seligmann, on tubercle 
bacilli in blood, ref., 296 
Klose, on dysthyreosis theory, ref., 489 INDEX 
1297 
Klose and Vogt, on thymus and its 
relation to rickets, ref., 581 
Klotz, O., on arteriosclerosis, ref., 645; 
on calcareous degeneration, ref., 63; 
on formation of fat in cells, ref., 49; 
on periarteritis nodosa, ref., 646 
Knauer, on tumors of the veins, ref., 657 
Knauss, on neuroma, ref., 418 
Knoepfelmacher, on cultivation of spiro- 
chetes, ref., 139 
Knott, on sarcoma of liver, ref., 839 
Knox, M., on epicardial nodules, ref., 598 
Kober, P. A., on absorption bands, ref., 
17; on tuberculosis in cattle, ref., 299 
Kober and Hanson, on poisoning by 
phosphorus, ref., 474 
Kobert, on poisons, ref., 481 
Koch, on adenoma of pancreas, ref., 806; 
on B. tuberculosis, ref., 301 
Koch, G., on tuberculosis of prostate, ref., 
1027 
Koch, M., on leontiasis ossea, ref., 1046 
Koch and Bruck, on gonococcus, ref., 253 
Koch-Weeks bacillus, 265 
Kocher, R. A., on effects of fatigue on 
neurones, ref., 1138; on parasites in 
ventricles, ref., 1109 
Koechlin, on Lambl's excrescences, ref., 
634 
Koelsch, F., on tetrachlorethane poison- 
ing, ref., 479 
Kohn, on neurocytes, ref., 409 
Kolb, K., on myoma of uterus, ref., 938 
Kolisko, A., on poisons, ref., 481; on 
sarcoma of vagina, ref., 916; on 
thrombi in carbon monoxide poison- 
ing, ref., 481 
Kollaczek, on chondrolipoma of muscle, 
ref., 1041 
Kolle, W., on specificity of infectious 
agents, ref., 191 
Kolle and Hetsch, on animal inoculation 
in hydrophobia, ref., 327; on immunity, 
ref., 224; on infectious diseases, ref., 
354; on tuberculosis, ref., 301 
Kolle and Schiirmann, on cholera organ- 
ism, ref., 280 
Kolle and Wassermann, on bacteriology, 
ref., 158; on immunity, ref., 224; 
on infectious diseases, ref., 353; on 
serum therapy in meningitis, ref., 256 
Kolmer, J. A., on antigens, ref., 201; on 
B. diphtherise, ref., 316; on comple- 
ment fixation test in gonorrhea, ref., 
253; on serum therapy, ref., 191; on 
smallpox, ref., 337; on tests for syphilis, 
ref., 312; on vaccines, ref., 212 
Kolmer and Steinfield, on pneumococcus 
carriers, ref., 249 
Konig, on chronic mastitis, ref., 993 
Konigstein, H., and Hess, L., on effect of 
light on the organism, ref., 17 
Konjetzny, G. E., on carcinoma of gall- 
bladder, ref., 846; on cholesteatoma of 
mamma, ref., 1006; on diseases of 
gall-bladder, ref., 846; on Hirsch- 
sprung's disease, ref., 763 
Koplik and Van Arsdale, on acute 
osteomyelitis, ref., 1064 
Kornmann, on hemangioma, ref., 423 
Korschelt, on regeneration, ref., 83 
Korte, on fibroma of pancreas, ref., 806 
Kotlar, on cardiac thrombi, ref., 609 
Kraepelin, E., on paresis, ref., 1165 
Krasting, K., on statistics of brain 
tumors, ref., 1179 
Kratter, on poisons, ref., 481 
Kraurosis vulvse, 911 
Kraus, on autointoxication, ref., 482; on 
regeneration of fat tissue, ref., 91 
Kraus and Levaditi, on immunity, ref., 
191; on immunization, ref., 224 
Kreglinger, on carcinoma of bronchi, ref., 
675 
Krehl, on edema of lungs, ref., 678; on 
fever, ref., 502; on heart lesions, ref., 
632 
Krehl and Marchand, on effects of heat 
and cold, ref., 11 
Kretschmer, H. L., and Moody, A. M., on 
carcinoma of kidney, ref., 891 
Kretz, R., on cause of calculus formation, 
ref., 848; on cirrhosis of liver, ref., 825; 
on repair of liver, ref., 828 
Kromayer, E., on Molluscum contagi- 
osum, ref., 141 
Krompecher, E., on basal-cell carcinoma, 
ref., 462; on chronic gastritis, ref., 
749; on complex tumors of mamma, 
ref., 1006; on cysts of mamma, ref., 
1003; on mixed tumors, ref., 444; 
on naevus, ref., 447 
Kruger, on hyperplastic periostitis, ref., 
1046 
Krukenberg, on fibrosarcoma ovarii mucu- 
cellulare, ref., 971 1298 
INDEX 
Krukenberg tumor of ovary, 971 
Krumwiede and Puatt, on fusiform bacilli, 
ref., 326 
Krumwiede, Pratt, and Kohn, on para- 
typhoid, ref., 277 
Krumwiede and Valentine, on precipitin 
reaction in pneumonia, ref., 248; on 
Streptococcus viridans, ref., 238 
Kruse and Pasquale, on abscess of liver, 
ref., 824; on necrotic colitis, ref., 774 
Kuhnau, on bacteriology of blood, ref., 
533 
Kiilbs, on gonorrheal endocarditis, ref., 
622 
Kumita, on pyelonephritis with cystitis, 
ref., 884 
Kundrat, on lymphosarcomatosis, ref., 
431 
Kunkel, on poisons ref., 481 
Kuru, H., on adamantinoma, ref., 448; 
on fibroadenoma of mamma, ref., 1004; 
on structure of mamma, ref., 986 
Kustner, O., on carcinoma of vulva, ref., 
913 
Kutscher, on typhoid fever, ref., 274 
Kuttner, on carcinoma of penis, ref., 1013 
Labia, hemorrhage in, 909 
malformations of, 909 
Lachner-Sandoval, on ray fungi, ref., 262 
Ladinski, L. J., on carcinoma of uterus, 
ref., 943 
La grippe, 263 
Lamarand Meltzer, on experimental pneu- 
monia, ref., 691; on induced pneumonic 
lesions, ref., 247 
Lambert, A., on sunstroke, ref., 495 
Lambert, R. A., on carcinoma of lung, ref., 
722; on connective tissue regeneration, 
ref., 89; on cytotoxins, ref., 200; on 
fibrin in repair of wounds, ref., 112; on 
growth of cells in vitro, ref., 373; on 
neuroblastoma, ref., 409 
Lambert, S. W., and Patterson, H. S., on 
corrosive sublimate poisoning, ref., 
863 
Lamblia intestinalis, 140 
Lambl's excrescences of heart, 634 
Lamson, P. D., on polycythemia, r.ef., 517 
Lamy and Mayer, on renal secretions, ref., 
854 
Landau, M., on neuroblastoma, ref., 
408 
Lando, on chronic interstitial pancreati- 
tis, ref., 806; on pancreas lesions in 
hepatic cirrhosis, ref., 829 
Landois, on tumors of muscle, ref., 1040 
Landry's paralysis, 1162 
Landsteiner, on adenomata of sweat 
gland, ref., 453; on sarcoma of gall- 
bladder, ref., 847 
Landsteiner and Popper, on acute polio- 
myelitis, ref., 1157 
Landsteiner and Stoerk, on cystite en 
plague, ref., 901 
Lang and Ullmann, on syphilis, ref., 
308 
Langerhans, islands of, degeneration of, 
803 
development of, ref., 803 
hypertrophy of, ref., 803 
lesions of, in diabetes, 803, 806 
Langhans' cells, in chorionic villi, 949 
giant cells in sarcoma, 434 
Langmann, on hemosporidia, ref., 143; on 
snake poisons, ref., 479 
Langstein, on albuminuria in children, 
ref., 855 
Lanz and Tavel, on appendicitis, ref., 782 
Lapin, on bronchiectasia in children, ref., 
673 
Lardaceous degeneration, 57 
Larkin, J. H., and Levy, I. Jon syphil- 
itic arteritis, ref., 647 
Larson and Barron, on fusiform bacilli, 
ref., 326 
Laryngitis, 665 
catarrhal, acute, 665 
chronic, 666 
croupous, 666 
phlegmonous, 666 
pseudomembranous, 666 
syphilitic, 667 
tuberculous, 667 
Larynx, 664 
amyloid masses in, 668 
cysts of, 668, 669 
edema of, 664 
examination, post-mortem, of, 1211, 
1225 
hemorrhage from, 664 
inflammation of (see Laryngitis), 665 
malformations of, 664 
preservation of, 1211 
syphilis of, 667 
tuberculosis of, 667 INDEX 
1299 
Larynx, tumors of, 668 
Lasio, G., on regeneration of mucous mem- 
brane of bladder, ref., 85, 900 
Launoy, L., on thyroid, parathyroid, and 
thymus, ref., 489 
Lavenson, R. 8., on aplastic anemia, ref., 
538 
Laveran, on leishmaniases, ref., 140 
Laveran and Mesnil, on trypanosomes, 
ref., 137 
Layman, on carcinoma and tuberculosis, 
ref., 723 
Lead line on gums, 67 
poisoning, 475 
Lec'ene, Proust, and Tixier on spina bifida, 
ref., 1112 
LeComte, R., on adenoma of islands of 
Langerhans, ref., 803 
Ledingham, on typhoid carriers, ref., 275 
Leduc, on mitosis, ref., 78 
Lee, Z. B., on technique, ref., 1227 
Lee, F. 8., on temperature adaptation, 
ref., 10 
Lee, O. 1., on preparation of colloidal gold 
solution, ref., 312 
Leers, on precipitin test, ref., 222 
Legry, on lung stones, ref., 726 
Lehman, on neuroblastoma, ref., 409 
Lehmann, K. B., on tetrachlorethane 
poisoning, ref., 479 
Lehndorff, on chloroma, ref., 542 
Leiomyoma, 419, 1040 
differential diagnosis of, 421 
malignant, 421 
of esophagus, 744 
ovary, 961 
stomach, 754 
testicle, 1021 
veins, 657 
Leishman, on Leishmania donovani, ref., 
139; on opsonins, ref., 210 
Leishmania donovani, 139 
infantum, 140 
in spleen, 581 
tropica, 139 
Leith, on phlegmonous gastritis, ref., 
750 
Lenhartz, on bacteriology of blood, ref., 
533 
Lentz, O., on dysentery, ref., 278, 770 
Leonard, on fibroma of vulva, ref., 912 
Leontiasis ossea, 1046 
Leopold and Levi, on moulds, ref., 172 
Lepra, 302 
ansesthetica, nerve fibers in, 1176 
bacillus of, 303 
Leprosy, 302 
bacillus of, 303 
of nervous system, 1176 
testicle, 1021 
Leptomeningitis, 1095 
Leptothrix, 161, 263 
in vagina, 918 
Leri, A., on acromegaly, ref., 1045; on 
senile dementia, ref., 1167 
Leriche, on carcinoma, ref., 806 
L' Esperance, E., on adamantinoma, ref., 
448; on hepatoma, ref., 376; on malig- 
nant hepatoma, ref., 839 
Lesser, on poisons, ref., 482 
Leucocyte extract, 214 
Leucocytes, 521 
abnormal, 523 
basophile, 522 
classification of, 522 
degenerative changes in, 527 
emigration of, 100 
eosinophile, 522 
ferments in, 523 
in inflammation, 124 
inclusions in, in scarlatina, 340 
mononuclear, large, 522 
normal, 521 
phagolysis of, 205 
polynuclear neutrophile, 522 
small, 522 
transitional, 522 
Leucocytoid cell, ref., 89 
Leucocytolysis, 527 
Leucocytosis, 525 
cachectic, 526 
hypo-, 526, 527 
mixed, 525 
polynuclear, 525 
eosinophile, 527 
pathological, 525 
physiological, 525 
Leucomains, ref., 164 
Leucoplakia buccalis, 731 
Leucoprotease, 12 
Leukemia, 538 
benzol in, 528 
bone-marrow in, 1071 
effect of radiation in, 16 
lesions of liver in, 835 
lymphatic, acute, 538 1300 
INDEX 
Leukemia, lymphatic, acute, bacillus in, 
539 
chronic, 540 
lymph-nodes in, 555 
lymphoma of intestine in, 783 
myelogenous, acute, 540 
chronic, 541 
spleen in, 578 
Leukocythemia, 538 
Leukoplakia of vagina, 917 
vulvaris, 912 
Levaditi and Roche, on syphilis, ref., 309 
Levene, P. A., on autolysis, ref., 123; 
on chemistry of tissue elements, ref., 
200; on proteolytic ferments, ref., 121; 
on resolution of exudate in pneumonia, 
ref., 690 
Lewandowsky, M., on hemorrhage of 
spinal cord, ref., 1126 
Lowers, H. N., on fibroma of vagina, ref., 
916 
Lewin, on poisons, ref., 481 
Lewis, on acromegaly, ref., 497; on 
pseudomyxoma peritonei, ref., 797; 
on types of B. tuberculosis, ref., 299 
Lewis, D., on hemorrhage from nipple, 
ref., 990 
Lewis, T., on disorders of the heart beat, 
ref., 628 
Lewis and Lewis, on mitochondria, ref., 77 
Lewis and Rosenow, on primary portal 
thrombosis, ref., 812 
Lexer, on cysts of bone, ref., 1081; on 
leiomyoma of bladder, ref., 421 
Lhermitte, J., on death from shell shock, 
ref., 1121 
Libman, E., on bacteria in blood, ref., 
622; on lymphosarcoma of intestine, 
ref., 784; on sarcoma of intestine, ref., 
784 
Libman and Celler, on bacteria in blood, 
ref., 622 
Lice, 156 
Lichtenhahn, F., on chronic mastitis, ref., 
993 
Lieber, on leiomyoma of skin, ref., 419, 
1040 
Liefmann, on hay fever, ref., 662 
Liepmann, W., on female generative 
organs, ref., 909 
Life, chemistry of, 3, 7 
Light, ultraviolet, effect of, 17 
Lightning, death from, 12 
Lillie, R. S., on muscular contraction, 
ref., 1031 
Limping, intermittent, 639 
Linck, on chordoma in pharynx, ref., 404 
Lindemann, on cancer statistics, ref., 453 
Lindfloss, on myoma of mamma, ref., 1005 
v. Lingelsheim, on B. tetanus, ref., 319; 
on dysentery, ref., 770; on strepto- 
coccus, ref., 240 
Linitis plastica, 749 
Link, on cardiac tumors, ref., 634; on 
glioma of ependyma, ref., 1109 
Linser, on effect of light on the organism, 
ref., 17 
Lipemia, 532 
Lipoid degeneration, 52 
Lipoma, 401 
arborescens, 1087 
chemistry of, 373 
degeneration, mucoid, in, 400 
molle, 402 
of appendix vermiformis, 785 
bone, 1081 
brain, 1176 
bronchi, 675 
dura mater cerebralis, 1092 
spinalis, 1103 
ependyma, 1109 
esophagus, 744 
Fallopian tubes, 981 
heart, 634 
hypophysis, 1180 
intestine, 782 
» joints, 1087 
kidney, 890 
larynx, 668 
liver, 836 
mamma, 1005 
mouth, 733 
muscle, 1041 
pancreas, 806 
penis, 1013 
pericardium, 599 
peritoneum, 794 
pharynx, 740 
pia mater cerebralis, 1101 
pleura, 728 
scrotum, 1014 
spinal cord, 1179 
stomach, 754 
testicle, 1021 
tongue, 735 
tonsil, 741 INDEX 
1301 
Lipoma of uterus, 936 
vulva, 912 
Lipomatosis, 52 
Liposarcoma, 439 
Liposis, 52 
Lipschutz, B., on infectious disease of 
unknown origin, ref., 353; on Mollus- 
cum, contagiosum, ref., 141 
Liquefaction necrosis, 67 
Lissauer, M., on experimental cirrhosis 
of liver, ref., 831; on meningeal 
carcinomatosis, 1092 
Litchkous, on omentum, ref., 794 
Little, on B. aerogenes capsulatus in 
puerperal infections, ref., 322 
Little's disease, 1144 
Laver, 808 
abscess of, 822 
amebic, 823 
metastatic, 824 
multiple, 824 
tropical, 822 
absence of, 808 
accessory, 808 
adrenal tissue in, 836 
agglutinative thrombi in, 815 
anemia of, 809 
atrophy of, 814 
acute yellow, 816 
experimental, 818 
bacteria in, 823 
calcification of, 822 
calculi of, 847 
capsule, inflammation of, 834 
chloroform, effect of, on, 816, 818, 
831 
cirrhosis of, 825 
ascites in, 828 
associated lesions in, 827 
atrophic, 825 
biliary, 829 
congenital, 826 
excitants of, 830 
experimental, 826 
Hanot type, 830 
hypertrophic, 830 
in Wilson's disease, 1171 
lacunar, of, ref., 825 
Laennec's, ref., 825 
nature of, 830 
portal, ref., 825 
portal circulation in, 827, 828 
congestion of, 810 
Liver, cysts of, 839 
cytolysis in, 815 
degeneration of, 816, 820 
displacements of, 808, 1203 
examination, post-mortem, of, 1202, 
1216, 1226 
fat in, 819 
fibrous, ref., 825 
fluke, 144, 657 
foamy, 322, 840 
gas in, 840 
granular, ref., 825 
gumma in, 832 
hemochromatosis, 831 
hemorrhage in, 809 
hobnail, ref., 825 
hydatids of, 840 
hyperemia of, 809 
hyperplasia of lymphatic tissue in, 
835 
hypertrophy of, 74, 829 
"iced," 792, 834 
infarction of, 37, 811, 812, 813 
infiltration, fatty, of, 819 
inflammation of (see Hepatitis), 
822 
jaundice with necrosis of, 815 
lesions of, in eclampsia, 816, 818 
in malaria, 821 
in typhoid fever, 271 
malformations of, 808 
malpositions of, 808 
metabolism of, disturbances of, 818 
movable, 808 
necrosis of, 814 
nutmeg, 810, 819 
parasites of, 840 
perihepatitis, 834 
pigmentation of, 814, 821, 830 
position of, 1202 
preservation of, 1217 
regeneration of, 86, 817 
reversion of cells, in cirrhosis, 827 
rupture of, 809 
size of, 1216 
changes in, 808 
syphilis of, 831 
thrombosis of, 811, 814, 815 
agglutinative, 815 
tubercles, solitary, of, 833 
tuberculosis of, 832 
tumors of, 835 
vessels, lesions of, 811 1302 
INDEX 
Liver, weight of, 1217 
in new-born, 1226 
wounds of, 808 
Lividity, cadaveric, 1186 
Lobelia poisoning, 481 
Lochte, on hyperplasia of thymus, ref., 581 
Locke, on visceral changes following 
burns, ref., 11 
Lockjaw (see Tetanus), 317 
Lockyer, C., on fibroids of uterus, ref., 937 
Locomotor ataxia, 1145 
Lode, on cooling of body and infection, 
ref., 698 
Loeb, J., on cell regeneration, ref., 94 
Loeb, Leo, on carcinosarcoma of thyroid, 
ref., 587; on growth of tissue, ref., 120; 
on irradiated tumors, ref., 15 
Loeffler, bacillus of, 315 
Lohlein, on hemorrhagic focal glomerulo- 
nephritis, ref., 867; on inflammation, 
ref., 101; on opsonins, ref., 210 
Lohrisch, on cysts of mediastinum, ref., 
723 
Lommel, on ciliated epithelium of respira- 
tory organs, ref., 670 
Londe, on cerebellar ataxia, ref., 1154 
Longcope, on anaphylaxis, ref., 217; on 
bone-marrow in infections, ref., 273; 
on Hodgkin's disease, ref., 562; on 
pneumococci, ref., 249; on reduction of 
complement, ref., 220; on relation of 
cirrhosis to chronic protein intoxica- 
tion, ref., 831; on syphilitic aortitis, 
ref.. 648 
Longcope and Donhauser, on ferments of 
blood, ref., 523 
Longcope and Fox, on pneumococci, ref., 
249 
Lonicer, M., on syphilitic hepatitis, ref., 
831 
Loomis, H., on gumma of heart, ref., 619 
Looser, E., on osteotabes infantum, ref., 
1055 
Lopez-Silvero, on cheloid, ref., 398 
Lord, on B. influenza, ref., 264; on flies 
and tuberculosis, ref., 299 
Lorenz, H., on myositis, ref., 1039 
Losson, on exudative peritonitis, ref., 791; 
on splenic anemia, ref., 544 
Loschcke, on emphysema, ref., 682 
Louria, on myxoma of heart, ref., 634 
Louse, 156 
Low, on appendicitis, ref., 782 
Low, L., on bacteria in blood of cadaver, 
ref., 1188 
Lowenstein, on mixed tumors of salivary 
glands, ref., 801; on trauma and forma- 
tion of malignant tumors, ref., 386; on 
tumors of hypophysis, ref., 1182a 
Lower, IF. E., on tumors of renal pelvis, 
ref., 892 
Lowit, on hypoleucocytosis, ref., 527 
Lowy, on tumors of thyroid and hyper- 
thyroidism, ref., 587 
Lubarsch, on B. tuberculosis, ref., 289; on 
carcinoma of gall-bladder, ref., 846; on 
emboli, ref., 36; on experimental tuber- 
culosis, ref., 297; on fetal infection, ref., 
183; on hyaline degeneration, ref., 57; 
on pigmentation of intestine, ref., 788; 
on relation between heterotopic epi- 
thelium and carcinoma, ref., 383; on 
squamous epithelium, ref., 462; on tu- 
mors, ref., 467 
Lucas, IF. S., on polycythemia, ref., 518 
Lucas and Prizer, on measles in monkeys, 
ref., 342 
Luce, on carcinoid tumors of appendix, 
ref., 786 
Luce, R. F., and Hamilton, A., on anilin 
poisoning, ref., 478 
Lucksch, on adenoma of adrenal, ref., 592 
Luetin test, 312 
Luhe, on malaria, ref., 349 
Lung stones, 674, ref., 726 
Lungs, 676 
abscess of, 696 
absence of, 676 
accessory, 676 
actinomyces in, 696 
anemia of, 676 
anthracosis of, 703 
apical vulnerability of, ref., 718 
atelectasis of, 680 
autolysis of exudate in, 690 
bacteria in, 684, 691, 696, 697 
bronchopneumonia, 692, 693 
brown induration of, 678 
calcification of, 674, 726 
"carnified," ref., 680 
cavity formation in, 715 
chalicosis of, 703 
circulation in, study of, 129 
circulatory changes in, 676 
congestion of, 677 
cysts of, 723 INDEX 
1303 
Lungs, dust particles in, 684 
edema of, 678 
embolism of, 38, 678, 679 
emphysema of, 681, 683 
epithelium of, inflammation of, 685 
reversion of, 703 
examination, post-mortem, of, 1209, 
1225 
exudation in, 687, 690 
gangrene of, 683 
hemorrhage of, 679 
hepatization of, 687, 689 
hyperemia of, 677 
hypostatic congestion of, 677 
infarction of, 38, 679 
inflammation of (see Pneumonia), 
684 
injuries of, 676 
lesions of, in typhoid fever, 273 
lobule, ref., 685 
lymph-vessels of, 685 
malformations of, 676 
perforation of, 676 
phthisis, 704 
pigmentation of, 685, 703 
pneumokoniosis, 704 
portal of entry for bacteria, ref., 698, 
701 
tubercle bacilli, 704 
preservation of, 1210 
reaction of tissue in, 705 
resolution, commencing, in, 689 
delayed, in, 691 
siderosis of, 703 
streptothrix in, 696 
structure of, 684 
syphilis of, 720 
thrombosis of, 679 
transposition of. 676 
tuberculosis of (see Tuberculosis, 
pulmonary), 704 
tumors of, 721 
Lupus, 300 
Lusk, G., on metabolism in diabetes, ref., 
491; on nutrition, ref., 4 
Lymphadenitis, 549 
Lymphadenoma of mediastinum, 723 
Lymphangiectasis, 658 
Lymphangioendothelioma, 443 
Lymphangioma, 424, 658 
cavernosum, 424 
cysticum, 424 
differential diagnosis of, 425 
Lymphangioma, of bone, 1081 
dura mater cerebralis, 1092 
spleen, 580 
Lymphangitis, acute infective, 659 
syphilitic, 660 
tuberculous, 659 
Lymphatic constitution, 500 
Lymph-follicles, 546 
Lymph-nodes, 546 
atrophy of, 547 
bacteria in, ref., 546 
bronchial, as portals of entry for 
bacteria. 676 
lesions of, 675 
pigmentation of, 675 
tubercle bacilli in, 676 
degeneration of, 548 
edema of, 548 
general characters of, 546 
germicidal action of, ref., 176 
hemo-, 546 
Hodgkin's disease, 556 
hyperplasia of, 396, 550, 554 
inflammation of, 549 
in status lymphaticus, 501 
mesenteric, lesions of, in typhoid 
fever, 270 
parasites in, 565 
pigmentation of, 548 
regeneration of, 91; ref., 546 
scrofula of, 552 
suppuration of, 550 
syphilis of, 553 
tracheal, lesions of, 675 
pigmentation of, 675 
tuberculosis of, 551, 553 
tumors of, 564 
Lymph-nodules, 546 
Lymphoblastoma, 430 
differential diagnosis of, 431 
metastasis of, 431 
Lymphocytes, 522 
as inhibitory agents, 553 
large, 523 
Lymphocytoma, 430 
Lymphocytosis, 525, 527 
Lymphoma, 554 
of intestine, 783 
mediastinum, 723 
stomach, 755 
Lymphomata, 396 
leukemic, 555 
pseudoleukemic, 555 1304 
INDEX 
Lymphoprotease, 121 
Lymphorrhagia, 659 
Lymphosarcoma, 430 
of intestine, 784 
lung, 722 
lymph-nodes, 564 
mediastinum, 723 
spleen, 580 
Lymphosarcomatosis, 431 
Lymph-vessels, 658 
dilatation of, 658 
formation of, 90 
inflammation of, 659 
of lung, 685 
nose, ref., 662 
syphilis of, 660 
thrombosis of, 659 
tuberculosis of, 659 
tumors of, 422, 441, 660 
Lynch, on congenital infection, ref., 176 
Lynch, K. M., on trichomonas, ref., 140 
Lyon, on lipomatosis, ref., 52 
MacCallum, J. B., on changes in myo- 
cardium, ref., 614 
MacCallum, W. G., on angioma of in- 
testine, ref., 782; on angioma of 
stomach, ref., 755; on endotheliomata, 
ref., 443; on hematozoan infections of 
birds, ref., 348; on hypertrophy of 
islands of Langerhans, ref., 803; on 
lesions of goiter, ref., 489; on metabo- 
lism in fever, ref., 502; on parathy- 
roids, ref., 588; on phlegmonous 
enteritis, ref., 765; on regenerative 
changes in liver, ref., 817; on repair of 
liver, ref., 828; on streptococcal 
bronchopneumonia, ref., 694 
MacCallum and Voegtlin, on parathy- 
roidectomy and tetany, ref., 588 
MacCarty, 17. C., and Broders, A. C., on 
chronic ulcers of stomach, ref., 
753 
Mace, on typhoid bacilli, ref., 274 
MacFadyen and MacConkey, on tubercle 
bacilli in mesenteric lymph 
nodes, ref., 766 
MacGowan, on hypertrophy of prostate, 
ref., 1027 
Machard, on perforation of gall-bladder, 
ref., 842 
Macintosh and Fildes, on paresis, ref., 
1165 
Mackenzie, J., on disease of heart, ref., 
628 
Macklin, C. C., on mitosis, ref., 81 
MacLean, H., on lipoids, ref., 53 
MacLeod, on diabetes, ref., 492; on physi- 
ology, ref., 516 
MacNeal, W. J., and Taylor, R. M., on 
coccidioidal granuloma, ref., 
169 
Macrocheilia, 425 
Macrocytase, 205 
Macrocytes, 121 
Macroglossia, 425, 735 
Macrophages, 109, 120 
Maculae gonorrhoicse, 910 
tendineae, 597 
Madura foot, 262 
Magnesium salts in gall-stones, 847 
Magnusson, on cardiac tumors in animals, 
ref., 634 
Major, R. H., on metastatic carcinoma of 
ovary, ref., 971 
Maladie cystique, 993, 997 
de Reclus, 452 
pyocyanique, 244 
Malakoplakia, 901 
Malaria, 342 
bibliography of, ref., 349 
blood, lesions of, in, 342 
methods of examination of, 349 
chronic, 343 
estivoautumnal type, 345 
excitant of, 344 
haematozoon of, 344 
lesions of, 342 
mosquitoes as intermediary host in, 
346 
quartan type, 344 
tertian type, 344 
Malassez, on adamantinoma, ref., 448 
Malassez and Galippe, on odontoma, ref., 
406 
Malformations, 355 
involving single individuals, 356 
two individuals, 362 
tissue, 370 
Malignancy of tumors, 376 
attributes of, 377 
Malignant edema, 323 
pustule, 258 
Mall, F. P., on malformations of heart, 
ref., 600 
Mallory anilin-blue stain, 1237 1305 
INDEX 
Mallory, F. B., on congestion of liver, 
ref., 811; on excitant of scarlet fever, 
ref., 340; on fibroglia, ref., 396; on 
focal lesions in typhoid fever, ref., 271; 
on focal necrosis of liver, ref., 815; 
on giant cells in sarcoma of bone, ref., 
1080; on glioma of ependyma, rei., 
1109; on Hodgkin's disease, ref., 563; 
on muscle and connective-tissue stain, 
ref., 421; on necroses of liver, ref., 814; 
on sacral tumors and cysts, ref., 1112; 
on staining myoglia fibrils, ref., 420; 
on typhoid fever, ref., 270; on dural 
endothelioma, ref., 1092 
Mallory and Hornor, on bacillus of 
whooping-cough, ref., 351 
Mallory, Hornor, and Henderson, on 
bacillus of whooping-cough, ref., 
351 
Mallory and Medlar, on excitant of 
scarlet fever, ref., 340 
Mallory and Wright, on anilin-blue stain, 
ref., 1237; on Kaiserling's method of 
fixation, ref., 1242; on methylene- 
blue stain, ref., 1237; on staining fat- 
acid, ref., 53; on technique, ref., 1227 
Malta fever, 319 
Mamma, 986 
abscess of, 991 
absence of, 987 
accessory, 987 
actinomycosis of, 994 
anatomy of, 986 
circulation in, 987 
cystic disease of, 997 
cysts of, 997, 1010 
embryology of, 986 
function of, 987 
hemorrhage in, 990 
hypertrophy of, 988 
inflammation of (see Mastitis), 990 
lactating, 986 
male, lesions of, 1030 
malformations of, 987 
nipple, hemorrhage from, 990 
inflammation of, 990 
Paget's disease, 1009 
, senile involution of, 986 
sporotrichosis, 995 
sprue, 995 
syphilis of, 994 
tuberculosis of, 993 
tumors of, 995 
Mandlebaum, F. S., on primary spleno- 
megaly, ref., 578; on teratoma of 
mediastinum, ref., 723 
Mandlebaum, F. S., and Celler, H. L., on 
myasthenia gravis, ref., 1035 
Manfredi, L., on germicidal action of 
lymph-nodes, ref., 176 
Manifold, on cavernous angioma of heart, 
ref., 634 
Mankowsky, A., on preparation of brain 
sections, ref., 1242 
Manley, 0. T., and Marine, D., on 
transplantation of spleen, ref., 93; 
on transplantation of thyroid, ref., 93; 
on transplantation of tissues, ref., 388 
Mann, on melanin, ref., 66; on micro- 
chemical reactions for iron, ref., 64; 
on poisons, ref., 481 
Mann, F. C., on infarction of lung, ref., 
679 
Mannasse, on amyloid tumors of tongue, 
ref., 668 
Manz, on aneurysm, ref., 649 
Marburg, 0., on muscular dystrophy, 
ref., 1035; on myasthenia gravis, ref., 
1035 
Marchand, F., on endothelioma, ref., 441; 
on inflammation, ref., 101; on malfor- 
mations, ref., 355; on neurocytoma, 
ref., 409; on pseudomyxoma peritonei, 
ref., 797; on syphilitic arteritis, ref., 
647; on teratoma of testicle, ref., 
1023; on tissue regeneration, ref., 76, 
92 
Marchand and Krehl, on pathology, ref., 7 
Marchi, on degeneration of nerve fibers, 
ref., 1142 
Marchi's method of staining nerve tissue, 
1181 
Marchiafava and Bignami, on malaria, 
ref., 349 
Marcus, on entrance of bacteria through 
intestine, ref., 792 
Marf, on sarcomata of thyroid, ref., .587 
Marfan, A. B., on bronchial lymph-nodes, 
ref., 676 
Marfan, Bouchard, and Brissaud, on 
tuberculous bronchial lymph- 
nodes in children, ref., 553 
Margulis, on hydrocephalus, ref., 1107 
Marie, P., on arteriosclerosis of brain, 
ref., 1129; on hyperplastic periostitis, 
ref., 1046; on tabes dorsalis, ref., 1144 1306 
INDEX 
Marine and Lenhart, on anatomy of 
thyroid, ref., 585; on lesions of goiter, 
ref., 489 
Marine, D., and Manley, O. T., on trans- 
plantation of thymus, ref., 93 
Marinescu, on chromatolysis, 1139 
Markoe, F. FL, and Schley, W. S., on 
sacral tumors and cysts, ref., 
1112 
Marrow, bone- (see Bone-marrow). 
Martin, C. F., on ulcers of stomach, ref., 
753 
Martin and Rennie, on cardiac thrombo- 
sis, ref., 609 
Martius, on autointoxication, ref., 469; 
on sympathoblastoma, ref., 411 
Martland, H. S., on giant-cell sarcoma, 
ref., 436; on trinitrotoluene poisoning, 
ref., 477 
Marx, on sarcoma of liver, ref., 839 
Massaglia, on extirpation of carotid in 
animals, ref., 594 
Mast cells, 109 
Mastigophora, 135 
Mastitis, 990 
acute exudative, 990 
chronic, 991, 997 
cirrhosing, 997 
interstitial, 997 
cystic, chronic, 452, 997 
suppurative, 991 
syphilitic, 994 
tuberculous, 993 
Matas, R., on hair balls in stomach, ref., 
759 
Mathews, on malignant tumors of tonsil, 
ref., 741 
Mathews, A. P., on action of light, ref., 17; 
on the chemistry of fats, ref., 49; on 
physiological chemistry, ref., 4 
Matsuoka, on lipomatosis, ref., 52 
Matti, on thymus and its relation to 
rickets, ref., 581 
Mayer, on carcinoma of epiglottis, ref., 
669 
Mayer, E., on exposure of body to sun's 
rays, ref., 18 
Mayer, M., on trypanosomes, ref., 137 
Maximow, A., on amyloid degeneration, 
ref., 59; on polyblasts, ref , 89; on re- 
generation of ovary, ref., 87 
Mayer and Baehr, on bismuth poisoning, 
ref., 857 
Mayesima, on primary acute polymyo- 
sitis, ref., 1039 
Mayo, C. FL, on carcinoid tumors of ap- 
pendix, ref., 786; on extroversion of 
bladder, ref., 896 
Mayo, W. J., on acute diverticulitis, ref., 
760; on chronic ulcers of stomach, ref., 
753; on duodenal ulcers, ref.. 767; on 
tuberculous peritonitis, ref., 793 
McC ampbell, on Mexican typhus, ref., 
334 
McCarrison, on diseases of thyroid, ref., 
585 
McClendon, J. F., on physical chemistry, 
ref., 4 
McCollum, E. V., on dietary diseases, ref., 
496 
McConnell, on mitotic figures in carci- 
noma, ref., 457 
McConnell and Spiller, on softening of 
lenticular nuclei, ref., 1172 
McCord, on growth rate in cells, ref., 
95 
McCrae, J., on visceral changes following 
burns, ref., 11; on coilodium sacs, ref., 
353; on mycotic aneurysms, ref., 649 
McCrae and Coplin, on pseudomyxoma 
peritonei, ref., 797 
McCrae, Fyshe, and Ainley, on acute lobar 
pneumonia, ref., 690 
McCrae and Klotz, on fat in liver, ref., 
820 
McCrudden, F. EL, on muscular dystro- 
phy, ref., 1034 
McCrudden, F. H., and Sargent, C. S., on 
muscular dystrophy, ref., 1034 
McFarland, J., on vaginitis, ref., 915 
McFarland, W. L., on pigmentation of in- 
testine. ref., 789 
McFarland and McConnell, on xanthoma, 
ref., 425 
McGaffin, C. G., on senile dementia, ref., 
1167 
McGrath, B. F., on tumors of prostate, 
ref., 1028 
McLean, A., on myxoma of omentum, 
ref., 794 
McLean, E. H., on sporotrichosis, ref., 
173 
McLean, F. C., on excretion of kidney, 
.ref., 882 
McMahon and Carman, on carcinoma of 
lung, ref., 722 INDEX 
1307 
McMurrich, on size of human embryo, 
ref., 1223 
McNeal and Novy, on cultivation of pro- 
tozoa, ref., 143 
McNee, on calculus formation, ref., 848 
McNee, Renshaw, and Brunt, on trench 
fever, ref., 352 
McWeeney, on rupture of esophagus, ref., 
742 
McWilliams, on carcinoid tumors of ap- 
pendix, ref., 786 
McWilliams, C. A., and Hanes, F. M., on 
leukemic tumors of mamma, 
ref., 1006 
Meakins, on acute rheumatism, ref., 351 
Means, J. H., and Aub, J. C., on exoph- 
thalmic goiter, ref., 489 
Means and Forman, on tumors of mouth, 
ref., 733 
"Measle," 146 
Measles, 342 
and pneumonia, 694 
inoculation of, 342 
Meat poisoning, 323 
Meckel's diverticulum, 358, 759 
Mediastinitis, 723 
Mediastinum, 723 
cysts of, 723 
inflammation of, 723 
tumors of, 723 
Meek, on mitosis, ref., 78 
Megaloblasts, 520, 521 
Megalocytes, 520 
Mehrdorf, on sarcoma of pleura, ref., 729 
Melanemia, 533 
Melanin in melanosarcoma, 432 
in tumors, 447 
Melanins, 66 
Melanoblast in nsevus, 447 
Melanocarcinoma, 433, 460, 467 
of liver, 839 
vulva, 913 
Melanoma, 433 
Melanosarcoma, 432 
differential diagnosis of, 433 
of intestine, 784 
liver, 839 
mamma, 1006 
nose, 662 
salivary glands, 798 
spleen, 580 
thyroid, 587 
vulva, 912 
Melanosis of intestine, 788 
Melchior, E., on duodenal ulcers, ref., 767 
Mellon, on Hodgkin's disease, ref., 557 
Meltzer, on edema, ref., 29; on functional 
provision, ref., 83; on protection of 
body against bacteria, ref., 176; on pul- 
monary edema, ref., 678 
Membranes and ventricles of brain, 1089 
Mendel, L. B., on deficient diet, ref., 9 
Mendel, on paralysis agitans, ref., 1171 
Mendelsohn, on apoplexy of thymus, ref., 
581 
Menetrier, on cancer, ref., 468; on epi- 
thelial metaplasia, ref., 75 
Menge, on carcinoma of vagina, ref., 917 
Meningitis, 253, 1095 
acute, 1095 
basilar, 1099 
cellular, acute, 1096 
cerebrospinal, acute, 253 
epidemic, 254 
chronic, 1099 
exudative, acute, 1096 
meningococcus, 254 
relation of middle ear to, ref., 1098 
serum therapy in, 256 
spinal, 1104 
acute exudative, 1104 
chronic, 1104 
syphilitic, 1101, 1173 
tuberculous, 1099, 1104 
typhoid, ref., 273 
Meningocele, 359 
Meningococcus, 254, 255 
Menorrhagia, 929 
Mense, C., on animal parasites, ref., 132 
Menstruation, changes in uterus, 928 
vicarious, 987 
Mental deficiency, 1114 
Menzell, on larynx, ref., 669 
Mercuric chloride poisoning, 475 
Merismopedia, 160 
Merkel, H., on angioma of liver, ref., 836; 
on bone in lymph-nodes, ref., 552; 
on pseudomyxoma peritonei, ref., 797; 
on tumors, ref., 467 
Meroz, on cardiac tumors, ref., 634 
Merozoites in malaria, 345 
Mesentery, circulation in, study of, 127 
cysts of, 796 
tumors of, ref., 794 
Meslay and Parent, on tuberculous in- 
flammation of parotid, ref., 798 1308 
INDEX 
Mesothelioma, 442 
of adrenals, 592 
lung, 721 
peritoneum, 795 
pleura, 729 
Mesothelium, ref., 107 
Messmates, 167 
Mestrezat, W., on composition of cere- 
brospinal fluid, ref., 1107 
Metabolism, anomalies of, 1050 
in fever, 502 
Metamorphosis, reversionary, 75 
Metaplasia, 74, 371 
Metastasis of carcinoma, 454 
of sarcoma, 428 
tumors, 372, 378 
by contact, 378 
organs involved in, 379 
retrograde, 378 
Metazoa, 143 
Metcalf and Safford, on carcinoma of 
ureter, ref., 904 
Metchnikoff, on immunity in infectious 
diseases, ref., 224; on the phagocytic 
powers of cells, ref., 122; on phago- 
cytosis, ref., 124; on protective action 
of skin, ref., 175 
Metchnikoff and Roux, on animal inocula- 
tions in syphilis, ref., 308 
Methylamino-acetocatechol, 491 
Methylene blue stain, 1237, 1238 
Metritis, 925 
acute, 930 
chronic, 932 
para-, 931 
peri-, 930 
Metrorrhagia, 28, 929 
Metzger, M., on metastatic carcinoma of 
ovary, ref., 971 
Meulengracht, on polypoid tumors of 
stomach, ref., 754 
Meves, on mitochondria, ref., 77 
Meyer, on carcinoid tumors of appendix, 
ref., 786; on hemolymph-nodes, ref., 
547; on obstruction of venae cavae, 
ref., 655; on regeneration of lymph- 
nodes and lymph-vessels, ref., 91, 546; 
on sporotrichosis, ref., 173 
Meyer, J., on Trichinella spiralis, ref., 153 
Meyer, P., on melanosarcoma of vulva, 
ref., 912 
Meyer, R., on adenomyoma of intestine, 
ref., 782; on double ureters, ref., 852; 
on sarcoma of vagina, ref., 916; on 
teratoma of testicle, ref., 1023; on 
tissue displacement during embryonic 
life, ref., 355 
Meyer and Aird, on sporotrichosis, ref., 
173 
Meyer and DuBois, on metabolism in 
pernicious anemia, ref., 536 
Meyer and Heineke, on blood formation 
in spleen and liver in pernicious 
anemia, ref., 537 
Meyers, on inanition, ref., 9 
Meyers, A. E., on tuberculous menin- 
gitis, ref., 1099 
Meynert's method of opening brain, 1196 
Michaelis, L., on reaction of blood, ref., 
516 
Michaelis, M., on osteitis fibrosa, ref., 
1049 
Micrencephalia, 360 
Microcephalia, 1110 
Micrococci, 159 
Micrococcus catarrhalis, 256 
flavus, 256 
gonorrhoese, 251 
melitensis, 320 
pyogenes, 238 
aureus, 234 
tetragenus, 245 
Microcytase, 205 
Microcytes, 520 
Micromastia, 987 
Micron, ref., 159 
Microorganisms, forms of, 158 
in inflammation, 104 
mouth, 736 
relation of, to disease, 175 
ultramicroscopic, 353 
Microphages, 120 
Microsporon furfur, 172 
Microtomes, types of, 1234 
Middledorpf, on carcinomata of thyroid, 
ref., 587 
Mieczkowski, on calculus formation, ref., 
848 
Miescher's tubes, 142 
Mignot, on calculus formation, ref., 848 
v. Mikulicz-Radetsky and Kummel, on 
tumors of mouth, ref., 733 
Milium, 394 
Milk cysts, 394 
Miller, on active immunity, ref., 189; 
on lymph-channels of lung, ref., 685; INDEX 
1309 
on sarcoma of intestine, ref., 784; on 
tubercle bacilli, ref., 292 
Miller, H. R., on complement fixation in 
tuberculosis, ref., 293 
Miller, J. W., on gonorrheal salpingitis, 
ref., 978 
Miller and Lusk, on active immunity, ref., 
189 
Miller and Wynne, on endothelium and 
mesothelium, ref., 442; on mesothe- 
lioma of peritoneum, ref., 795 
Milne, L. S., on repair of liver, ref., 817 
Miloslavich, on carcinoma of appendix, 
ref., 786 
Miloslavich and Namba, on tumors of 
appendix, ref., 785 
Minkowski, on gout, ref., 494 
Minot, C. S., on body changes, ref., 45; 
on cell development, ref., 83; on cell 
proliferation, ref., 377; on endothelium 
and mesothelium, ref., 442; on meso- 
thelium, ref., 107; on regressive proc- 
esses, ref., 44 
Minot and Lee, on metabolism in per- 
nicious anemia, ref., 538 
Misick, on teratoma of liver, ref., 840 
Misumi, on carcinoma of peritoneum, 
ref., 796 
Mitchell, A. P., on foreign bodies in 
appendix, ref., 781; on tonsillar tuber- 
culosis, ref., 739 
Mitchell, P., on types of B. tuberculosis, 
ref., 299 
Mitochondria, 77 
in red cells in anemia, 535 
Mitosis, 78 
abnormal phases of, 80 
heterotypical, 382 
in carcinoma, 457 
tumors, 348 
significance of, 80 
Mitotic figure, 79 
Mitulescu, on tubercle bacilli on books, 
ref., 299 
Miyata, on tumors of testis, ref., 1021 
Mole, 447 
blood, 983 
hydatid of placenta, 954 
placental, 953, 954 
Moller, on action of light on intracellular 
enzymes, ref., 17 
Moller-Barlow disease, ref., 496, 1055 
Molluscum contagiosum, 141 
Monaster, 78 
Monckeberg, J. G., on arteriosclerosis, ref., 
641; on carotid gland, ref., 592; on 
endothelium and mesothelium, ref., 
442; on paraganglioma of carotid, 
ref., 413; on rhabdomyoma of seminal 
ducts, ref., 1024; on sarcoma of vagina, 
ref., 916 
Monilia albicans, 171 
Monomorphism in bacteria, 161 
Monsters, 355 
double, 363 
Monstra duplicia, 363 
Montgomery, on cell division, ref., 80 
Montgomery, E. M., on lung pigment, 
ref., 675 
Monti and Berggrun, on Von Jaksch 
anemia, ref., 543 
Moore, on acute cerebrospinal meningitis, 
ref., 254; on diseases of animals, ref., 
183; on infectious diseases of animals, 
ref., 353; on vaccination, ref., 339 
Moore, W. C., on syphilitic arteritis, ref., 
647 
Morbus gelatinosus, 797 
maculosus neonatorum, 29 
Morestin, on lipoma of muscle, ref., 
1041 
Morgan, T. H., on heredity and sex, ref., 
21; on regeneration, ref., 83 
Morley, on epithelioma of scrotum, ref., 
1014 
Morphine poisoning, 476 
Morris, R. S., on dermoid cysts of 
mediastinum, ref., 723; on hyperplasia 
of lymphatic tissue in liver, ref., 835 
Morse, J. L., on cirrhosis of liver in 
childhood, ref., 830 
Morse, P. F., and Stott, E., on tissue 
reactions and tubercle bacillus, 
ref., 293 
Moschcowitz, E., on carcinoid tumors of 
appendix, ref., 786; on non-parasitic 
cysts of liver, ref., 839; on osteoma of 
ovary, ref., 961; on splenomegaly, ref., 
544; on tetanus, ref., 318 
Mosenthal, H. O., on diet in nephritis, ref., 
882 
Moser, on cardiac thrombi, ref., 609; 
on tuberculous endocarditis, ref., 626; 
on tuberculosis of heart, ref., 619 
Moser and v. Pirquet, on agglutination of 
streptococci, ref., 239 1310 
INDEX 
Mosquitos in malaria, 346 
in yellow fever, 335 
Moss, W. L., on blood groups, ref., 531, 
on blood transfusion, ref., 531 
Most, A., on lymph-vessels of nose and 
pharynx, ref., 662 
Mott, F. W., on death from shell shock, 
ref., 1121 
Mottram, J. C., on radium exposures, ref., 
13 
Mouisset and Mouriquand, on sublimate 
poisoning, ref., 475 
Moulds, 158, 171 
higher, 172 
methods of study of, 173 
Mouse, cancer in, 388 
Mouth, 730 
bacteria in, 736 
cysts of, 734 
disinfection of, ref., 249 
inflammation of (see Stomatitis), 730 
malformations of, 730 
microorganisms in, 736 
syphilis of, 733 
tuberculosis of, 732 
tumors of, 733 
Moynihan, Sir Berkeley, on duodenal 
ulcers, ref., 767 
Much, H., on immunity, ref., 224; on 
stain for tubercle bacilli, ref., 296 
Mucin in carcinomata, 467 
in myxomata, 400 
stains for, 56, 1238 
Mucous degeneration, 54 
membranes, polypi of, 401 
regeneration of, ref., 85 
patches in syphilis, 306 
tissue, tumors of, 399 
Muhlens, P., on relapsing fever, ref., 325 
Muhlmann, M., on body changes, ref., 45 
Muir, R., on immunity, ref., 224; on 
repair of liver, ref., 817 
Muir and Ritchie, on bacteriology, ref., 158 
Muller, F., on abrin and ricin intoxica- 
tion, ref., 232; on malignant rhabdo- 
myoma in man, ref., 422 
Muller, on adipocere, ref., 1188; on 
comparative histology of lungs, ref., 
685; on heredity in chondromata, ref., 
403; on hypertrophy of heart, ref., 633; 
on infection and immunity, ref., 224 
Muller, Fr., on natural immunity, ref., 
186; on phagocytes, ref., 121 
Muller, W., on hypertrophy of heart, ref., 
1209 
Muller and Speese, on malignant tumors 
of thyroid, 587 
Muller's fluid, 1229 
Mummification, 69 
Mumps, 797 
Munk, F., on syphilitic nephritis, ref., 883 
Murphy, J. B., on action of lymphocytes, 
ref., 120; on growth of tumors in chick 
embryo, ref., 388; on tissue growth, 
ref., 93 
Murphy, J. B., and Morton, J. J., on ir- 
radiated tumors, ref., 15; on tissue 
growth, ref., 93 
Murray, on cancer in animals, ref., 387; 
on heredity in cancer, ref., 387 
Muscle, 1031 
abscess of, 1038 
anatomy of, 1031 
atrophy of, 1032, 1035 
lipomatous, 1035 
progressive, spinal, 1143 
bone in, 1040 
calcification of, 1038 
cartilage in, 1040 
congenital disease of, 1036 
degeneration of, 1036, 1037 
dystrophy of, 1033 
embolism of, 1038 
fat in, 1035 
hemorrhage of, 1038 
hyperplasia, replacement of, 1039 
hypertrophy of, 1035 
pseudo-, 1035 
infarction of, 1038 
infiltration, fatty, of, 1036 
hydropic, of, 1038 
inflammation of (see Myositis), 1038 
injuries of, 1038 
myasthenia gravis, 1035 
necrosis of, 1032 
ossification of, 1039 
parasites of, 1041 
pigmentation of, 1032 
relation of, to circulation of blood, 
23 
rigor mortis, 1031, 1188 
rupture of, 1038 
syphilis of, 1040 
tissue, regeneration of, 84 
tuberculosis of, 1040 
tumors of, 419, 1040 INDEX 
1311 
Musgrave and Clegg, on ameba, ref., 134; 
on trypanosomiasis, ref., 137 
Musser, Pearce, and Gwyn, on actinomy- 
cosis, ref., 262 
Mustard gas, 472 
Myasthenia gravis, 1035 
Mycelium, 171 
Mycetoma, 262 
Mycosis, intestinal, 260, 775 
pharyngis, 736 
Myelin bodies, ref., 53 
Myelinic substances in cells, ref., 49 
Myelitis, acute disseminated, 1158 
central, 1159 
chronic disseminated, 1152 
interstitial, 1152 
transverse, 1152 
infectious, 1162 
osteo-, 1063 
parenchymatous, ref., 1156 
peripheral, 1159 
polio-, acute anterior, 1159 
transverse, 1159 
unilateral, 1159 
Myeloblasts, 525 
Myelocytes, 523, 1071 
Myelocytoma, 1074 
Myeloma, 431, 1073 
of dura mater cerebralis, 1093 
plasma-cell, 431 
Myelomeningocele, 359 
Myeloplaxes, 1078 
Myocarditis, 615 
chronic interstitial, 616 
gonorrheal, ref., 616 
interstitial, 615 
suppurative, acute, 615 
syphilitic, 619 
tuberculous, 619 
Myocardium, inflammation of (see Myo- 
carditis), 615 
lesions of, in diphtheria, ref., 314 
segmentation and fragmentation of, 
613 
" Myofibroma," 420 
Myoma, 419 
levicellulare, 419 
malignant, 440, 1040 
of uterus, 941 
of appendix vermiformis, 785 
esophagus, 744 
intestine, 782 
kidney, 890 
Myoma of mamma, 1005 
stomach, 754 
testicle, 1021 
uterus, 936, 937 
sarcomatodes, 421 
striocellulare, 421 
Myomalacia, ref., 615 
Myosarcoma, 421, 440 
of uterus, 942 
Myositis, chronic, 1039 
dermato-, 1039 
interstitial, 1039 
ossificans, 404, 1039 
poly-, 1039 
suppurative, 1038 
syphilitic, 1040 
tuberculous, 1040 
Myotonia congenita, 1036 
Myxedema, 485, 1044 
Myxochondroma, 403 
Myxofibroma of pharynx, 740 
Myxoglioma of brain, 1177 , 
Myxolipoma, 402 
Myxoma, 399 
gelatinosum, 400 
medullare, 400 
molle, 400 
of bone, 1075 
brain, 1176 
dura mater spinalis, 1103 
esophagus, 744 
Fallopian tubes, 981 
heart, 634 
larynx, 668 
lymph-nodes, 564 
mamma, 1004 
male, 1030 
nerves, 418 
pancreas, 806 
peritoneum, 794 
pia mater cerebralis, 1101 
spinalis, 1105 
salivary glands, 798 
testicle, 1021 
thymus, 582 
pseudo-, of peritoneum, 967 
Myxogumma of heart, 634 
Myxosarcoma, 401, 440 
of bladder, urinary, 903 
kidney, 890 
nerves, 1180 
umbilical cord, 797 
Myxosporidia, 142 1312 
INDEX 
Nabothian glands, 394, 1220 
Naegeli, 0., on blood, ref., 514; on 
diseases of blood, ref., 533; on statistics 
of tuberculosis, ref., 296 
Naevus, 447 
cavernosus, of liver, 835 
prominens, 423 
vascular, 423 
Nagana, 136 
Nagel, on malformations of female gen- 
erative organs, ref., 909 
Nakayama, ongiant-cellsarcoma,ref., 434; 
on sacral tumors and cysts, ref., 1112 
Napp, on cardiac tumors, ref., 634 
Nash, on angiosarcoma of omentum, ref., 
794 
Naunyn, on repair of liver, ref., 828 
Nauwerck, C., on post-mortem examina- 
tions, ref., 1186 
Naville and Fromberg, on brain emboli, 
ref., 42 
Nebelthau, on intestinal tuberculosis, ref., 
766 
Necator americanus, 151 
Neck, appearance of, in strangulation, 
504, 1189, 1224 
cysts of, 736 
wry, 1039 
Necker, on statistics of tuberculosis, ref., 
296 
Necrobiosis, 45 
Necrosis, 67 
coagulation, 69, 71 
fat, 71 
of pancreas, 804 
focal, 69, 232 
in liver, 814 
in typhoid fever, 271 
in inflammation, 113 
liquefaction, 67 
of appendix vermiformis, 777 
bone, 1067 
kidney, 857 
liver, 814 
muscle, 1032 
phosphorus, of bone, 1069 
Negri bodies, 328 
staining, impression method, 329 
methods for, 329 
Negri and Mier emet, on organism of 
Hodgkin's disease, ref., 563 
Neisser, on animal inoculations in syphilis, 
ref., 308; on S. pyogenes aureus, ref., 237 
Neisser and Baermann, on animal in- 
oculations in syphilis, ref., 308 
Neisser and Gins, on B. diphtherise and its 
toxins, ref., 316 
Neisser and Sachs, on hemolysis tests, 
ref., 208 
Nematoda, 149 
Neoplasms (see Tumors), 372 
Nephritides, 861 
Nephritis, acute focal interstitial, 869 
chronic, 872 
degenerative type, 874 
excitants of, 880 
indurative type, 877 
inflammatory type, 874 
interstitial type, 877 
parenchymatous type, 874 
pyelo-, 885 
syphilitic, 883 
tuberculous, 882 
vascular type, 872 
diffuse, acute, 865 
excitants of, 870 • 
degenerative type, 869 
exudative type, 869 
experimental, 880 
functional pathology of, 880 
general considerations, 861 
glomerulo-, 867 
hemorrhagic type, 869 
interstitial type, 870 
lesions following, 871 
malarial, 871 
parenchymatous type, 869 
peri-, 886 
productive, 869 
suppurative, 864, 874, 884 
variations in type, 869 
Nephrocirrhosis glomerularis, 876 
Nephropathies, arteriosclerotic, 861, 872 
Nephroses, 861, 862 
Nerve cell, degeneration of, 1133, 1163 
nature of, 1129 
pigment in, 1130 
structure of, 1129 
fibers, degeneration of, 1133 
, Marchi's method of staining, 1181 
tissue, Bielchowsky's method of 
staining, 1182 
eosin-hematoxylin stain for, 1181 
Held's method of staining, 1182 
Marchi's method of staining, 1181 
Nissl's method of staining, 1181 INDEX 
1313 
Nerve cell tissue, preparation and study 
of, 1180 
regeneration of, 83, 1139 
tracts, crossed pyramidal, 1140 
degeneration of, 1141 
direct pyramidal, 1140 
degeneration of, 1141 
Nerves, degeneration of, 1133, 1163 
fixation of tissue, 1199 
inflammation of (see Neuritis), 1163 
injuries of, 1116 
leprosy, 1176 
lesions of, in diphtheria, ref., 314 
morphology of, 1129 
neurofibroma of, 414 
preservation of, 1201 
regeneration of, 1139 
tic douloureux, 1164 
tumors of, 416, 1180 
Nervous system, 1089 
artefacts of, ref., 1112 
central, dementia, senile, 1169 
paralysis agitans, 1170 
paresis, general, 1165 
degeneration of, 1133, 1140 
primary, of, 1143 
progressive lenticular, 1171 
secondary, of, 1141 
examination, post-mortem, of, 1191, 
1199, 1201 
leprosy of, 1176 
lesions of, in typhoid fever, 273 
neurone theory of, 1129 
regeneration of, 1139 
relation of, to circulation of blood, 
23 
sympathetic, development of, 408 
tumors of, 408 
syphilis of, 1173 
tuberculosis of, 1172 
tumors of, 1176 
Netter, on bacteria in exudative pleuritis, 
ref., 725; on pneumococcus in em- 
pyema, ref., 727; on preventive inocu- 
lation in plague, ref., 321 
Neuberg, on amyloid degeneration, ref., 
59 
Neuberger, J., on sublimate poisoning, 
ref., 857 
Neufeld, on agglutination of streptococci, 
ref., 239 
Neufeld and Handel, on pneumococcus, 
ref., 251 
Neufeld and Rimpau, on opsonins, ref., 
210 
Neufeld and Topfer, on opsonins, ref., 211 
v. Neugebauer, on malformations of male 
generative organs, ref., 1011 
Neuhoff, S., on clinical cardiology, ref., 
628 
Neumann, A., on bacterial calculi in 
kidney, ref., 905 
Neumann, R. O., on bacteria of nose, ref., 
662 
Neumann and Mayer, on animal para- 
sites, ref., 132 
Neurath, R., on tuberous cerebral 
sclerosis, ref., 1114 
Neurilemma, 1134 
Neurinoma, 415 
Neuritis, chronic, interstitial, 1164 
exudative, 1163 
multiple, 1163 
optic, 1146 
Neurnberg, on leiomyoma of kidney, ref., 
1040 
Neuroblastoma, 408, 409, 411 
differential diagnosis of, 411 
of adrenals, 592 
Neurocytoma, 408 
Neurofibromatosis, 414 
and paraganglioma, 413 
Neuroglia, 1133 
cells, hyperplasia of, 1139 
nature of, 1133 
types of, 1133 
Neuroglioma ganglionare, of brain, 1176 
of pineal gland, 1182 
Neuroma, 416 
amputation, 419 
false, 416, 1180 
fibrillar, 418 
amyelinicum, 416 
myelinicum, 416 
gangliocellulare, 416 
of nerves, 1180 
plexiform, 414 
racemose, 414 
true, 416 
Neurones, action of fatigue on, 1138 
toxins on, 1137 
degeneration of, 1133, 1136, 1141, 
1143 
primary, of, 1143 
secondary, of, 1141 
toxic, of, 1163 1314 
INDEX 
Neurones, motor and sensory, degenera- 
tion of, 1150 
corticospinal, 1140 
degeneration of, 1144 
peripheral, 1140 
degeneration of, 1143, 1144 
upper, 1140 
nature of, 1129 
nutritional disturbance of, 1136 
sensory, lower, 1140 
peripheral, 1140 
degeneration of, 1145 
upper, 1141 
systems of, 1140 
theory of nervous system, 1129 
Neuroretinitis albuminurica, 874 
Neuroryctes hydrophobia, 329 
v. Neusser, on status lymphaticus, ref., 
500 
New, G. B., on granulomata of tongue, 
ref., 736 
Newberger, J., on sublimate poisoning, 
ref., 475 
New-born, examination, post-mortem 
of, 1223 
size and characters of, 1223 
Newman, H. H., on biology of twins, ref., 
362 
Newmark, L., on diabetes insipidus, ref., 
493 
Newton, on rupture of heart, ref., 604 
Nichols, H. J., on experimental yaws, 
ref., 326; on syphilis, ref., 309 
Nichols, J. L., on ganglion cells in 
typhoid fever, ref., 273 
Nichols and Richardson, on arthritis 
deformans, ref., 1085 
Nicholls, on adenoma of pancreas, ref., 
806 
Nicholson, on carcinoma of gall-bladder, 
ref., 846 
Nicolas and Beau, on spleen in infection, 
ref., 177 
Nicolle, on infective agent in typhus 
fever, 334; on Leishmania infantum, 
ref., 140 
Nicolle, Blaizot, and Conseil, on relapsing 
fever, ref., 325 
Nipple, absence of, 987 
hemorrhage from, 990 
inflammation of, 990 
Paget's disease, 1009 
supernumerary, 987 
Nissl and Alzheimer, on nervous system, 
ref., 1129; on paresis, ref., 1165 
Nitric acid, 471 
oxide fumes, poisoning by, 471 
poisoning, pneumonia from, 698 
Nitrobenzol poisoning, 477 
Nitrogen tetroxide poisoning, pneumonia 
from, 698 
Nix, J. T., on hairpins in stomach, ref., 
759 
Nocard and Leclainche, on infectious 
diseases of animals, ref., 353 
Nocardia, 161, 262 
Nodes, singers', 668 
Noguchi, H., on cultivation of spiro- 
chetes, ref., 139, 326; on demonstra- 
tion of Treponema pallida, ref., 311; 
on rabies, ref., 329; on relapsing 
fever, ref., 325; on serum diagnosis of 
syphilis, ref., 312; on Spirochaeta ictero- 
haemorrhagiae, ref., 139; on syphilis, 
ref., 309; on Treponema in mouth, ref., 
736; on Treponema pallidum, ref., 309; 
on Wassermann reaction, ref., 312 
Noguchi and Cohen, on Chlamydozoa, 
ref., 141; on trachoma, ref., 341 
Noma, 731 
of vagina, 916 
vulva, 910 
von Noorden, on diseases of blood, ref., 
533 
N ordmann, A., on cysts of mamma, ref., 
1010 
Normoblasts, 521 
Norrie, V. H., and Wallace, G., on Paget's 
disease of bone, ref., 1050 
Norris, on carcinoid tumors of appendix, 
ref., 786; on tuberculous pericarditis, 
ref., 599 
Norris, C., on bacterial precipitins, ref., 
208; on myeloma, ref., 1074; on 
precipitins in typhoid fever, ref., 276 
Norris, G. W., on diseases of heart, ref., 
632 
Norris and Larkin, on streptothrix 
pneumonia, ref., 262, 696 
Norris and Pappenheimer, on pneumo- 
cocci, ref., 249 
Norris, Pappenheimer, and Flournoy, on 
relapsing fever, ref., 325 
Norris, Symmers, and Shapiro, on splenic 
anemia, ref., 544 
North, C. E., on streptococcus, ref., 240 INDEX 
1315 
Northrup, W. P., on emphysema of 
lung, ref., 681; on lesions of bronchial 
lymph-nodes, ref., 676; on reptilian 
heart, ref., 600; on tuberculous bron- 
chial lymph-nodes in children, ref., 553 
Northrup and Crandall, on scurvy in 
infants, ref., 496 
Norton, on persistent thymus, in sudden 
death, ref., 581 
Nose, 661 
adenoids, 664 
bacteria in, 662 
cysts of, 662 
hay fever, 661, ref., 662 
hemorrhage from, 661 
inflammation of (see Rhinitis), 661 
lymph-vessels of, ref., 662 
malformations of, 661 
mucous membrane of, 661 
polyp of, 445, 662 
syphilis of, 662 
tuberculosis of, 662 
tumors of, 662 
Notochord, chordoma in, 403 
Novy, F. G., on trypanosomes, ref., 137 
Novy, F. G., and DeKruif, P. H., on toxic 
bodies causing anaphylactic 
shock, ref., 178 
Novy and Knapp, on relapsing fever, ref., 
325; on tick fever, ref., 325 
Noyes, W. B., on adrenals in liver, ref., 
588; on adrenal remnants in liver, ref., 
836 
Nuernberg, F., on tumors of kidney, ref., 
890 
Nutmeg liver, 810, 819 
Nutrition, disturbances of, 9 
relationship of, to disease, 9 
Nuttall, on blood relationships, ref., 198; 
on relapsing fever, ref., 325; on r61e of 
insects in infection, ref., 176 
Nuttall and Shipley, on anopheles in 
malaria, ref., 349 
Nux vomica poisoning, 479 
Nuzum, J. W., on acute poliomyelitis, 
ref., 333 
Oberndorfer, on carcinoid tumors of ap- 
pendix, ref., 786; on carcinoid tumors 
of intestine, ref., 783, 784; on cysts of 
appendix, ref., 788; on diseases of ap- 
pendix, ref., 785; on skin pigments, ref., 
66 
O'Brien, F. W., on hair balls in stomach, 
ref., 759 
Occupation, relation of, to disease, 9 
Ochronosis, 66 
Ochsner, A. J., on chronic ulcers of stom- 
ach, ref., 753 
Oderfeld and Steinhaus, on fetal adenoma 
of thyroid, ref., 586 
Odiorne and Simmons, on cryptorchismus, 
ref., 1015 
Odontoblastoma, 406 
Odontoma, 406 
Oerie, R., on uterine polyps, ref., 937 
Oertel, H., on echinococcus in liver, ref., 
841; on necrosis of liver, ref., 815; on 
nephritis, ref., 874; on tuberculosis and 
carcinoma of lung, ref., 723 
Ogata, T., on blood-plates, ref., 528; on 
experimental cirrhosis of liver, ref., 831 
Ogilvie, on cysts of appendix, ref., 787 
O'Hare, J. P., on experimental nephritis, 
ref., 880 
Oidiomycosis, 171 
Oidium albicans, 171 
in vagina, 918 
Oligocythemia, 517, 518 
Oliver, T., on poisoning by phosphorus, 
ref., 474 
Olsen, G. M., on argyria, ref., 67 
Omentum, cysts of, 795 
examination, post-mortem, of, 1202, 
1211 
tumors of, ref., 794 
Onodi, on polypoid tumors of nasal sep- 
tum, ref., 664 
Oophoritis, 958 
acute exudative, 958 
chronic, 959 
syphilitic, 960 
tuberculous, 959 
Ophuls, W., on "acid-proof" bacilli in 
gangrene of lung, ref., 684; on corpora 
amylacea, ref., 60; on experimental 
nephritis, ref., 880; on nephritis, ref., 
874; on typhoid fever, ref., 273; on ulcer 
of stomach, ref., 751 
Opie, E. L., on bronzed diabetes, ref., 492; 
on disease of pancreas, ref., 492; on 
emboli in lymph-vessels, ref., 659; on 
enzymes in phagocytes, ref., 205; on 
experimental atrophy of Ever cells, ref., 
827; on filarial lymphatic varix, ref., 
155, 658; on hemachromatosis, ref., 65; 1316 
INDEX 
on lesions of pancreas, ref., 803; on 
leucocytic exudates after intraperi- 
toneal injection of bacteria, ref., 792; 
on liver in chloroform anesthesia, ref., 
816; on phagocytes, ref., 121; on pig- 
mentation of liver, ref., 821; on zonal 
necrosis of liver, ref., 815 
Opie and Meakins, on hemorrhagic necro- 
sis of pancreas, ref., 805 
Opikofer, on malignant tumors of nasal 
pharynx, ref., 740 
Opisthorchis felineus, 144 
in gall-ducts, 841 
Opitz, E., on entrance of bacteria through 
intestine, ref., 791; on suppurative 
salpingitis, ref., 978 
Opium poisoning, 476 
Oppel, on air embolism, ref., 42; on re- 
generation of endothelium, ref., 89; on 
technique of tissue culture, ref., 96 
Oppenheim, on brain tumors, ref., 1172; 
on cerebellar ataxia, ref., 1154 
Oppenheimer, B. S., on method of opening 
heart, ref., 1208 
Oppenheimer, C., on ferments, ref., 514 
Opsonic index, 213 
power, determination of, 213 
Opsonins, 209 
clinical significance of, 212 
in typhoid fever, 276 
Orchitis, 1016 
acute exudative, 1017 
chronic, 1017 
leprous, 1021 
syphilitic, 1020 
tuberculous, 1019 
Ordway, T., on carcinoma following x-ray 
burns, ref., 14 
Oriental plague, 320 
Ors6s, on emphysema, ref., 683 
Orth, J., on complex tumors of mamma, 
ref., 1006 
Orth's fluid, 1229 
Orthmann, E. G., on carcinoma of Fallo- 
pian tubes, ref., 981 
Osborne and Mendel, on deficient diet- 
aries, ref., 9 
Oshima, T., on tumors of kidney in chil- 
dren, ref., 892 
Osler, on cachexia, ref., 380; on cretinism, 
ref., 486; on purpura, ref., 500 
Osler and McCrae, on carcinoma of stom- 
ach in children, ref., 756 
Osmic acid as fixative, 1280 
Ossification of penis, 1013 
Osteitis, 1060 
condensing, 1060, 1062 
deformans, 1049 
and sarcoma, 437 
fibrosa, 1046 
differential diagnosis of, 1047 
peri-, 1046 
rarefying, 1050, 1060, 1061 
suppurative, 1063 
syphilitic, 1066 
tuberculous, 1065 
ulcerative, 1069 
Osteoblasts, 1042, 1059 
Osteochondroma, 403, 404 
of mamma, 1005 
Osteoclasts, 72, 119, 1042, 1061 
Osteofibroma, 404 
Osteogenesis imperfecta, 1043 
Osteoid tissue, 1070 
Osteoma, 404 
eburneum, 405 
malignant, 1079 
of bone, 1075 
brain, 1176 
dura mater cerebralis, 1092 
lung, 721 
mamma, 1005 
ovary, 961 
peritoneum, 794 
pia mater cerebralis, 1101 
spinal cord, 1174 
spleen, 580 
thyroid, 587 
spongiosum, 405 
Osteomalacia, 1051 
differential diagnosis of, 1048 
Osteomyelitis, 1063 
chronic, 1065 
fibrosa, 1049 
infectious, acute, 1064 
malignant, 1064 
Osteophytes, 405, 1057, 1076 
Osteoporosis, 1060, 1061 
Osteopsathyrosis, 1043 
Osteosarcoma, 404, 428, 434, 436 
Osteosclerosis, 1060, 1062 
Osteotabes infantum, 1055 
Oswald, A., on nervous system and 
thyroid, ref., 489 
Otis and Evans, on pathogenic blasto- 
mycetes, ref., 171 INDEX 
1317 
Ottenberg, R. and Kaliski, D. J., on blood 
transfusion, ref., 531 
Ovaries, 957 
absence of, 957 
actinomycosis of, 960 
cysts of, 962, 971 
ectopic pregnancy in, 986 
examination, post-mortem, of, 1220, 
1226 
hemorrhage of, 957 
hernia of, 957 
hyperemia of, 957 
hyperfunction of, bleeding due to, 
929 
inflammation of {see Oophoritis), 958 
malformations of, 957 
malpositions of, 957 
microcystic, 959 
position of, 1220 
preservation of, 1221 
regeneration of, 87 
removal of, effect of, on mammary 
carcinoma, 987 
size of, 1220 
syphilis of, 960 
thyroid tissue in, 973 
tuberculosis of, 959 
tumors of, 960 
weight of, 1220 
Ovula nabothi, 394, 1220 
Oxalic acid, 472 
Oxidase reaction in muscle cells, 1031 
Oxydase granulations in myeloma, 431 
Oxyuris in appendix vermiformis, 782 
bladder, urinary, 905 
Fallopian tubes, 981 
vagina, 918 
vermicularis, 150 
Oysters and typhoid fever, 275 
Pacchionian bodies, 1094, 1192 
Pachydermia diffusa, 666 
verrucosa, 666 
Pachymeningitis, 1090, 1103 
chronic, 1091 
externa, acute, 1090, 1103 
interna, acute, 1090 
chronic, 1103 
hemorrhagica, 1091, 1103 
syphilitic, 1092 
tuberculous, 1092, 1103 
Packard, C., on effect of radium ex- 
posures, ref., 13; on sarcoma and 
carcinoma of lungs, ref., 721; on ton- 
sillitis, ref., 738 
Page, H., on diphtheria carriers, ref., 
317 
Paget, J., on Paget's disease of bone, ref., 
1050 
Paget's disease of bone, 1049 
and sarcoma, 437 
differential diagnosis of, 1048 
of nipple, 1009 
Palate, malformations of, 730 
Pallasse and Roubier, on tumors of pleura, 
ref., 728 
Paltauf, A., on blood, ref., 514; on 
cirrhosis of liver, ref., 825; on lympho- 
sarcomatosis, ref., 431; on osteo- 
malacia, ref., 1044; on paraganglioma 
of carotid, ref., 413; on status lym- 
phaticus, ref., 500 
Pancreas, 801 
absence of, 801 
accessory, 801 
atrophy of, 801 
auto-digestion of, 802 
concretions in ducts of, 807 
cysts of, 807 
degeneration of, 802 
displacements of, 801 
examination, post-mortem, of, 1217 
fat necrosis of, 803 
foreign bodies in ducts of, 807 
gangrene of, 805 
hemorrhage in, 804 
infiltration, fatty, of, 802 
inflammation of {see Pancreatitis), 
805 
Langerhans' islands, degeneration of, 
803 
lesions of, in diabetes, 803, 806 
lesions of, in cirrhosis of liver, 828 
in diabetes, 492, 803, 806 
malformations of, 801 
necrosis of, 803 
preservation of, 1218 
secretions, internal, of, 492 
size of, 1217 
syphilis of, 806 
tuberculosis of, 806 
tumors of, 806 
weight of, 1217 
Pancreatic ducts, concretions in, 807 
foreign bodies in, 807 
malformations of, 801 1318 
INDEX 
Pancreatitis, 805 
chronic interstitial, 805 
hemorrhagic, 805 
suppurative, 805 
syphilitic, 806 
tuberculous, 806 
Pandemic disease, 185 
Panton, P. N., on trinitrotoluene poison - 
ing, ref., 477 
Pape, on tumors of Bartholin's glands, 
ref., 913 
Papilloma, 445 
of bladder, urinary, 903 
esophagus, 744 
Fallopian tubes, 981 
gall-ducts, 846 
kidney, 890 
larynx, 668 
mouth, 733 
ovary, 961 
penis, 1013 
stomach, 754 
vagina, 917 
vulva, 912 
Pappenheimer, A M., on cysts of esopha- 
gus, ref., 745; on thymus, ref., 581 
Pappenheim's method of staining tuber- 
cle bacilli, 291 
Paraffin embedding, 1233 
Paraganglioma, 413 
of carotid, 594 
Paragonimus ringeri, 144 
westermanni, 144 
Paralysis, acute ascending, 1162 
agitans, 1170 
infantile, 331, 1159 
Landry's 1162 
spinal, spastic, 1144 
Paramecium, cultivation of, 96 
Parametritis, 931 
Paraphimosis, 1012 
Paraplegia, ataxic, 1150 
spastic, 1144 
Parasites, 367 
animal, 130 
bacterial, 158, 167 
in blood, 533 
tumors, 385 
plant, 158 
Parasitism, 130, 167 
Parathyroid glands, 587 
tumors of, 588 
Paratyphoid, 277 
Parenchymatous degeneration (see De- 
generation, albuminous), 48 
Paresis, general, 1165 
etiology of, 1165 
relation of syphilis to, 1165 
Paris green poisoning, 475 
Park, R., on osteomyelitis, ref., 1065 
Park, W. H., on agglutination tests, ref., 
207 
Park and Krumwiede, on bovine and 
human types of tubercle bacilli, 
ref., 299 
Park and Williams, on B. influenza, ref., 
264; on infection of children with 
bovine tuberculosis, ref., 299; on 
infectious diseases, ref., 354; on patho- 
genic microorganisms, ref., 133, 158; 
on pneumococci, ref., 249; on pre- 
ventive inoculations in hydrophobia, 
ref., 330; on rabies, ref., 331; on tra- 
choma bodies, ref.. 342; on typhoid 
carriers, ref., 275 
Park and Zingher, on Shick test, ref., 317 
Parotid gland, 797 
inflammation of, 797 
rhabdomyoma of, 422 
tuberculosis of, 798 
tumors of, 798 
Parotitis, acute, 797 
suppurative, 798 
Parovarium, cysts of, 976 
Parsons, on bone lesions in typhoid fever, 
ref., 273 
Pdssler, on emphysema, ref., 682 
Pdssler and Heineke, on relation of hyper- 
trophy of heart to kidney dis- 
ease, ref., 632, 874 
Pater and Rivet, on sarcoma of lung, ref., 
721 
Pathological specimens, preservation of. 
1227 
Pathology, classifications of, 6 
comparative, 7 
definitions of, 3, 6 
divisions of, 6 
general introduction to, 3 
morphological, 6 
physiological, 6 
special, 513 
Paton, Gulland, and Fowler, on accessory 
spleens, ref., 565 
Patrick, H. T., on myastheniagravis, 
ref., 1035 INDEX 
1319 
Paul, T., on hypertrophy of prostate, 
ref., 1027 
Pawlowsky, on elimination of bacteria in 
body, ref., 176 
Payne, R. L., on hematuria, ref., 856 
Payne, R. L. and MacNider, W. B., on 
hematuria from surgical stand- 
point, ref., 856 
Payr, E., on malformation of thyroid, 
ref., 583; on sarcoma of penis, ref., 
1013; on transplantation of organs, 
ref., 93; on transplantation of thyroid, 
ref., 93, 485 
Peabody, F. W., on acidosis in nephritis, 
ref., 882 
Peabody, Draper, and Dochez, on acute 
poliomyelitis, ref., 1156 
Pearce, R. M., on bone in kidney, 
ref., 861; on cytolysins, ref., 200; on 
degeneration of heart muscle, ref., 617; 
on edema, ref., 29; on experimental 
cirrhosis of liver, ref., 831; on hemag- 
glutinins and liver necroses, ref., 815; 
on islands of Langerhans, ref., 803; 
on leptothrix, ref., 263; on pancreas 
in congenital syphilis, ref., 806; on 
regeneration of the kidney, ref., 86; 
on regenerative changes in liver, ref., 
817: on thrombi, ref. 33 
Pearce, Hill, and Eisenbrey, on experi- 
mental nephritis, ref., 880 
Pearce, Krumbhaar, and Frazier, on spleen 
and anemia, ref., 566 
Pearce and Winne, on hemagglutinins and 
liver necroses, ref., 815; on thrombi, 
ref., 33 
Pearls, epithelial, 460 
Pearson, K., on animal immunization 
against tuberculosis, ref., 294; on 
hereditary anomalies, ref., 21; on try- 
panosomes, ref., 137 
Peck, C. H., on hemolytic icterus, ref., 575 
Pediculus capitis, 156 
corporis, 157 
pubis, 156 
vestimenti, 157 
Pellagra, 496 
Pellew, on arsenic poisoning, ref., 475 
Penis, 1011 
absence of, 1011 
balanitis, 1012 
calcification of, 1013 
calculi of, 1013 
Penis, condyloma of, 1012 
corpora cavernosa, inflammation of, 
1012 
cysts of, 1013 
elephantiasis of, 1013 
enlargement of, 1012 
epispadias, 1011 
erysipelas of, 1013 
furuncles of, 1013 
hemorrhage in, 1012 
herpes of, 1013 
hypospadias, 1011 
indurations of, 1012 
inflammation of, 1012 
injuries of, 1012 
malformations of, 1011 
ossification of, 1013 
paraphimosis, 1012 
phimosis of, 1012 
congenital, 1011 
syphilis of, 1012 
tuberculosis of, 1012 
tumors of, 1013 
ulcers of, 1012 
Penkert, M., on chondrosarcoma of 
uterus, ref., 942 
Pentastoma denticulatum in liver, 841 
spleen, 580 
Pentastomum in lymph-nodes, 565 
Pentmann, I., on splenomegaly, ref., 578 
Pepper, 0. H. P., and Pearce, R. M., on 
myeloma, ref., 1074; on multiple mye- 
loma, ref., 431 
Percy, N. M., on heredity in chondro- 
mata, ref., 403; on transfusion in per- 
nicious anemia, ref., 538 
Periarteritis, 637 
nodosa, 646 
Pericarditis, 596 
bacteria in, 597 
chronic, 597 
exudative, 596 
fibrinous, 596 
obliterative, 598 
purulent, 597 
sei ofibrinous, 596 
tuberculous, 598 
Pericardium, 595 
air in, 595 
calcification of, 598 
cysts of, 599 
dropsy of, 595 
fibroid nodules in, 598 1320 
INDEX 
Pericardium, gas in, 596 
examination, post-mortem, of, 1204 
hemo-, 595 
hemorrhage in, 595 
hydro-, 595 
inflammation of (see Pericarditis), 
596 
injuries to, 595 
pneumo-, 595 
sac of, obliteration of, 598 
tuberculosis of, 599 
tumors of, 599 
Perihepatitis, 834 
Perimetritis, 930 
Perinephritic suppuration, 886 
Periosteum, hemorrhage in, 1056 
hyperemia of, 1056 
inflammation of (see Periostitis), 
1056 
thickening of, 1046 
tumors of, 1073 
Periostitis, 1056 
exudative, 1057 
fibrous, 1057 
hyperplastic, 1046 
ossifying, 1057 
suppurative, 1057 
syphilitic, 1059 
tuberculous, 1059 
Periphlebitis, 656 
chronic, 657 
Perisplenitis, 575 
Perithelioma, 443 
of ependyma, 1109 
Perithelium, 443 
Peritoneum, 789 
absorption from, 792, ref., 127 
ascites of, 789 
cysts of, 795, 797 
hemorrhage in, 789 
inflammation of (see Peritonitis), 790 
malformations of, 789 
parasites of, 797 
phagocytosis in, 792 
pseudomyxoma of, 797, 967 
tuberculosis of, 793 
tumors of, 794 
Peritonitis, 790 
acute, 790 
bacterial excitants of, 791 
cellular, 790 
chronic, 792 
exudative, 790 
Peritonitis, gonococcus, ref., 791 
suppurative, 791 
tuberculous, 793 
Perkins, on B. mucosus capsulatus, ref,, 
245 
Perkins and Pay, on bacteria in smallpox, 
ref., 337 
Peronne, on appendicitis, ref., 782 
Pertik, 0., on tuberculosis of stomach, 
ref., 750 
Pertussis, 350 
Petechiae, 28 
Peter, on kidney structure, ref., 850 
Peters, on ganglioneuroma, ref., 411 
Peters, J., on oxidase in lymphocytes, 
ref., 539 
Petersen, on metastasis of tumors, ref., 
378 
Peterson, on non-malignant rectal stric- 
tures, ref., 776 
Peterson and Haines, on legal medicine 
and toxicology, ref., 482 
Petren, K., on tumors of pituitary body, 
ref., 1182a 
Petruchsky, on streptothrix, ref., 262 
Pettit, on concurrent infection in tuber- 
culosis, ref., 718 
Peyer's patches in typhoid fever, 266 
Pfaff- on esophageal diverticula, ref., 743 
Pfahler, G. E., on carcinoma following 
x-ray burns, ref., 14 
Pfeiffer, on desmoid of muscle, ref., 1041; 
on immunity, ref., 196, 224 
Pfeiffer and Friedberger, on tubercle 
bacilli, ref., 296 
Pfeiffer phenomenon, 196 
Phagocytes, 114, 115, 124, 127 
action of, 121, 127 
in cytolysis, 204 
enzymes of, 121 
forms of, 119 
Phagocytosis, 114, 209 
in peritoneum, 792 
Phagolysis, 205 
Phaochromoblastoma, 413 
Pharyngitis, 737 
catarrhal, 737 
diphtheritic, 738 
phlegmonous, 738 
tuberculous, 739 
Pharyngomycosis leptothrica, 263 
Pharynx, 736 
abscess in, 738 INDEX 
1321 
Pharynx, adenoid polyps, 741 
diverticula of, 736 
examination, post-mortem, of, 1211, 
1225 
fistulae of, 736 
hyperplasia of, 738, 739 
inflammation of (see Pharyngitis), 
736 
malformations of, 736 
mycosis of, 736 
polyps of, 741 
portal of entry for tubercle bacilli, 
739 
preservation of, 1211 
tuberculosis of, 739 
tumors of, 740 
Phenacetin poisoning, 478 
Phenocoll poisoning, 478 
Phenol poisoning, 477 
Philips, J., on acute yellow atrophy of 
liver in children, ref., 818 
Phimosis, 1011, 1012 
para-, 1012 
Phlebectasia, 654 
Phlebitis, 656 
acute infective, 656 
endo-, 656, 657 
peri-, 656, 657 
syphilitic, 657 
tuberculous, 657 
Phleboliths, 34, 655 
Phlegmon, 229 
gaseous, 322, 323 
Phloridzin diabetes, ref., 492 
Phosphorus necrosis of bone, 1069 
poisoning, 473 
stomatitis in, 731 
Phthirius inguinalis, 156 
Phthisis (see Tuberculosis, pulmonary), 
704 
Pia mater cerebralis, 1094 
blood in, 1094 
bone in, 1103 
cysts of, 1103 
edema of, 1094 
examination, post-mortem, of, 
1192, 1198 
hemorrhage in, 1095 
hyperemia of, 1095 
inflammation of (see Meningitis), 
1095 
Pacchionian bodies in, 1094 
parasites of, 1103 
Pia mater cerebralis, pigmentation of, 
1095, 1103, 1118 
structure of, 1094 
syphilis of, 1101 
thickening of, 1094 
tuberculosis of, 1099 
tumors of, 1101 
spinalis, 1104 
bone in, 1105 
cartilage in, 1105 
hemorrhage in, 1104 
inflammation of (see Meningitis, 
spinal), 1104 
parasites of, 1105 
tuberculosis of, 1104 
tumors of, 1105 
Pic and Bonnamour, on arteriosclerosis, 
ref., 646 
Pick, A., on post-mortem cyst formation 
in brain, ref., 1178 
Pick, E. P., on bacterial poisons, ret., 177 
Pick, L., on adenoma hydradenoides, ref., 
913; on adenoma of testis, ref., 1022; 
on aneurysms of cerebral vessels, ref., 
1122; on chorionepithelioma, ref., 956; 
on diagnosis of malignant tumors of 
lungs, ref., 723; on examination of 
brain tissue, ref., 1180; on ganglioma 
of uterus, ref., 942; on ochronosis, ref., 
66; on pigmentation of brain, ref., 1118; 
on pigmentation of intestine, ref., 789; 
on sarcoma of vagina, ref., 916; on 
tumors of pleura, ref., 729 
Pick and Bielschowsky, on fibrillar 
neuromata, ref., 419 
Picric acid poisoning, 477 
Picro-acid fuchsin stain, 1236 
Pielsticker, F., on calcification of muscle 
fibers, ref., 1038; on regeneration of 
muscle, ref., 85; on regeneration of 
muscle fibers, ref., 1038 
Pierce, F. E., on cysts of vagina, ref., 918 
Pierson, P. H., on pathogenic yeasts, ref., 
169 
Pierson and Ravenel, on moulds, ref., 172 
Pigment, extraneous, 63, 67 
hematogenous, 63, 64 
hepatogenous, 63, 65 
in blood, 533 
metabolic, 63, 66 
Pigmentation, 63 
of adrenals, 589 
brain, 1118 1322 
INDEX 
Pigmentation of intestine, 788 
kidney, 861 
liver, 814, 821, 830 
lung, 685, 703, 728 
lymph-nodes, 548 
bronchial, 675 
tracheal, 675 
muscle, 1032 
pia mater cerebralis, 1095, 1103, 
1118 
pleura, 728 
spleen, 568 
Piles, 777 
Pineal gland, lesions of, 1182 
structure of, 1182 
Pinkus and Pick, on xanthoma, ref., 425 
Pinworm, 150 
Pirondini, on bone in kidney, ref., 861 
v. Pirquet, on anaphylaxis, ref., 216; on 
tuberculin, ref., 294; on tuberculin test, 
ref., 182 
v. Pirquet and Schick, on anaphylaxis, ref., 
216 
Pituitary body, lesions of, 1182a 
structure of, 1182a 
Pityriasis versicolor, 172 
Placenta, 953 
apoplexy of, 953 
calcification of, 953 
cysts of, 957 
degenerations of, 953 
hemorrhage in, 953 
infarction of, 953 
inflammation of, 953 
moles of, 954 
polyps in, 954 
syphilis of, 954 
tuberculosis of, 954 
tumors of, 954 
Placentitis, 953 
Plague, bacillus of, 320 
bubonic, 320 
pneumonia of, 696 
oriental, 320 
preventive inoculation in, 321 
swine, bacillus of, 321 
Plasma cells, 88, 109, 525 
in pyosalpinx, gonorrheal, 979 
Plasmocytoma, 431 
of bronchi, 675 
Plasmodium malariae, 344 
in kidney, 871 
Plasmoma, 431 
Plasmomyeloma, 431 
Plasmosomes, 77 
Plastosomes, 77 
Plaut, H. C., on yeasts and moulds in dis- 
ease, ref., 173 
Plehn, on tumors in cold-blooded animals, 
ref., 387 
Pleomorphism in bacteria, 161 
Plethora, 23, 518 
Pleura, 724 
air in, 724 
calcification of, 726 
cysts of, 729 
echinococcus of, 729 
empyema, 725 
gas in, 724 
hemorrhage in, 724 
hydropneumothorax, 724 
hydrothorax, 724 
inflammation of, 724 
pigmentation of, 728 
pyopneumothorax, 724 
tuberculosis of, 727 
tumors of, 728 
Pleural cavity, air in, 724 
examination, post-mortem, of, 
1203, 1209, 1225 
gas in, 724 
Pleurisy (see Pleuritis), 724 
Pleuritic adhesions, 727 
Pleuritis, 724 
acute, 724 
chronic, 727 
with adhesions, 727 
dry, 724 
exudative, 724 
fibrinous, simple, 724 
serofibrinous, 725 
excitants of, 725 
sicca, 724 
suppurative, 725 
tuberculous, 727 
with effusion, 725 
Pleuropneumonia of cattle, 353 
Plimmer's bodies, 382 
Plotz, on typhus fever, ref., 333 
Plotz, Olitsky, and Baehr, on typhus fever, 
ref., 333 
Pneumococcus (see Diplococcus pneu- 
moniae), 246 
lanceolatus, 246 
mucosus, 238 
of Frankel, 246 INDEX 
1323 
Pneumokoniosis, 704 
Pneumonia. 684 
and measles, 694 
aspiration, 695 
broncho- (see Bronchopneumonia), 
692, 693 
tuberculous, 711 
cheesy, 714 
chemical, 698 
classification of, 687 
crisis in, 690 
croupous, 687 
diplococcus of, 246 
experimental, ref., 691 
exudative, 687 
fibrinous, 687 
hematogenous, 696 
hypostatic, 696 
inhalation, 698 
interstitial, 701 
lobar, acute, 246, 687 
associated lesions in, 690 
complications of, 691 
concurrent infection in, 691 
crisis in, 249 
diplococcus of, 246 
excitants of, 247, 691 
experimental, 247, ref., 691 
mixed infection in, 691 
resolution, commencing, in, 689 
delayed, in, 691 
serum therapy in, 248 
statistics of, ref., 690 
suppurative inflammation in, 
691 
lobular, 692 
excitants of, 696 
exudate in, 693 
persistent, 695 
resolution in, 695 
"organizing," 691 
"patchy," 692 
purulent infiltration in, 692 
pyemic, 696 
septic, 696 
streptococcal, 694 
syphilitic, 720 
tuberculous, 704 
Pneumonitis (see Pneumonia), 684 
Pneumonokoniosis, 67 
Pneumonomykosis, ref., 172 
Pneumopericardium, 595 
Pneumothorax, 724 
Podwyssozki, on irregular mitoses, ref., 
385 
Poikilocytes, 520 
Poisoning, examination, post-mortem, 
in cases of, 1215, 1216, 1222 
lesions of kidney in, 857, 862 
Poisons, 469 
abrin, 178, ref., 232 
acetanilide, 478 
aconite, 481 
alcohol, 478 
aloes, 476 
amidobenzol, 478 
amido compounds, 478 
amidophenol group, 478 
ammonia, 473 
anilin, 478 
animal venom, 479 
aromatic, 477 
arsenic, 474 
bacterial, 164, 177 
bibliography of, 481 
bismuth subnitrate, 473 
cantharides, 476 
carbolic acid, 477 
carbonic monoxide, 480 
oxide, 480 
chloral hydrate, 479 
chloroform, 478 
colchicum, 476 
colocynth, 476 
conium, 481 
copper, 476 
corrosive sublimate, 475 
croton oil, 476 
cyanide of potassium, 477 
digitalis, 481 
elaterium, 476 
endogenous, 469, 482 
ether, 479 
exogenous, 469, 471 
fungi, 477 
gamboge, 476 
gas, 480 
hellebore, 476 
histogenic, 482 
hydrochloric acid, 472 
hydrocyanic acid, 477 
jalap, 476 
lead, 475 
lesions induced by, 469 
lobelia, 481 
meat, 323 1324 
INDEX 
Poisons, mercuric chloride, 475 
methods of combating, 469 
morphine, 476 
mustard gas, 472 
neutralization of, 470 
nitric acid, 471 
nitrobenzol, 477 
nitro compounds, 477 
nux vomica, 479 
opium, 476 
oxalic acid, 472 
phenacetin, 478 
phenocoll, 478 
phenol, 477 
phosphorus, 473 
picric acid, 477 
potash, 473 
potassium nitrate, 473 
ptomaine, 481 
removal of, from body, 470 
ricin, 178, ref., 232 
savin, 476 
scammony, 476 
soda, 473 
stramonium, 481 
strychnine, 479 
sulphuric acid, 471 
tartar emetic, 476 
tartaric acid, 472 
tetrachlorethane, 479 
tolerance to, 470 
trinitrophenol, 477 
trinitrotoluene, 477 
turpentine, 476 
vegetable irritants, 476 
veratria, 476 
Polaillon, on lung stones, ref., 726 
Polano, O., on angiosarcoma of uterus, 
ref., 942 
Polar body, 78 
Poliomyelitis, acute anterior, 331, 1156 
communicability of, 333 
excitants of, 333 
immunity in, 333 
Pollack, on sarcoma of veins, ref., 657 
Pollak, E., on amyloid tumors of tongue, 
ref., 668; on cysts of vagina, ref., 918 
Polyblast, 89, 109 
Polychromatophilia, 537 
Polycythemia, 517 
Polymastia, 987 
Polymyositis, 1039 
Polyneuromatosis, 418 
Polyps, adenoid, 741 
mucous, 401 
nasal, 445 
of bladder, 445 
heart, 606 
intestine, 445, 782 
pharynx, 741 
placenta, 954 
urethra, 908 
uterus, 936 
Polyserositis fibrosa, 749, 792 
Polythelia, 987 
Polyuria, 492 
Poor and Steinhardt, on rabies, ref., 329 
Popon, on arsenic poisoning, ref., 475 
Porcelli-Titone, on mitochondria, ref., 77 
Porencephalus, 1181 
Porter, W. T., on coronary arteries, ref., 
614; on fat embolism and shock, ref., 
42 
Port-wine stain, 423 
Posselt, A., on bile pigment, ref., 65; on 
echinococcus in liver, ref., 841; on 
icterus in infectious disease, ref., 576 
Post-mortem changes in blood distribu- 
tion, 1186, 1191 
in cholera, 279 
pyemia, 233 
septicemia, 233 
contusions, 1189 
cooling of body, 1188 
cultures, 1221 
decomposition, 1187 
discoloration of viscera, 1202 
examination, 1185 
after asphyxia, 503 
drowning, 505 
strangulation, 504 
closure of body after, 1221 
external inspection, 1186 
for bacteria, 1221 
in cases of suspected poisoning, 
1222 
internal inspection, 1190 
lividity, cadaveric, 1186 
medicolegal, 1222 
method of making, 1185 
of abdomen, 1201, 1202. 1211, 
1221, 1226 
adrenals, 1213, 1226 
aorta, 1218 
base of cranium, 1198 
bladder, 1219, 1226 INDEX 
1325 
Post-mortem examination of bones, 1226 
brain, 1191, 1193, 1198 
bronchi, 1210 
diaphragm, 1203, 1225 
dura mater, 1192, 1198 
ear, internal, 1198 
esophagus, 1211 
eye, 1198 
Fallopian tubes, 1220 
gall-bladder and -ducts, 1216 
genitourinary organs, female, 
1219, 1226 
male, 1218, 1226 
head, 1191, 1224 
heart, 1204, 1225 
hemolymph nodes, 1218 
intestine, 1202, 1214, 1226 
kidney, 1212, 1226 
larynx, 1211, 1225 
liver, 1202, 1216, 1226 
lung, 1209, 1225 
new-born, 1223 
omentum, 1202, 1211 
ovaries, 1220 
pancreas, 1217 
pericardium, 1204 
pharynx, 1211, 1225 
pia mater, 1192, 1198 
pleural cavities, 1209, 1225 
prostate gland, 1219 
rectum, 1219 
solar plexus, 1218 
spinal cord, 1199, 1225 
spleen, 1214, 1226 
stomach, 745, 1203, 1215, 1226 
testicles, 1219 
thoracic duct, 1218 
thorax, 1203, 1225 
thymus, 1225 
thyroid, 1211, 1225 
trachea, 1211, 1225 
umbilical cord, 1224 
urethra, 1218 
uterus, 1219 
vagina, 1219 
vesiculae seminales, 1219 
vulva, 1219 
fractures, 1190 
gas formation, 1187 
hypostasis, 1187 
identification, 1186 
lividity, 1186 
marks of violence, 1189 
Post-mortem putrefaction, 1187 
rigidity, 1188 
rise of temperature, 1188 
wounds, 1190 
Potash poisoning, 473 
Potassium cyanide poisoning, 477 
nitrate poisoning, 473 
Potter, Ditman, and Bradley, on opsonins, 
ref., 213 
Poulsen, on ochronosis, ref., 66 
Powers, on carcinoma of branchial cleft, 
ref., 741 
Pratt, on coronary arteries, ref., 614 
Pratt, J. H., on histology of acute lobar 
pneumonia, ref., 690; on typhoid bacil- 
lus, ref., 274 
Preble, H. B., on pneumococcus endocar- 
ditis, ref., 622 
Preble, R. B., on esophageal varices, ref., 
742; on gastrointestinal hemorrhage in 
hepatic cirrhosis, ref., 829 
Precipitin test in forensic medicine, 208 
technique of, 222 
Precipitins, 207 
anti-, 209 
in typhoid fever, 276 
nature of, 209 
specific, 208 
Pregnancy, abdominal, 984, 985 
chorionepithelioma of, 948 
ectopic, 982 
extrauterine, 982 
ovarian, 986 
toxemia of, liver in, 819 
tubal, 982 
tuboabdominal, 984 
twin tubal, 986 
Preiser, S. A. and Davenport, C. B., on 
neurofibromatosis, ref., 414 
Preiswerk, on carcinoma of urethra, ref., 
908 
Prepuce, absence of, 1011 
lesions of, 1013 
Preservation of tissues, 1229 
Pribram, on bacterial hemolysins, ref., 
179; on hemolytic power of bacteria, 
ref., 231 
Price, on Strongyloides stercoralis, ref., 
155 
Prickle cells in epithelioma, 462 
Prime, F., on increased growth rate from 
z-ray exposure, ref., 95; on radium ex- 
posures, ref., 16 1326 
INDEX 
Prince, M., on Paget's disease of bone, 
ref., 1050 
Processus vaginalis, hydrocele of, 1016 
Proescher and Reddy, on paratyphoid, ref., 
277 
Prolapsus uteri, 922 
Prosopothoracopagus, 365 
Prostate, 1024 
abscess of, 1027 
atrophy of, 1024 
concretions in, 1029 
cysts of, 1029 
degenerations of, 1024 
enlargement of, 1025 
examination, post-mortem, of, 1219 
hypertrophy of, 1025 
inflammation of, 1027 
parasites in, 1029 
preservation of, 1219 
tuberculosis of, 1027 
tumors of, 1028 
Prostatitis, 1027 
acute exudative, 1027 
tuberculous, 1027 
Proteins, 3 
defensive, 187 
protective, 125 
Prothrombin, 515 
Protoplasmic processes, 1130 
Protozoa, 132 
characters of, 132 
cultivation of, 96, 133 
methods of study of, 143 
modes of transmission of, 132 
pathogenic, 132, 353 
Proud flesh, 111 
Prowazek, S., on protozoa, ref., 133 
Prudden, T. M., on bacteria in exudative 
pleuritis, ref., 725; on concurrent infec- 
tion in tuberculosis, ref., 299, 718; on 
experimental tuberculosis, ref., 718; on 
malignant endocarditis, ref., 624; on 
pseudohypertrophy of muscle in multi- 
ple neuroma, ref., 1035; on pseudo- 
membranous inflammation, ref., 241; 
on rhabdomyoma of parotid, ref., 422; 
on rhabdomyoma of salivary glands, 
ref., 801; on tubercle bacilli, ref., 
292 
Prudden and Hodenpyl, on tubercle ba- 
cilli, ref., 292 
Prym, on adenoma of adrenal, ref., 592; 
on endothelioma, ref., 442; on fibroma 
of mamma, ref., 997; on sacral tumors 
and cysts, ref., 1112 
Psammoma of dura mater, 442, 1093, 
1094 
of pia mater, 1101 
Pseudodiphtheria, 241 
bacillus, 317 
Pseudohermaphroditism, 1011 
Pseudohypertrophy, 73 
of muscle, 1035 
Pseudoleukemia, 555 
Pseudomyxoma of peritoneum, 967 
peritonei, 797 
Ptomaine poisoning, 481 
Ptomaines, 164 
Puech and Massabuau, on sarcoma of 
vagina, ref., 916 
Puerperal fever, 933 
Puls, on Hirschsprung's disease, ref., 763 
Purpura hemorrhagica, 499 
Pus, 105, 230 
cells, 230 
Pusey, W. A., on Treponema pallidum, 
ref., 308 
Pustules, 228 
malignant, 258 
Putnam, on hemorrhagic encephalitis, 
ref., 1157 
Putnam and Taylor, on diffuse degenera- 
tion of spinal cord, ref., 1151 
Putrefaction, post-mortem, 1187 
Pycnosis, 68 
Pyelitis, 883 
suppurative, 883 
Pyelonephritis, chronic, 885 
suppurative, with cystitis, 884 
Pyemia, 232 
Pygopagus, 366 
Pylorus, stenosis of, 745, 754 
Pyometra, 930 
Pyopneumothorax, 724 
Pyorrhea, amebas in, 135 
Pyosalpinx, 978 
Pyosepticemia, ref., 233 
Pyramids, anterior, 1140 
Pyrexia, 501 
Quarella, on teratomata of tonsil, ref., 741 
Quarter-evil, 323 
Quenu, on sporotrichosis of mamma, ref., 
995 
Quenu and Branca, on regeneration of 
intestinal epithelium, ref., 775 INDEX 
1327 
de Quervain, on tumors of parathyroid, 
ref., 588 
Quinby, W. C., on suppurative pyelitis, 
ref., 883 
Quineke and Hoppe-Seyler, on cirrhosis of 
liver ref., 825 
Quinsy, 738 
Rabaud, on malformations, ref., 355 
Rabies (see Hydrophobia), 326 
Race, relationship of, to disease, 20 
Rachitis, 1052 
and chondromata, 403 
Radium, effect of, in leukemia, 16 
on tumors, 14 
injuries, from, 12 
Radziewsky, on bacterial infection, ref., 
179 
Rainey's tubes, 142 
Rainy, H., on nerve lesions in diphtheria, 
ref., 314 
Ramsey, on malignant growths of adrenal, 
ref., 592 
Ransom, B. H., on tapeworms, ref., 149 
Ranula, 394, 735, 798 
Ranvier, on clasmatocytes, 109 
Ranzi, on thrombosis, ref., 40 
Rappleye, W. C., on arteriosclerotic 
kidney, ref., 873 
Raschkes, H., on endothelioma of vagina, 
ref., 917 
Rat, cancer in, 388 
-bite fever, 138 
flea, 157 
Raubitschek, H., on witch-milk, ref., 987 
Rauschbrand, 323 
Ravenel, M. P., on entrance of bacteria 
through intestine, ref., 792; on human 
and bovine tuberculosis, ref., 299; on 
portals of entry of B. tuberculosis, ref., 
297 
Ravenel and McCarthy, on lesions in 
hydrophobia, ref., 326 
Raviart, on tuberculosis of heart, ref., 619 
Ray fungus, 262 
Reaction, decidual, of pregnancy, tubal, 
986 
of blood, 515 
Receptors, 192 
v. Recklinghausen, on osteosclerosis, ref,. 
1063; on rachitis and osteomalacia, 
ref., 1044, 1051 
v. Recklinghausen's disease, 414, 1046 
Reclus, P., on cystadenoma of mamma, 
ref., 993 
Rectocele vaginal, 914 
Rectum, 776 
examination, post-mortem, of, 1219 
hemorrhoids, 777 
inflammation of, 776 
strictures of, 776 
syphilis of, 776 
Redlich, on cancer statistics, ref., 453; 
on multiple carcinomata, ref., 454 
Reed, on focal lesions in typhoid fever, 
ref., 271; on Hodgkin's disease, ref., 
562 
Reed and Carroll, on excitant of yellow 
fever, ref., 335; on mosquito in yellow 
fever, ref., 335 
Reed, Carroll, Agramonte, and Lazear, on 
mosquito in yellow fever, ref., 335 
Reed, Vaughan, and Shakespeare, on 
typhoid fever in army camps, 
ref., 275 
Regeneration, 76 
cell, impulse to, 94 
of bladder mucosa, ref., 85 
blood, 91 
bone, 90 
bone-marrow, 91 
cartilage, 90 
connective tissue, 87 
endothelium, 89 
epithelium, 85 
fat tissue, 91 
kidney, 86 
liver, 86 
lymph-nodes, 91 
mammary glands, 86 
mucous membranes, ref., 85 
muscle tissue, 84 
nerve tissue, 83, 1139 
ovary, 87 
salivary glands, 86 
testicle, 87 
thyroid, 86 
Rehder, on rhabdomyoma, ref., 422 
Reiche, on metastatic carcinomata of 
adrenal, ref., 592 
Reinbach, on granulation tissue, ref., 
Ill 
Reineboth and Kohlhardt, on cooling of 
body and pneumonia, ref., 698 
Relapsing fever, 324 
Renon, on aspergillus, ref., 172 1328 
INDEX 
Renton and Robertson, on thymus and its 
relation to rickets, ref., 581 
Repair of tissues, 111 
Reproductive organs, female, 909 
male, 1011 
Resolution in inflammation, 106 
Resorption, 30 
Respiration, relation of, to circulation of 
blood, 23 
Respiratory system, lesions of, 661 
Rettger, Berman, and Sturges, on bacterial 
ferments, ref., 164 
Reuter, on teratomata of pharynx, ref., 
741 
Reversion, 75 
Rhabdomyoma, 421, 1040 
heterologous, 422 
homologous, 421 
of esophagus, 744 
salivary glands, 801 
seminal vesicles, 1024 
testicle, 1021 
Rhabdomyosarcoma of prostate, 1028 
of vagina, 916 
Rheumatism, acute, 351 
articular, 1084 
Rhexis, hemorrhage by, 27 
Rhinitis, 661 
catarrhal, acute, 661 
chronic, 662 
pseudomembranous, 662 
syphilitic, 662 
tuberculous, 662 
Rhinoscleroma, 313 
Rhizopoda, 133 
Rhodes, on hemorrhage of larynx, ref., 
664 
Ribbert, H., on adenogenous carcinoma, 
ref., 464; on adenoma, ref., 450; on 
adenoma of prostate, ref., 1028; on 
adenoma of thyroid, ref., 586; on 
angioma, ref., 425; on angiosarcoma, 
ref., 438; on appendicitis, ref., 782; 
on cell regeneration, ref., 94; on choles- 
teatoma of brain, ref., 1174; on chor- 
doma, ref., 404; on chromatophoroma, 
ref., 432; on Cohnheim's hypothesis, 
ref., 383; on complex tumors, ref., 393; 
on endothelioma, ref., 441; on endo- 
thelium and mesothelium, ref., 442; 
on gelatinous carcinoma, ref., 467; on 
glioma, ref., 408; on hemangioma, ref., 
424; on hypertrophy of prostate, 
ref., 1026; on infiltrative growth of 
tumors, ref., 378; on liver cirrhosis, 
ref., 831; on lymphoblastoma, ref., 431; 
on malignant myoma, ref., 440; 
on malignant polyps, ref., 445; on 
metaplasia, ref., 75; on miliary tuber- 
cles, ref., 283; on mixed tumors of 
salivary glands, ref., 443; on myeloma, 
ref., 1074; on myxoma, ref., 399; on 
myxoma of heart, ref., 634; on naevus, 
ref., 447; on origin of miliary tubercu- 
losis, ref., 708; on osteomalacia, ref., 
1051; on osteosarcoma, ref., 437; on 
papilloma and nasal polyp, ref., 445; 
on pleural pigmented tubercles, ref., 
728; on plasmocytoma, ref., 431; on 
regeneration and inflammation of 
lymph-nodes, ref., 551; on regenera- 
tion of mammary and salivary glands, 
ref., 86; on rhabdomyoma, ref., 422; 
on spongioblastoma, ref., 407; on 
suppurative pyelitis, ref., 884; on 
teratoma of testicle, ref., 1024; on 
tuberculosis of veins, ref., 657; on 
tumors, ref., 467 
Hibbert's hypothesis of origin of tumors, 
383 
Rice, H. IF., on hemorrhage of spinal 
cord, ref., 1126 
Rice bodies, 1088 
Richet, on anaphylaxis, ref., 216 
Ricin poisoning, 178, ref., 232 
Ricker, G., on fibromyoma, ref., 421; 
on relationship of yeasts and moulds 
to human diseases, ref., 173 
Rickets, 1052 
Ricketts, H. T., on pathogenic blastomy- 
cetes, ref., 171; on Rocky Mountain 
spotted fever, ref., 334 
Ricketts and Gomez, on Rocky Mountain 
spotted fever, ref., 334 
Ricketts and Wilder, on Mexican typhus, 
ref., 334 
Rider's bone, 404 
Riechelmann, on cancer statistics, ref., 
453 
Rieder, on leucocytosis, ref., 526 
Ries, E., on fibromyoma of vagina, ref., 
916; on salpingitis, ref., 978 
Riesman, on Meckel's diverticulum, ref., 
759; on pulmonary edema, ref., 678 
Riggs' disease, amebas in, 135 
Rigor mortis, 1031, 1188 INDEX 
1329 
Ringworm, 172 
Rischbieth, H., on pneumococcus peri- 
tonitis, ref., 791 
Risel, W., on actinomycosis of mamma, 
ref., 994; on chorionepithelioma, ref., 
949; on chorionepithelioma of testis, 
ref., 1024; on lymphosarcoma of lung, 
ref., 722; on sarcoma of spleen, ref., 
580 
Ritchie, W. T., on bacteria in bronchitis, 
ref., 671; on cystic kidney, ref., 888; 
on immunity, ref., 225 
von Ritook, S., on arterial hypoplasia, ref., 
635; on size of aorta, ref., 1218 
Ritschel, on lymphangioma of muscle, 
ref., 1041 
Ritter, on hematoma of umbilical cord, 
ref., 797 
Roberts, on pellagra, ref., 496 
Robertson, on ganglioneuroma, ref., 411; 
on muscular contraction, ref., 1031; on 
physical chemistry of proteids, ref., 4; 
on tonsillar calculi, ref., 739 
Robinson, on pulmonary complications 
in typhoid fever, ref., 273 
Rocky Mountain spotted fever, 334 
Roder, on leiomyoma of bladder, ref., 421 
Rodet, Lagriffoul, and Aly Wahby, on 
soluble poisons of typhoid bacil- 
lus, ref., 265 
Roentgen rays, effect of, on tumors, 14 
injury from, 12 
Roffo, on cancer, ref., 468 
Roger, on autointoxication, ref., 482; 
on poisoning and intoxications, ref., 
481 
Roger and Garnier, on tuberculosis of 
thyroid, ref., 584 
Rogers, on Asiatic cholera, ref., 278 
Rogg, on carcinoid tumors of appendix, 
ref., 786 
Roggenbau, on hemangioma of liver, ref., 
424; on tumors of liver, ref., 836 
Rogowitsch, N., on cysts of mamma, ref., 
1010 
Rohdenburg, G. L., on chorionepithe- 
lioma of epiphysis, ref., 1182a; on 
sarcoma of mamma, ref., 1006; on 
spontaneous cure of carcinoma, ref., 
454 
Rohdenburg, G. L. and Vander Veer, A., 
on D. pneumoniae in spinal 
fluid, ref., 247 
Rolleston, on carcinoma of intestine, ref., 
785; on cirrhosis of liver, ref., 825 
Rolleston and Hayne, on congenital 
cirrhosis of liver, ref., 830 
Rolleston and James, on carcinoid tumors 
of appendix, ref., 786 
Rollett, H., on adenoma of pancreas, ref., 
806; on calcification of liver, ref., 822 
Rollier, on exposure of the body to the 
sun's rays, ref., 18 
Rolly and Liebermeister, on death of 
bacteria in small intestine, ref., 
774 
Roman, on cysts of pancreas, ref., 807 
Rosary, rachitic, 1054 
Rosenau, on coilodium sacs, ref., 353; 
on viability of B. tuberculosis, ref., 290 
Rosenau and Anderson, on anaphylaxis, 
ref., 216 
Rosenbaum, on mesothelioma, ref., 442 
Rosenberger, R., on acid-fast bacteria, ref., 
300; on bacteriology of blood, ref., 
533; on tuberculosis of mesenteric 
nodes, ref., 767 
Rosenbloom, J., on chemical composition 
of gall-stones, ref., 847; on diabetes and 
syphilis, ref., 492; on renal calculi, ref., 
890 
Rosenheim, on acute diverticulitis, ref., 
760 
Rosenow, E. C., on blood cultures in 
pneumonia, ref., 690; on calculus for- 
mation, ref., 848; on D. pneumoniae in 
blood, ref., 247; on experimental endo- 
carditis, ref., 624; on experimental 
gastric and duodenal ulcer, ref., 752 
Rosenow, Wheeler, Towne, v. Hess, and 
Gray, on acute poliomyelitis, 
ref., 332 
Rosenstirn, J., on myositis ossificans, ref., 
1039 
Rosenthal, F., on enlargement of penis, 
ref., 1012 
Rosettes in glioma, 407, 408 
in neuroblastoma, 411 
Ross and Milne, on tick fever, ref., 325 
Rossie, on "bronzed diabetes," ref., 830; 
on pigmentation of liver, ref., 821; on 
pigmentation of liver cells in per- 
nicious anemia, ref., 821 
Roth, on pseudomyxoma peritonei, ref., 
797 
Round worms, 149 1330 
INDEX 
Rous, on diet and tumor growth, ref., 
373; on mixed grafts, ref., 457 
Rous and Jones, on phagocytosis, ref., 116 
Roussy, G., on lesions of thyroid, ref., 489 
Roux, on infectious diseases of unknown 
origin, ref., 353 
Rowley-Lawson, on malarial parasites, 
ref., 344 
Rowntree, L. G., on functional tests in 
nephritis, ref., 882 
Rowntree and Geraghty, on phenolsul- 
phonephthalein test, ref., 881 
Ruge, H., on adenoma hydradenoides, 
ref., 913 
Ruge, R., on infectious colitis, ref., 770 
Ruppanner, E., on emphysematous 
cystitis, ref., 901 
Russell, B. R. G., on acquired immunity 
to cancer, ref., 390; on carcinosarcoma 
in mice, ref., 440; on typhoid fever, ref., 
276 
Russell, Batten, and Collier, on spinal cord 
degeneration, ref., 1151 
Russell and Fuller, on typhoid bacillus in 
water, ref., 275 
Rutherford, E., on arrays and radium, ref., 
12 
Rutimeyer, L., on hereditary ataxia, ref., 
1154 
Ruttan, R. F., and Marshall, M. J., 
on post-mortem decomposition, 
ref., 1188 
Ruzicka, on vital staining, ref., 1227 
v. Sadr, G., on cystadenoma of mamma, 
ref., 993; on cysts of mamma, ref., 
1003 
•Sabouraud's medium, 173 
Saccharomyces, 169 
Sacerdotti, C., on hypertrophy of kidney 
ref., 853 
-Sachs, B., on amaurotic family idiocy, 
ref., 1115 
Sachs, B., and Strauss, I., on amaurotic 
family idiocy, ref., 1115 
Sachs, M., on indurations of corpora 
cavernosa penis, ref., 1012 
Sacrum, cysts of, 1112 
tumors of, 1112 
Sago spleen, 568 
Sailer, on endothelioma, ref., 442 
Sailer and Rhein, on eventration of dia- 
phragm, ref., 789 
St. Arnold, on chondrosarcoma of 
mamma, ref., 1006 
Sakaguchi, on tumors of epididymis, ref., 
1021 
Salis, H. V., on emphysema, ref., 682 
Saliva, action of, on bacteria, ref., 175 
Salivary glands, 797 
calculi in ducts of, 798 
ducts of, 798 
inflammation of, 797, 798 
tumors of, 798 
mixed, of, 443, 444, 798 
Salomonsen, on enchondromata in larynx, 
ref., 668 
Salpingitis, 977 
acute, 978 
chronic, 978 
nodosa, 977 
pyo-, 978 
suppurative, 97 
syphilitic, 981 
tuberculous, 980 
Saltykow, on adenomyoma of intestine, 
ref., 782; on carcinoid tumors of in- 
testine, ref., 783, 784; on carcino- 
sarcoma, ref., 440; on carcinosarcoma 
of esophagus, ref., 744; on carcino- 
sarcoma of thyroid, ref., 587; on experi- 
mental arteriosclerosis, ref., 645; on 
paratyphoid, ref., 277; on sarcoma of 
thyroid, ref., 587 
Salvarsan, 138 
Salvetti, C., on rachitis, ref., 1052 
Samelson-Kliwansky, L., on cysts of 
mamma, ref., 1010 
Sand, brain, 1091, 1094, 1101, 1109 
intestinal, 788 
Sappington, C. O., on mitochondria in red 
blood-cells, ref., 535 
Saprophytes, 167 
Sarcina, 160 
Sarcocystis muris, 1412 
Sarcoma, 427 
adeno-, 440 
age distribution of, 427 
alveolar, 427, 439 
differential diagnosis of, 439 
and neuroma, 414 
angio-, 438 
botryoides, 916 
central, 437 
chondro-, 440 
chondro-osteo-, 440 INDEX 
1331 
Sarcoma, connective-tissue stain for, 1241 
cystic, of ependyma, 1109 
cysto-, 440 
differential diagnosis of, 391, 439, 
465 
endosteal, 437 
endothelial, 441 
fibro-, 428, 437 
giant-cell, 433 
differential diagnosis of, 1049 
glio-, 440 
incidence of, 454 
lipo-, 439 
lympho-, 430 
melano-, 432 
differential diagnosis of, 433 
mixed forms, 439 
myelogenic, 1077, 1078 
myeloid, 433 
myo-, 440 
myxo-, 440 
of adrenals, 592 
appendix vermiformis, 785 
arteries, 653 
bladder, urinary, 903 
bone, 1077 
brain, 1173 
bronchi, 675 
dura mater cerebralis, 1093 
spinalis, 1103 
esophagus, 744 
Fallopian tubes, 981 
gall-bladder, 847 
heart, 635 
hypophysis, 1182a 
intestine, 784 
joints, 1086 
kidney, 890 
larynx, 668 
liver, 839 
lung, 721 
lymph-nodes, 564, 565 
mamma, 1006 
male, 1030 
muscle, 1040 
nerves, 1176 
nose, 662 
ovary, 961 
pancreas, 806 
penis, 1013 
pericardium, 599 
peritoneum, 794 
pharynx, 740, 741 
Sarcoma of pia mater cerebralis, 1101 
spinalis, 1105 
pineal gland, 1182a 
pleura, 729 
prostate, 1028 
salivary glands, 798 
spinal cord, 1179 
spleen, 580 
stomach, 755 
testicle, 1022 
thyroid, 587 
thymus, 582 
tongue, 735 
tonsil, 741 
urachus, 897 
uterus, 941 
vagina, 916 
veins, 657 
osteo-, 428, 434, 436 
osteoid, 1078 
of mamma, 1006 
parosteal, 1078 
periosteal, 437, 1077, 1078 
peripheral, 437 
perithelial, 438 
polymorphous-cell, 428 
round-cell, 429 
differential diagnosis of, 430 
spindle-cell, 428 
differential diagnosis of, 398, 421 
vascular, 439 
Sarcoptes scabiei, 156 
Sarcosporidia, 142 
Sato, T., on parasites in ventricles, ref., 
1109 
Satre, on cirrhosis of liver in childhood, 
ref., 830 
Sauerbeck, on aggressins, ref., 178; on 
malformations of male generative or- 
gans, ref., 1011 
Savin poisoning, 476 
Sawyer, on efficiency of vaccines in ty- 
phoid fever, ref., 276 
Saxer, on epithelial tumors of ependyma, 
ref., 1109 
Sayer, on moulds, ref., 172 
Scagliosi, G., on lesions of the myocar- 
dium in diphtheria, ref., 314 
Scammony poisoning, 476 
Scarlatina, 339 
excitants of, 340 
Scarlet fever, 339 
Scars, post-mortem examination of, 1190 1332 
INDEX 
Schaefer, on diabetes insipidus, ref., 493 
Schafer, E. A., on cell canaliculi, ref., 78; 
on kidney structure, ref., 850 
Schaffer, J., on islets of gastric mucosa in 
esophagus, ref., 742; on plasma cells, 
ref., 88 
Scharlach R stain for fat, 53 
Schaudinn, on malarial parasite, ref., 
346 
Schaudinn and Hoffman, on Treponema 
pallidum, ref., 308 
v. Scheibner, on tonsils as portals of entry 
for tubercle bacilli, ref., 740 
Scheller, R., on B. influenza, ref., 263 
Schellong, on tumors of pharynx, ref., 
740 
Schenck, on sporotrichosis, ref., 173 
Schepelmann, on trauma and formation of 
malignant tumors, ref., 386 
Scheuer, on malformation of kidney, ref., 
851 
Schick, on diphtheria test, ref., 317 
Schick test in diphtheria, 317 
Schickele, G., and Keller, R., on endo- 
metritis, ref., 930 
Schilder, P., on glioma, ref., 408; on amy- 
loid degeneration, ref., 59 
Schilling, C., and Meyer, K. F., on Texas 
fever, ref., 143 
Schimmelbusch, C., on cystadenoma of 
mamma, ref., 993 
Schimmelbusch's disease, 452 
Schirokogorojf, on sarcoma of pancreas, 
ref., 806 
Schistosoma haematobium, 145 
in bladder, urinary, 905 
liver, 841 
veins, 657 
japonicum, 145 
in liver, 841 
mansoni, 145 
Schizomycetes, 158 
Schlagenhauf er, on chorionepithelioma of 
testicle, ref., 1024; on complex tumors 
of mamma, ref., 1006 
Schlayer and Hedinger, on diet in nephri- 
tis, ref., 882 
Schlegel, on streptothrix, ref., 262 
Schlesinger, on hemolysis of streptococcus, 
ref., 238 
Schloss, O. M., on blood of children, ref., 
523; on intestinal parasites in children, 
ref., 149, 150 
Schmaus, H., on acute myelitis, ref., 1158; 
on Landry's paralysis, ref., 1162; 
on paresis, ref., 1165 
Schmidt, on amyloid tumors of tongue, 
ref., 735; on lymphosarcoma of intes- 
tine, ref., 784; on malignant growths 
of adrenal, ref., 592; on metastasis of 
tumors, ref., 378; on squamous epi- 
thelium in prostate, ref., 1029; on 
tumor emboli in arteries, ref., 654 
Schmidt, M. B., on blood in bladder, ref., 
905; on cysts of spleen, ref., 580; on 
leontiasis ossea, ref., 1046; on muscle 
degeneration, ref., 1037; on rachitis 
and osteomalacia, ref., 1051; on pa- 
thology of bone, ref., 1042; on tumors 
and cysts of jaw, ref., 1082; on tumor 
emboli, ref., 42 
Schmidtmann, on carbon monoxide pois- 
oning, ref., 481; on poisons, ref., 481 
Schmieden, on concretions in joints, ref., 
1087 
Schmincke, A., on regeneration of muscle, 
ref., 85 
Schmorl, G., on embolism of chorionic 
cells, ref., 956; on metastasis of tumors 
in bone, ref., 379; on osteotabes in- 
fantum, ref., 1055, 1056; on rachitis, 
ref., 1052; on staining fat, ref., 53; on 
technique, 1227 
Schnarrwyler, on phlegmonous gastritis, 
ref., 750 
Schnyder, on cysts of intestine, ref., 785; 
on leiomyoma of veins, ref., 419; on 
tumors of veins, ref., 657 
Schbdel and Nauwerck, on osteotabes 
infantum, ref., 1056 
Schoenlank, on sarcoma of gall-bladder, 
ref., 847; on tumors of gall-bladder, 
ref., 846 
Schone, on transplantation of organs, 
ref., 93 
Schbppler, on trauma and formation of 
malignant tumors, ref., 386 
Schorr, on complex tumors of mouth, 
ref., 734 
Schotten, B., and Veit, J., on embolism of 
chorionic cells, ref., 950 
Schottmuller, H., on groups of streptococci, 
ref, 238; on paratyphoid, ref., 277; 
on streptothrix muris ratti, ref., 138 
Schramm, on sacral tumors and cysts, 
ref., 1112 INDEX 
1333 
Schridde, H., on gonorrheal salpingitis, 
ref., 978; on inflammation, ref., 101; 
on plasma cells in pyosalpinx, ref., 
979; on stain for tissues, ref., 1238 
Schridde and Naegeli, on examination and 
fixation of blood, ref., 530; on blood 
technique, ref., 1227 
Schroder, R., on adenoma hydradenoides, 
ref., 913 
Schuchardt, K., on sarcoma of vagina, 
ref., 916 
Schiiller, A., on tumors of pineal gland, 
ref., 1182a 
Schulte, E., on xanthoma, ref., 425 
Schultze, on cyst of stomach, ref., 758; on 
degeneration of nerve fibers, ref., 1143 
Schultze, W., on crypts of Lieberkuhn, 
ref., 775 
Schultze, W. H., on oxidase in lympho- 
cytes, ref., 523 
Schulze, on B. tuberculosis, ref., 289 
Schuster, on cavernous angioma of heart, 
ref., 634 
Schutte, E., on porencephalus, ref., 1181 
Schwalbe, on malformations, ref., 355 
Schwann, sheath of, 1131 
tumors of, 415 
Schwartz and McNeil, on complement 
.fixation test in gonorrhea, ref., 
253 
Schwarz, on bacteria in blood, ref., 176 
Scirrhus, 459 
Sclerose en plaque, 1165 
Sclerosis, amyotrophic lateral, 1144 
multiple, of spinal cord, 1165 
of brain, 1165 
coronary arteries, 614 
spinal cord, 1144, 1165 
posterior spinal, 1145 
tuberous, cerebral, 1114a 
Scorbutus, 495 
infantile, 495 
Scott, F. H., on polycythemia, ref., 517 
Scott, G. D., on hydronephrosis, ref., 
885 
Scott and Forman, on malignant growths 
of lung, ref., 722 
Scrofula, 552 
Scrotum, 1013 
cysts of, 1014 
elephantiasis of, 1013 
malformations of, 1011 
tumors of, 1014 
Scudder, C. L., on cold abscess of mamma, 
ref., 994; on hypernephroma, ref., 892 
Scurvy, 495 
Sebileau, on leprous orchitis, ref., 1021 
Seckel, on amyloid tumors of pharynx 
and larynx, ref., 740; on amyloid 
tumor of tongue, ref., 668 
Secretions, internal, action of, 483 
Section cutting, 1232 
Sedgwick and Kingsbury, on uric acid in 
blood of infants, ref., 861 
Seelig, on lymphoblastoma, ref., 431 
Sehrt, E., on actinomycosis of breast, 
ref., 994; on osteoid sarcoma of 
mamma, ref., 1006 
Seitz, L., on malformation of mamma, 
ref., 987 
Selberg, on malignant adenoma, ref., 452 
Sellards, A. W., on Asiatic cholera, ref., 
278; on bacteria in spleen, ref., 581; on 
principles of acidosis, ref., 516 
Sellheim, H., on gigantism, ref., 1045 
Selling, L., on aplastic anemia, ref., 538 
Setter, on bacteria of body surfaces, ref., 
175 
Seminal vesicles, inflammation of, 1024 
tuberculosis of, 1024 
tumors of, 1024 
Seminoma of testicle, 1022 
Senator, on polycythemia, ref., 518 
Senile dementia, 1169 
plaques in brain, 1170 
Senility, 45, 47 
Sensibilizing substance, 205 
Septicemia, 177, 182, 232 
hemorrhagic, 321 
Septicopyemia, 233 
Septic sore throat, 240 
Sequestrum, 71 
of bone, 1068 
Serous infiltration, 54 
Serra, on hemangioma of muscle, ref., 
1041 
Serum, 102 
antitoxic, 190 
collection of, for tests, 223 
hemolytic, 198 
hemotoxic, 198 
inactivated, 198 
lytic, 200 
reactivated, 198, 219 
spermolytic, 200 
therapy, 191, 218 1334 
INDEX 
Serum therapy in diphtheria, 190 
meningitis, 256 
pneumonia, 248 
Seven-day fever, 324 
Sex, relation of, to disease, 20 
Shaw, E. H., on chylous ascites, ref., 789; 
on flora of vagina, ref., 915; on infec- 
tions of vagina, ref., 918 
Sheath of Schwann, 1131 
Shell shock, 1121 
Shennan, on hemangioma, ref., 423; on 
metastasis of tumors, ref., 379 
Sherrill, on carcinoma of gall-bladder, 
ref., 846 
Sherrington, C. S., on elimination of bac- 
teria in secretions, ref., 176 
Shiga, on dysentery bacillus, ref., 278 
Ship fever, 333 
Shipley and Fearnsides, on influence of 
parasites on host, ref., 144 
Shober, J. B., on displacements of colon, 
ref., 759 
Shock, shell, 1121 
Side-chain hypothesis of Ehrlich, 191 
Siderosis of lung, 703 
Siegert, on carcinoma of gall-ducts, ref., 
846 
Sikemeier, on xanthoma, ref., 425 
Silbermann, on sudden death following 
burns, ref., 10 
Silberschmidt, on peritonitis, ref., 791 
Siler and Garrison, on pellagra, ref., 496 
Silvergleit, H., on miliary tuberculosis, 
ref., 284 
Silver stain, Bielschowsky's, 1239 
Simchowicz, T., on senile dementia, ref., 
1170 
Simmonds, M., on carcinoma of gall- 
bladder, ref., 846; on carcinosarcoma 
of thyroid, ref., 587; on chronic orchi- 
tis, ref., 1018; on complex tumors of 
gall-bladder, ref., 846; on sarcoma of 
thyroid, ref., 587; on thymoma, ref., 
376; on tuberculosis of gall-bladder, 
ref., 845; on tuberculous salpingitis, 
ref., 980 
Simmons, C. C., on Hodgkin's disease, 
ref., 562 
Simmons and Benet, on Hodgkin's dis- 
ease, ref., 562, 563 
Simon, on changes in blood, ref., 533; on 
resolution of exudate in pneumonia, 
ref., 690; on sarcoma of spleen, ref., 580 
Simon and Judd, on lymphatic leukemia, 
ref., 539 
Simonds, J. P., on B. welchii, ref., 323 
Simonds and Jones, on antibody forma- 
tion, ref., 201 
Simons, I., on infective endocarditis, ref., 
622 
Singers' nodes, 668 
Sinoauricular node, 627 
Sinus pocularis, dilatation of, 908 
Sisson, W. R., on hypernephroma, ref., 
892 
Sittenfield, M. J., on tissue growth, ref., 
94 
Sittmann, on bacteria in kidney, ref., 871 
Sjbvall, E., on teratoma of ovary, ref., 974 
Skin, blastomycosis, 171 
"bronze," 65 
effect of cold on, 11 
heat on, 10 
ultraviolet light on, 17 
x- rays and radium on, 13 
Hodgkin's disease of, 557 
protective action of, against bac- 
teria, ref., 175 
transplantation of, 93 
tuberculosis of, 300 
tumors of, 398, 445, 460, 462, 467 
warts, 423, 445 
Skinner, M., on cysts of bone, ref., 1081 
Skull, examination, post-mortem, of, 1191 
thickening of, 1046, 1050 
Slaughter, on Haffkine method in plague, 
ref., 321 
Sleeping sickness, 137 
Slye, on heredity in cancer, ref., 387 
Slye, Holmes, and Wells, on heredity in 
cancer, ref., 387 
Smallpox, 336 
bacteria in, 337 
excitant of, 337 
immunization, artificial, in, 336, ref., 
337 
protozoa in, 337 
Smegma bacillus, 300 
Smith, A. H., on carcinoma of thoracic 
duct, ref., 658 
Smith, M. K., on inflammation of bursae, 
ref., 1088 
Smith, R. B., on fibromyoma of vagina, 
ref., 916 
Smith, R. M., on suppurative pyelitis, 
ref., 883 INDEX 
1335 
Smith, Theobald, on adaptation of bac- 
teria, ref., 186; on bacterial association 
in infection, ref., 183; on immunity, 
ref., 225; on problems of tuberculosis, 
ref., 295; on resistance to tuberculosis, 
ref., 553; on sarcosporidia in mice, ref., 
142; on spleen in infection, ref., 572; on 
Texas fever, ref., 143; on tuberculosis, 
ref., 295; on vaccines, ref., 212; on 
varieties of B. tuberculosis, ref., 291 
Smith, W. H., on chronic pericarditis, 
ref., 598 
Smith and Brown, on tonsillitis epidemic, 
ref., 738 
Smith and Cook, on Abderhalden reaction, 
ref., 218 
Smith and Motley, on sarcoma of ovary, 
ref., 962 
Smithies, F., on cancer of stomach, ref., 
753; on syphilis of stomach, ref., 750 
Soaps, role of, in formation of fat in cells, 
ref., 49 
Sobernheim, G., on anthrax, ref., 260; 
on Treponema pallidum, ref., 309 
Socin-Burckhardt, on tumors of prostate, 
ref., 1028 
Soda poisoning, 473 
Soil, bacteria in, 166 
Sokoloff, on adenocarcinoma of liver, ref., 
837 
Solar plexus, examination, post-mortem, 
of, 1218 
Somatochromes, 1129 
Sommer, on lipoma of tonsil, ref., 741 
Sonnenschein, on sarcoma of nose, ref., 
662 
Soor, 731 
Sorenson, S. P. L., on reaction,ref., 516 
Soret, on absorption bands, ref., 17 
Southard, E. E., on encephalitis and brain 
abscess, 1155; on senile dementia, ref., 
1167 
Spaces, Virchow-Robin, 1119 
Specimens, preservation of, in gross, 1241 
Speese, on fibroma of mamma, ref., 997 
Spencer, H., on tumors of Bartholin's 
glands, ref., 913 
Spengler, on concurrent infection in 
tuberculosis, ref., 299 
Spermatocele, 1016 
Spider cells," 406 
Spielmeyer, W., on amaurotic family 
idiocy, ref., 1115; on microscopical 
examination of nervous system, ref., 
1180; on nerve lesions in sleeping sick- 
ness, ref., 1168; on paresis, ref., 1165; 
on sleeping sickness, ref., 137 
Spiess, on giant-cell sarcoma, ref., 436 
Spina bifida, 1112 
ventosa, 1066 
Spinal cord, 1111 
absence of, 1111 
amyelia, 1111 
apoplectic clots in, 1125 
artefacts of, 1112, 1199 
atelomyelia, 1111 
atrophy of, 1143 
blood-vessels, lesions of, 1128 
circulatory changes in, 1118 
cysts of, 1181, 1178 
degeneration of, 1128, 1129, 1141, 
1143, 1151 
diffuse, 1151 
diastematomyelia, 1111 
diplomyelia, 1111 
embolism of, 1128 
examination, post-mortem, of, 
1199, 1225 
hematomyelia, 1125, 1126 
hematomy elopore, 1126 
hemorrhage in, 1125 
heterotopia, 1111 
false, 1112 
holes in, 1181 
hydromyelia, 1111 
hydrorrhachis externa, ref., 1111 
interna, 1111 
inflammation of (see Myelitis), 
1159 
injuries of, 1116 
lesions of, in tabes, 1147 
malformations of, 1111 
membranes, nature and lesions of, 
1089 
morphology of, 1129 
paresis, general, 1162 
preservation of, 1201 
sclerosis of, 1144, 1152, 1162 
spina bifida, 1112 
structure of, 1129 
syphilis of, 1173 
syringomyelia, 1153 
false, 1126 
thrombosis of, 1128 
trauma of, 1152 
tuberculosis of, 1173 1336 
INDEX 
Spinal cord, tumors of, 1179 
vascular changes in, 1118 
weight of, 1200 
paralysis, 1144 
Spiremes, 78 
Spirillum, 138, 159 
cholera? asiatica?, 278, 279 
reproduction of, ref., 160 
toxic products of, 280 
fever, 324 
of Finkler and Prior, 281 
tyrogenum, 281 
Spirochaeta, 138 
duttoni, 138 
icterohaemorrhagiae, 139, 352 
morsus muris, 138 
novyi, 325 
obermeieri, 138, 325 
in spleen, 580 
pallida (see Treponema pallidum), 
138, 308 
pertenuis, 138 
in yaws, 326 
recurrentis, 138, 325 
refringens in syphilis, 308 
Spitzer, W. M., on hematuria, ref., 856 
Spleen, 566 
abscess of, 572 
absence of, 566 
accessory, 566, 1214 
anemia of, 569 
atrophy of, 567 
bacteria in, 581 
circulation in, 566 
disturbances of, 569 
degeneration of, 567 
displacements of, 566 
embolism of, 570 
enlargement of, 544, 575 
examination, post-mortem, of. 1214, 
1226 
hemorrhage of, 567 
hyperemia of, 569 
hyperplasia of, 571 
endothelial of, 576 
hypertrophy of, 74 
in anemia, 578 
Hodgkin's disease, 578 
infection, ref., 177 
leukemia, 578 
infarction of, 38, 70, 570 
inflammation of (see Splenitis), 571 
lesions of, in cirrhosis of liver, 828 
Spleen, lesions of, in typhoid fever, 271 
lymph-vessels of, 566 
malformations of, 566 
parasites of, 580 
pigmentation of, 568 
position of, 1214 
preservation of, 1214 
rupture of, 567 
sago, 568 
size of, 1214 
syphilis of, 574 
thrombosis of, 571 
tuberculosis of, 574 
tumor metastasis in, 379 
tumors of, 580 
weight of, 1214, 1226 
wounds of, 567 
Splenectomy in splenic anemia, 544 
Splenic anemia, 544 
fever, 258 
Splenitis, hyperplastic, 571 
indurative, chronic, 572 
peri-, 575 
suppurative, 572 
syphilitic, 574 
tuberculous, 574 
Splenomegaly, primary, 576 
Gaucher's, 544, 576 
hemolytic, 575 
Spongioblastoma, 407 
of brain, 1177 
Sporangium, 172 
Spores, bacterial, 161 
yeast, 169 
Sporotrichosis, 173, 263 
of mamma, 995 
Sporotrichum Beurmanni, 173 
Gougeroti, 173 
Jeanselmei, 173 
Schencki, 173 
Sporozoa, 141 
Spotted fever, 333 
Sprue, 171 
in mamma, 995 
Sprunt, T. P., on diabetes, ref., 492 
Spuler, on mixed tumors, ref., 422 
Sputum, examination of, for tubercle 
bacilli, 291 
Squier, J. B., on rhabdomyosarcoma of 
prostate, ref., 1028 
Squier, J. B., and Myers, V. C., on 
tests in nephritis, ref., 882 
Stadtler, on heart lesions, ref., 632 INDEX 
1337 
Staehelin-Burckhardt, on cysts of esopha- 
gus, ref., 745 
Staining methods, 1228, 1235 
Stains for amyloid, 59 
for fatty-acids crystals, 53 
glycogen, 53 
nerve tissue, 1180 
vital, 535, 1227 
Stamer, on changes in myocardium, ref., 
614 
Staphylococcus cereus, 237 
epidermidis albus, 237 
pyogenes albus, 237 
aureus, 234 
salivarius pyogenes, 237 
Starck, on esophageal diverticula, ref., 
726 
Stark, on gangrene of lung, ref., 684 
Starling, on hormones, ref., 492; on inter- 
nal secretions, ref., 483 
Stasis, 26 
Status lymphaticus, 500 
lymph-nodes in, 554 
Staubli, on animal parasites in blood, 
ref., 533; on trichinosis, ref., 153 
Steele, on retroperitoneal sarcoma, ref., 
794 
Stein, A. and Heimann, W. J., on esthio- 
mene and elephantiasis vulvae, 
ref., 912 
Steinhardt, Lambert, Israeli, and Grund, on 
cultivation of vaccinia virus, 
ref., 339 
Steinharter, E, C., on gastric and duo- 
denal ulcer, ref., 752 
Steinhaus, on liver infarcts, ref., 813 
Steinke, on tumors of adrenal in lower 
animals, ref., 591 
Stenosis, congenital, of esophagus, 743 
of aorta, 631, 653 
esophagus, 743, 744 
mitral valve, 631 
pylorus, 745, 754 
Stepanow, on celloidin embedding, ref., 
1233 
Stephens and Fantham, on trypanosoma 
rhodesiense, ref., 137 
Stern, on malignant tumors in childhood, 
ref., 467; on trauma and formation of 
malignant tumors, ref., 386 
Sternberg, C., on acute myelogenous 
leukemia, ref., 540; on chloroma, ref., 
542; on Hodgkin's disease, ref., 557; on 
hyperplasia of lymphatic tissue in liver, 
ref., 835; on lesions of bronchial 
lymph-nodes, ref., 675; on lympho- 
sarcomatosis, ref., 431; on pathogenic 
blastomycetes, ref., 171; on regenera- 
tion of blood, ref., 92; on spindle-cell 
sarcoma of heart, ref., 635 
Stetten, on lipoma of intestine, ref., 782 
Stevenson, H. N., on growth of tissue in 
chick embryo, ref., 96; on tissue growth, 
ref., 94 
Stewart, G. N., and Rogoff, J. M., on 
adrenal function, ref., 589 
Stewart, M. J., on cholesterin in tissues, 
ref., 118 
Sticker, G., on leprosy, ref., 303 
Stiles, C. W., on animal parasites, ref., 
132; on Treponema pallidum, ref., 
308; on Uncinaria americana, ref., 151 
Stiles, H. J., on carcinoma of mamma, 
ref., 1008 
Stiles and Garrison, on intestinal worms in 
man, ref., 149 
Stilling, H., on osteoid sarcoma of 
mamma, ref., 1006; on Paget's disease 
of bone, ref., 1050 
Stillman, C. K., on edema of pia arach- 
noid, ref., 1095 
Stimson, on preventive inoculations in 
hydrophobia, ref., 330 
Stimulins, 209 
Stober, A. M., on pathogenic blasto- 
mycetes, ref., 171 
Stoddard, J. L., and Cutler, E. C., on 
torula infection in man, ref., 169 
Stoebe, on cysts of esophagus, ref., 745 
Stoerk, O., on cystitis cystica, ref., 900; 
on hypernephroma, ref., 892; on 
malignant rhabdomyoma in man, ref., 
422; on pigmentation of brain, ref., 
1118 
Stoerk and Erdheim, on cholesteatoma of 
mamma, ref., 1006 
Stokes, J. E., on cysts of vagina, ref., 918 
Stokes-Adams disease, 628 
examination, post-mortem, of heart 
in, 1208 
Stoll, on metastatic carcinoma of tonsil, 
ref., 741 
Stolz, M., on edema of labia majora, ref., 
909 
Stomach, 745 
absence of, 745 1338 
INDEX 
Stomach, atrophy of, 747 
bacteria of, ref., 750 
cadaveric changes in, 745 
cysts of, 758 
degenerations of, 747 
dilatation of, 754 
displacement of, 754 
erosions, hemorrhagic of, 753 
etat mamelonne, 748 
examination, post-mortem, of, 745, 
1203, 1215 
foreign bodies in, 758 
hair balls in, 758 
hemorrhage in, 746, 753 
inflammation of (see Gastritis), 747 
injuries of, 746 
lesions of, in cirrhosis of liver, 828 
malformations of, 745 
malpositions of, 745 
preservation of, 1216 
rupture of, 746 
syphilis of, 750 
tuberculosis of, 750 
tumors of, 754 
ulcers of, 751 
ulcers of, and carcinoma, 753 
Stomatitis, 730 
aphthous, 731 
catarrhal, 730 
chronic, 731 
croupous, 731 
gangrenous, 731 
parasitic, 731 
phlegmonous, 731 
syphilitic, 733 
tuberculous, 732 
ulcerative, 731 
Stone, on typhoid carriers, ref., 275 
Stone, W. S., on metastatic carcinoma of 
ovary, ref., 971 
Stones, lung, 674, ref., 726 
vein, 34 
Stoppato, on tumors of testicle, ref., 1022 
Storch, on sarcoma of intestine, ref., 
784; 
Stramonium poisoning, 481 
Strangulation, 9 
death from, 504, 1189, 1224 
Strauch, A., on infantilism, ref., 1043 
Straus, on tuberculosis, ref., 301 
Strauss, A., on congenital pyloric stenosis, 
ref., 745; on eclampsia, ref., 818 
Strawberry mark, 423 
Strep tobacillus, 160 
Streptococci, 160 
anaerobic, ref., 239 
Streptococcus enteritidis, ref., 774 
epidemicus, 240 
erysipelatus, 238, ref., 241 
longus, 238 
mitior, 238 
mucosus capsulatus, 238 
pyogenes, 238 
agglutination of, ref., 239 
viridans, 238 
Streptothrix, 161, 262 
muris ratti, 138 
Stricture of appendix vermiformis, 779 
of intestine, 763 
rectum, 776 
urethra, 906 
Stroebe, on irregular mitoses, ref., 385; 
on structure of glioma, ref., 407 
Strong, R. P., on uta, ref., 140 
Strong and Musgrave, on Balantidium 
coli, ref., 140; on dysentery bacillus, 
ref., 278 
Strongyloides stercoralis, 155 
Strongylus gigas, 151 
Struma, 584 
colloid, 585 
cystic, 585 
hypersemica, 584 
ovarii, 973 
suprarenalis, 591 
telangiectatic, 585 
Strumitis, 583 
v. Strumpel, on primary acute poly- 
myositis, ref., 1039 
Struppler, on lipoma of pericardium, ref., 
599 
Strychnine poisoning, 479 
Stuhlern, on B. mucosus capsulatus, ref., 
245 
Stumpf, R., on rhabdomyoma, ref., 
422 
on tumors of bladder, ref., 903 
Sturgis, on tumors of mouth, ref., 733 
Sturm, on pseudomyxoma of retroperi- 
toneal tissues, ref., 797 
Sublimate poisoning, lesions of kidney in, 
857, 863 
Substance sensibilisatrice, 205, 210 
Sublingual gland, 797, 798 
Submaxillary gland, 797, 798 
Sudan III stain for fat, 53, INDEX 
1339 
Sudeck, P., on atrophy of bones, ref., 
1050 
Suffocation, 9, 503 
Sugar tolerance in acromegaly, 497 
in diabetes insipidus, 493 
hypophyseal adiposity, 498 
Suggillations, 28 
Sulphuric acid, 471 
Sumita, M., on achondroplasia, ref., 1043 
Sundell, C. E., and Nankivell, A. T., on 
trench fever, ref., 352 
Sunstroke, 494 
Suppuration, 110, 227 
excitants of, 242 
Suprarenal bodies (see Adrenals), 588 
capsules (see Adrenals), 588 
Surra, 136 
v. Sury, on chronic gastritis, ref., 749 
Suzuki, K., on Oxyuris vermicularis in 
appendix, ref., 151; on parasites in ap- 
pendix, ref., 782 
Suzuki, T., on excretion of bacteria by 
kidney, ref., 864; on kidney structure, 
ref., 850 
Sweet and Stewart, on pyelonephritis with 
cystitis, ref., 884 
Swelling, cloudy, 48 
Symbiosis of bacteria, 131, 137, 138, 167, 
175 
Symmers, D., on necrosis of liver, ref., 
815; on status lymphaticus, ref., 500; 
on syphilitic hepatitis in children, ref., 
831 
Symmers, D., and Wallace, G. H., on syphi- 
litic arteritis, ref., 647 
Sympathoblastoma, 411 
Sympathogonion, 409 
Sympson, on fibroma of peritoneum, ref., 
794 
Syncytium, 467, 949 
Synophthalmia, 360 
Synotia, 356 
Syphilis, 304 
animal inoculations in, 308 
colloidal gold reaction in, 312 
communicability of, 309 
congenital, 307 
constitutional, 305 
diagnosis of, 308 
dioxydiamido-arsenobenzol in, 138 
immunization in, 309 
luetin test in, 312 
of adrenals, 590 
Syphilis of aorta, 647 
arteries, 647 
bladder, urinary, 901 
bone, 1059, 1066 
brain, 1173 
bronchi, 672 
cervix uteri, 933 
dura mater cerebralis, 1092 
esophagus, 744 
Fallopian tubes, 981 
heart, 619 
intestine, 767, 776 
joints, 1086 
kidney, 883 
larynx, 667 
liver, 831 
lung, 720 
lymph-nodes, 553 
lymph-vessels, 660 
mamma, 994 
mouth, 733 
muscle, 1040 
nervous system, 1173 
nose, 662 
ovaries, 960 
pancreas, 806 
penis, 1012 
pia mater cerebralis, 1101 
placenta, 954 
spinal cord, 1173 
spleen, 574 
stomach, 750 
testicle, 1020 
thymus, 582 
thyroid, 584 
tongue, 735 
urethra, 908 
uterus, 930 
vagina, 916 
veins, 657 
vulva, 910 
primary, 304 
relation of, to paresis, 1165 
to tabes dorsalis, 1150 
secondary, 305 
Spirochseta pallida in, 308 
tertiary, 306 
Treponema pallidum in, 308 
Wassermann reaction in, 311 
Syring, on malignant polyps, ref., 445 
Syringomyelia, 1153 
false, 1126 
joint lesions in, 1086 1340 
INDEX 
Tabardillo, 334 
Tabes dorsalis, 1145 
joint lesions in, 1086 
syphilis, relation of, to, 1150 
Taenia cucumerina, 149 
echinococcus, 147 
flavopunctata, 149 
mediocanellata, 147 
nana, 149 
saginata, 147 
solium, 146 
Takahashi, on tumor emboli in arteries, 
ref., 654 
Takano and Hanser, on angioma of mes- 
entery, ref., 794 
Talbot, on anaphylaxis, ref., 217 
Talipes, 361 
Talipomanus, 361 
Talke, L., on formation of lymph-vessels, 
ref., 90 
Tanaka, T., on bone in kidney, ref., 861 
Tandler, J., on gigantism, ref., 1045 
Tapeworms, 146 
v. Tappeiner, H., and Jodbauer, A., on 
action of light, ref., 17 
Tartar emetic poisoning, 476 
Tartaric acid, 472 
Tashiro, S., on transmission of physiolog- 
ical impulses to cells, ref., 5; on vital 
activities of cells, ref., 96 
Tattoo marks, 1190 
Tavel and Lanz, on peritonitis, ref., 791 
Tawara, S., on abnormal chordae tendinae, 
ref., 602; on conducting system of 
heart, ref., 628 
Tawara's node, 627 
Taylor, on autointoxication, ref., 482; 
on fatty degeneration, ref., 49; on 
volvulus of Meckel's diverticulum, 
ref., 759 
Taylor, H. C., on carcinoma of vagina, 
ref., 917 
Taylor, K., on sporotrichosis, ref., 173 
Taylor and Davies, on necrosis of bone, 
ref., 1068 
Tay-Sachs disease, 1115 
Tchistovitch, on crisis in pneumonia, ref., 
690 
Teacher, J. H., on regression of chorion- 
epithelioma, ref., 951 
Teague and Torrey, on gonococcus, ref., 
252 
Teeth, tumors of, 406, 448 
Teller, R., on carcinoma of vulva, ref., 913 
Tendeloo, on metastasis of tumors, ref., 
378; on retroperitoneal lymph-nodes, 
ref., 794 
Teratoids, 368 
Teratoma, 368, 393 
of hypophysis, 1182a 
liver, 840 
lung, 721 
mediastinum, 723 
ovary, 971, 974 
pharynx, 741 
pineal gland, 1182 
scrotum, 1014 
testicle, 1023 
thyroid, 587 
tonsil, 741 
vagina, 916 
sacral, 367 
Terry, B. T., on chemical therapy in 
trypanosomiasis, ref., 137 
Testicle, 1014 
abscess of, 1017 
absence of, 1014 
actinomycosis of, 1021 
atrophy of, 1016 
chorionepithelioma of, 952 
cryptorchismus, 1015 
examination, post-mortem, of, 1219 
fibrosis of, 1018 
glanders, 1021 
hematocele, 1016 
hydrocele, 1015 
inflammation of (see Orchitis), 1016 
leprosy of, 1021 
malformations of, 1014 
malpositions of, 1015 
parasites of, 1024 
preservation of, 1219 
regeneration of, 87 
retained, 1015 
spermatocele, 1016 
syphilis of, 1020 
tuberculosis of, 1019 
tumors of, 1021 
varicocele, 1015 
Tetanotoxins, 318 
Tetanus, 317 
antitoxin, 190, 318 
diagnosis of, 319 
Tetany after removal of parathyroids, 
588 
Tetrachlorethane poisoning, 479 INDEX 
1341 
Texas fever, hematozoon of, 143 
Thacher, J. 8., on melanuria, ref., 432 
Thalhimer, on cysts of intestine, ref., 785 
Thalhimer and Rothschild, on experi- 
mental focalized myocarditis, ref., 616; 
on myocarditis in relation to Aschoff 
nodules, ref., 351 
Thayer, W. 8., on endarteritis in typhoid 
fever, ref., 638; on malarial nephritis, 
ref., 871; on venous thrombosis in 
typhoid fever, ref., 273 
Thayer and Hewetson, on malaria, ref., 
349 
Theile, P., on cystadenoma of mamma, 
ref., 993; on tumors of spleen, ref., 
580 
Theilhaber and Edelberg, on multiple 
carcinomata, ref., 454; on spontaneous 
cure of carcinoma, ref., 454 
Thiersch, on tumor origin, ref., 384 
Thiersch and Waldeyer's hypothesis of 
origin of tumors, 384 
Thiomn stain, 1238 
Thiroloix and Debre, on thymoma, ref., 
376 
Thoma, R., on arteriosclerosis, ref., 633, 
645; on fissures in cervical region, ref., 
736; on hypertrophy of kidney, ref., 
853; on inflammation, ref., 126; on 
malformations, ref., 355; on mal- 
formations of central nervous system, 
ref., 1110; on mitosis, ref., 82; on 
pathological anatomy, ref., 21; on 
waxy degeneration of muscle, ref., 
1037 
Thoma's frog plates, 128 
use of, 42 
Thomas, on cancer, ref., 468 
Thomas, B. A., and Birdsall, J. C., on 
functional tests in nephritis, 
ref., 882 
Thomas, E., on lactating mamma, ref., 
986 
Thomas, G. J., on diverticula of bladder, 
ref., 897 
Thomas, J. J., on cholesteatoma of brain, 
ref., 1177 
Thomas, T. G., on sarcoma of vagina, ref., 
916 
Thomas and Hibbard, on lesions of myo- 
cardium in diphtheria, ref., 314 
Thompson, on metastatic tumors of 
parathyroids, ref., 588 
Thompson, E. S., on hyperplastic perios- 
titis, ref., 1046 
Thompson, R. L., on parathyroids, ref., 
588 
Thompson and Leighton, on transplanta- 
tion of parathyroids, ref., 588 
Thompson, T., and Turnbull, H. M., on 
obstruction of hepatic veins, 
ref., 814 
Thomsen's disease of muscle, 1036 
Thoracic duct, examination, post-mor- 
tem of, 1218 
obstruction of, 658 
Thoracopagus, 364 
parasitic, 367 
tribrachius, 365 
tripus, 365 
Thorax, deformation of, in emphysema, 
682 
examination, post-mortem, of, 1201, 
1203, 1225 
Thorel, C., on angioma of aorta, ref., 653; 
on arteriosclerosis, ref., 645; on kidney 
infarcts, ref., 854; on lesions of salivary 
glands, ref., 798; on lesions of stomach, 
ref., 758; on myxoma of heart, ref., 634; 
on syphilitic arteritis, ref., 647; on 
tumors of heart valves, ref., 634; on 
tumors of muscle, ref., 1040; on tumors 
of veins, ref., 657 
Thorn, J., on ganglia, ref., 1087 
Threadworm, 150 
Throat, septic, 240 
Thrombi, 31 
agglutinative, 33 
alterations in, 34 
arterial, 33 
blood-plates in, 528 
canalized, 33 
forms of, 31, 33 
hyaline, 34 
infective, 33 
marantic, 32, 811 
mixed, 31 
obstructing, 33 
organization of, 34 
parietal, 33 
primary, 33 
propagated, 33 
red, 31 
secondary, 33 
simple, 33 
softening of, 34 1342 
INDEX 
Thrombi, solid, 33 
stagnation, 32 
venous, 33 
white, 31 
Thromboangiitis obliterans, 639 
Thromboarteritis, 637 
proliferans, 638 
Thrombosis, 31 
causes of, 31 
effects of, 34 
of adrenals, 590 
brain, 1126 
coronary arteries, 614 
dura mater cerebralis, 1089 
heart, 608 
kidney, 854 
liver, 811, 814, 815 
lung, 679 
lymph-vessels, 35, 659 
spinal cord, 1128 
splenic vein, 571 
veins, 655 
venous, in typhoid fever, 273 
Thrombus, formation of, 111 
Thrush, 171, 731 
Thymoma, 376 
Thymus, 581 
accessory, 581 
examination, post-mortem, of, 1225 
function of, 581 
gland, size of, in new-born, 1225 
weight of, in new-born, 1225 
hemorrhage in, 581 
hyperplasia of, 581 
hypertrophy of, 581 
in myasthenia gravis, 1035 
inflammation of, 582 
malformations of, 581 
syphilis of, 582 
tuberculosis of, 582 
tumors of, 582 
Thyroid, 583 
accessory, 583 
adenoma of, and goiter, ref., 489 
degeneration of, 583 
enlargement of (see Struma), 584 
examination, post-mortem, of, 1211, 
1225 
extracts of, in myxedema, 486 
fetal adenoma of, 586 
gland extract in cretinism, 1045 
goiter, 584 
exophthalmic, 488 
Thyroid, hyperemia of, 583 
hyperplasia of, 584 
hypertrophy of, 74 
inflammation of, 583 
lesions of, in myxedema, 485 
iodine, in, 489 
malformations of, 583 
para-, 587 
parasites in, 587 
regeneration of, 86 
syphilis of, 584 
tissue in ovary, 973 
transplantation of, ref., 94, 485 
tuberculosis of, 584 
tumors in tongue, 735 
tumors of, 586 
weight of, 1211, 1225 
Tibia, adamantinoma of, 448 
Tic douloureux, 1164 
Tick fever, 325, 334 
of cattle, hematozoon of, 143 
Tidy, C. M., on post-mortem examina- 
tion,-ref., 1189 
Ti'eche, on najvus, ref., 447 
Tietze, on cystadenoma of mamma, ref., 
997; on cysts of bone, ref., 1081 
Tiffany, W. J., on senile dementia, ref., 
1170 
Tilger, A., on cysts of pancreas, ref., 807 
Tilney, F., on myasthenia gravis, ref., 
1035; on Wilson's disease, ref., 1168 
Tilney and Mackenzie, on familial cir- 
rhosis of liver, ref., 830 
Tilney and Riley, ref., 1129 
Timme, W., on angioma of pericardium, 
ref., 599; on hemangioma of heart, ref., 
634; on muscular dystrophy, ref., 1034, 
1035 
Tinea circinata, 172 
Tischner R., on closure of hepatic artery 
and gall-ducts, ref., 811 
Tissue changes, progressive, 44, 73 
regressive, 44- 
cicatricial, 109 
cultivation of, 93 
dead, disposal of, 119 
decalcification of, 1232 
embedding of, 1232 
fixation of, 1228 
rapid, 1227 
fresh, study of, 1227 
frozen section of, 1227 
granulation, 108 INDEX 
1343 
Tissue, healing of, by first intention, 98 
by second intention, 110 
method of preservation and staining, 
1227 
necrotic, disposal of, 71 
non-vascular, injury to, 98 
repair of, 111 
tension, 94 
in tumors, 382, 384 
transplantation of, 96 
vascular, injury to, 99 
Tobiesen, on sarcoma of pericardium, ref., 
599 
Todd and Wolbach, on tick fever, ref., 325 
Toenniessen, on lobar pneumonia, ref., 
692 
Tomita, on pseudomyxoma peritonei, ref., 
797 
Tongue, 734 
absence of, 734 
actinomycosis of, 736 
black hairy, 735 
cysts of, 735 
"furred," 735 
geographic, 732 
granuloma of, 736 
hypertrophy of, 735 
inflammation of, 735 
malformations of, 734 
tumors of, 735 
Tonsil, 736 
calculi of, ref., 739 
cartilage in, 741 
hypertrophy of, 736 
inflammation of (see Tonsillitis), 738 
portal of entry for tubercle bacilli, 
ref., 740 
tuberculosis of, ref., 739 
tumors of, 741 
Tonsillitis, 737, 738 
chronic, 739 
exudative, 738 
follicular, 738 
phlegmonous, 738 
suppurative, 736 
Tooth, H. H., on degeneration of spinal 
cord, ref., 1143 
Tophi, 494 
Torrey, J. C., on bacteria in abnormal 
lymph-nodes, ref., 546; on gonococcus, 
ref., 252 
Toxalbumins, 177 
Toxalbumoses, 177 
Toxemia, 178, 231 
of pregnancy, lesions of liver in, 818 
Toxin, bacterial, 164, 177 
binding of, ref., 193 
diphtheria, 190 
fixing of, ref., 193 
in fever, 502 
Toxoids, ref., 193 
Toxophorous group, 193 
Trachea, 664 
examination, post-mortem, of, 1211, 
1225 
lesions of, 668 
malformations of, 664 
preservation of, 1211 
tumors of, 669 
Trachoma, 340 
bodies, 341 
Tracy, M., on microchemical reactions 
for iron, ref., 64 
Transplantation of organs, 93 
of tissue, 92 
autoplastic, 92 
homoplastic, 92 
tumors, 93, 388 
technique of, 390 
Transudates, 30 
Transudation, 29 
Trappe, on adenomyoma of intestine, ref., 
782; on adenosarcoma, ref., 440 
Trauma, 18 
in etiology of tumors, 386 
Trautmann, on carcinoma of nose, ref., 
662 
Trematoda, 144 
Trench fever, 351 
Trepiaski, on tabes dorsalis, ref., 1150 
Treponema pallidum, 138, 308 
demonstration of, 310 
in nervous system, 1166 
methods of staining, 310 
pertenue, 138 
in yaws, 326 
Treutlein, on carcinoma of gall-bladder, 
ref., 846 
Trichina spiralis, 153 
Trichinella in lymph-nodes, 565 
spiralis, 153 
in muscle, 1041 
Trichiniasis, 154 
Trichocarcinoma, 464 
Trichocephalus dispar, 152 
in appendix vermiformis, 782 1344 
INDEX 
Trichomonas vaginalis, 140 
in vagina, 918 
Trichophyton tonsurans, 172 
Trichuris trichiura, 152 
Trinitrophenol poisoning, 477 
Trinitrotoluene poisoning, 477 
Triplets, 362 
Tromp, on lipoma of intestine, ref., 782 
Trypanosoma brucei, 136 
cruzi, 137 
evansi, 137 
gambiense, 137 
lewisi, 136 
rhodesiense, 137 
Trypanosomes, 135 
adaptation of, to arsenic, 470 
pathogenic, 136 
Tsetse-fly disease, 136 
Tube, Fallopian (see Fallopian tubes), 
976 
Tubercle, 282 
bacillus (see Bacillus tuberculosis), 
289 
chronic, 709 
conglomerate, ref., 282 
diffuse, 287 
foreign-body, 118 
form of, 286 
granulum, ref., 282 
"healed," 709 
lymphoid, 287 
miliary, 282, 283, 708 
in pleura, 728, 729 
polyhedral-cell, 287 
solitary, of liver, 834 
subcutaneous, painful, 416 
tissue, ref., 284 
Tuberculin, diagnostic, use of, 294 
reaction in conjunctiva, 215 
therapeutic use of, 294 
Tuberculosis, 282 
and cancer, 723, 948 
animal, 296 
autopsy findings in, ref., 296 
bacillus of (see Bacillus tuberculosis), 
282 
bibliography of, 301 
blood in, 526 
bovine, infection of children with, 
ref., 299 
complement fixation in, 293 
complex factors in, 295 
concurrent infection in, 299 
Tuberculosis, diffuse, 283 
effect of exposure to sun's rays in, 18 
of lung, chronic, 711 
frequency of, 296 
lesions of, 282 
, "localized, " 282 
miliary, generalized, 282 
of adrenals, 490, 590 
appendix vermiformis, 778 
arteries, 646 
bladder, urinary, 901 
bone, 1059, 1065 
brain, 1172 
bronchi, 672, 674 
bursae, 1088 
cervix uteri, 933 
dura mater cerebralis, 1092, 1172 
spinalis, 1103, 1173 
ependyma, 1106 
esophagus, 744 
Fallopian tubes, 980 
gall-bladder and -ducts, 844 
heart, 619, 626 
ileocecal region, 775 
intestine, 765 
joints, 1085 
kidney, 882 
larynx, 667 
liver, 832 
lungs (see Tuberculosis, pulmo- 
nary), 704 
lymph-nodes, 551, 553 
lymph-vessels, 659 
mamma, 993 
mouth, 732 
muscle, 1040 
nervous system, 1092, 1099, 1103 
1104, 1106, 1169 
nose, 662 
ovaries, 959 
pancreas, 806 
parotid, 798 
penis, 1012 
pericardium, 598 
peritoneum, 793 
pharynx, 739 
pia mater cerebralis, 1099 
spinalis, 1104 
placenta, 954 
pleura, 727 
prostate, 1027 
seminal vesicles, 1024 
skin, 300 INDEX 
1345 
Tuberculosis of spinal cord, 1173 
spleen, 574 
stomach, 750 
testicle, 1019 
thymus, 582 
thyroid, 584 
tongue, 735 
urachus, 897 
urethra, 908 
uterus, 930 
vagina, 916 
veins, 657 
vulva, 910 
predisposition in, ref., 283 
pulmonary, 704 
acute, 714 
and pigmentation, 728 
apex in, 718 
bacteremia in, 718 
broncho, 711 
cavities in, 713, 715 
chronic, 714 
classification of, 706 
complex forms of, 714 
concurrent infection in, 718 
diffuse, 714 
distribution of lesions in, 717 
experimental, 718 
exudative, 714 
fibrous tissue formation in, 717 
focal, 706 
healing in, 717 
miliary, acute, 706 
modes of infection in, 704, 707, 728 
nodular, 714 
secondary lesions in, 716 
statistics of, ref., 296 
tuberculin in, 294 
Tuberculum dolorosum, 416 
Tuberous sclerosis, 1114a 
Tubes, Fallopian (see Fallopian tubes), 
976 
of Miescher, 142 
Rainey, 142 
Tumors, 372 
anaplasia in, 374, 384 
anemia in, 379 
benign, 376 
infiltrative growth of, 378 
metastasis of, 379 
structure of, 381 
bibliography of, 467 
blood-vessels in, 391 
Tumors, cachexia in, 380 
carcinoid, 783, 786 
cells, altruistic, 372 
egoistic, 372 
emboli, 42 
inclusions in, 380 
proliferation of, 373 
race, new, in, 384 
chemistry of, 386 
chronic irritation in, 386 
classification of, 390 
collagen in, 397, 437 
complex, 393 
composite, 393 
connective-tissue, benign, 396 
immature, 391 
mature, 390 
contagion in, 385, 389 
definition of, 373 
degeneration, malignant, in, 382, 384 
degenerative processes in, 376 
dissemination of, through lymph- 
vessels, 660 
effect of x-ray and radium on, 14 
embryoid, 392 
embryonal rests in, 382, 383 
epithelial, benign, 444 
immature, 392 
malignant, 453 
mature, 391 
etiology of, 382 
age in, 388 
chronic irritation in, 386 
civilization as factor in, 387 
Cohnheim's hypothesis, 383 
diet in, 385 
v. Hansemann's hypothesis, 384 
Hauser's hypothesis, 384 
heredity in, 387 
parasitic hypothesis, 378, 385 
Hibbert's hypothesis, 383 
Tiersch and Waldeyer's hypothe- 
sis, 384 
trauma in, 386 
fetal inclusions in, 393 
fibroepithelial, 445 
"fibroplastic," 429 
general nature of, 372 
growth of, 372 
central, 376 
expansive, 376 
infiltrative, 376 
peripheral, 376 1346 
INDEX 
Tumors, growth of, rate of, 376 
heterologous, 374 
heterotypical, 374 
histioid, 375 
homeotypical, 374 
homologous, 374 
immature, 374 
immunity to, acquired, 389 
infiltrative growth of, 377 
Krukenberg, of ovary, 970 
malignant, 376 
cells, size of, 380 
examination of, removal of frag- 
ment for, 381 
structure of, 381 
mature, 374 
melanotic, 432 
metastasis of, 372, 378 
organs involved in, 379 
mitosis in, 384 
mixed, 392 
of bladder, urinary, 903 
kidney, 891 
salivary glands, 443, 444 
of animals, 387 
bladder in aniline workers, 386 
organoid, 375 
parasites in, 385 
parenchyma of, 375 
physiological secretions in, 373, 587, 
592, 735 
pigmented, 432 
recurrence of, 379 
regression of, 373 
sacral, 1112 
special forms of, 396 
splenic, acute, 571 
chronic, 572 
statistics of, 386 
stroma of, 375 
structure of, 373, 381 
terminology of, 375 
tissue tension in, 382, 384 
transplantation of, 93, 388 
Tunica vaginalis, hydrocele of, 1015 
Tunnicliff, R., on bacteriology of measles, 
ref., 342 
Turk, on "irritation forms" of leucocytes, 
ref., 525; on leucocytosis, ref., 526 
Turner, on spinal cord tumors, ref., 1179 
Turpentine poisoning, 476 
Tuttle, on streptothrix pneumonia, ref., 
262 
Tuxen, on carcinoid tumors of appendix, 
ref., 786 
Twins, 362 
Typhoid fever, 265 
bacillus of, 265 
blood in, 526 
carriers of, 275 
flies as carriers of, 275 
immunity in, 275 
lesions of, 266 
of appendix vermiformis in, 778 
secondary, in, 272 
mixed infection in, 274 
para-, 277 
preventive inoculations in, 275, 
276 
septicemic forms of, 273 
meningitis, ref., 273 
Typhus fever, 333 
mouse, bacillus of, 321 
recurrens, 324 
Tyzzer, E. E., on adenoma of lung in mice, 
ref., 722; on Coccidium oviforme, ref., 
142; on heredity in cancer, ref., 387; on 
metastasis of tumors, ref., 381 
Uffenheimer, A., on permeability of in- 
testinal wall for bacteria, ref., 
774 
Uffreduzzi, on undescended testicle, ref., 
1015 
Uhlenhuth and Hubener, on paratyphoid, 
ref., 277 
Uhlenhuth and Weidanz, on precipitin 
test, ref., 222 
Ulceration, 69 
Ulcers, 69 
differentiation from epithelioma, 462 
Jacob's, 463 
of intestine, 767, 769, 775 
penis, 1012 
stomach, 751 
carcinomatous changes in, 753 
vulva, 910 
rodent, 462 
Ullman, on tonsils, ref., 740 
Ultraviolet light, effect of, 17 
Ultzmann, R., on renal calculi, ref., 890 
Umber, on splenic anemia, ref., 544 
Umbilical cord, examination, posUmor 
tem, of, 1224 
Umbilicus, dilatation of veins of, 828 
tumors of, 797 INDEX 
1347 
Uncinaria americana, 151 
anemia due to, 534 
duodenalis, 151 
Uncinariasis, 151 
Underhill, F. P., and Rand, R. F., on acute 
yellow atrophy of liver, ref., 818 
Underhill, Wells, and Goldschmidt, on 
poisoning by tartaric acid, ref., 
472 
Unger, on cystadenoma of male breast, 
ref., 1030; on tumors of lymph-vessels, 
ref., 660 
Ungermann, on thyroid tumors of tongue, 
ref., 735 
Unna, on naevus, ref., 447 
Unna's polychrome methylene-blue stain 
1238 
Unruh, on endothelioma, ref., 442 
Unverricht, on primary acute polymyo- 
sitis, ref., 1039 
Urachus, cysts of, 896 
malformations of, 896 
tuberculosis of, 897 
tumors of, 897 
Ureter, carcinoma of, ref., 904 
inflammation of, 884 
malformations of, 851 
Ureteritis, suppurative, 884 
Urethra, 906 
cysts of, 908 
dilatation of, 906 
diverticula of, 906 
examination, post-mortem, of, 1218 
gonorrhea of, 907 
hemorrhoids of, 908 
inflammation of (see Urethritis), 907 
malformations of, 906 
malpositions, of, 906 
perforations of, 907 
polyps of, 908 
prolapse of, 907 
rupture of, 907 
strictures of, 906 
syphilis of, 908 
tuberculosis of, 908 
tumors of, 908 
ulceration of, 907 
wounds of, 907 
Urethritis, catarrhal, 907 
chronic, 907 
gonorrheal, 907 
membranous, 908 
syphilitic, 908 
Urethritis, tuberculous, 908 
Urinary organs, 849 
Uta, 140 
Uterus, 918 
absence of, 918 
atrophy of, 924 
bacteria in, 936 
bicornis, 918 
cervix, erosions of, 932 
inflammation of, 932 
tumors of, 941 
chorionic villi, 949 
degenerations of, 925 
dilatation of, 920 
displacements of, 920 
double, 918 
elevation of, 922 
endometrium, inflammation of (see 
Endometritis), 925 
enlargement of, 919 
examination, post-mortem, of, 1219 
flexions of, 920 
hematometra, 920 
hemorrhage of, 923 
hernia of, 923 
hour-gass, 920 
hydrometra, 920 
hyperemia of, 923 
inflammation of (see Endometritis, 
Metritis, and Endocervicitis), 
925, 932 
inversion of, 922 
malformations of, 918 
malpositions of, 920 
menstrual changes, 926 
parasites of, 953 
perforation of, 923 
placenta, lesions of, 953 
polyps of, 936 
pregnant, inflammation of, 933 
preservation of, 1221 
prolapse of, 922 
pus in, 930 
rupture of, 923 
size of, 1220 
changes in, 919 
syphilis of, 930, 933 
tuberculosis of, 930, 933 
tumors of, 936 
versions of, 921 
weight of, 1220 
Uvula, atrophy of muscle of, 1038 
Uy eno, S., on phenol poisoning, ref., 477 1348 
INDEX 
Vaccination in smallpox, 336 
Vaccine bodies, 338 
Vaccines, 212, 213 
sensitized, 188 
Vaccinia, virus of, cultivation of, 339 
Vacuolization, of cells, 54 
Vagina, 913 
abscess of, 915 
absence of, 913 
bacteria in, 915, 918 
closure of, 913 
cystocele, 897, 914 
cysts of, 918 
dilatation of, 914 
double, 914 
examination, post-mortem, of, 1219 
fistulae of, 914 
gangrene of, 916 
hernia of, 914 
inflammation of (see Vaginitis), 915 
injuries of, 914 
lengthening of, 914 
malformations of, 913 
malpositions of, 914 
narrowing of, 914 
parasites in, 918 
perforation of, 914 
preservation of, 1221 
prolapse of, 914 
rectocele, 914 
syphilis of, 916 
tuberculosis of, 916 
tumors of, 916 
Vaginitis, 915 
catarrhal, 915 
emphysematous, 916 
gangrenous, 916 
granular, 916 
membranous, 915 
senile, 916 
suppurative, 915 
syphilitic, 916 
tuberculous, 916 
Vance, B. M., on carcinoid tumors of 
intestine, ref., 7S3; on multiple mye- 
loma, ref., 1073; on myeloma, ref., 431 
Van Cott, J. M., and Lintz, TV., on Trichi- 
nella spiralis, ref., 153 
Van der Loeff and Pfeiffer, on smallpox, 
338 
Vander Veer and Kellert, on melanotic 
sarcoma of rectum, ref., 784 
van Ermengem, on botulism, ref., 324 
Van Gehuchten, A., on nervous system, 
ref., 1129 
Van Gieson, I., on artefacts of nervous 
system, ref., 1112; on hematomyelo- 
pore, ref., 1126; on post-mortem 
examination of brain, ref., 1198; on 
post-mortem examination of spinal 
cord, ref., 1199; on sunstroke, ref., 
495 
Van Gieson's picro-acid fuchsin stain, 
1236 
stain for Negri bodies, ref., 329 
Van Slyke, D. D., on Abderhalden reac- 
tion, ref., 218; on reaction of blood, 
ref., 516 
Varices, aneurysmal, 651 
esophageal, 742 
venous, 654 
Varicocele, 1015 
Variola, 336 
Varix lymphatic, filarial, 658, ref., 155 
Vassmer, on chorionepithelioma of vulva, 
ref., 913 
Vaughan, on anaphylaxis, ref., 177, 216, 
502; on spread of typhoid, ref., 275 
Vaughan, W. T., on acute lobar pneu- 
monia, ref., 248 
Vaughan and Novy, on cellular toxins, ref., 
177, 481 
de Vecchi, on adrenal remnants in liver, 
ref., 836 
Vedder, on beriberi, ref., 496; on gono- 
coccus, ref., 252 
Veil, W., on sarcoma of prostate, ref., 
1028 
Vein stones, 34 
Veins, 654 
calcification of, 655 
circulation in, 24 
degeneration of, 655 
dilatation of, 654 
hepatic, lesions of, 814 
inflammation of (see Phlebitis), 656 
parasites of, 657 
perforation of, 655 
portal, lesions of, 811 
rupture of, 655 
syphilis of, 657 
thrombosis of, 655 
tuberculosis of, 657 
tumors of, 657 
varicose, in vulva, 909 
wounds of, 655 INDEX 
1349 
Veit, J., on female generative organs, ref., 
909 
Vena cava, thrombosis of, 655 
Venom, animal, 479 
Ventricles of brain, lesions of, 1089 
Veratria poisoning, 476 
Verocay, on neurofibromatosis, ref., 415 
Verploegh, Kehrer, and v. Hoogenhuyze, 
on organism of Hodgkin's dis- 
ease, ref., 563 
Verruca vulgaris, 445 
Verse, on adenomata of intestine, ref., 
453; on carcinoma of stomach, ref., 
755; on malignant polyps, ref., 445; on 
plasmocytoma of bones, ref., 431; on 
ulcers of stomach, ref., 753 
Verworn, M., on chemotaxis, ref., 102; 
on muscular contraction, ref., 1031 
Vesiculse seminales, examination, post- 
mortem, of, 1219 
preservation of, 1219 
Vibrio cholera) asiaticse, 278, 279 
massawah, 281 
metschnikovi, 281 
proteus, 281 
Vierordt, on weight of viscera, etc., ref., 
1190 
Vincent, on angina, ref., 326; on internal 
secretions, ref., 483; on Paget's dis- 
ease of bone, ref., 1050 
Vincent's angina, 326 
Virchow, R., on pigmentation of brain, 
ref., 1118; on tumors, ref., 467 
Virus, fixed, in hydrophobia, 328, 330 
Viscera, changes in, following extensive 
burns, 11 
exposure to cold, 11 
weight of, ref., 1190 
Vital stains, 535, 1227 
Vitamines, 496 
Voeckler, on lipoma of peritoneum, ref., 
794 
Voegtlin, C., and Bernheim, B. M., on 
obliterative thrombosis of portal 
vein of liver, ref., 812 
Vogel, K. M., on colloidal gold reaction, 
ref., 312; on diaphragmatic hernia, 
ref., 789; on Paget's disease of bone, 
ref., 1050 
Vogel, K. M., and McCurdy, U. F., on 
regeneration in pernicious ane- 
mia, ref., 535 
Vogel, R., on accessory lung, ref., 676 
Volhard and Fahr, on albuminous de- 
generation, ref., 858; on casts in urine, 
ref., 857; on nephritis, ref., 862 
Volkmann, on endothelioma, ref., 441; 
on mixed tumors of salivary glands, 
ref., 801 
Voluntary muscle, 1031 
Volvulus of intestine, 760 
of Meckel's diverticulum, ref., 759 
Voss, on B. pyocyaneus, ref., 244 
Vulva, 909 
condyloma of, 911 
cysts of, 913 
edema of, 909 
elephantiasis of, 912 
erysipelas of, 910 
esthiomene of, 912 
examination, post-mortem, of, 1219 
gangrene of, 910 
gonorrhea, 910 
hemorrhage of, 909 
hyperemia of, 909 
inflammation of, 910 
kraurosis of, 911 
malformations of, 909 
noma of, 910 
syphilis of, 910 
tuberculosis of, 910 
tumors of, 912 
ulcer of, 910 
varicose veins in, 909 
Vulvitis, 910 
Wachenheim, F. L., on pyloric stenosis, 
ref., 745 
Wachter, on plasmocytoma of upper air 
passages, ref., 675 
Wadsworth, A., on agglutination of D. 
pneumoniae, ref., 247; on experimental 
pneumonia, ref., 691; on induced pneu- 
monic lesions in rabbits, ref., 247; on 
mouth disinfection, ref., 249; on pneu- 
mococcus infection, ref., 250; on 
puerperal infection, ref., 936; on stain- 
ing D. pneumoniae, ref., 247; on stain- 
ing encapsulated pneumococci, ref., 
250 
Wadsworth, W. S., on post-mortem ex- 
aminations, ref., 1186 
Wagener, on intestinal tuberculosis, ref., 
766 
Wahl, on neuroblastoma, ref., 411; 
on paraganglioma, ref., 413 1350 
INDEX 
Waldeyer, on tumor origin, ref., 384 
Walker, on Balantidium coli, ref., 140 
Walker, G., on renal tuberculosis, ref., 
883; on inflammation of seminal 
vesicles, ref., 1024 
Walker, C. A., and Cummins, W. T., on 
echinococcus cysts of bones, ref., 
1082 
Walker and Haller, on Wassermann reac- 
tion, ref., 312 
Wallart, J., on salpingitis, ref., 977 
Waller, law of, 1134 
Ward, on influence of parasites on host, 
ref., 144 
Ward, G. G., on thyroid and pregnancy, 
ref., 584 
Warfield, on carcinoma of male breast, 
ref., 1030; on meningococcus endo- 
carditis, ref., 622 
Warren, M., and Herrick, W. W., on 
animal parasites in blood, ref., 533; 
on septicemia, ref., 234 
Warrington, W. B., on structural altera- 
tions in nerve cells, ref., 1136 
Warstat, on plasmocytoma of bones, ref., 
431 
Wart, 445 
blue, 423 
venereal, 911 
Warthin, A. S., on adrenals in broad liga- 
ment, ref., 588; on calcification of 
kidney, ref., 857; on cancer statistics, 
ref., 453; on carcinoma of gall-ducts, 
ref., 846; on emboli, ref., 36; on focal 
fatty degeneration of heart, ref., 612; 
on hemolymph-nodes, ref., 547; on 
lesions of pancreas, ref., 805; on 
myxoma of heart, ref., 634; on multiple 
carcinomata, ref., 454; on tuberculosis 
and tumors of mamma, ref., 994 
Warthin and Cowie, on placental and con- 
genital tuberculosis, ref., 297 
Warthin, A. S., and Weller, C. V., on 
poisoning by mustard gas, ref., 
472 
Waschkewitsch, T., on lesions of diph- 
theria, ref., 314 
Washbourn, on infective endocarditis, 
ref., 622 
Wasielewski, on vaccine bodies, ref., 338 
Wassermann, on radium exposures, ref., 
13 
Wassermann reaction in syphilis, 311 
Wassermann and Keysser, on congenital 
transmission of infectious agents, ref., 
176; on mixed infections, ref., 183; on 
nature and conditions of infection, ref., 
181 
Wassermann, Neisser, and Bruck, on test 
for syphilis, ref., 311 
Watkins, J. A., on carbon monoxide poi- 
soning, ref., 480 
Watson, E. N., on Negri bodies, ref., 
329 
Watson, W. T., on Paget's disease of bone, 
ref., 1050 
Watters, on preparation of museum speci- 
mens, ref., 1242 
Watzold, on adenoma of liver, ref., 836; 
on perithelioma of ependyma, ref., 1109 
Waxy degeneration, 57 
Weaver, on agglutination of streptococci, 
ref., 239 
Weaver and Rappaport, on Shick test, ref., 
317 
Weber, F. P., on polycythemia, ref., 518 
Weber, L. W., on cause of hydrocephalus, 
ref., 1109 
Weber, O., on osteomalacia, ref., 1051 
Weber and Schmidt, on diabetes insipidus, 
ref., 493 
Wechsberg, F., on tuberculosis, ref., 284 
Wegelin, on myxoma of heart, ref., 634; 
on tumors of heart valves, ref., 634 
Weichselbaum and Ghon, on meningococ- 
cus, ref., 256 
Weidenreich, on examination and fixation 
of blood, ref., 529; on hemolymph- 
nodes, ref., 87, 547; on lymph-nodes, 
ref., 546; on plasma cells, ref., 88; on 
spleen, ref., 566 
Weigert, C., on gumma of hypophysis, 
ref., 1182a; on immunity, ref., 224; on 
neuroglia, ref., 1133 
Weil's disease, 352 
spirochetes in, 139 
Weil, R., on anaphylaxis, ref., 216, 217 
Weiler, F., on pseudomembranous colitis, 
ref., 773 
Weinberg, M., on antiserum for B. aero- 
genes capsulatus, ref., 322 
Weinberg and Gastpar, on age distribution 
of sarcoma, ref., 427 
Weinberg, M., and Seguin, P., on anti- 
serum for B. aerogenes capsu- 
latus, ref., 322 INDEX 
1351 
Weiner, on melanotic sarcoma of rectum, 
ref., 784 
Weintraub, on autointoxication, ref., 482 
Weir, W. H., on chronic inflammation of 
appendix, ref., 781; on duodenal ulcers, 
ref., 767 
Weiss, S., on osteotabes infantum, ref., 
1055; on bacteria in stomach, ref., 750 
Welch, W. H., on adaptation in patholog- 
ical processes, ref., 126; on agglutinative 
thrombi, ref., 34; on B. aerogenes cap- 
sulatus, ref., 323; on arteriosclerosis, 
ref., 644; on bacteria of body surfaces, 
ref., 175; on cardiac hypertrophy, ref., 
628; on cardiac thrombosis, ref., 609; 
on carcinoma of stomach, ref., 755; on 
cirrhosis hepatis anthracotica, ref., 830; 
on embolism, ref., 532; on gastric ulcer, 
ref., 751; on immunity, ref., 225; on 
pulmonary edema, ref., 678; on stain- 
ing D. pneumoniae, ref., 251; on throm- 
bosis and embolism, ref., 35; on throm- 
bosis of mesenteric veins, ref., 763; on 
thrombosis of pulmonary artery, ref., 
680; on venous thrombosis, ref., 655 
Weleminsky, F., on bronchial lymph- 
nodes, ref., 676 
Weller, on age distribution of sarcoma, 
ref., 427; on carcinoma of bronchi, ref., 
675; on incidence of sarcoma and car- 
cinoma, ref., 454 
Wells, H. G., on Abderhalden reaction, 
ref., 218; on antigens, ref., 200; on 
autolysis, ref., 72; on bacterial poisons, 
ref., 177; on calcification, ref., 63; on 
carcinosarcoma of thyroid, ref., 587; on 
chemical pathology, ref., 4; on chem- 
istry of tumors, ref., 386; on endogen- 
ous poisons, ref., 482; on fat content of 
cysts of mamma, ref., 1010; on fat 
necrosis of pancreas, ref., 804; on in- 
farcts, ref., 37; on inflammation, ref., 
123; on proteolytic enzymes, ref., 
117 
Wells and Scott, on paratyphoid, ref., 277 
Wenglowski, on branchial cysts of neck, 
ref., 736 
Wengraf, on adenosarcoma, ref., 440 
v. Werdt, F., on atrophy of muscle fibers, 
ref., 1034; on malignant edema, ref., 
323 
Werigo, on disposal of bacteria in blood, 
ref., 176 
Werth, R., on ectopic pregnancy, ref., 982; 
on pseudomyxoma peritonei, ref., 797 
zur Werth, M., and Scheele, K., on indura- 
tion of penis, 1013 
Werzberg, on regeneration of blood, ref., 
92 
Westenhoeffer, on cerebrospinal menin- 
gitis, ref., 256; on mode of infection by 
B. tuberculosis, ref., 297; on plethora, 
ref., 518 
Wetterdal, on paraganglioma of carotid, 
ref., 413 
Wharton's duct, dilatation of, 798 
Wheeler, on viability of typhoid bacillus, 
ref., 275 
Whipham, on carcinoid tumors of appen- 
dix, ref., 786; on mediastinitis, ref., 723 
Whipple, C. H., on autointoxication, ref., 
483; on nodular colitis, ref., 771; on 
typhoid fever, ref., 270 
Whipple, Chaffee, and Fisher, on chronic 
interstitial pancreatitis, ref., 806 
Whipple, G. H., and Hooper, C. W., on 
icterus, ref., 65 
Whipple, G. H., and Sperry, J. A., on 
chloroform poisoning, ref., 479; on 
chloroform liver necroses, ref., 816 
Whip-worm (see Trichocephalus dispar), 
152 
White, on acute yellow atrophy of liver, 
ref., 818; on S. pyogenes aureus in skin 
lesions, ref., 237; on tumors, ref., 468 
White, F. W., on septicemia, ref., 234 
White and Mair, on adrenal remnants in 
liver, ref., 836 
White, B. and Avery, 0. T., on toxic prod- 
ucts of tubercle bacillus, ref., 
292 
Whitney, C. M., on spermatocele, ref., 
1016 
Whooping-cough, 350 
Wichmann, G., on amyloid degeneration, 
ref., 59 
Wickman, I., on acute poliomyelitis, ref., 
1160 
v. Wiczkowski, on carcinoma of lung, ref., 
722 
Widal, Ambard, and Weill, on edema, ref., 
30 
Wieland, E., on gigantism, ref., 1045; on 
rachitis, ref., 1052 
Wiener, G., on melanosarcoma of vulva, 
ref., 912 1352 
INDEX 
Wiener, J., on ileocecal tuberculosis, ref., 
776 
Wiesel, on arteriosclerosis, ref., 644; on 
neuroblastomata, ref., 408 
Wiesel, J., on lesion of coronary arteries, 
ref., 614; on thymus and its relation 
to rickets, ref., 581 
Wiesner, R., on lesion of coronary 
arteries, ref., 614 
Wieting and Hamdi, on melanin, ref., 
66 
Wiggers, C. J., on circulation, ref., 628; 
Wilcox, W. H., on tetrachlorethane 
poisoning, ref., 479 
Wilder, J. A., on sarcoma of bladder, 
ref., 903 
Wilensky and Thalhimer, on chronic 
ulcers of stomach, ref., 753 
Williams, on plasma cells, ref., 88; on 
Trichinella spiralis, ref., 153 
Williams, A. W., on B. diphtherite, ref., 
316; on carbon monoxide poisoning, 
ref., 480; on trachoma, ref., 265 
Williams, Roger, on age distribution of 
sarcoma, ref., 427; on cancer statistics, 
ref., 453; on natural history of cancer, 
ref., 467 
Williams and Lowden, on excitant of 
scarlet fever, ref., 340; on Negri bodies, 
ref., 329; on staining Negri bodies, 
ref., 329 
Willimann, on amyloid tumors of tongue, 
ref., 668' 
Willis, circle of, 1118 
Willis and Budd, on cysts of pancreas, 
ref., 807 
Wilke, on inflammation of thyroid, ref., 
584 
Wilms, M., on embryoid and mixed 
tumors, ref., 393; on mixed tumors of 
kidney, ref., 891; on sarcoma of vagina, 
ref., 916; on teratoma of ovary, ref., 
974; on teratoma of testicle, ref., 1023 
Wilson, C. R. T., on photographing ions, 
ref., 12 
Wilson, E. B., on cell development, ref., 
81; on mitosis, ref., 81 
Wilson, L. B., on exophthalmic goiter, 
ref., 67, 489; on pulmonary embolism, 
ref., 40 
Wilson, L. B., and McDoivell, I. E., on 
chronic ulcers of stomach, ref., 
753 
Wilson, L. B., and McGrath, B. F., on 
pathology of prostate, ref., 1025 
Wilson, S. A. K., on Wilson's disease, 
ref., 1171 
Wilson and Chowning, on Rocky Moun- 
tain spotted fever, ref., 334 
Wilson and Kalteyer, on melanosarco- 
mata of skin, ref., 432 
Wilson and Willis, on hypernephroma, 
ref., 892; on mixed tumors of salivary 
glands, ref., 443, 801 
Wilson's disease, 1171 
Winiwarter, H., on cell division, ref., 79 
Winkler, on adrenal tumors, ref., 591; 
on cysts of appendix, ref., 781; on 
diseases of appendix, ref., 785; on 
tuberculosis in children, ref., 296 
Winslow, on cystic hygroma, ref., 425 
Winternitz, M. C., on carcinoma of liver 
with cirrhosis, ref., 837; on tubercu- 
losis of spleen, ref., 575; on tubercu- 
losis of stomach, ref., 750 
Wirsung, duct of, obstruction of, 807 
Witch-milk, 987 
Witte, J., on perforation of aorta, ref., 635 
Wittelshofer, R., on gigantism, ref., 1045 
Witthaus and Becker, on nitrogen te- 
troxide poisoning, ref., 698 
Wladimiroff, on B. mallei, ref., 257 
Woglom, on carcinosarcoma, ref., 440; on 
chorionepithelioma, ref., 949; on diet 
and tumor growth, ref., 373; on experi- 
mental cancer, ref., 468; on metastasis 
of tumors, ref., 378, 379; on trans- 
plantation of tumors, ref., 388 
Wohlgemuth, on soluble ferments, ref., 
164 
Wohlwill, F., on cysts of spleen, ref., 580 
Wolbach, S. B., on chronic z-ray der- 
matitis, ref., 14; on infectious diseases 
of unknown origin, ref., 353; on 
rhabdomyoma of heart, ref., 422; on 
Rocky Mountain spotted fever, ref., 
334; on ultramicroscopic bacteria, ref., 
159 
Wolbach, S. B., and Ernst, H. C., on 
bovine tubercle bacillus ref., 291 
Wolbach and Honeij, on human and rat 
leprosy, ref., 303 
Wolbach and McKee, on trachoma bodies, 
ref., 341 
Wolfensber ger, on rhabdomyomata of 
esophagus, ref., 744 INDEX 
1353 
Wolff, J., on cancer statistics, ref., 453; 
on regeneration of cartilage and bone, 
ref., 91; on trauma and formation of 
malignant tumors, ref., 386; on tuber- 
culosis and carcinoma of lung, ref., 723; 
on tumors, ref., 467 
Wolff-Eisner, on anaphylaxis, ref., 216 
Wolfler, on fetal adenoma of thyroid, ref., 
586 
Wolfsohn, on typhoid ulcers, ref., 270 
Wollstein, M., on acute parotitis, ref., 798; 
on B. influenza, ref., 264; on bacilli 
from whooping-cough, ref., 351; on 
tuberculosis in children, ref., 298 
Wollstein and Meltzer, on induced pneu- 
monic lesions, ref., 247; on lesions 
from bronchial insufflation of strep- 
tococci, ref., 691 
Wolman, H. W., on degeneration of 
ganglion cells, ref., 1137 
Wood, E. J., on Monilia albicans, ref., 171 
Wood, F. C., on agglutination tests, ref., 
206; on aplastic anemia in malignant 
disease, ref., 379; on blood technique, 
ref., 1227; on changes in blood, ref., 
514, 533; on chemical pneumonia, ref., 
698; on chordoma, ref., 404; on 
endothelioma of lymph-nodes, ref., 
564; on healing of wounds, ref., 107; 
on hypophysis cerebri, ref., 1182a; on 
irradiated tumors, ref., 16; on mixed 
tumors of salivary glands, ref., 443; 
on pneumococci in sputum, ref., 249; 
on poisoning by nitric acid fumes, ref., 
471; on repair of kidney, ref., 853; on 
stain for blood, ref., 350; on stellate 
bodies in giant cells, ref., 119; on 
tests for carbon monoxide in blood, 
ref., 480; on thyroid tumors of tongue, 
ref., 735; on viability of D. pneumonia?, 
ref., 247 
Wood., F. C., and Prime, F., on irradiated 
tumors, ref., 16 
Wood, G. B., on lymph-vessels of tonsils, 
ref., 738; on tonsils as portals of entry 
for tubercle bacilli, ref., 740; on tuber- 
culous inflammation of parotid, ref., 
798 
Woodman and Tidy, on poisons, ref., 481 
Woodruff, on growth of paramecium, ref., 
96 
Woolley, P. G., on adrenal tumors, ref., 
591; on tuberculous aortitis, ref., 646; 
on tuberculous inflammation in adre- 
nals, ref., 590; on vascular dilatation, 
ref , 99 
Woolley and Adami, on mesotheliomata 
of adrenal, ref., 592 
Wool-sorter's disease, 258 
Wormley, on poisons, ref., 482 
Worms, 144 
hook-, 151 
guinea, 154 
method of study of, 155 
pin-, 150 
round, 149 
tape-, 146 
thread-, 150 
whip- (see Trichocephalus dispar), 
152 
Wounds, granulation tissue in, signifi- 
cance of, ref., 177 
healing of, 107 
post-mortem, appearance of, 1190 
Wright, A. E., on opsonic technique, ref., 
213; on opsonins, ref., 213; on pre- 
ventive inoculation in typhoid fever, 
ref., 276 
Wright, J., on actinomyces-like struc- 
tures in tonsillar crypts, ref., 739; 
on absorption in tonsils, ref., 738 
Wright, J. H., on blood-plates, ref., 528; 
on leishmania tropica, ref., 139; on 
Madura foot, ref., 262; on mucous 
polyps, ref., 401; on multiple myeloma, 
ref., 1073; on nasal polyps, ref., 662; on 
stain for malarial parasite, ref., 530 
Wright and Douglas, on opsonins, ref., 210 
Wright, J. H., and Richardson, O., on 
syphilitic aortitis, ref., 648 
Wright's method for rapid sections, 1228, 
Writer's cramp, 1139 
Wrzosek, A., on infection, ref., 176 
X-ray cancers, 386 
dermatitis, 13 
effect of, in leukemia, 16 
on antibody formation, 204 
lesions from, 12 
Xanthelasma, 425 
Xanthoma, 425 
multiplex, 425 
palpebrarum, 425 
Xanthomatosis, 425 
Xenopsylla cheopis, 157 1354 
INDEX 
Xerosis bacillus, 317 
Xiphopagus, 364 
Yamagiwa, K., and Ichikawa, K., on 
irritation and epithelioma, ref., 
95 
Yates, Bunting, and Kristjanson, on 
splenic anemia, ref., 544 
Yaws, 326 
Yeasts, 158, 169 
methods of study of, 173 
Yellow fever, 334 
excitant of, 335 
mode of infection in, 335 
Yersin antiplague serum, 321 
Young, on gonorrhea, ref., 251; on nerves 
in tumors, ref., 391 
Zahn, F. W., on ciliated cysts of pleura, 
ref., 729; on cysts, ref., 396; on cysts of 
mediastinum, ref., 723; on statistics of 
intestinal tuberculosis, ref., 766 
Zahn, H, on stenosis of esophagus, ref., 
743 
Zenker's degeneration of muscle, ref., 
1037 
fluid as fixative, 1230 
Ziegler, K., on angioma simplex hyper- 
trophicum, ref., 424; on arteriosclerotic 
kidney, ref., 861; on Hodgkin's dis- 
ease, ref., 562; on tumors, ref., 467 
Zimmermann, on plasmocytoma, ref., 431 
Zingher, on Schick test, ref., 317 
Zinsser, H., on alexin, ref., 200; on 
leucocyte extract, ref., 214 
Zipkin, R., on fatty degeneration of 
muscles, ref., 1036 
Zooglea, ref., 160 
Zuber, on bronchial lymph-nodes, ref., 
676 
Zullig, J., on xanthosarcoma of joint, 
ref., 1087 
Zuntz, Lowy, Muller, and Caspari, on 
polycythemia, ref., 517 
Zurhelle, E., on pulmonary embolism, 
ref., 40 
Zypkin, S. M., on congenital malforma- 
tions of liver, ref., 808 
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