GENERAL 
PATHOLOGY 
DR. ERNST ZIEGLER 
BY 
PROFESSOR OF PATHOLOGICAL ANATOMY AND OF GENERAL PATHOLOGY 
IN THE UNIVERSITY OF FREIBURG IN BREISGAU 
FROM 
THE ELEVENTH REVISED GERMAN EDITION 
(GUSTAV FISHER, JENA, 1905) 
DOUGLAS SYMMERS, M.D. 
REVISED BY 
DIRECTOR OF LABORATORIES, BELLEVUE AND ALLIED HOSPITALS, FORMERLY 
PROFESSOR OF PATHOLOGY IN THE UNIVERSITY AND BELLEVUE 
HOSPITAL MEDICAL COLLEGE 
iWITH 604 ILLUSTRATIONS IN BLACK AND IN COLORS 
NEW YORK 
WILLIAM WOOD AND COMPANY 
MDCCCCXXI Copyright, 1921, 
Br WILLIAM WOOD AND COMPANY. PREFACE. 
This revision is an attempt to present the subject of Pathology from 
the standpoint primarily of the needs of the medical student, while pre- 
serving the usefulness of the book as a convenient reference for the 
practitioner. Advantage has been taken of the fact that the book was to 
be reprinted to make almost numberless changes in the language of the 
translation, in order more simply and directly to express the views of 
the author, and to add a considerable amount of new subject matter, in 
addition to making certain needed alterations in portions of the old, 
including the subjects of acromegaly, Addison’s disease, status lymph- 
aticus, eunuchoidism, autolytic, amyloid and Zenker’s degenerations, 
ochronosis, hemochromatosis, and bronzed diabetes, carotinaemia, lipo- 
matoses and the embryonal fat cells, ossifying myositis and multiple 
exostoses, the skin moles, malignant transformation of myomata, neuro- 
blastoma, polycystic kidneys, lymphosarcoma, pseudoleukemia, Hodgkin’s 
disease, the multiple myeloblastomata, Martland’s tumor of the bone 
marrow and Barrie’s hemorrhagic osteomyelitis, surgical tuberculosis of 
the intestine, Wilms’ tumor, anthrax, ascariasis, oxyuris in the appendix, 
trichina embryos in the blood, juvenile gangrene, the effects of the so- 
called pandemic influenza, botulism, the reactions to arsphenamine, a 
somewhat drastic rearrangement of the chapter on thrombosis, etc. Some 
of these changes appear in small type while others have been interpolated 
in the original text. The general arrangement of the book has not been 
disturbed, although many of the old illustrations have been eliminated. 
In general, these have been replaced by photographic reproductions from 
the wards and laboratories of Bellevue Hospital; for these I am indebted 
to Mr. William B. Morrison. In the same way, some of the older liter- 
ature has been omitted and in its place, wherever possible, references 
to works in English have been substituted as more easily reached and 
read. 
I am amply repaid for all the difficulties of the work by the conscious- 
ness that it should be helpful to the medical profession generally and 
especially to students of medicine, inasmuch as the book, as written by 
Ziegler and as modified by my distinguished predecessor, Professor 
Warthin, was far too valuable to be abandoned for the lack of someone 
to bring it up to date. I wish especially to acknowledge my debt to my 
secretary, Miss Martha Wirth, without whose tireless support and inter- 
ested co-operation I could not well have completed the great amount of 
technical work involved in preparing this new edition. 
Douglas Symmers. 
The Pathological Laboratories, Bellevue Hospital, 
New York, October, 1920. AUTHOR’S PREFACE TO THE ELEVENTH EDITION. 
In the preparation of this new edition I have endeavored to utilize as 
fully as possible the researches of the last several years, and, in so far as 
these have given us new facts and represent actual advances in our knowl- 
edge of pathological processes, to incorporate them into the contents of 
the book. It has become almost impossible to review the great mass of 
literature concerning the pathogenic micro-organisms, their life history, 
and their effects upon the human organism; but I hope that the essential 
and established results of recent investigations have not escaped me, and 
that I have estimated them at their proper worth. I may mention with 
especial emphasis the researches of Schaudinn on the spirochaetse and the 
parasites of malaria; also those of other authors on the trypanosomata, 
various pathogenic bacteria, the agglutinins, precipitins, cytolysins, and 
haemolysins, as well as the numerous investigations and theoretic observa- 
tions that, based upon Ehrlich’s side-chain theory, have been carried out 
concerning the toxic action of bacterial products and the formation of 
antitoxic and antibacterial substances. 
During recent years an immense amount of literature concerning 
tuberculosis has appeared; but our previous views concerning its etiology 
and genesis have not been materially altered. Koch’s view as to the 
difference between human and bovine tuberculosis is applicable only in 
so far as certain differences in the characteristics of the two strains of 
bacilli are concerned. For all these differences it is true that bovine 
tuberculosis is communicable to man, and the domestic animals may be- 
come infected from tuberculous human beings. Von Behring’s publica- 
tion that infants may be easily infected through milk containing tubercle 
bacilli has only confirmed well-known views. The attempt of von Behring 
to refer all cases of tuberculosis to an intestinal infection occurring in 
infancy is doubtless an error, and is not likely to destroy the belief 
that tuberculosis is most frequently an air-borne infection and enters 
primarily through the lungs. 
The researches concerning the etiology, genesis, and morphology of 
neoplasms have likewise been numerous and extensive; nevertheless, any 
expectations of a great advance in our knowledge of the etiology of neo- 
plasms are doomed to disappointment. The attempts to establish a para- 
sitic etiology for tumors have entirely failed, and the extensive statistics 
that have been amassed concerning the distribution of carcinoma have 
led to results that can be regarded only as antagonistic to the parasitic 
theory. Of greater value have been the researches on the histogenesis of 
tumors; yet I find in these essentially only a confirmation and a more thor- 
ough grounding of our older views. I cannot bring myself to the accept- 
ance of all the latest views, for example, the assumption that the prelimi- 
nary condition of tumor development is to be found in the isolation, 
disconnection, and misplacement of germinal anlage or of single cells AUTHOR’S PREFACE TO THE ELEVENTH EDITION. 
during embryonal or extrauterine life (Ribbert, Borrmann), or that the 
epithelial cells of a carcinoma can become transformed into connective- 
tissue cells (Krompecher). 
Significant advances in the theory of fatty degeneration and glycogen 
deposit are also to be noted; and although many problems must still wait 
a solution, our knowledge concerning these processes lias been greatly 
furthered through the labors of recent years. 
The long discussion over the significance of the cells appearing in the 
tissues during the course of inflammation has at last reached certain 
conclusions. The questions still unsettled are of minor importance. 
The arrangement of the book is left, on the whole, as in the last 
edition; but I have not simply inserted the new facts and views, many 
sections having been entirely recast to agree with the additions. The 
number of illustrations has been increased from 586 to 604. The bibli- 
ography has been given a careful revision and brought up to the autumn 
of this year. 
E. Ziegler. 
Freiburg im Breisgau, December, 1904. 
Note.— Because of the difference in the size of the page it has been found 
necessary to reduce slightly some of the illustrations. In such cases the magnifica- 
tion or amplification has been changed to meet the amount of reduction. GENERAL PATHOLOGY 
INTRODUCTION. 
Physiology is the science of normal life and teaches us concerning its 
activities. At the same time it shows us that vital functions are performed 
according to laws having their foundation in structure. Changes in 
organic structure, manifesting themselves as vital phenomena differing 
from those regarded as normal, form the basis of disease. The return to 
the normal is known as recovery or healing. 
Permanent cessation of all vital functions constitutes death. Tempo- 
rary interruption of the vital activities without loss of the possibility of 
return to the normal may be seen in the condition of apparent death or 
congelation, which may be followed by either death or by return to life 
(anabiosis). 
When pathological changes are present in the tissues, arising either 
before the appearance of symptoms or persisting after their cessation, so 
that at any time a new outbreak of the latter may take place, the disease 
is spoken of as latent. 
The science of disease is embraced by Pathology. There falls to it 
the determination of the causes and origin of pathological processes, these 
two divisions constituting etiology and pathogenesis. A second task 
lies in the investigation of the anatomical changes underlying the altera- 
tions of function; and that branch of the science to which this is assigned 
is known as pathological anatomy. Since the finer organization of 
different tissues varies according to their functions, and since we cannot 
conceive of vital manifestations without a material substratum, it is 
reasonable to assume that pathological manifestations must likewise be 
the expression of material changes in the tissues concerned. Moreover, 
experience has taught us that in the case of any alteration of function 
in any tissue or organ, there may be demonstrated changes of structure, 
in part even macroscopically, while at other times they can be made out 
only with the aid of the microscope and by special histological methods. 
A third field belonging to pathology is concerned with the observa- 
tion and interpretation of the symptoms of disease as seen in the patient, 
and this branch is designated clinical pathology, pathological physi- 
ology, physiological or biological pathology. Its facts are ascertained 
by observation and examination of the patient, and through special 
physical and chemical methods. Successful application of the results 
obtained by the methods of clinical or biological pathology requires a 
knowledge of the pathological-anatomical changes present, as well as 
of their etiology and pathogenesis. As a further help to the interpre- 
tation of disease a knowledge of the chemical processes taking place in 
the living organism under the influence of the activity of cells is essential. 
This knowledge is specialized in the science of pathological chemistry. 2 
INTRODUCTION. 
The many-sided domain of Patnology demands division into various 
branches according to special points of view. A knowledge of clinical 
pathology is best gained at the bedside or in the clinic. Likewise chemical 
pathology requires special theoretical and practical training. In this 
text-book General Pathology will be considered as including etiology, 
pathogenesis, and pathological anatomy. Chemical Pathology will be 
touched on only in so far as it is necessary to an understanding of the 
anatomical changes in diseased organs. CHAPTER I. 
The Extrinsic Causes of and the Congenital Foundations for 
Disease. 
1. Deficient Supply of Food and Oxygen, Fatigue, Heat and Cold, 
Changes of Atmospheric Pressure, and Electrical Influences. 
§ 1. From birth to death man is exposed to the influences of the world 
surrounding him, many of these influences being favorable to the exer- 
cise of his functions, while others are not. 
As long as the human organism is able to offset these influences, 
through independent changes of its relations to the world or through 
adaptation of its functions to external conditions, it will remain in health. 
If his regulating mechanism no longer suffices for successful opposition 
to unfavorable influences, and if he cannot escape these or change his 
conditions of life, man becomes ill or dies. 
For its preservation the body needs a certain amount of food, water, 
and oxygen; and though it may exist for a short time without these, an 
insufficient supply beyond a certain limit and after a certain time must 
lead to disease or death. 
Total deprivation or diminution in the supply of oxygen to the 
tissues may take place at any period of life, either because of lack of 
oxygen in the surrounding medium, or obstruction to the entrance of the 
oxygen into the lungs or blood, or inability on the part of the blood to 
take up sufficient. The foetus in utcro may be insufficiently supplied 
with oxygen as a result of diminished supply to the mother, premature 
separation or disease of the placenta, or compression of the cord, whereby 
the interchange of gases between maternal and foetal blood is hindered. 
After birth an insufficient supply of oxygen may be due to hindrances to 
respiration, or the child may be so weak that its respiratory movements 
are insufficient to expand the lungs. 
When the supply of oxygen is completely shut off, as may happen 
from the entrance of water or other fluid into the respiratory tract or 
from closure of the air-passages, the affected individual dies in a short 
time from choking or suffocation. Animals confined in closed chambers 
die as soon as the oxygen of the air reaches two or three per cent by 
volume, the normal volume percentage being 20.8 (Cl. Bernard, P. Bert). 
If the supply of oxygen is not wholly shut off, but greatly diminished, 
as in carbon-monoxide poisoning, in which the firm combination of 
carbon monoxide with hsemoglobin prevents the taking up of oxygen by 
the red blood-cells, death by suffocation may take place only after 
several days. In gradually increasing hindrances to the entrance of 
oxygen and resulting accumulation of carbonic acid in the blood, as in 
narrowing of the lumen of the larynx through inflammatory exudates, 
compression of the trachea, weakening or obstruction of respiration, etc., 
a condition of breathlessness, cyanosis, convulsions, and disturbances of 
consciousness is produced, which is termed asphyxia. 4 
THE EXTRINSIC CAUSES OF DISEASE. 
If the taking up of oxygen is diminished in slight degree but for a long 
time, as in the lessened number of red blood-cells in oligocythaemia, de- 
generative processes characterized by fatty changes may occur in various 
tissues and may lead not only to disease but to death. 
Total deprivation of food and water leads to rapid loss of body- 
weight, inasmuch as fat and albumin continue to be decomposed; death 
finally enspes. According to Lehmann, Muller, Munk, Senator, and 
Zuntz, the total amount of oxidation in starvation does not fall below that 
of the same individual in the fasting state under the same conditions. In 
animals death occurs after the loss of about forty per cent of the body- 
weight, about one-half being due to the waste of muscle. 
The fat disappears most rapidly; even as much as ninety-three per 
cent may be lost. The other organs show diminution of substance in the 
following order: liver, spleen, testicles, muscles, blood, intestines, skin, 
kidneys, and lungs. The heart, nervous system, and bones show the 
least loss of weight; but destruction of bone-tissue does take place during 
starvation, as is shown by the increase of calcium and phosphoric acid 
in the urine, following ingestion of water. In the blood there is rapid 
diminution of the leucocytes (Luciani) ; the red blood-cells, on the other 
hand, may be relatively increased. The organs of animals dying from 
starvation show simple atrophy of the tissue-elements, particularly of 
the liver (Lukjanow). 
After total deprivation of food and water, death occurs in man in 
from seven to twelve days; exercise hastens the end, ingestion of water 
may delay it markedly, so that individuals have been enabled through the 
use of water to endure a period of abstinence from food for thirty days 
or longer, without suffering permanent harm. 
Life may be maintained for a long time on insufficient nourishment, 
but wasting of the body takes place which may lead to extreme emacia- 
tion, marasmus, or cachexia, and finally to death. The same thing hap- 
pens when the composition of the food is unsuitable and only a portion 
of the necessary elements is present, so that the body is starved either in 
albumin, fat, salts, or water. Dogs deprived of all nitrogenous food 
die in from thirty-one to thirty-four days (Magendie). When the food 
is abundant but poor in albumin, there occur after a time (in dogs after 
six weeks) loss of appetite and repugnance to proffered food, with 
impairment of digestion and assimilation (Munk). This is especially 
the case when the food is lacking in fat, less so when albumin or carbo- 
hydrates are wanting. 
If for experimental purposes an animal well supplied with food be 
totally deprived of water, there is rapid loss of weight followed in from 
eight to twelve days by death. The pathological changes found in the 
different organs are similar to those resulting from starvation. 
Literature. 
Lehman, Miiller, Munk, Senator, und Zuntz: Untersuchung an zwei hungernden 
Menschen. Virch. Arch., 131 Bd., Supplement, 1893. 
Luciani: Das Hungern (iibersetzt von O. Frankel), Leipzig, 1890. 
Lukjanow: Verand. d. Zelkerne unt. d. Einfl. d. Hungerns. Arch, des Sc. biol., 
vi. und vii., 1897 u. 1898. 
Munk: Ueber die Folgen einer ausreichenderj aber eiweissarmen Nahrung. 
Virch. Arch., 132 Bd., 1893, FATIGUE; HIGH TEMPERATURES. 
5 
§ 2. An unusual demand on the functional activity of an organ 
for an extended period leads sooner or later to a state of exhaustion, 
which is due to the consumption of cell-substance, and to the formation 
of toxic products of metabolism, whereby the organ is incapacitated for 
extended activity. Most often the results of overwork are manifested 
in the muscles and nervous system by such symptoms as soreness and 
stiffness of the muscles, mental excitement, sleeplessness, loss of appe- 
tite, weakness, unnatural sweating, and sometimes elevation of tempera- 
ture. Overwork of the heart may cause death. This may occur either 
when the heart is for a short time taxed to the limit of its power or 
when for a longer period it works slightly under its maximum capacity. 
If the exhausted tissues are permitted to rest and are supplied with an 
abundance of nourishment, the loss of cell-material will be replaced, the 
abnormal products of metabolism removed, and the part restored to 
normal. If a tissue be frequently subjected to excessive functional de- 
mands, and if the periods of rest are too short to admit of complete 
restoration, there will ultimately result a condition of permanent func- 
tional insufficiency which may manifest itself by degeneration or atrophy. 
For example, a muscle through overwork may become atrophic, and a 
brain constantly stimulated without proper periods of rest may reach 
such a state of exhaustion that it is incapable of performing its normal 
functions. Through rest and proper nourishment such a brain may 
recover; but beyond a certain limit the functional insufficiency may be- 
come permanent and manifest itself in anatomical changes. 
Overwork of any organ is more quickly followed by fatigue and 
functional insufficiency if its nutrition is defective. Fatigue and insuffi- 
ciency of the heart are most frequently observed when the general nutri- 
tion is lowered, as in fever, or when there is deficient oxygenation of 
the blood, as in poorly compensated heart or pulmonary diseases. 
Finally, overwork and poor nourishment lower the resistance of the 
body to infection. 
When the functional demands on a muscle or gland are only mod- 
erately increased, and if the nutrition is maintained in proportion to the 
increase of labor, the tissue becomes hypertrophied, and is enabled to 
perform increased work permanently. 
Permanent diminution or cessation of activity causes in organs that 
normally perform a definite and constant function (muscles and glands) 
loss of tissue-substance {atrophy). 
§ 3. High temperatures act, either by local destruction of tissue 
(burning) or by overheating of the entire body. The latter is possible 
only when the body is exposed to increased temperature for such a time 
that it cannot protect itself by increased heat-dispersion. In dry air of 
from 55-60° C. (131-140° F.) even profuse perspiration is no longer 
able to protect the body from overheating, and in a moist atmosphere the 
same is true at still lower temperatures. 
If the human body is subjected to high temperature, it becomes over- 
heated, and the condition known as heat-stroke results. The pulse-rate 
is increased, respiration is rapid and labored, the pupils dilate, and 
death may occur as in animals made the subject of experiment. The 
occurrence of heat-stroke is favored by heavy bodily labor, by inter- 
ference with heat-dispersion through impermeable clothing, or by lack 
of water in the body. 6 
THE EXTRINSIC CAUSES OF DISEASE. 
The direct action of the rays of the sun on the head may cause 
cerebral and meningeal irritation, characterized by hypersemia and in- 
flammatory exudation, and the resulting condition is known as sun-stroke 
or insolation. 
The local effects of heat on the skin, burns, are shown, according to 
the intensity of the heat and the time of its duration, either by hyper- 
semia (burn of first degree), by the formation of a blister (second 
degree), by tissue-eschar (third degree), or by carbonization (fourth 
degree). The heat produces local changes in the tissues, and kills them 
at a certain height or after a certain exposure. 
When a large part of the surface of the body, about one-third, is 
burned, the individual usually dies, even though the burn be only of 
slight degree and eschars are not formed. The anatomical findings in 
fatal cases of superficial burns would indicate, when death has not re- 
sulted quickly from shock, that the cause of death is to be sought in 
changes in the blood and in disturbances of the circulation. The blood- 
changes consist in the loss of a portion of its water and in destruction of 
the red cells, or in such injury to them as diminish their function and 
give rise to a deposit of the products of destruction of haemoglobin in 
the liver, spleen, and kidneys. The circulatory changes are characterized 
by a tendency on the part of the blood to stasis, hemorrhages, and intra- 
vascular coagulation, through which vessels of both the pulmonary and 
the systemic circulation may be obstructed, so that local tissue-degen- 
eration and necroses occur in certain organs, for example, in the kidneys, 
liver, mucosa of the stomach and intestine, bones, and soft parts. 
Low temperatures act in the same manner as high ones, in part by 
local injury and death of tissues, in part by refrigeration of the entire 
body. Severe and lasting lowering of temperature causes tissue death; 
after mild chilling there occur, as the result of tissue-degeneration, throm- 
bosis, hypersemia, and exudations which are relatively rich in leucocytes. 
Short refrigeration at the freezing-point is sufficient to produce degener- 
ative changes followed by regenerative proliferation on the part of the 
uninjured cells. Epithelial thickenings may be produced (Fuerst) by 
repeated slight refrigerations (as well as by repeated slight increase of 
temperature). The tips of the extremities, nose, and ears are the most 
easily frozen. After repeated chillings of mild degree redness and swell- 
ing of the skin, associated with severe itching, often occur (chilblains, 
perniones). 
If the temperature of the entire body be markedly lowered, general 
paralysis results from diminished excitability of the tissues, the nervous 
system and heart being especially affected. The sensorium becomes 
dulled, the heart-beat and respiration grow weaker, and finally cease. 
If the body be warmed, before the excitability of the tissues is wholly 
lost by crystalization, the power of movement in the limbs is gradually 
restored, and after a time consciousness returns. In man, instances of 
complete recovery have been observed, even after refrigeration of the 
body to from 24-30° C. (75-86° F.). 
Besides the more severe forms of local or general lowering of the tis- 
sue temperature there may occur mild, general or local chillings, the 
so-called colds, as the result of which disease-phenomena may manifest 
themselves at the seat of chilling, and in distant parts. For example, 
after wide-spread refrigeration of the skin there may occur diarrhoea, THE EFFECTS OF HIGH AND LOW TEMPERATURES. 
7 
catarrh of the respiratory tract, or disturbances in the kidneys; after 
local chilling of the skin, painful affections of the deep-seated muscles. 
The exact relation between these phenomena and refrigeration is un- 
known (the oft-repeated hypothesis that they are due to hypersemia of 
the internal organs caused by the chilling of the surface has not been 
proved), but there is no reason on this account to deny the existence of 
diseases caused by cold. Though many diseases formerly attributed to 
“ catching cold ” have been shown to be of infectious origin, there yet 
remain a number of disease conditions for which we know no other eti- 
ology than that of refrigeration. Conditions in which the skin is hyper- 
jemic and the perspiratory function active favor the taking of cold. Many 
individuals appear to possess a predisposition on the part of certain tis- 
sues to the effects of refrigeration; in one person certain muscles, in an- 
other the mucous membranes may be affected. 
According to many writers, refrigeration of the body increases the 
susceptibility to infection, so that, for example, pathogenic bacteria which 
may be present in the cavities of the body may, after such refrigeration, 
be able to exert injurious influences upon the tissues. 
If rabbits are placed in well-ventilated incubators at a temperature of 36-40° C. 
(96.5-104° F.), the body temperature will rise to 39-40° C. (102.3-104° F.), the 
respiration and pulse being at the same time greatly increased in frequency. A very 
marked elevation of body temperature may lead in one to three days to death 
through paralysis of the nervous and muscular systems, the chief symptoms being 
increase of both respiratory and cardiac activity. If the increase of body tempera- 
ture is not greater than 2-3° C. (3-5° F.), the animals may, if properly nourished, 
live from ten to thirty days or even longer, but they will lose in weight and ulti- 
mately die, showing before death a gradually increasing diminution of haemoglobin 
and of red blood-cells. Degenerative changes, particularly fatty degeneration, occur 
in the liver, kidneys, and heart muscle. 
According to Pfliiger and others, all the vital processes may be brought to a 
standstill through refrigeration, without it being impossible for recovery to take 
place. Preyer also holds that the continuity of life may be wholly interrupted by 
refrigeration, and designates subjects who are thus “lifeless,” but still capable of 
living, as anabiotic. Frogs are said to remain capable of life for many hours, even 
though the temperature be reduced to —2.5° C., at which point the heart is frozen. 
According to the investigations of Koch, such anabiosis of frozen animals is possible 
when only a portion of the water in the body is frozen and when the thawing process 
takes place slowly. In the case of rapid thawing, strong diffusion currents are set 
up between the water coming from the ice-crystals and the concentrated albuminous 
solutions of the blood and the tissues; and these currents exert a damaging effect. 
According to the investigations of 7. Dewar (Proc. of the Royal Soc., London, 
1900), the seeds of wheat, barley, mustard, peas, and pumpkins do not lose their 
germinative power when put into liquid hydrogen; that is, in a temperature of 
—250°. Further, the protoplasm under these conditions is not changed by the cold. 
Not only do the heat-rays of the sun-light or the arc-light affect the human body, 
but their chemically active violet and ultraviolet rays also have an important 
action upon tissues. According to Young, Beclard, Schnetsler, Godnew, and others 
(for literature see Sack, l.c.), the processes of growth and regeneration are carried 
on more rapidly under the influence of blue and violet rays than in ordinary con- 
ditions. According to Finsen, variola-lesions in the skin run a more favorable 
course when protected from the violet rays by means of red glass. According to the 
investigations of Maklakow the violet and ultraviolet rays of the arc-light can pro- 
duce a peculiar erythema of the skin, even when the heat-rays are excluded 
(Widmark). Finsen holds that “sunburn” is produced chiefly by the violet and 
ultraviolet rays. Bacteria in plate-cultures are killed within a short time by exposure 
to the ultraviolet rays of the arc-light. According to the investigations of Godnew, 
Finsen, Moller, and others, the violet and ultraviolet rays penetrate the skin, but are 
absorbed by the blood. Basing his views upon these facts, Finsen has treated skin 
diseases, especially lupus, vascular nsevi, acne, etc., with the ultraviolet rays of the 8 
THE EXTRINSIC CAUSES OF DISEASE. 
sun and the arc-light. The heat-rays are excluded by means of quartz lenses and 
chambers of running water. A hollow lens of quartz through which water is flowing 
is pressed firmly against the affected area in order to exclude the blood, which 
absorbs the ultraviolet rays. 
According to investigations by Dreyer, confirmed by Neisser and Halberstaedter, 
infusoria, bacteria, and animal tissues when impregnated with erythrosin (solution 
of 1:1,000-1:4,000) become sensitized to red and yellow rays, so that these rays act 
upon them in the same manner as the violet and ultraviolet. Since the red and 
yellow rays possess a greater power of penetration into the tissues, a more marked 
and deeper effect of irradiation can be obtained by the previous treatment of the 
tissues with solutions of erythrosin. 
Roentgen-Rays, acting upon the skin for some time, cause at point of entrance 
and exit, degenerative changes affecting chiefly the epithelium, but also the connec- 
tive-tissue cells. These are followed by inflammatory processes. Clinically these 
changes show themselves usually about fourteen days after exposure, and reach 
their acme after some weeks. The hair and finger-nails may be lost. If tissue- 
necrosis occurs, the healing of the resulting ulcer is slow and difficult. The 
Roentgen-rays have also been used with some success in the treatment of lupus and 
carcinoma of the skin. Exposures of 30 to 60 minutes are given, and repeated two 
or three times. After one or two weeks the cancer shows an inflammatory reaction. 
Healing takes place through the destruction of the tumor cells, which are especially 
■susceptible to the action of the rays; and the resulting ulcer heals through the 
formation of scar-tissue and regeneration of the epidermis. In the case of carci- 
noma of the mamma a certain amount of destruction of the neoplasm may be 
accomplished, but not to the extent of cure. Recent cases have been observed of 
cancer developing in skin frequently exposed to Roentgen-rays. 
According to investigations by Heineke and Warthin, the experimental irradi- 
ation of rats, mice, guinea-pigs, rabbits, and dogs causes, even after fifteen-minute 
exposures, marked destruction of the lymphoid cells of the spleen, bone-marrow, 
and lymph-nodes. The disintegration of the lymphoid cells is evident almost imme- 
diately after the exposure, and persists for some hours. After single exposures 
regeneration is rapid, but after prolonged or repeated exposures the spleen may 
finally become practically devoid of lymphoid cells. In exposures of this degree the 
death of the animal usually takes place within ten days, after it has exhibited 
marked symptoms of intoxication. Small animals may be rendered blind by pro- 
longed exposures. In the use of Roentgen-rays as a curative agent in leukemia it 
has been shown that the size of the spleen may be greatly diminished, the white-cell 
count brought to normal and the general condition temporarily improved. Warthin 
has shown that this improvement is due wholly to the destructive action of the rays 
upon the white cells of the blood-cell-forming organs, and that the essential disease- 
process is not cured. He has also emphasized the dangers of intoxication arising 
from the products of proteid disintegration, and has shown the occurrence of 
extensive degeneration and calcification of the kidneys in cases so treated. His 
investigations show also that slight changes occur in the renal epithelium as the 
result of short exposures. Capps believes that a leukotoxin is produced in the sera 
of animals exposed to the rays. Schols, Seldin, Philipp, Halberstaedter, and others 
have demonstrated the production of azoospermia in man and animals by means of 
Roentgen irradiation. Numerous cases of sterility in Roentgen-ray operators have 
been observed. Bardeen found that the death of spermatozoa is hastened by irradi- 
ation, and that spermatozoa injured by short exposures to Roentgen-rays, but still 
capable of fertilization, may cause the development of monsters from ova fertilized 
by them. He concludes that nuclear material may be so influenced by exposures to 
the rays that after a latent period it may show marked abnormalities in develop- 
ment. Foersterling warns against the dangers of irradiation in young children. 
Edsall has reported an instance of death following Roentgen irradiation, and the 
present tendency is to regard the rays as agents capable of producing serious damage 
to the animal organism. 
According to certain observers, the lymphocyte is an important agent in the 
defensive mechanism against tuberculosis. A number of investigators have 
attempted to show that exposure of guinea-pigs to massive doses of X-ray, follow- 
ing inoculation with urine and other fluids containing tubercle bacilli, brings about a 
positive result more quickly than otherwise. Kellert, however, in a carefully con- 
trolled series of investigations has shown that when fluids containing no micro- 
organisms other than tubercle bacilli are injected, radiated guinea-pigs are found to 
be no more susceptible to tuberculosis than the control animals. If, however, the ROENTGEN RAYS. 
9 
injected fluids are contaminated by other micro-organisms, the radiated guinea-pigs 
are rendered more susceptible to secondary infection. (Journal of Medical Research, 
Vol. 39, 1918, p. 93.) 
Becquerel-Rays act similarly to the Roentgen. Tissue-degenerations and in- 
flammations appear in the second or third week after the exposure and reach their 
acme in 20-30 days (Halkin, l.c.). Slowly healing ulcers may be formed. Some 
success has been claimed in the treatment of cancer of the skin and lupus. Accord- 
ing to Pfeiffer, Friedberger, and Scholtz the rays are bactericidal, and a portion of 
the active rays can penetrate the tissues to a depth of several millimetres. Roentgen- 
and Becquerel-rays are not, like light, heat, and electricity, special forms of undula- 
tions of the ether, but consist of extremely minute particles of matter, electrons, 
which are given off into space with great rapidity. In the case of the Roentgen-rays 
the projecting power is the electrical energy supplied to the Roentgen tube. The 
Becquerel-rays represent a property of certain bodies designated by Becquerel as 
radio-activity. In 1896 this investigator discovered that uranium and its salts give 
off rays that act upon photographic plates in the dark and are capable of penetrating 
bodies impervious to light. In 1898 Madame Curie succeeded in separating from 
pitchblende two radio-active bodies which were named radium and polonium. In 
1899 a third radio-active body (actinium) was discovered by Curie and Debierne. 
Radium has been produced in a pure form and has been the most carefully studied. 
It is a new element, the salts of which are radio-active in the highest degree and 
project electrons into space at a velocity of 160,000 kilometres per second, at the 
same time giving off heat-rays. The air about it becomes ionized, that is, becomes 
a conductor for electrical discharges. The action of radium upon the tissues is 
similar to that of Roentgen-rays. 
According to Hinstedt (Ann. der Physik, 1903), numerous springs, hot ones in 
particular, are radio-active, and it is not improbable that their special action is in 
part dependent upon this property. 
Literature. 
(Effects of High and Low Temperatures.) 
Bardeen: A Review of the Pathology of Superficial Burns, Johns Hopkins 
Hosp. Rep., vol. vii. 
Finsen: Ueber die Bedeutung d. chem. Strahlen des Lichtes f. Medizin, Leipzig, 
1899. 
Fuerst: Verand. d. Epidermis durch leichte Warme- und Kalteeinwirkung. 
Beit. v. Ziegler, xxiv., 1898. 
Koch: Wirkung der Kalte und Anabiose. Biol. Cent., 1890, u. xv., 1895. 
Neisser u. Halberstaedter: Lichtbehandlung nach Dreyer. D. med. Woch., 
1904. 
Pfliiger: Die allgemeinen Lebenserscheinungen, Bonn, 1889. 
Preyer: Ueber Anabiose. Biol. Centralb., xi., 1891. 
Sack: Wesen d. Finsenschen Lichtbehandlung. Munch, med. Wochenschr., 
1902. 
(The Effects of Radio Activity.) 
Bardeen: The Action of Roentgen Rays upon Spermatozoa. Amer. Medicine, 
1906. 
Capps: On the Production of a Leukotoxin by Roentgen Irradiation. Trans. 
Assoc, of Amer. Phys., 1906. 
Edsall: Dangers of Roentgen Irradiation. Jour. Amer. Med. Assoc., 1906. 
Halkin: Einfluss der Becquerelstrahlen auf die Haut. A. f. Derm., 65 Bd., 
1903 (Lit.). 
Heineke: Einwirk. d. Roentgenstrahlen auf inn. Organe. Munch, med. Woch., 
1904. 
Scholtz: Einfluss der Roentgenstrahlen auf die Haut. Arch. f. Derm., 59 Bd., 
1902; Roentgenstrahlen. Eulenburg’s Jahrb., ii., 1904; Wirk. d. Radiums. 
D. med. Woch., 1904. 
Warthin: The Effects of Roentgen Rays upon the Blood-forming Organs. 
International Clinics, Jan., 1906; ibid. With Especial Reference to the 
Treatment of Leukemia. Physician and Surgeon, 1907 (Lit.); Action of 
Roentgen Rays upon the Kidney. Am. Jour, of Med. Sciences, 1907 (Lit.). 10 
THE EXTRINSIC CAUSES OF DISEASE. 
§ 4. Sudden lowering of atmospheric pressure, as in mountain- 
climbing and balloon ascents, may cause great exhaustion, with marked 
palpitation of the heart, unconsciousness, irregular breathing, and some- 
times vomiting, and bleeding from the gums and lips. These symptoms 
depend upon lack of oxygen (P. Bert), the capillaries of the lungs being 
unable to take up sufficient oxygen from the rarefied air. Kroenecker 
believes that they are to be referred to disturbances of the pulmonary 
circulation. According to the investigations of Schumburg and Zuntz, 
it appears that a given amount of labor calls for a greater amount of 
oxygen at an increased elevation than at a lower level. The symptoms of 
mountain-sickness appear at a lower elevation than those of balloon-sick- 
ness, owing to the demands made upon the muscles in the former case 
during the climbing. During the building of the Gorner Grat Railway it 
was found that at a height of 2,700—3,000 metres the capacity of the 
laborers was diminished to a third. 
According to the researches of Egger, Miescher, and others, sojourn 
in high altitudes leads, after a short time, to increase in the number 
of red cells and a greater hsemoglobin-content of the blood. 
Schaumann and Rosenquist hold that the same phenomenon may be 
observed in animals confined for some time in bell-jars at a lower atmos- 
pheric pressure. Other authors (Schumburg, Zuntz, Gottstein) oppose 
this view, and maintain that the phenomenon is due either to concen- 
tration of the blood, from loss of water and to changes in the distribu- 
tion of the blood, or to changes in volume of the measuring-apparatus; 
they endeavor to explain the favorable effects which many individuals 
experience from a residence at high altitudes by certain stimulating influ- 
ences (greater exposure to sun’s rays) which affect the nervous system 
and cause increased metabolism. According to Marti, intense and pro- 
longed irradiation of the body stimulates the formation of red blood-cells 
and to a lesser degree also that of the haemoglobin. 
A sojourn in diving-bells or caissons, such as are employed in build- 
ing operations beneath the water, in which the atmospheric pressure is 
increased, under certain conditions, as high as four atmospheres or even 
greater, causes a slight difficulty in breathing and a relatively unimpor- 
tant increase of the pulse-rate. If a change be made quickly from the 
compressed atmosphere to air of ordinary pressure, there may occur 
within an hour a condition of great fatigue, tightness of the chest, ring- 
ing of the ears, cramps in the muscles, pains in the joints and limbs, 
haemorrhages from the nose, ears, and lungs, dilatation of the pupils, and 
under certain conditions paralysis, coma, delirium, and even death after 
an interval of from one to twenty days (Caisson disease). The cause 
of these phenomena is probably to be found in the obstruction of blood- 
vessels of the spinal cord by bubbles of nitrogen that has been absorbed 
under high pressure (Hoche). According to experimental investigations 
of Heller, Mager, and von Schrotter, the blood, after rapid removal of 
pressure, contains free gas (almost exclusively nitrogen). In fatal cases 
associated with paralysis areas of degeneration (Nikiforofif) are found 
in the white columns of the spinal cord, in which individual nerve-fibres 
present marked changes in the form of swelling of the axis-cylinders, 
and disintegration of the medullary sheaths, with the formation of vacu- 
oles in the place of the nerve-fibres that have been destroyed. If the 
gray matter is involved, the ganglion-cclls may degenerate. ELECTRIC CURRENTS. 
11 
Changes in the electrical condition of the atmosphere and in the mag- 
netic state of the earth have no demonstrable influence upon the human 
body; on the other hand, electric discharges, as lightning-stroke, may 
cause, in part, local lesions of the skin resembling burns, haem- 
orrhages in the skin, and burning of the hair, and, in part, lesions of the 
whole body. Under certain circumstances lightning-stroke causes lacera- 
tion of internal organs, as, for example, the heart and liver. The most 
frequent and important effect of lightning-stroke is paralysis of the 
nervous system, which gives rise to severe dyspnma, which may be 
immediately fatal, or after a few minutes or hours, or may gradually 
pass away after several hours, days, or weeks. Only rarely do individual 
nerve-trunks remain permanently paralyzed. A transitory paralysis may 
occur when the electrical discharge has not passed through the body, 
but has descended in its neighborhood. 
In individuals who' have been struck by lightning there may be found 
slight or severe burns of the skin corresponding to the points of entrance 
and exit of the current, and various injuries to the tissues in the course 
of its path through the body. The marks of the burn are for the greater 
part red, and form peculiar zigzag lines, the so-called lightning figures 
which soon disappear if the burns are not severe. 
The passage of powerful electric currents of high tension, such as 
are generated by dynamos, through the human body, as may happen 
when an individual is placed in a circuit or comes into contact with an 
uninsulated conductor, may give rise to severe disturbances or cause 
death. According to Kratter, the lower limit of danger occurs at a ten- 
sion of about five hundred volts. Alternating currents are more danger- 
ous than continuous ones of the same strength and tension. When 
the effects are not fatal, the injured person is suddenly rendered uncon- 
scious, this condition lasting for a few minutes or several hours, and for 
several days afterward vertigo, prostration, headache, and palpitation 
of the heart may persist (Kratter). At the points of contact more or 
less severe burns are produced. 
In fatal cases, death takes place suddenly or rarely after ten or thirty 
minutes. The autopsy findings, aside from the burns at the points of 
contact, are indicative of suffocation and hypervenosity of the blood, 
stasis within the thoracic vessels, and often small scattered haemorrhages 
due to the direct action of the current. The cause of death is paralysis 
of the centre governing respiration or the heart’s action. 
Literature. 
(Effects of Changes of Atmospheric Pressure and of Solarization.) 
Egger: Veranderungen d. Blutes im Hochgebirge. Congr. f. inn. Med., Wies- 
baden, 1893; u. Arch, f. exp. Path., 39 Bd., 1897. 
Gottstein: Klimat. Einfliisse als Krankheitsursachen. Ergebn. d. allg. Path., 
iv., Wiesbaden, 1899; Vermehrung der rothen Blutkorp. im Hochgebirge. 
Miinch. med. Woch., 1899. 
Heller, Mager, Schrotter: Mitth. iiber Caissonarbeiter, Klin. Woch., 1895; 
Untersuch, iiber d. Wirkung rascher Veranderungen d. Luftdruckes. 
Pfliiger’s Arch., 67 Bd., 1897; Luftdruckerkrankungen, Wien, 1900. 
Hoche: Luftdruckerkrankung d. Centralnervensystems. Berl. klin. Wochenschr., 
1897. 
Kronecker: Die Bergkranheit. Deutsche Klinik, Bd. xi., 1903. 12 
THE EXTRINSIC CAUSES OF DISEASE. 
Marti: Wirkung der Hautreize und Belichtung. Verh. d. Congr. f. inn. Med., 
Wiesbaden, 1897. 
Miescher: Bezieh. zwisch. Meereshohe u. Beschaftenh d. Blutes. Corrbl. f. 
schweiz. Aerzte, 1893. 
Nikiforoff: Veranderungen d. Riickenmarks in Folge schneller Herabsetzung 
des barometrischen Druckes. Beitr. v. Ziegler, xii., 1892. 
Schaumann u. Rosenqvist: Blutverand. im Hohenklima. Zeit. f. klin. Med., 35 
Bd., 1898. 
Schumburg und Zunz: Einwirkung des Hochgebirges. Pfliiger’s Arch., 63 Bd., 
1896. 
D’Arsonval: L’energie electrique. Path. gen. publ. par Bouchard, i., Paris, 
1895. 
Kratter: Wirkung d. Blitzes. Vierteljahrsschr. f. ger. Med., 1891; Tod durch 
Elektricitat, Wien, 1896 (Lit.); Elektrische Verungliickungen. Eulenb. 
Jahrb., vi., 1896 (Lit). 
Mills and Weisenburg: The Effects on the Nervous System of Electric Cur- 
rents of High Potential. Univ. of Penn. Med. Bull., 1903. 
{Effects of Lightning and Electrical Currents.) 
2. The Origin of Disease through Mechanical Influences. 
§ 5. Traumatic influences of various kinds leading to concussion, 
bruising, and laceration of tissue are of frequent occurrence, and act 
through the tearing of tissue, through changes in tissue-organization not 
recognizable by the naked eye, through rupture of blood- and lymph- 
vessels, and through irritation and paralysis of nerves. The sequelae are 
represented by necrosis, disturbances of circulation, inflammation, and 
regenerative proliferations. Frequently repeated traumatism of slight 
degree, such as rubbing, may give rise to liypercemia and inflammation, 
which may lead to hyperplastic growth of tissue. If large quantities of 
insoluble dust particles are continuously taken into the lungs induration 
of the pulmonary tissue may develop. As a result of prolonged pressure, 
atrophy of an organ or tissue may occur (corset-liver). 
After a single or after frequently repeated trauma, there may de- 
velop under conditions at present unknown to us, malignant new-forma- 
tions called tumors. Trauma may further pave the way for infection, 
in that the wound caused by the trauma is infected at the time of injury 
or is secondarily infected from without; or that micro-organisms pre- 
viously present in the body under conditions inhibiting their growth find 
in the injured tissues a suitable soil for proliferation. 
Traumatic influences affect, first of all, the external parts of 
the body; but it may happen, either with or without visible injury, 
that internal organs are injured, and the lacerations, necroses, and haem- 
orrhages thus produced, may be followed, not by inflammation and 
reparative tissue proliferation, but also by malignant neoplasms, and by 
infective processes. 
Mechanical lesions (also thermal, electrical, and corrosive) run a spe- 
cial course, if through local injury the nervous system becomes in- 
volved. Such involvement occurs either through the direct action of 
the trauma upon the central nervous system; or, by the stimulation of 
the sensory or sympathetic nerves, the central nervous system may be 
so affected that a number of additional nervous symptoms follow. 
If direct concussion of the cranium is followed by paralysis of the 
cerebral function and unconsciousness, the condition is called commotio SHOCK; TRAUMATIC NEUROSES. 
13 
cerebri or cerebral concussion. This term is specially used when the 
trauma has produced no visible changes in the structure of the brain, or 
at least none of notable size. 
Excessive stimulation of the peripheral nerves may cause reflex in- 
hibition or paralysis, involving chiefly the functions of the heart and 
respiratory apparatus; the symptoms thus produced being collectively 
designated as shock. The most frequent causes of shock are injuries to 
the spinal column, abdominal contents, and scrotum, less frequently to 
the extremities and thorax. Further, shock may be caused by lightning- 
stroke, burns, corrosions of the skin; fear, and other strong emotions. 
Individuals whose nervous systems are in a certain condition of irrit- 
ability are specially liable to shock; conditions of narcosis and drunken- 
ness inhibit its occurrence. 
Shock is characterized chiefly by diminished energy on the part of the 
heart and irregular breathing, which lead to decrease in the inter- 
change of gases in the tissues and to lowering of the temperature 
(Roger). The consciousness is usually preserved, the skin and visible 
mucous membranes are pale, the pulse is small and markedly quickened, 
often irregular and intermittent. 
Further, the individual suffering from shock may be excited, groan, 
shriek, and exhibit fearful anxiety associated with dyspnoea (erethistic 
shock) ; or he may lie quiet, with sunken countenance, and evidences of 
great weakness of both sensory and motor functions (torpid shock). 
In severe cases death takes place from stoppage of the heart and of 
respiration. 
Shock, being due to the over-stimulation of the peripheral nerves, 
is allied etiologically to the phenomenon known as syncope; but the last- 
named condition differs essentially from shock in that its chief symptom 
is transitory loss of consciousness, while the functions of the heart and 
respiration show no marked disturbance. Syncope, furthermore, is usu- 
ally preceded by prodromal symptoms, such as dizziness, ringing in the 
ear, and darkening of the visual field, these being absent in shock. 
Not infrequently, following injury to some part of the body, there 
arises a more or less pronounced functional disturbance of the nervous 
system, which may often persist long after the local injury has healed, 
so that such disturbance is in no way dependent on anatomical changes 
in the peripheral or central nervous system, but must be regarded as a 
disturbance of psychical origin. Such conditions are termed traumatic 
or accident neuroses, and are characterized chiefly by subjective but in 
part by objective symptoms. To the first belong pains not definitely 
localized at the seat of injury, as headache, pain in the chest, backache; 
difficulty in movement, lassitude, inability to perform mental labor, dul- 
ness of perception, disturbances of sight, flashes before the eyes, dizzi- 
ness, restless sleep, loss of appetite, and disturbances of digestion. With 
these last symptoms are associated psychical depression of a hypochon- 
driacal or melancholic character, irregularly placed areas of cutaneous 
anaesthesia, enfeeblement of the senses of taste, hearing, and smell, motor 
paralysis, cramps, and hyperaesthesia, concentric narrowing of the visual 
field, pareses, muscular spasms, tremors, acceleration of the pulse, and 
tendency to sweating. 
All of these phenomena depend essentially on psychical shattering of 
the perceptive life, a psychoneurosis. The condition may partake of 14 
THE EXTRINSIC CAUSES OF DISEASE. 
the nature of hysteria, as characterized by disturbance of the normal 
relation between the mental and bodily processes; of hypochondria, as 
recognized by the spontaneous occurrence of abnormal sensations; and 
of neurasthenia, which reveals itself by the production of abnormal 
sensations through relatively slight stimulation. If the will no longer 
controls the motor centres, hysterical paralyses arise; if the normal con- 
trol and inhibition of the will are lost, so that unreasonable will-stimuli 
are created and influence the muscles, hysterical twitchings, contractures, 
or convulsions take place. If a nervous stimulus arising in the sensory 
tract fails to reach the consciousness, there follows hysterical anaesthesia; 
if there arise in the consciousness the images of expected or feared sen- 
sations, and if these images are intensified into actual subjective stimuli 
of consciousness, hysterical pains and neuralgias result (Striimpell). 
Rosenbach designates as kinetoses those diseases which arise when energetic 
and continuous movements of the body in one direction are changed into the oppo- 
site direction, so that a shifting of the internal organs results. In this class belong 
the pathological phenomena observed in seasickness, and in the conditions caused by 
seesawing, whirling, movement in a vertical direction, and sudden stoppage of 
motion. As a result of the rapid change in direction of bodily motion, the molecules 
which are moving in the line of the primary direction are forced to move in tlje 
opposite direction, and, according to Rosenbach, such a change is sufficient to cause 
more or less important molecular disturbance. He explains the symptoms of sea- 
sickness, as, for example, the abnormal secretion of the stomach, the increase of 
intestinal peristalsis, the vomiting, etc., as the results of purely mechanical influences 
on the tissues, and believes that the liver, intestine, brain, and nerve-plexuses are 
similarly affected through mechanical influences acting upon their protoplasm. On 
the other hand, Bins refers seasickness to an acute anaemia of the brain which causes 
the nausea and vomiting. A horizontal position and the administration of a water 
solution of chloral hydrate, which dilates the arteries of the head, have a favorable 
action upon the condition. 
Literature. 
(Effects of Trauma.) 
Roger: Choc nerveux. Arch, de phys., v., 1893, vi., 1894. 
Rosenbach: Die Seekrankheit, Wien, 1896; u. Eulenburg’s Realencyklop., xxii., 
1899. 
Striimpell: Traumat. Neurosen. Munch, med. Woch., 1889; Verb. d. XII. 
Congr. f. inn. Med., 1893. 
3. The Origin of Disease through Intoxication. 
It is difficult to give an exact definition of poison and poisoning, since 
the action of the substances considered in this connection varies greatly 
according to the dose and attenuation, as well as the method of introduc- 
tion into the tissues of the body. The most powerful poisons when in- 
troduced in minute doses may not only be harmless, but may exert a 
beneficial or curative effect. On the other hand, substances which are 
not usually classed with poisons, such as the non-corrosive sodium salts, 
when introduced into the body in large quantities or in concentrated solu- 
tions, may produce effects which must be regarded as of the nature of 
poisoning. Further, poisons in certain dilutions (phenol) may serve as 
food-material. 
§ 6. By poisoning or intoxication is meant that impairment of health, 
caused by the injury to a tissue, which certain substances, by virtue of 
their chemical nature, are able to produce under certain conditions. Such POISONS. 
15 
substances are termed poisons, and are derived partly from the mineral 
kingdom, partly from the vegetable, and partly from the animal king- 
dom. They may occur in a natural state or be produced artificially 
from inorganic or organic substances. Many of the most important 
poisons are products of plant or animal life, and are formed within the 
tissues of the plant or animal. Other poisons belonging in the same 
category are derived from the decomposition of food-stuffs brought 
about by the growth of certain lower forms of vegetable life. 
The most important poisons belonging to the mineral kingdom or which 
are produced from minerals are: metallic mercury, chlorine, bromine, 
iodine, sulphur, and various combinations of these substances, different 
combinations of arsenic, antimony, lead, barium, iron, copper, silver, zinc, 
potassium, sodium, chromium, etc. Of the poisons containing carbon, 
which are artificially produced, the most important are: chloroform, 
chloral hydrate, ether, alcohol, iodoform, carbon bisulphide, hydro- 
cyanic acid, potassium cyanide, oxalic acid, nitroglycerin, amyl nitrite, 
petroleum, carbolic acid, nitrobenzole, picric acid, and aniline. It may 
be observed in this connection that modern chemistry is constantly pro- 
ducing new substances, some of which are poisons. 
Of the poisons produced by plants of the higher order, those of chief 
importance are: the vegetable alkaloids, such as morphine, quinine, colchi- 
cine, atropine, hyoscyamine, veratrine, strychnine, curarine, solanine, 
nicotine, digitaline, santonin, aconitine, cocaine, coniine, muscarine, and 
ergotine, all of which in relatively small doses cause poisoning. 
The lower forms of plant life, especially bacteria, produce an extraordi- 
nary variety of both poisonous and non-poisonous substances, out of the 
food material in which they develop. Some of these substances are simi- 
lar to the vegetable alkaloids, others to the ferments, and are therefore 
designated toxic cadaveric alkaloids, toxic ptomains, toxins, and toxen- 
symes (compare § 11). It may happen that the blood, flesh, or any organ 
of a healthy animal acquires poisonous properties through the presence in 
it of products of bacterial growth. Examples of disease due to bacterial 
poisons in the food are botulismus, sausage, meat, fish, and cheese 
poisoning. These conditions are to be explained, in part by the growth 
of bacteria (B. botulinus) in the food and the formation of poisonous 
products, (§ 11) ; in part by the fact that germs were present in the 
tissues of the animal before death, and the animal having been slaugh- 
tered while diseased, the use of its flesh as food causes either symptoms 
of poisoning or of the same disease as that which affected the animal. 
Under certain conditions foods which are not spoiled may contain bac- 
teria, and these may develop in the intestine of the individual eating the 
food and cause poisoning through the production of toxins, or enzymes. 
According to Lombroso, the disease pellagra, which is of common 
occurrence in Italy, Roumania, and Greece, is caused by the eating of 
decomposed corn. The disease kakke or beri-beri, which is endemic in 
Japan, is regarded by Miura and Yamagiva as due to the extended use 
of rice which has been spoiled in drying. 
Among the animals which normally produce poisons within certain 
tissues of their bodies, the best known are: serpents, toads, salamanders, 
fish, mussels, oysters, scorpions, Spanish flies, and many stinging insects. 
Certain forms of sea-fish are poisonous at all times, others only at certain 
periods, and observations have been made particularly of such fish found in Jap- 16 
THE EXTRINSIC CAUSES OF DISEASE. 
anese waters. According to Saotschenko, the poison of many poisonous fishes is 
secreted by certain skin-glands found at the roots of the dorsal and caudal fins, and 
may be found also in the eggs of such fish. According to Remy, Miura, and 
Takesaki, the poison is secreted in the sexual glands alone in the case of the poison- 
ous fish belonging to the family Gymnodontes (tetrodons). According to Masso, 
there is found in the blood-serum of eels a toxic substance (ichthytoxin) which, 
when introduced into the small intestine of animals experimentally, causes symptoms 
of poisoning and may kill the animal. According to M. Wolff, the liver of mussels 
(Mytilus ednlis) contains the poison; its action, according to Schmidtmann, 
Virchow, Salkowski, and Brieger, is similar to that of curare. Brieger has also 
shown that from the poisonous mussels there can be obtained basic substances closely 
related to ptomains, the basic products of decomposition. To what extent the pro- 
duction of poisons in poisonous fishes and mollusks is to be ascribed to normal and 
to what extent to pathological processes cannot at present be decided. From the fact 
that the mussels and oysters are poisonous only in certain places where the water 
is impure, and as the starfish found in the same localities are similarly effected, it 
is probable that the poisonous action of these mollusks may in part be due to their 
contamination with bacteria or to the occurrence of certain diseased conditions. 
The venom of serpents is formed exclusively in the poison-glands lying in the 
upper portion of the corner of the mouth. It is a green or yellowish fluid and its 
activity is not influenced by drying or by preservation in spirits. 
Snake venom, the poison of spiders and toads and of the blood of the eel and 
murcena, ricin (obtained from the seed of the castor-oil bean), and abrin (from the 
seed Abrus precatorius) show properties similar to those of the bacterial toxins 
(compare § 11). Snake-poison and that of the blood of the eel have also a 
haemolytic action. 
§ 7. Poisons may be divided according to their action into three 
groups: first, those producing local tissue-changes; second, those acting 
injuriously upon the blood; third, those affecting chiefly the nervous 
system and the heart without producing recognizable anatomical lesions. 
The poisons which cause marked local lesions injure the tissues with 
which they first come into contact. If such poisons are diffused by 
means of the body-fluids, diverse organs and tissues may be injured; but 
their action is usually limited to that organ in which they are stored up 
or through which they are excreted, especially the liver, intestine, and 
kidneys. 
The primary seat of injury is most often the mucosa of the upper 
portion of the intestinal tract and the respiratory passages, but in many 
cases the skin is first affected. Frequently poisons, which are employed 
for disinfecting, are brought into contact with wounds for the purpose 
of killing bacteria or preventing their growth, and in this way cause 
local changes or are absorbed and damage deeper tissues. 
The poisons belonging to this class are those which cause tissue- 
changes at the point of contact, similar to those of burns, and for this 
reason are designated caustics or corrosives. If the action of a caustic 
reaches its greatest degree of severity, the affected tissue is destroyed and 
converted into either a dry, hard eschar, or a moist, soft slough. If 
the action is of moderate intensity as the result of a less concentrated 
solution of the caustic agent, or of incomplete action of the chemical 
even when applied in strong solution or in substance, or because the tissue 
itself is resistant as in the case of the skin, the changes produced are less 
severe, and are characterized by inflammation and haemorrhage. Diverse 
changes are often found in the same organ, such as local sloughing 
(necroses), haemorrhages, inflammations, and local hyperaemia. If the 
changes have existed for some time, the local eschars are surrounded by 
an inflammatory zone, which in the case of certain caustics may be of 
limited extent. POISONS. 
17 
The caustic poisons are: first, the corrosive acids, sulphuric, nitric, hydrochloric, 
phosphoric, oxalic, arsenic, arsenious, osmic, acetic, lactic, trichloracetic, carbolic, 
and salicylic; the corrosive combinations of the alkalies and alkaline earths, potas- 
sium and sodium hydroxide (watery solutions of KOH and NaOH), caustic 
ammonia (solution of NH3 in water), ammonium carbonate, caustic lime, and 
barium sulphate. In this class are also certain corrosive salts, chiefly of the heavy 
metals, such as salts of antimony (tartar emetic and antimony trichloride), salts of 
mercury (corrosive sublimate and red precipitate), nitrate of silver, zinc chloride, 
zinc sulphate, copper sulphate and copper acetate, aluminum acetate, potassium 
chromate and bichromate, and chloride of iron. 
The caustic poisons derived from animals are: cantharidin, from the beetle 
Lytta vesicatoria; phrynin, the secretion from the cutaneous glands of the toad; the 
secretions from the poison-glands of snakes and scorpions; the secretion of the 
sting-gland of bees, wasps, and hornets; the secretion of the salivary glands of 
stinging-gnats, flies, and gad-flies; and the secretion of the poison-glands of the 
maxillary palpse of spiders (tarantula) — all of which cause local necrosis, or 
haemoirhage and inflammation. Many of the higher plants produce in their blos- 
soms, seeds, stems, or roots substances which, when brought into contact with the 
tissues, cause irritation and inflammation, as, for example, daphne, different forms 
of Ranunculus, varieties of anemone Primula obconica (pubescent portion), marsh- 
marigold, different varieties of Calla, dragon-root, Croton tiglii (from the seeds of 
which croton-oil is obtained), buckthorn (Rhamnus cathartica), black elder 
(Rhamnus frangulg). 
The nature of the local changes which these and similar substances produce is 
varied, and is dependent partly on the activity of the poison, and partly on the 
location and manner of application. The mineral acids, solutions of caustic potash 
and mercuric chloride, when concentrated, cause marked tissue-eschars, associated 
with haemorrhagic inflammation, especially when taken into the stomach. Through 
the action of acids there is marked withdrawal of the alkaline constituents of the 
body fluids, leading to disturbances of respiration and circulation. The venom of 
snakes usually causes severe local inflammation and haemorrhages, which often 
extend beyond the region of the bite, and sometimes may cause widespread gangrene. 
There are snake-venoms, however, which produce only insignificant local changes, 
the general symptoms of poisoning being more prominent. The volatile or gaseous 
poisons affect chiefly the mucous membranes of the eye and respiratory tract 
(irrespirable gases'). To this class belong especially the fumes of ammonia, chlorine, 
sulphurous acid, nitric oxide, nitric dioxide, nitric trioxide, osmic acid, formalin 
and mustard-oil. The action of these poisons is varied, often causing only transitory 
hypersemia, but being able also to give rise to tissue necrosis and inflammation. The 
irritation of the respiratory tract gives rise to coughing, and spasmodic narrowing 
of the glottis may interfere with breathing. 
To the local irritation and inflammation caused by these poisons at the seat of 
contact may be added effects upon internal organs. After the absorption of these 
poisons, those organs suffer most in which the poison is stored up or through which 
it is eliminated, though organs of varied structure may be affected, as well as those 
not concerned in the excretion of the poison. In the case of certain poisons, the 
changes at the point of entrance are slight and often not recognizable, the important 
anatomical lesions occurring in other tissues, to which the poison has been carried. 
Finally, a given poison may act as a nerve and heart poison, so that clinically the 
effects of this action are more prominent than the local lesion. In poisoning with 
corrosive sublimate, cell necrosis and the deposition of calcium take place in the 
secreting part of the kidneys, and there is also severe inflammation of the colon. 
The salts of chromic acid, cantharidin, and. many acids- cause more or less marked 
degenerative, inflammatory or haemorrhagic changes in the kidney and urinary 
passages. 
Phosphorus, arsenic, antimony, produce tissue-degeneration, particularly fatty 
degeneration, and haemorrhages, in the kidneys, liver, heart, muscles, bone-marrow, 
and other organs, these changes being particularly marked in cases of phosphorus 
poisoning. 
The effects of arsenic are particularly important in view of the frequency with 
which arsphenamin and related compounds are administered in the modern treat- 
ment of syphilis. The method is by no means free from danger. The untoward 
reactions of the drug are classified by Blanton (American Journal of Syphilis, 1919) 
as follows: (a) Anaphylactoid reactions, which appear during the administration 
of the drug, last 15 to 30 minutes, and are characterized by sensations of burning in 18 
THE EXTRINSIC CAUSES OF DISEASE. 
the mouth, flushing of the skin, injection of mucous membranes, facial oedema, 
nausea, vomiting, a sensation of suffocation, sometimes ending in unconsciousness 
(b) Deferred reactions, which appear several hours after the administration of the 
drug, last from 12 to 24 hours, and are characterized by chills, headaches, vertigo, 
nausea, vomiting, diarrhea, generalized aches and pains and, occasionally, by skin 
eruptions, (c) Late reactions, which appear after 24 hours or even later. Probably 
the majority of fatal cases fall into this group. Beginning with vomiting, diarrhea 
and fever, these patients rapidly develop headache, muscular twitchings, dilated 
pupils, disappearance of various reflexes and, after a brief illness, may die in coma. 
In fatal cases, Blanton and others have described widespread acute haemorrhagic 
encephalitis, (d) Herxheimer’s reaction, characterized by intensification of the 
syphilitic rash, said to be due to the sudden liberation of endotoxin or to insufficient 
doses; the so-called neuro-recurrences, in which neuritis develops in the cranial 
nerves, particularly the auditory and optic, an effect which is probably due to 
awakening of pre-existing processes in these localities; morbilliform skin eruptions, 
jaundice, and albuminuria. Moreover, the intensive treatment of syphilis by a 
combination of arsphenamin and mercury compounds occasionally gives rise to 
necrotic lesions in the liver, simulating acute yellow atrophy, and to degenerative 
and necrotic lesions in the kidney, associated with calcification of the dead epithelial 
structures, comparable to that of bichloride of mercury poisoning. 
If an individual is exposed for long periods to the fumes of yellow phosphorous, 
there may take place an inflammation of the jaw bones leading to necrosis, but only 
when the occurrence of inflammatory changes is favored by other causes, such as 
decaying teeth. Formerly, this variety of necrosis constituted an important occupa- 
tional disease, particularly in match factories, but strict attention to dental hygiene 
among the workers has almost completely eliminated it. 
The long-continued use of silver nitrate may be followed by a deposit of black 
granules of silver in diverse tissues, the skin, kidneys, intestinal villi, and choroid 
plexus. In such circumstances the deposit of metallic silver in the skin gives a 
ghastly greyish hue to the complexion (argyria). 
The venom of snakes possesses, in addition to its local effects, a paralyzing 
action on the nervous system and heart, and may cause death through paralysis of 
the respiratory centre. 
Soluble salts of lead when ingested may cause irritation and inflammation of the 
intestine, with such symptoms as vomiting, diarrhoea, constipation, cramps in the 
stomach, associated with such nervous phenomena as anaesthesia, motor paralysis, 
convulsions, vertigo, and loss of consciousness. When ingested continuously for a 
long time, lead gives rise to anaemia (lores), general disturbances of nutrition, intes- 
tinal colic, pains in the limbs, anaesthesia, motor paralysis, cerebral disturbances, and 
kidney disease. These disturbances are without doubt dependent upon the distribu- 
tion and deposit of lead throughout the body, leading to anatomical lesions of varied 
nature. 
The active principles of ergot (Secale cornutum), sphacelinic acid and cornutin, 
when taken in large doses, or when repeatedly eaten in bread, cause itching, pain, 
and cramps in the limbs, followed by numbness and feeling of cold in the toes and 
finger tips, and finally there may occur more or less extensive gangrene of the parts 
(ergotism, “ Kribbelkrankheit”). In cases of chronic poisoning, degenerations of 
the spinal cord take place (Tucsek). The feeding of chickens with ergot causes 
gangrene of the comb through stasis and hyaline thrombosis in the blood-vessels. 
So characteristic is this change that it is employed as a test of the physiological 
activity of preparations of ergot intended for medicinal use. In animals fed 
for a long time with ergot degenerative changes are found in the central and 
peripheral nervous system, in the blood-corpuscles, and in the endothelium of the 
blood-vessels (Grigorjeff). 
§ 8. The poisons which affect the blood chiefly, and are therefore 
termed blood-poisons, are partly gases and partly fixed substances. The 
latter are absorbed mainly from the intestine, but may also enter the body 
through wounds, or be injected directly into the blood-vessels. Some of 
the blood-poisons produce local lesions at the point of entrance; further, 
there may be joined to the action on the blood a direct effect upon the 
nervous system, which under certain conditions may cause death before 
the action on the blood is recognizable. Finally, it should be empha- POISONS. 
19 
sized that the blood-changes produced by the poison may cause numerous 
secondary changes in different organs, for instance, in the kidneys, liver, 
intestine, and brain. 
Carbon monoxide, hydrocyanic acid, potassium cyanide, and hydrogen 
sulphide form combinations with haemoglobin giving rise to carbon-mon- 
oxide-haemoglobin, cyan-methaemoglobin, and sulphur-methaemoglobin, 
inhibiting or destroying the functional capacity of the red blood-cells. 
They also produce an effect upon the nervous system which is most 
marked in the case of hydrocyanic acid and potassium cyanide. These 
poisons in small doses attack the central nervous system, producing 
death almost immediately through paralysis of the centres of respiration 
and circulation. 
Potassium chlorate, toluylendiamin, hydrazin, nitrobenzol, nitro- 
glycerin, amyl nitrite picric acid, phallin (a poison obtained from the 
mushroom, Agaricus phalloides), helvellic acid (poison of Helvetia 
esculenta), arseniuretted hydrogen, and other substances cause haemolysis 
of red blood-cells and lead to the formation of methaemoglobin, that is, 
to an oxygen combination of haemoglobin, the oxygen content of which 
is the same as that of oxyhaemoglobin, but in which the oxygen is more 
firmly bound. 
Certain bacterial products, called bacterial hcemolysins, have a specific 
action on the red blood-cells, leading to the production of haemoglo- 
binaemia. The best known are those occurring in infections with certain 
varieties of streptococci. 
When the blood of an animal is introduced into the blood stream of 
man or of an animal of another species, specific hcemolysins become 
active, that is, poisons which cause haemolysis of the foreign red blood- 
cells. Recognition of this fact is of the utmost importance in view of 
the frequency with which the transfusion of blood from one human 
being to another is now employed as a therapeutic measure. 
Carbon-monoxide poisoning most often results from the carbon monoxide in 
coal- or illuminating-gas, but may occur under other conditions, as in the case of 
vapors produced by gun-powder or gun-cotton. The effects of the inhalation of 
carbon monoxide result from the combination of the gas with the haemoglobin of 
the blood and the formation of carbon-monoxide-haemoglobin. The amount of 
oxygen combined with the haemoglobin is thereby decreased, and the taking up of 
oxygen is reduced, even when the respired air contains only 0.05 per cent, or even 
0.02 per cent, of CO (Gruber). The red blood-cells themselves present no changes. 
A rapid supply of carbon monoxide to the nervous system may cause direct injury 
to the nerves, giving rise to convulsions and later to paralysis (Geppert). In cases 
of long-continued poisoning the displacement of the oxygen from the greater por- 
tion of the red cells leads to asphyxia. If the affected individual does not die, there 
may result, in addition to the poisoning, severe disturbances of nutrition, occurring 
especially in the nervous system. The poisoning itself is characterized by headache, 
tinnitus aurium, vertigo, malaise, vomiting, fainting, convulsions, paralysis, and 
coma. The blood, as a result of the presence of carbon monoxide, becomes a bright 
violet or cherry-red color, so that the hypersemic skin and internal organs also 
appear bright red. In many individuals who recover from the immediate effects of 
carbon monoxide, death occurs within ten days or two weeks and, at autopsy, char- 
acteristic areas of softening are to be found in the lenticular nucleus on both sides. 
Hydrocyanic acid (CNH) is found in unstable combination in the leaves, bark, 
and seeds of many plants (bitter almonds, cherry- and peach-stones, apple-seeds, 
leaves of the laurel, bark of Primus padus, tubers of many of the Euphorbiaceae, 
flaxseed, etc.). Potassium cyanide (CNK) is used in many of the technical arts. 
The action of both of these poisons on the blood leads to the formation of 
cyanmethaemoglobin, which gives the blood a bright red color and produces a bright 
red post-mortem lividity. 20 
THE EXTRINSIC CAUSES OF DISEASE. 
Hydrogen- sulphide (H2S) is a constituent of the gas of sewers and dung-pits. 
When inhaled in large amounts, it may cause sudden death from paralysis of the 
nervous system. When hydrogen sulphide is for some time brought into contact 
with blood containing oxygen (as is usually the case in decomposing cadavers), a 
sulphur-methsemoglobin is formed, which gives a greenish color to those tissues in 
which it is deposited. 
The poisons that dissolve the red blood-cells, with the formation of methaemo- 
globin, belong partly to the oxidizing substances (ozone, iodine, sodium hypochloride, 
chlorates, nitrites, and nitrates) ; partly to the reducing agents (nascent hydrogen, 
palladium hydride, pyrogallol, pyrocatechin, hydrochinon, and alloxanthin) ; and 
partly to substances which have neither a reducing nor oxidizing action (salts of 
aniline and toluidin, acetanilid). In the transformation of haemoglobin into methae- 
moglobin through oxidizing substances, oxyhaemoglobin is present as an intermediate 
body. 
The formation of methaemoglobin can occur either in the red blood-cells or in 
the haemoglobin which has escaped into the blood-plasma; but the destruction of the 
blood-cells and the escape of haemoglobin into the plasma are not always followed 
by the formation of methaemoglobin. In the case of marked destruction of red 
cells, as in poisoning from phallin, helvellic acid, arseniuretted hydrogen, only a 
portion of the haemoglobin is changed into methaemoglobin. Haemoglobin and 
oxyhaemoglobin have a red color, methaemoglobin a sepia-brown. 
Large doses of potassium chlorate (ClOsK) may cause death in a few hours 
through the destruction of red blood-cells and the action of the potassium, with the 
symptoms of vomiting, diarrhoea, dyspnoea, cyanosis, and cardiac insufficiency. The 
blood becomes chocolate-brown in color. In more protracted cases of poisoning 
through smaller doses, products of blood destruction are found in the spleen, liver, 
bone-marrow, and kidneys; and the urine may show a brown-red to black color 
(methaemoglobin). Delirium, numbness, coma, and convulsions occur during the 
course of the intoxication, showing that the central nervous system suffers severely. 
Pyrogallol (CeHe[OH]3) produces similar effects; hydrazin (H2N—NH2) and 
phenylhydrazin cause, in addition to haemolysis and the formation of methaemo- 
globin, multiple thromboses. In poisoning with toluylendiamin (CeHs[NH2]2CH3) 
the chief action is the destruction of red blood-cells leading to deposits of iron- 
containing pigment in the spleen, liver, and bone-marrow. In cats methaemoglobin 
may be excreted through the urine (Biondi). In poisoning with picric acid 
(CeH2[N02]30H) there occurs, in addition to the blood changes and the formation 
of methaemoglobin, severe irritation of the central nervous system finding expression 
in violent convulsions. Small doses produce a yellowish discoloration of the skin 
and conjunctivae, simulating jaundice. 
According to Kob'ert, ricin derived from the seeds of the castor-bean, and abrin 
from the seeds of abrus precatorius, should be classed with the haemolytic-poisons, 
in that in the test-tube they cause agglutination of the red cells and the formation 
of a flocculent precipitate. In animals poisoned experimentally, local irritations, 
tissue-degenerations and inflammation, similar to those caused by certain bacterial 
toxins, are produced, as well as disturbances in the centres of the medulla oblongata, 
leading to cessation of respiration with progressive falling of blood-pressure. 
Tissue-degenerations, inflammation, and haemorrhage are found, after longer action, 
at the point of application and in the intestine, where the poison is excreted. 
Degenerative changes are also found in lymphocytes, liver and kidney cells, and 
heart muscle. 
§ 9. The last group of poisons, classed as nerve and heart poisons, 
is characterized chiefly by the fact that, in spite of the severity of 
symptoms, as shown in the form of irritations and paralyses, anatomical 
changes cannot be recognized at all or are confined to structural 
changes in the protoplasm of individual nerve-cells, which are of 
similar character in the case of different poisons. This is especially the 
case when the poison is quickly fatal, while if the poisoning runs a pro- 
tracted course, or in the case of chronic poisoning from small doses, ex- 
tending over months and years, there are often found marked anatomical 
changes. POISONS; INFECTION. 
21 
Of the great number of poisons which act especially upon the ner- 
vous system and may cause death through its paralysis, the most im- 
portant are: chloroform, chloral hydrate, alcohol, ether, opium and its 
alkaloids, notably morphine; cocaine, atropine, hyoscyamine, daturine 
(stramonium-atropine), nicotine, coniine, cicutoxin, santonin, quinine, 
veratrine, colchicine, aconitine, strychnine, cytisin, curarine, and saman- 
darine (salamander-poison). 
Of the heart-poisons, digitalin, helleborin, muscarine, and phrynin 
(poison of toads) are of importance. 
Chloroform (CHCL), when applied to mucous membranes, causes local irri- 
tation and transitory inflammation. When conveyed to the blood by inhalation or 
by absorption from the intestinal tract, it gives rise, after a short period of stimu- 
lation, to diminished irritability of the cerebral gray and white matter. According 
to Bins, the protoplasm of the ganglion-cells suffers slight coagulation. Death may 
be caused by paralysis of the central nervous system, as well as by heart-failure; 
the latter, however, occurring more especially when the heart is weak or degem 
erated. Certain individuals show a special susceptibility to the action of chloro- 
form. The long-continued use of chloroform may cause degenerative changes in 
different organs, as the heart, kidneys, liver, muscles, and blood. 
Alcohol (C2H5OH), after transitory stimulation, has a depressing and paralyz- 
ing action on the brain, at the same time causing dilatation of the capillaries of the 
skin, so that in intoxicated individuals severe chilling may easily occur. Death may 
take place suddenly, with symptoms similar to those of apoplexy; more frequently 
there is a gradual loss of consciousness and of sensory perception, the respiration 
becomes slower, the pulse small, the face cyanotic; complete coma and general 
paralysis forming the closing symptoms. The immoderate use of alcohol for 
months or years may cause degenerative atrophies of liver and kidneys associated 
with increase of connective tissue; further, sclerosis and atheroma of the arteries, 
degeneration of the brain, etc., are ascribed to the action of alcohol. At the present 
time it is impossible to say in what manner, how often, and to what extent these 
changes are dependent on the use of alcohol Much is ascribed to the action of 
alcohol that is not in any way caused by it and is due wholly to the action of other 
injurious agents. It is certain, however, that drunkards suffer frequently from 
disturbances of digestion and circulation, catarrhal inflammations of pharynx, 
larynx, and bronchi, and of cerebral function; and that the disease known as 
delirium tremens, which is characterized by general muscular tremors, obstinate 
insomnia, anxiety, and hallucinations, is to be ascribed to alcoholism. 
Opium and Morphine (CnHnNOf) depress the cerebral functions, Inducing 
sleep; in individual cases there may be a preceding period of stimulation. Large 
doses lead to unconsciousness, paralysis of muscles, slowing and weakening of 
the heart’s action, contraction of the pupils, slowing of intestinal peristalsis, diminu- 
tion in the exchange of gases in the blood dependent upon diminished excitability 
of the respiratory centre. There is no characteristic autopsy finding; the blood is 
usually dark and fluid, as in any variety of asphyxia. 
4. Origin of Disease through Infection or Parasitism. 
§ 10. The entrance of living micro-organisms into the tissues, and 
their multiplication there zvith the production of pathological processes, 
is known as infection. Since these micro-organisms take their food 
from the tissues, they are to be regarded as parasites. 
The parasites causing the majority of the infectious diseases are now 
known. In those diseases in which they are not yet discovered (small- 
pox, measles, scarlatina, etc.) the existence of a parasite may be assumed 
since the diseases in question are characterized by phenomena common 
to other infections. It may happen that a given disease spreads from 
one affected individual to other individuals, giving rise to pestilence or 
epidemic, which may sweep through a house or city or through the land 
or over many lands. The spread of disease sometimes occurs by direct 22 
THE EXTRINSIC CAUSES OF DISEASE. 
passage from man to man, direct contagion (smallpox, gonorrhoea, 
syphilis, and leprosy) ; at other times, as if the causal agent of the dis- 
ease clung to certain regions as a so-called miasma (malaria) and in- 
fected the individuals who came into its neighborhood. 
The parasites that cause the infectious diseases belong, for the 
greater part to the schizomycetes or bacteria; but certain of the higher 
plants, the mould-fungi (eumycetes), and the yeasts may also cause 
infectious diseases. Animal parasites are also represented by numerous 
species, belonging to the protozoa, to the worms, and to the arthropoda. 
It has been the custom to accord the animal parasites a special position, 
since many of them do not increase in the host in whom they live, but 
only pass through certain stages of development without causing symp- 
toms characteristic of the infectious diseases. Such a distinction does 
not hold good, since certain infectious diseases (malaria) are caused by 
animal parasites. Further, in the case of many of the animal parasites 
a definite increase takes place within the human organism. 
With the recognition that infectious diseases are caused by living 
microorganisms, the view was soon reached that contagious diseases must 
be caused by parasites that thrive only within the human or animal 
organisms; while miasmatic diseases arose from agents living in the 
outer world and which occasionally gain entrance into man or animals. 
In the first case the microorganisms are designated endogenous parasites, 
the second ectogenous. It was assumed in regard to the miasmatic dis- 
eases that the microorganisms could increase either within the body or 
in the outer world; but, in the latter place, only when they passed from 
the human or animal body into water, food, or earth. 
With certain limitations this view is still regarded as correct; but, 
according to later experiences, its original application is not always cor- 
rect, since many microorganisms that ordinarily increase only in living 
tissues as parasites require for their growth outside of the human body 
certain conditions of life that make their multiplication possible. The 
causal agents of measles, scarlatina, and of syphilis can develop only 
inside the human body; that of smallpox, within the body of man and 
cattle, and we have not yet succeeded in growing them in artificial media. 
Tubercle bacilli ordinarily develop only in the tissues of man and certain 
other vertebrates; but they may be cultivated on artificial media at the 
temperature of the body, and be successfully inoculated into man and 
other susceptible animals. Staphylococci and streptococci, which pro- 
duce suppuration, anthrax bacilli, typhoid bacilli, cholera spirilla, and 
others grow easily in different solid and fluid media and can after artificial 
cultivation cause disease in man. But it should be noted that, even in the 
last-named cases, the bacteria concerned have not spontaneously in- 
creased in the outer world, so that, for example, water used for drink- 
ing becomes only the conveyor of the infective agent. 
Malaria, which is considered the chief type of so-called miasmatic 
disease, is produced by a microorganism, which, outside the human body, 
must pass through definite stages of development in certain mosquitoes. 
Through the taking up of blood from a malarial patient the infected 
mosquitoes (Anopheles) represent the malaria-producing miasm, and 
man is infected through their bite, and not, as was originally supposed, 
through mists arising from marshes. It is also possible to produce in- 
fection with malaria by the transfusion of blood from a malarial patient 
to a healthy individual. INFECTION. 
23 
The view that certain diseases are of parasitic origin is old, and found expression 
in the works of Kirchner (1602-1680), Lancisi (1654-1720), Linne (1707-1778), and 
others. It was left to recent times, however, to place the theory of the parasitic 
nature of the infectious diseases on a secure foundation. Though several decades 
ago Henle, Liebermeister, and others asserted that the peculiarities of infectious 
diseases could be explained only by the assumption of a contagium animatum, the 
establishment of this doctrine is due to the investigations of recent years. 
Climate is often held responsible for the origin of disease, and we are inclined 
to consider a region having a uniform temperature, much sun, and little wind as a 
healthy one, while one having marked variations of temperature, abundant precipita- 
tion, little sun, and much wind is regarded as unhealthy. This is true to a certain 
extent, in so far as invalids or individuals susceptible to the influences of weather 
are concerned, but a better criterion of the healthfulness of a region is the presence 
or absence of specific agents of disease, vegetable or animal parasites that may 
infect man. Such disease-producing agents may exist in affected members of the 
population of the region, in the drinking-water, in the earth, or in animals, etc. 
In the tropics malarial parasites play the most important role, their transmission 
to man being brought about through the agency of mosquitoes. Therefore, a beauti- 
ful region which seems to offer the best climate may be unhealthy; while raw, cold, 
and inhospitable climates may be healthy because of the absence in them of the 
causal agents of disease. 
§ 11. The bacteria are small, unicellular micro-organisms, which 
appear in the form of minute spheres (cocci), and fine, straight, or 
curved rods (bacilli and spirilla), frequently uniting in peculiar com- 
binations. Many possess motile organs in the form of flagella. Under 
special conditions some of them produce spores. 
From the standpoint of the physician bacteria may be divided into 
the non-pathogenic and the pathogenic. To the latter belong all those 
that are able to increase in the human and animal organism. But this 
classification is not altogether satisfactory, inasmuch as pathological con- 
ditions may be caused by bacteria that are not able to increase within 
living tissues. This rests on the fact that all bacteria, not only the 
pathogenic, but also the non-pathogenic, in their growth in nutritive 
media (albumin, peptone, gelatin), decompose these, and thereby often 
produce substances that are toxic for man and for the higher animals. 
The most important of the substances produced by the decomposition 
of proteids are the basic cadaveric alkaloids or ptomains, many of 
which are poisons for man. For example, the toxic products neuridin, 
cadaverin, putrescin, neurin, and methylguanidin, the last three of which 
are poisons, may be obtained in pure form from decomposing meat. If 
these enter with the food into the human body symptoms of intoxica- 
tion may be produced without the development of bacteria in living tissue. 
On the whole, their activity is not considered very great, and it is ques- 
tionable whether the artificially produced poisonous ptomains ever arise 
during the processes of decomposition. 
Besides the property of producing ptomains and other poisonous sub- 
stances (for example, hydrogen sulphide), which belongs to many dif- 
ferent bacteria, the pathogenic bacteria produce other specific poisons. 
The first of these to be considered are the toxins in the narrower sense, 
that is, poisonous substances which do not belong to the ptomains and are 
also not albuminous bodies (toxalbumins). They are products of secre- 
tion of the bacterial cells and can be separated by filtration from the 
bacteria. The most important representatives of such poisons are those 
produced by the bacilli of diphtheria and tetanus, both in cultures and in 
the human organism. The toxins are unstable bodies and quickly lose 24 
THE EXTRINSIC CAUSES OF DISEASE. 
their activity through heating above 50° C., the effect of light, and 
through the action of acids and other chemical substances; when dry they 
will stand 100° C. without injury. Their chemical structure is not 
known; they may be compared with the enzymes. When injected into 
susceptible animals, their action takes place after a period of incubation 
known as the period of latency. In the affected organism they cause the 
production of antitoxins, which render the toxin harmless in the organ- 
ism and also neutralize it in vitro. 
As a second form of specific poison there occur intracellular toxins 
or endotoxins, that is, poisons which cling to the bacterial cell and are 
separated from it only with difficulty. Even less is known of their 
nature than of the true toxins. Typhoid bacilli, cholera spirilla, and 
pneumococci form such poisons, and it is assumed that they are released 
and become active after the destruction of the bacteria in the human 
organism (bacteriolysis). 
A third form of poison is found in the bacterial proteins, that is, 
the substance of the cell itself. They produce chiefly a local effect, find- 
ing expression in inflammatory reactions. It is probable that such reac- 
tion occurs in all bacterial infections in which the bacteria develop locally. 
If the bacteria concerned produce antitoxins the action of these is com- 
bined with that of the bacterial proteins. 
In individual cases it is often impossible to decide to what extent 
ptoma’ins or specific bacterial toxins and proteins are concerned in the 
production of pathological conditions. The term toxin is often used to 
cover all of the poisonous substances produced by bacteria. 
Some pathogenic bacteria increase first in the outer world (for ex- 
ample, the tetanus bacillus), and only occasionally develop in the human 
or animal body; other forms develop ordinarily only in the human or ani- 
mal organism (tubercle bacilli, glanders, leprosy, diphtheria, and in- 
fluenza bacilli) and need for their development outside of the body special 
nutritive media, or, indeed, they cannot be cultivated at all. Still others 
increase with energy in human and animal tissue, but are also easily grown 
upon nutritive media (streptococcus, staphylococcus, anthrax bacillus, 
typhoid bacillus, cholera spirillum), and are able to multiply under 
natural conditions in the outer world. 
The distribution of pathogenic bacteria from the affected indi- 
vidual to the outer world takes place through coughing, sneezing, expec- 
toration, speaking, through intestinal and urinary discharges, secretions 
from wounds, sloughing of tissue, etc. When thrown into the air they 
may float for some time and be carried to- a distance, but, sooner or later, 
become attached to some object. Through drying and sunlight many are 
quickly destroyed. Others remain alive for a period, often a long time, 
2specially in the form of spores, and may be found in either a dry or 
moist state, in the water or earth. If they find the proper food-material 
and if the temperature is favorable they may multiply. 
From the place where they are thrown down, or from the objects to 
which they cling, or where they have undergone development, the 
bacteria may suffer a wider distribution. Strong currents of air may 
carry them away, especially from the objects to which they cling, or in 
the dust of the room or of the street. Many of them are brought to the 
human and animal organism through food and drink, through the air, or 
through contamination of the fingers. INFECTION. 
25 
The avenues of entrance for bacteria are, in general, the mucous 
membranes of the intestinal canal, respiratory tract, the conjunctiva, the 
alveoli of the lungs, and open wounds. But it should be noted that many 
bacteria are able to enter only through certain tissues, for example, the 
typhoid bacillus and the cholera spirillum gain entrance only from the 
intestine. Through recent wounds, both pathogenic and non-pathogenic 
bacteria are rapidly taken into the lymph and blood; while through 
wounds showing healthy, granulating surfaces, the entrance of bacteria 
into the tissues is hindered. Pathogenic bacteria (pus cocci) not infre- 
quently enter through the skin, either by way of the hair-follicles or the 
sebaceous or sweat-glands. Under certain conditions (coitus, surgical 
operations, dribbling of urine, childbirth) infection may take its start 
from the mucous membranes of the uro-genital tract. Some infections 
are transmitted by insects, which have taken up bacteria from the blood 
or secretions of a diseased individual or animal, or, having become con- 
taminated externally, infect an open wound by scraping the bacteria from 
their legs, or by the introduction of germs into the skin or mucous mem- 
branes during the act of stinging or sucking. If meat containing bacteria 
be eaten, and if the animal while alive were affected by an infectious dis- 
ease to which man is susceptible, this particular disease may thus be 
transmitted. 
If toxic bacterial products enter in consideral amount into the in- 
testinal canal or wounds at the same time with bacteria, the symptoms of 
intoxication may be produced without infection, that is, without increase 
of the bacteria in the tissues. This may also happen when bacteria pro- 
ducing such poisons develop in the contents of the intestine, in wound- 
secretions or in necrotic tissue, and increase as saprophytes. Strictly 
speaking, we cannot regard this as an infection, but as an intoxication; 
although it is not always possible to draw a sharp line between intoxica- 
tion and infection, since bacteria originally developing as parasites not 
infrequently penetrate into the tissues and multiply. 
Intestinal intoxications dependent upon bacterial toxins occur 
when meat or fluids in a condition of bacterial decomposition has been 
eaten as food. To such intoxications belong the affections designated as 
meat-, sausage-, fish-, and cheese-poisoning, in which the poison is either 
taken as such into the intestinal canal, or is formed there. Likewise, 
vegetables in a condition of fermentation and decomposition, for example, 
cabbage, peas, beans, corn, rice, etc., may exert a harmful influence on 
the intestine or on the entire organism, especially when they have been 
eaten in large amounts or for a long period. 
If bacteria which have entered the body through one of the above- 
mentioned avenues are pathogenic, so that they give rise to infection, 
they may increase first at the point of entrance, in the intestinal mucous 
membrane, in a wound, in the skin, etc. The local effects of their growth 
depend on the individual characteristics of the bacteria, as well as on 
the peculiarities of the affected tissue. In general, the local action is 
characterized by tissue-degenerations, necrosis, inflammation, and new- 
formation of tissue, so that it is possible in many cases to determine the 
specific nature of the infection, that is, the species of bacteria causing it, 
from the character of the local changes. It is however, difficult or im- 
possible to determine in every case the mode of action of the multiplying 
bacteria; in general, it may be said that the processes of chemical meta- 
morphosis excited by the multiplication of the bacteria produce certain 26 
THE EXTRINSIC CAUSES OF DISEASE. 
changes in the tissue-cells, in that different substances of active chemical 
nature either kill the cells, or at least induce degenerative changes in 
them, or excite increased cell-activity. In the further development of the 
process the substances derived from dead and dissolving bacteria may 
also react on the surrounding tissue. In a sense, therefore, there occurs 
through the growth of bacteria a local intoxication, which is of greater 
significance than the withdrawal of nutritive material through the con- 
sumption by the bacteria of food substances. The latter is, however, not 
without significance, inasmuch as the chemical changes produced by the 
bacteria in the tissue juices often render these unfit for the nourishment 
of the tissue-cells. 
The participation of the body as a whole in a local bacterial infec- 
tion may be slight or absent, so that the disease remains a purely local 
affection (tuberculosis). In other cases the toxins and toxalbumins 
formed at the focus of infection are absorbed into the blood, and a gen- 
eral intoxication (toxincemia) is produced. In such diseases as tetanus 
and diphtheria the sytemic reactions to local poisoning are especially 
prominent. 
If healing does not take place at the primary seat of infection, the 
neighboring tissues may be involved by invasion of bacteria by con- 
tinuity. Often the bacteria gain entrance to the lymph-vessels or 
blood-channels (bactericemia), and in this way are transported over 
the entire body. The result of this metastasis of bacteria is the produc- 
tion of a lymphogenous or haematogenous infection; that is, secondary 
foci of disease identical in character with those at the primary seat of 
infection are formed at a distance. In certain diseases (tuberculosis, 
suppuration, plague) the number of metastases is usually great, so that 
many parts of the body (lymph-nodes, liver, lung, brain, muscles, bones, 
kidneys, etc.)-contain diseased foci. In other infections metastasis of 
bacteria from the original focus to other organs does not occur (tetanus, 
diphtheria), or the transported bacteria cause changes of a milder type 
(typhoid fever). 
The entrance of bacteria into the blood constitutes the condition 
known as bacteriaemia. During transportation through the blood-vessels, 
there is usually no increase of the bacteria, the blood serving merely 
as a vehicle, multiplication occurring at those points where the bacteria 
come to rest. Nevertheless, in certain infections (anthrax) the bacteria 
increase enormously in the circulating blood. Through the obstruction 
of small blood-vessels by the multiplying bacteria, there may be added to 
the symptoms of intoxication local disturbances of circulation. 
The metastasis of bacteria or toxic substances, or both, from a local- 
ized seat of infection, and the production of secondary foci and symptoms 
of intoxication, gives rise to the condition termed sepsis. According to 
the predominant symptoms there may be distinguished septiccemia, 
pycemia and lymphangoitis. Through the combination of both the latter 
with septicaemia, septicopycemia is produced. Originally the designation 
septicaemia was applied to those cases in which localized infection was 
associated with intoxication caused by bacterial poison without the 
spread of bacteria through the body. At the present time, septicaemia is 
used to designate the condition characterized by the entrance of bacteria 
and their poisons into the blood, a coincident toxincemia and bactcricemia; 
indeed, by many authors toxincemia is separated from septiccemia. INFECTION. 
27 
The term pyaemia is employed to designate that condition in which 
the metastasis of pyogenic bacteria gives rise to the formation of meta- 
static abscesses at the point of lodgment. 
In septicopyaemia the symptoms of toxinsemia and bacteriaemia are 
combined with the formation of metastatic foci. Lymphangoitis is an 
inflammation of the lymph-vessels and their surroundings caused by 
transported bacteria. 
Sepsis is most frequently caused by the true pyogenic organisms, 
staphylococcus pyogenes aureus, and streptococcus pyogenes, but similar 
conditions occur in infection with the pneumococcus, typhoid bacillus, 
colon bacillus, plague bacillus, etc. 
If bacteria are deposited secondarily in the body-passages which are 
lined with mucous membrane, as in the respiratory or urogenital tract, 
they may multiply within these tracts and produce their characteristic 
pathological changes. Likewise, they may multiply within the large 
body-cavities, in the peritoneal, pleural, and subarachnoid spaces. In the 
case of infection occurring in a pregnant woman, several varieties of 
bacteria (anthrax, glanders, typhoid, the pyogenic bacteria), may be 
transmitted to the foetus. 
The description above given of the course of an infection may be 
taken as a general type, and many infections run such a course; but 
there are many deviations from this scheme. In the first place, it not 
infrequently happens that in an infection which in general runs a typical 
course, the primary seat is not demonstrable, either because no changes 
occurred at the point of entrance, or because the changes produced have 
since disappeared. Such forms of infection are known as cryptogenic; 
they may be lymphogenous or haematogenous. It is typical of many 
infections that the primary localization of the cause of the disease is not 
recongnizable, so that general symptoms occur before local changes are 
demonstrable, and the tissue-changes occurring later have more the char- 
acter of a secondary localisation of the poison of the disease. This 
occurs in a number of infectious diseases, the causes of which are un- 
known to us; for example, in scarlet fever, smallpox, and measles; yet in 
many infections whose causes are known we are not always able to 
discover at what point the first multiplications of the bacteria occurs. Thus 
we know that in relapsing fever the spirilla are found in the blood in 
large numbers at the time of the fever, but the place of their multipli- 
cation is unknown to us. 
Not infrequently a secondary infection may be joined to one already 
present. In many cases the association is accidental, in other cases the 
anatomical changes produced by the first infection cause a local predis- 
position to the new invasion. To the first group belong, for instance, 
croupous pneumonia occurring in an individual suffering from tubercu- 
losis of the kidney or bones; while infection with cocci causing suppur- 
ation and septic intoxication during the course of typhoid, influenza, 
diphtheria, scarlet fever, dysentery, ulcerating tuberculosis, etc., may be 
regarded as due to the production of local tissue-changes favoring the 
entrance of such bacteria. These secondary infections usually aggra- 
vate the sufferings of the patient in that a new disease is added to the 
one already present; but it may also happen that the microorganisms 
entering secondarily grow only as saprophytes in exudates or in tissues 
killed by the first infection. In certain infections, as, for example, in 28 
THE EXTRINSIC CAUSES OF DISEASE. 
many purulent processes, the tissues may contain, even at an early stage, 
two or more varieties of bacteria—a mixed or double infection. The 
associated bacteria can persist in their association and in common excite 
pathological changes; but they may also become separated from each 
other, so that one microorganism gains a wider distribution than the 
other. 
It has been known for many years that during decomposition poisonous sub- 
stances are formed. As early as 1852 Beck observed that ammonia hydrothionate, 
which occurs in pus, possessed septic properties when injected into animals. Panum, 
in 1863, obtained from decomposing material a putrid poison, that is, a body 
not destroyed by boiling and evaporation, which possessed an action similar to that 
of snake-poison and the vegetable alkaloids and caused in dogs salivation, dilatation 
of the pupils, diarrhoea, fever, and severe prostration. Von Bergmann and 
Schmicdeberg obtained from decomposing yeast a crystalline body, sepsin, which 
in animals produced the symptoms of intoxication. Senator, Hiller, and Mikulicz 
extracted from decaying tissue-masses by means of glycerin a substance which 
likewise possessed a septic action. Billroth called this poisonous substance putre- 
factive zymoid. Selmi endeavored to characterize all these substances more min- 
utely, and obtained from different constituents of cadavers extracts, partly soluble 
in ether, partly in water, which he recognized as fixed bases of alkaloid-like char- 
acter, and which he designated cadaveric alkaloids or ptomains. Gautier, Etard, 
Zuelzer, Sonnenschein, Bechamp, Schmiedeberg, Harnach, v. Nencki, Otto, Angerer, 
and others also found in decomposing tissues similar alkaloids, which in experi- 
ments on animals were partly inert, and partly toxic, producing in the latter case 
symptoms of poisoning similar to those of curare, morphine, and atropine. To von 
Nencki (1876) is due the honor of being the first to obtain a cadaveric alkaloid in 
pure form and to establish its formula; this was accomplished in the case of col- 
lidin, obtained from decomposing glue and albumin, its platinum salt crystallizing 
in flat needles. Following v. Nencki, Etard, Gautier, and Baumann, and especially 
Brieger, studied ptomains, the last named having obtained a large number of them 
in a pure state and determined their physiological action. For instance, Berger 
obtained from fibrin peptone a poison (peptotoxin) which in animals causes 
symptoms of paralysis and ultimately death. From decomposing horse-flesh he 
extracted three substances crystallizing in needles, namely, neuridin, neurin, and 
cholin, the second of which is markedly poisonous, and, like muscarine, causes 
salivation, disturbances of circulation and respiration, contraction of the pupils, 
and clonic convulsions. From fish-flesh he obtained, besides neuridin, other poison- 
ous bodies: ethylendiamin, a substance similar in its action to muscarine, and a 
substance called gadinin. From decomposing glue and cheese he obtained the 
poison neurin, and from decomposed yeast dimethylamin. 
The majority of ptomains are not found in fresh tissues, and it is therefore 
probable that they are derived from the splitting of chemical combinations present 
in the tissues. Thus it is probable that cholin is formed from the splitting of 
lecithin, and by the further decomposition of cholin the poison neurin is formed. 
Cholin and neuridin are, according to Brieger, demonstrable in the fresh human 
brain. 
After the poisonous nature of part of the ptomains had been made known 
through the researches mentioned above, there was developed the hypothesis that 
the toxic symptoms observed in infectious diseases could be entirely, or in a great 
measure, ascribed to the action of the toxic ptomains. Through the investigations 
of recent years (Roux, Yersin, Buchner, Brieger, C. Fraenkel, Pfeiffer, Ehrlich, 
Wassermann, and others) it has been shown that besides the ptomains there occur 
specific bacterial poisons, which are characteristic for the given bacterial species. 
These were first regarded as active albumin bodies and were called toxalbumins. 
Investigations of the poisons formed in diphtheria, tetanus, cholera, typhoid fever, 
pneumonia, and tuberculosis have shown that the so-called toxalbumins are not 
albumin bodies, and have led to the differentiation of different poisonous substances 
as given in the text above. 
The toxins, in the strict sense, may be compared, according to their origin, 
with the enzymes formed by the body cells (pepsin, trypsin, ptyalin) which pro- 
duce hydrolytic splitting. On the other hand, the endotoxins clinging to the cells 
may be compared with the expressed juice of yeast known as zymase (Buchner), 
which is able, in the same way as the living protoplasm of the yeast-cell, to excite INFECTION. 
29 
alcoholic fermentation in fluids containing sugar. Toxins and enzymes are mixed 
with albuminous substances which up to the present time have not been separated 
from them. This explains why they were earlier regarded as albuminous bodies. 
Brieger, who first characterized the toxic substances as toxalbumins, has himself 
prepared toxins that gave no albumin reaction. 
According to the views of Ehrlich, only those substances are poisons that 
possess a chemical affinity for some element of the body and through their union 
with this element cause an injurious action that may be recognized clinically (toxo- 
phorous affinity). A toxin or haptin is, according to him, a poison which possesses 
two specific atomic groups, a haptophore group which permits the union with the 
body cells through the haptophorous group of the latter, and a toxophore group 
which exerts the poisonous action. If in any poison the specific action of the 
toxophore group is lost, while the haptophore group remains, there arise toxoids 
or non-poisonous haptins which may anchor themselves to the body cells but are 
no longer poisons. Finally, there occur also primary bacterial products (in diph- 
theria), the toxons {Ehrlich), that is, poisons which have the same haptophore 
group as toxins but a less active toxophore group. 
Since the intracellular toxins, the endotoxins (typhoid bacilli, cholera spirilla, 
B. pyocyaneus, pus cocci), are stored in the bodies of the bacteria, the bacterial 
cell-substance is the most active. In old cultures the poisons pass into the fluid, 
but they probably no longer represent the primary endotoxin, but a modification. 
Cholera spirilla, typhoid bacilli, and pneumococci form endotoxins, which on 
the death of the 'bacteria are set free, and become active as such, or act in a 
modified form at the same time with the bacterial proteins. 
Anthrax and tubercle bacilli probably form no true toxins, but contain poisons 
of another kind whose action is combined with that of the bacterial proteins. 
The importance and the course of an infection depend, therefore, upon the 
character of the cells possessing receptors for the given toxin. In tetanus it is the 
nerve-cell; in tuberculosis the connective-tissue cell. Diphtheria poison does not 
injure the skin of the mouse, while the one-hundredth or one-thousandth part of 
the same dose will produce tissue-necrosis in the guinea-pig {Ehrlich). 
Aggressins: When bacteria are grown in the pleural or peritoneal cavities, in 
pleural or peritoneal exudates, blood-serum, or even in distilled water, there is 
formed a substance which, when the non-toxic sterilized culture fluid is inoculated 
at the same time with a sublethal dose of the bacteria, neutralizes the protective 
powers of the body and permits the growth of the bacteria. These substances have 
been called aggressins,'and are regarded by some as serving the bacterial organism 
in the same way that opsonins protect the animal body. {Bail: Arch. f. Hyq., 
1905.) 
Literature, 
{Bacterial Infection and Intoxication.) 
Bolduan and Koopman: Immune Sera, John Wiley & Sons, New York, 1917. 
Flexner: The Pathology of Toxalbumins, Baltimore, 1897. 
Vaughan and Novy: The Cellular Toxins, 1902 (Lit.). 
Woodhead: Bacteria and their Products, London, 1891. 
§ 12. The pathogenic moulds (eumycetes) and the budding fungi 
belong, as do the schizomycetes, to the non-chlorophyllaceous thallo- 
phytes. They occur in the human organism in the form of jointed or 
non-jointed and sometimes branching threads or hyphoc, and short oval 
cells, the so-called conidia. The eumycetes may be divided into the 
moulds, the fungus of thrush, and the cutaneous mould-fungi. At times 
they form fructification organs of peculiar structure. The single cells 
are larger than those of the schizomycetes. Outside the body the moulds 
develop as velvety films of different colors, on the surface of many organic 
substances and fluids, from the carbon-compounds and salts of which they 
derive their nourishment. The yeast-fungi are found chiefly in fluids con- 
taining sugar, and are the cause of alcoholic fermentation. 30 
THE EXTRINSIC CAUSES OF DISEASE. 
The spores or conidia, which represent reproductive elements, are for 
the greater part formed in special organs of fructification, but may also 
be developed by a simple process of constriction of the ends of the 
hyphse, and pass into the air from the surface of the mould-film. Like- 
wise, yeast-cells may be carried in the air, in the case of evaporation of a 
fermenting fluid and the conversion of its residue into dust. 
The moulds may, as do the bacteria, produce poisonous substances in 
the nutritive media in which they multiply, usually outside the human 
body, and when these are taken in with the food symptoms of intoxica- 
tion are produced. For example, the chronic disease, known as pellagra, 
which occurs particularly in Italy, Spain, southwestern portions of 
France, Roumania and certain Southern States, is characterized by 
gastro-intestinal disturbances, changes in the skin, spinal and cerebral 
disturbances, and marasmus, is, according to one view, the result of the 
eating of corn which has been spoiled through the growth of certain 
moulds. According to Ceni the active poisonous substances are pro- 
duced in the spores of the fungi. 
As parasitic agents causing disease the moulds and the yeasts cause, 
as a rule, local infections characterized by tissue degeneration and inflam- 
mation. 
The moulds develop in regions accessible from without, in the skin, 
the crypts of the tonsils, the ear, mouth, lungs, etc. They usually occur 
as saprophytes in cerumen, necrotic lung tissue, etc., but may also pene- 
trate living tissue. 
The thrush fungus occurs chiefly in the epithelium of the upper layer 
of the mucosa of the alimentary tract, but often penetrates into the con- 
nective tissue and causes inflammation. Hsematogenous metastasis is 
rare. 
The cutaneous moulds multiply in the epithelium of the skin and 
give rise to such lesions as favus, herpes tonsurans, pityriasis versi- 
color, and erythrasma. 
The yeast fungi develop most frequently in the stomach, particularly 
after the ingestion of fermenting fruit juices. In glycosuria they may 
multiply in the urinary bladder and excite fermentation of its contents. 
Yeast-like budding fungi occur also in a granulomatous and suppurative process 
affecting the skin and internal organs (blastomycetic dermatitis, blastomycosis, sac- 
charomycosis, coccidioidal granuloma, etc.). The majority of the cases have oc- 
curred in America. The parasites involved cannot at present be definitely classified. 
By some writers (Ricketts) they are believed to belong to the genius Oidium 
(oidiomycosis). Blastomycetes are supposed to be the cause of a peculiar suppura- 
tive disease in horses. 
Literature. 
(Infection by Moulds and Yeasts.) 
Bestarelli: Stand der Pellagrafrage. Cent. £. Bakt., xxxiv., 1904. 
Buschka: Ueber Hefenmykosen. Klin. Vortr., No. 18, Leipzig, 1898. 
Busse: Pathogene Hefen und Schimmelpilze. Ergebn. d. allg. Path., v., 1900. 
Ceni u. Besta: Aspergillus fumigatus und flavescens u. d. Bez. z. Pellagra. Cent. 
£. allg. Path., xiii., 1902. 
Lombroso: 'Die Lehre von der Pellagra, Berlin, 1898. 
Ricketts: Oidiomycosis. Journal of Med. Research, 1901. 
Toulerton: Pathogen. Action o£ Blastomycetes. Journ. of Path., vi., 1899. 
Harris, H. F.: Pellagra, The Macmillan Co., 1919. INFECTION BY ANIMAL PARASITES. 
31 
§ 13. The production of disease by animal parasites is most fre- 
quently brought about by the introduction of mature parasites, larvae, 
or eggs into the intestinal tract through the medium of food and drink 
or by unclean fingers. This is particularly true of those parasites whose 
habitat is in the intestine or other tissues within the body; such para- 
sites are designated Entozoa. Parasites living in the outer tissues, as 
the skin, are termed Epizoa; they remain on the surface of the skin or 
penetrate into the deeper structures from without. The animal para- 
sites for the greater part produce local changes, but can also cause symp- 
toms of general disease, particularly when they increase in the body, 
or produce toxic substances. 
Many of the parasitic protozoa are harmless. Other forms, on the 
contrary, penetrate into living tissues, increase within the cells, 
and give rise to morbid changes, characterized by new-formations of 
tissue (coccidia-disease of the rabbit’s liver, epithelioma contagiosum). 
Still other forms which are probably to be classed as Sporozoa, increase 
in the blood, and destroy the red cells. Others (trypanosomata) inhabit 
the blood-plasma. It is not impossible that such infectious diseases as 
small-pox are caused by parasites belonging to the Protozoa. 
The parasitic worms (Nematodes, Cestodes, Trematodes) occur in 
man, partly in the adult and fully developed sexual state, and partly 
in the larval state. Most of the adult worms are intestinal parasites, 
and obtain nourishment from the intestinal contents, rarely sucking the 
blood from the mucosa. Fully developed worms, however, are found 
in other reigions, as in the blood- and lymph-vessels, bile passages, lung, 
pelvis of the kidney, and in the skin. The eggs or fully developed 
larvae produced in the body by parasitic worms are either cast out with 
the dejecta or, by wandering through the blood or lymph, reach other 
organs, where they pass the first stage of their development. Here 
they remain, however, in a larval condition, and do not reach sexual ma- 
turity. The larvae are capable of further development only when they 
have been taken into a new host, or have been again eaten by the same 
host. 
Those worms which reach sexual maturity in the human body are 
taken in as larvae through the food and drink. Their first stage of de- 
velopment is passed in the majority of cases in animals whose flesh 
is used for food; in other cases in certain lower animals not used as 
food. Others develop in water or damp earth or even in the human 
intestine, so that the embryos or eggs, which pass off with the dejecta, 
develop at once if they are again introduced into the intestinal tract of 
man. 
Worms which occur in man in the larval condition only (hydatids) 
develop from eggs which have come from sexually mature worms, in- 
habiting different animals. They are taken into the intestinal tract usu- 
ally in the food or drink, but under special conditions eggs capable of 
development may be contained in the dust of the air, and, being inhaled 
and finally reaching the intestinal tract, complete the first stage of de- 
velopment. 
The intestinal parasites in most instances produce only slight me- 
chanical irritation of the intestine. The presence of blood-sucking 
worms, on the other hand (notably Anchylostoma duodenale and Un- 32 
THE EXTRINSIC CAUSES OF DISEASE. 
cinaria), are frequently productive of extremely severe anemia by the 
mechanical withdrawal of small quantities of blood for a prolonged 
period. Still other intestinal parasites manufacture poisons which are 
absorbed by the host. Thus Schaumann and others have demonstrated 
haemolytic substances in the segments of Bothriocephalus latus, whose 
presence in the human body is sometimes associated with anemia of 
the pernicious type. 
Those parasites which enter the tissues may cause in the vicinity 
mild inflammation and proliferation, producing marked clinical symp- 
toms when the number of the parasites (trichina larvcr) is great. 
Others are of pathological importance, in that they reach large size 
(echinococcus cysts) and compress the neighboring structures. A para- 
site situated in the muscles or subcutaneous tissue may cause slight 
symptoms, while one in the eye, medulla oblongata, heart, or blood-ves- 
sels may cause severe disturbances, and under certain conditions death. 
The parasitic arthropoda (Arachnida and Insects) come to the 
human body from the outer world, and from infected animals and 
human beings. They belong almost wholly to the Epizoa, which have 
their habitat in and on the skin and accessible mucous membranes (lice, 
bedbugs, fleas, mites) or occasionally take their nourishment from the 
skin (gnats, gad-flies, flies) ; a few multiply in the skin (itch-mite) or on 
its surface (lice). Flies and gad-flies occasionally lay their eggs on the 
mucous membranes or in wounds, and from the eggs so laid larvae 
develop. The larva of an arachnoid (Pentastoma denticulatum) is alone 
found in the internal organs. When these parasites penetrate into the 
tissues, they cause irritation and inflammation; the bite of insects that 
suck blood is also followed by inflammation in the neighborhood of the 
puncture. 
Attention has been directed to the fact that mosquitoes, stinging flies, 
gad-flies, bed-bugs, lice, etc., may be the conveyers of infection, in that 
bacteria or protozoa may be attached to their bodies, or that in the act of 
sucking blood of an infected man or animal they may take into their 
bodies bacteria or protozoa and convey them to other individuals. So far 
as experience goes, the danger of such conveyal is not great in the ma- 
jority of the infectious diseases, since the bacteria thus taken up die after 
a time. This method of conveyal is of great importance, however, in 
malaria, in that the plasmodia taken from the blood of infected individ- 
uals by mosquitoes (anopheles) undergo development in the body of the 
mosquito and produce a nezv generation, which through the bite of the 
mosquito is transferred to another individual. Similar conditions exist in 
the case of the tsetse-fly disease and Texas fever of cattle, the latter being 
conveyed by ticks. Further, it is claimed by Manson, Sonsino, and others 
that the infection of man with filaria is also brought about through the 
agency of mosquitoes. 
Of the parasitic protozoa there should be mentioned also the Amccba dysentericv, 
the cause of one form of dysentery in man; the Trypanosoma evansi, the cause of 
surra; Tr. brucei, the cause of the tsetse-fly disease or nagana; Tr. gambiense the 
etiological agent in human trypanosomiasis or sleeping-sickness; and the Tricho- 
monas as a probable causal agent in catarrhal conditions of intestine or genito- 
urinary tract. Supposed protozoan parasites have also been described as the causal 
factors of smallpox, scarlatina, tumors, etc., but convincing proofs are not at hand. IMMUNITY, PREDISPOSITION, IDIOSYNCRASY. 
33 
Literature. 
(Origin of Disease through Animal Parasites.) 
Blanchard: Parasites animaux. Path, gen., ii., Paris, 1896. 
Braun: Die thierischen Parasiten des Menschen, Wurzburg, 1893. 
Celli: Die Malaria, Berlin, 1900. 
Grassi: Die Malaria, Jena, 1901. 
Howard: Mosquitoes, New York, 1901. 
Huber: Bibliographic der klin. Helminthologie, Miinchen, 1891-1895. 
Laveran: Du paludisme et de son hematozoaire, Paris, 1904. 
Laveran et Mesnil: Trypanosomes et Trypanosomiasis, Paris, 1904. 
Leuckhart: Die therischen Parasiten des Menschen, 2 Aufl., 1879-1897. 
Liihe: Ergebnisse der neuren Sporozoenforchung. Cent. f. Bakt., xxvii. and 
xxviii., 1900. 
Nuttal: Die Mosquito-Malariatheorie. C. f. Bakt., xxv. and xxvi., 1899; die 
Rolle der Insecten, Arachnoiden u. Myriapoden als Trager bei der Ver- 
breitung von durch Bakterien u. thier. Parasiten verursachten Krankheiten. 
Hygien. Rundschau, ix., 1899, ref. Cent. f. Bakt., xxvi., 1899. 
Schneidemiihl: Die Protozoen als Krankheitserreger, Leipzig, 1898. 
II. Congenital and Inheritable Foundations for Disease. 
1. Immunity, Predisposition, and Idiosyncrasy. 
§ 14. Toward the injurious agents capable of producing disease 
different individuals show different powers of resistance. Such differ- 
ences are exhibited particularly in the case of the infections and poisons. 
When an individual is not susceptible to a given infection or poison, 
the property thus manifested is designated immunity and insuscepti- 
bility; but if an individual is easily infected by a pathogenic micro- 
organism, we assume that he possesses a predisposition to the disease 
caused by the microorganism in question. Hypersusceptibility to influ- 
ences having no effect on ordinary individuals is designated idiosyncrasy, 
and has particular reference to poisons, pollens, etc. 
Immunity and predisposition represent the opposite behavior of an 
organism to external injurious agents, but they cannot be sharply sep- 
arated from each other. In many cases immunity is not absolute but 
relative, so that an individual may be made ill through a given agent, 
for example, a pathogenic microorganism or poison, when the agent acts 
in its characteristic manner and strength. On the other hand predis- 
position may be so slight that disease arises only in extraordinary cir- 
cumstances. 
An absolute immunity or insusceptibility is possessed by man against 
many of the microorganisms pathogenic for animals, for example, 
against the bacteria of swine plague, swine erysipelas, and symptomatic 
anthrax. This may rest on the fact that the character of his tissue and tis- 
sue juices does not permit localization and multiplication of the causative 
bacteria, or that the poisons produced by the latter are not toxic for man. 
The human race is highly susceptible to smallpox, measles, and in- 
fluenza, so that many individuals acquire these diseases. In the case of 
scarlet fever, typhoid fever, diphtheria, the susceptibility seems less, but 
it is not possible to determine to what extent individuals who escape are 
not exposed to infection. 34 
THE INTRINSIC CAUSES OF DISEASE. 
In many infectious diseases greater susceptibility is shown in child- 
hood than in old age; for example, in diphtheria, whooping-cough, and 
scarlet fever. There are also variations in the degree of susceptibility 
at different times; for example, an individual may be exposed to measles 
without becoming infected, while at other times under apparently similar 
conditions he contracts the disease. 
In the case of many pathogenic organisms there appears to be neces- 
sary for the occurrence of infection a certain favoring condition or tem- 
porary increase of susceptibility. As evidence of this is the fact that in 
the human alimentary canal, especially in the mouth and throat, as well 
as in the respiratory tract, pathogenic organisms (streptococci, staphy- 
lococci, pneumococci), may be present without any indications of in- 
fection. It may also happen that cholera spirilla increase abundantly 
in the intestine without symptoms. 
Such occurrences may be explained by decrease or loss of virulence 
on the part of the bacteria, but this cannot be applied to all cases. In 
many instances it must be assumed that the harmlessness of the bacteria 
is due to the ability of the tissues to hinder their entrance into and their 
action on the deeper parts. In some cases this may depend on the 
structure and organization of the tissue, in other cases chemical sub- 
stances have a determining influence (see § 29). In favor of the first 
assumption is the fact that tissue-lesions permit the entrance of bacteria, 
and promote infection. A wound, therefore, in whatever way produced, 
forms a local predisposition, and the disease, in such cases, bears the 
character of a wound infection. Infections caused by pus-cocci, tetanus 
bacilli, glanders, and anthrax bacilli are of this character. 
Other causes leading to increased predisposition to infection are less 
easily recognized. It appears that severe chilling, “taking of coldf’ or 
hunger may have this efifect; also changes in tissues due to preceding 
infectious or noil-infectious local or general diseases (see § 11, Sec- 
ondary Infections). In the case of intestinal infections (typhoid, chol- 
era), gastro-intestinal disturbances, play a role. Not infrequently it is 
impossible to determine what causes have favored the production of an 
infection at a given time. 
Predisposition or lessened resistance is not infrequently shown to 
injurious agents other than those of infectious nature. Certain indi- 
viduals are less able than others to withstand high temperatures, particu- 
larly if at the same time bodily labor is performed. Of soldiers on the 
march only a fraction may suffer from heat-stroke, although all are 
under the same conditions. The altitude at which different individuals 
become sensitive to the deficiency of oxygen, varies greatly. The effects 
of chloroform anaesthesia differ in different individuals. Many persons 
become exhausted through physical or mental labor at a time when in 
other individuals, under like conditions, no trace of exhaustion is dis- 
coverable ; such influences operating daily in cases of special predispo- 
sition, may lead to disease. 
Occasionally individuals show a degree of sensitiveness to external 
influences, which is anomalous to that usually observed, so that symptoms 
of disease arise which ordinarily would not affect the majority of man- 
kind. Such sensitiveness is designated idiosyncrasy. It is exhibited 
particularly to certain chemical substances, in that articles of food or 
drink regarded as harmless act on such persons as poisons—eating of 
fresh fruit or sugar or salad produces nausea and vomiting. Others have IDIOSYNCRASY. 
35 
an aversion to dishes prepared from liver or kidneys, and become ill if 
they overcome this aversion and eat these foods. Still others, after eat- 
ing lobster, strawberries, raspberries, morels, or asparagus, are affected 
with urticaria, a symptom characterized by an eruption of itching wheals. 
Certain persons are unable to drink boiled milk without unpleasant re- 
sults. Alcohol, even in small doses, may cause marked excitation, or 
narcosis, or remarkable disturbances of the vaso-motor system. Doses 
of morphine or chloroform, which are borne by the majority without in- 
jury, may cause in certain individuals severe symptoms or even death. 
Some individuals show a high degree of sensitiveness, on the part of the 
mucous membranes of the respiratory tract, to the pollen of certain 
grasses, so that during the hay-harvest the inhalation of pollen gives rise 
to a catarrhal condition of the nose and conjunctiva, often of the 
larynx, trachea, and bronchi, which in severe cases may be associated 
with asthma and fever. These conditions are known as hay-fever, hay- 
asthma, or as pollen-diseases. According to the investigations of Dun- 
bar, pollen contains a substance that may be extracted, and which, when 
injected subcutaneously into those disposed to this disease, causes symp- 
toms of intoxication. Disinfecting fluids, such as corrosive sublimate or 
carbolic acid, in solutions which are ordinarily borne without discom- 
fort, may, when applied to the skin of certain individuals, cause not 
only local disturbances of sensation, but may excite dermatitis of wide- 
spread proportions. 
The importance of natural predisposition and immunity in the origin of in- 
fectious diseases has not only been made evident by the study of epidemics among 
men and animals, but has received confirmation by experimental investigation. If, 
for example, a mixture of bacteria be injected into an animal, only a part of these 
develop and produce tissue-changes; the others die. If the same mixture be in- 
jected into an animal of different species, the bacteria which develop are not the 
same as those in the first case. Further, bacteria which, when inoculated into a 
certain species of mouse, invariably cause death, may, when inoculated into a 
mouse of different species, be without effect. Mice are susceptible to anthrax, rats 
are nearly immune. The poison of the so-called septicaemia of rabbits kills rabbits 
and mice; guinea-pigs and rats are immune to it, while sparrows and pigeons are 
susceptible. The spirilla of relapsing fever may be successfully inoculated only into 
apes. Gonorrhoea, syphilis, and leprosy cannot be successfully inoculated into any 
of the lower animals with the exception of apes. 
In the case of natural antitoxic immunity the toxins that enter the organism 
remain as perfectly harmless material in the body, and only relatively late are 
split in the process of metabolism. In such cases the avidity between the toxin 
and the body cells, their receptors respectively, may be wanting or slight. When 
not entirely wanting, an increase of the dose may produce intoxication. Immunity 
against small doses may arise through anchoring of the poison (for example, 
tetanus poison) to tissue elements changes in which do not produce symptoms of 
disease; or antitoxins may be present which render the toxins inert. 
Nurslings and older children are more susceptible to certain infections than 
adults; particularly in the case of whooping-cough, diphtheria, measles, scarlet 
fever and tuberculosis. In the intestine of nursing infants, bacilli, tubercle bacilli in 
particular, are easily taken into the lymph-vessels; the skin of infants offers less 
resistance to the entrance of pus-cocci than that of older individuals. Young 
dogs may be infected with anthrax while old ones cannot. In this connection it 
should be noted that the slight susceptibility or the immunity of many adults is 
conferred by attacks of such diseases during childhood. 
In later life, haemorrhage into and softening of the brain, cardiac degenerations, 
cancerous growths, and the formation of gall-stones are of frequent occurrence. 
The predisposition in old age to certain diseases depends in part on degenerative 
processes, associated with premature senility of the tissues; in part on the fact that 
certain influences, which the years bring with them, gradually accumulate, so that 36 
THE INTRINSIC CAUSES OF DISEASE. 
finally the changes which they produce become so prominent that they lead to func- 
tional disturbances and recognizable morbid conditions. Moreover, it is to be re- 
marked that many symptoms occurring in old age are those of secondary diseases, 
which become apparent after other tissue-changes have reached a certain degree. 
For example, senile haemorrhages, senile gangrene, degenerations of the brain and 
heart are dependent on disease-processes occurring in the arteries. 
The predisposition of the sexes to certain diseases depends, in the first place, on 
the structure and function of the sexual apparatus. Pregnancy and the puerperium 
offer a favorable field for many diseases, for example, infection. 
Differences of predisposition of different races are shown particularly in regard 
to malaria and dysentery, toward which the negro in general shows less suscepti- 
bility than the European. Malarial parasites may be present in the blood of the 
former without giving rise to symptoms of disease. 
2. Inheritable Diseases Based on Congenital Defects. 
§ 15. Among the morbid conditions arising from congenital defects 
and which appear spontaneously or are developed through external in- 
fluences, there may be distinguished several groups; one in which the 
body as a whole is involved; another in which only part of the body is 
affected; and a third in which only a part of an organ presents changes 
of a pathological nature. There is no sharp dividing line between these 
groups. It is often impossible to determine what part congenital defects 
and what part extrinsic causes have taken in the production of such 
pathological conditions. 
Among the constitutional conditions arising from intrinsic causes 
are to be mentioned the development of dwarfs and giants. The first is 
marked by under-development of all parts of the body, both the skeleton 
and soft tissues, while the second is characterized by growth exceeding 
that of the ordinary individual. It cannot be doubted that both dwarfism 
and giantism are dependent on congenital defects in the fetal architecture, 
but it cannot always be told to what extent such abnormalities in bodily 
growth are traceable to foundational faults or to pathological influences 
exerted during the period of development, such, for example, as dis- 
ease of the thyroid gland, or of the pituitary. 
Another constitutional peculiarity is corpulence (obesity, adipositas, 
lipomatosis universalis), in which fat is deposited in excessive amount 
either in tissues normally containing fat, or in regions which normally 
contain none, for example, beneath the endocardium or between the 
muscles. The increased deposit of fat is to be referred to disproportion 
between the production or supply of fat, and its consumption, patholog- 
ical increase being at one time dependent on abnormal fat-production, 
at another on decreased consumption. Experience teaches that the 
energy with which metabolism goes on in the body varies at different 
periods of life, so that the normal amount of nourishment tends at one 
time to fatten, while at another time it does not. 
In the pathological condition termed obesity, which in part at least 
is attributable to a congenital tendency, the energy of destructive meta- 
morphosis is so altered that an abnormal amount of fat is deposited, even 
when a moderate or decreased amount is supplied. 
Gout, like obesity, is a constitutional disease, which is partly depend- 
ent on congenital peculiarities, and at the same time is favored by in- 
trinsic causes. The exact nature of the disease is not known. Accord- 
ing to Garrod and Ebstein, the acute attacks of gout are caused by an 
accumulation of uric acid. On the other hand Pfeiffer holds that the 
essential feature of gout consists in the fact that the uric acid is pro- INTRINSIC CAUSES OF DISEASE. 
37 
duced in a form which is soluble only with difficulty. According to von 
Noorden, the formation and deposit of uric acid is a secondary process, 
induced by the presence of a ferment having a local action, and is con- 
sequently not dependent on the amount of uric acid formed in other parts 
of the body. 
Pathological changes arising in single systems and organs on a 
congenital basis, may occur in any part of the body, and may involve an 
entire system or organ, or only part of one. 
In the skeleton there may occur abnormal development of single 
parts, as, for example, smallness of the extremities (micromelia) or of 
the head (microcephalus) in contrast to the size of the trunk; over- 
development of a bone or group of bones (macrocephalus, macrodactyl- 
ism, giant growth of a finger, entire foot, or of an extremity) ; malforma- 
tions of the extremities (cleft-hand, cleft-foot, etc.). Occasionally 
supernumerary bones, as carpal bones or phalanges, may develop, or 
atypical formations, such as bony outgrowths (exostoses, hyperostoses), 
which may extend over the skeleton to a greater or less extent, originat- 
ing either spontaneously or following traumatism. 
In the muscular system pathological bony formations are sometimes 
seen, notably in the condition known as myositis ossificans, which is apt 
to lead to progressive stiffness through the transformation of muscles 
into bony plates. 
In the vascular system there occur either gross anatomical changes, 
such as abnormal branching of the arteries or mal-development of the 
heart; or finer changes, which reveal themselves through haemorrhages 
(hemophilia) the severity of which is out of all proportion to the in- 
jury, e. g., in such subjects the withdrawal of a tooth may be followed 
by long and almost uncontrollable loss of blood. 
During the development of the central nervous system changes may 
occur which manifest themselves as disturbance of function or as a special 
predisposition to disease. Others are distinguished by gross anatomical 
changes, such as abnormal smallness of the brain (micrencephalon) or of 
the spinal cord (micromyelia), defective development or absence of par- 
ticular parts (see chapter on malformations), misplacement of the gray 
matter (heterotopia), abnormal formation of cavities (syringomyelia), 
or abnormal formations of neuroglia. These may involve the functions 
of the sensory organs and the motor centres, and even the psychical 
processes. 
Such conditions as idiocy and epilepsy have their origin in congenital 
predisposition. The tendency to crime has been ascribed to congenital 
predisposition, and Lombroso, in particular, has endeavored to prove 
that the man who lives through and for crime, the Homo delinquens, is 
a congenital criminal — that is, a man who possesses other physical and 
psychical characters than the normal in that he presents well defined 
stigmata of degeneration. According to Lombroso, subnormal develop- 
ment of the anterior half of the cranium, associated with corresponding 
lack of development of the anterior portion of the cerebrum, in connec- 
tion with over-development of the posterior portion, produces feebler 
development of intelligence and of the moral sense, and favors the in- 
stinct-life. Benedikt goes so far as to maintain that the criminal pos- 
sesses a peculiar configuration of the cerebral convolutions, similar in 
type to those of beasts of prey. 38 
THE INTRINSIC CAUSES OF DISEASE. 
The views of Lombroso and Benedikt have met with much opposition. 
There can be no doubt that there does exist a degenerate species of the 
human race, which is characterized by such anatomical peculiarities as 
make it possible to distinguish a class of Homo delinquens from that of 
Homo sapiens. All the somatic peculiarities regarded as characteristic 
of the criminal, for example, the beast-of-prey type of cerebral convolu- 
tions, slightly developed frontal brain, receding forehead, massiveness of 
the lower jaw, asymmetry of the cranium, marked prominence of the 
arcus superficialis and arcus frontalis, pathological conformations of the 
skull, etc.— while relatively frequent in criminals, are far from infre- 
quent in others. On the other hand, it is not to be doubted that the 
tendency to crime is frequently dependent on a congenital predisposition 
having its seat in some irregularity in the organization of the central 
nervous system. In this respect the criminal resembles the insane in- 
dividual. 
Pathological cerebral functions may develop in individuals of morbid 
predisposition without the occurrence of external injury, either during 
the period of development and growth or later. On the other hand such 
influences as over-work, sorrow, care, contribute to mental illness. In 
these cases the inherited tendency consists in a predisposition to mental 
disease so that influences which would produce no recognizable effects 
in a normal individual are sufficient to excite morbid phenomena. Since 
many influences, as diseases and infection, are adequate under certain 
conditions to produce mental disturbances in individuals who must be 
regarded as normal, it is difficult and often impossible to determine what 
part intrinsic and what part extrinsic causes have had. 
Among the congenital pathological conditions of the visual appa- 
ratus are dyschromatopsia and achromatopsia, congenital partial or total 
color-blindness, which are frequently spoken of as Daltonism, and are 
characterized by want of perception for certain colors (most frequently 
red and green) or for all the colors. In this category belongs a variety of 
degeneration of the retina, in which there occurs a peculiar spotted, 
black pigmentation, associated with diminution of central vision and 
light-perception, with narrowing of the visual field. Finally, certain 
forms of myopia and albinism (absence of pigment in the choroid), are 
to be considered in this connection. 
Of intrinsic conditions of the auditory apparatus deaf-mutism is of 
chief importance; this condition, in part at least, is dependent on dis- 
turbances of development. Further, certain malformations of the ex- 
ternal ear fall into this class. 
In the skin and subcutaneous connective tissue new-growths may 
develop on a congenital basis in the form of proliferations of connective 
tissue, at other times of epithelium. They often involve particular parts 
of the skin, as the nerves, blood-vessels, lymph-vessels, or the adipose 
tissue. When occurring as extensive thickenings of the skin and sub- 
cutaneous tissue, they constitute the foundations of the conditions known 
as fibromatous, neuromatous, haemangiomatous, lymphangiomatous, and 
lipomatous elephantiasis. As circumscribed growths they are known as 
birth-marks, fleshy moles, lentigines, and freckles. The epithelial hyper- 
trophies give rise to those conditions designated fish-scale disease or 
ichthyosis, ichthyotic warts, and cutaneous horns. INHERITANCE OF DISEASE. 
39 
In addition to the pathological conditions which have been mentioned, 
there are malformations of the body (see chapter on malformations) 
or of internal organs which must be regarded as primary — i.e., which 
are not produced by injurious influences exerted on the developing foetus. 
Finally, many forms of tumors (see chapter on tumors) are to be placed 
in this class, particularly those which are found at birth or which develop 
during childhood. 
§ 16. The origin of diseases in which extrinsic influences are either 
entirely absent during both intra- and extra-uterine life, or are of signifi- 
cance only as a source of irritation sufficient to excite into development 
pathological tendencies which are already present in the body — may be 
explained in two ways: Either the pathological peculiarities of the indi- 
vidual concerned are inherited from the ancestors, or they are developed 
from the seed, i.e., from the individual sexual nuclei that have copulated 
or from the segmentation nucleus resulting from their union. 
The inheritance of pathological qualities is clearly shown by clinical 
observations, inasmuch as many of the diseases due to intrinsic causes 
which are cited in § 15 also appear as inheritable characteristics in certain 
families. In some cases these characteristics are transmitted from the 
parents to the children, in other cases the grandchild may exhibit patho- 
logical peculiarities of the grandparents, the parents themselves remaining 
exempt; in other cases the pathological peculiarity may be manifested in 
the collateral branches, as from uncle to nephew. Dwarfishness and 
giantism are pathological peculiarities which frequently characterize cer- 
tain families. Six fingers, cleft-hand and cleft-foot, hare-lip, dextro- 
cardia, birth-marks, multiple exostoses, fibromatosis of the nerves, and 
multiple neurofibromata may appear in families for successive genera- 
tions. 
Haemophilia is an inheritable condition. It is ordinarily transmitted 
through the daughter to a male grandchild, the daughter not showing the 
disease. There may occur, however, direct transmission of haemophilia 
from parents to children. Partial or total color-blindness also occurs as 
a family disease, especially affecting the male members, and like haemo- 
philia is transmitted through the female line, which does not suffer, to 
the male descendants. The typical pigment-degeneration of the retina, 
myopia, deaf-mutism, certain forms of progressive muscular atrophy, and 
polyuria (Weyl) are also inheritable. 
According to Gairdner and Garrod, in about ninety per cent of all 
cases of gout there is a family history of the disease. 
Of the pathological conditions of the nervous system many are in- 
heritable ; to these belong periodic and circular insanity, epilepsy, hysteria, 
and to a somewhat less extent melancholia, mania, and alcoholism. Pro- 
gressive paralysis, the deliriums, and conditions of nervous exhaustion 
are but slightly influenced by heredity (Kraepelin). Plagen estimates 
the number of hereditary insane at 28.9 per cent, Liedesdorf at 25 per 
cent, Tigges at over 40 per cent of all cases, while Forel holds that 69-85 
per cent have hereditary taint. 
In the more severe forms of transmissible degeneration the patholog- 
ical condition itself is inherited. More frequently the predisposition is 
alone inherited and the morbid condition itself is developed later through 
the action of extrinsic influences on the central nervous system. The 
character of the disease in the descendants may be the same as in the 40 
THE INTRINSIC CAUSES OF DISEASE. 
ancestors (identical heredity). More often the character of the disease 
is changed (transformational heredity), not infrequently in the sense 
that the severity of the condition increases from generation to generation 
(degenerative heredity). 
According to Morel, there may appear, for example, in the first gen- 
eration, nervous temperament, moral depravity, excesses; in the second, 
a tendency to apoplexy, severe neuroses, alcoholism; in the third, psychi- 
cal disturbances, suicidal tendency, intellectual incapacity; in the fourth, 
idiocy, malformations, and arrests of development. 
The occurrence of inheritable diseases is comparable to the well- 
known fact that in a family not only the peculiarities of race, but also 
of that particular family are inherited, and that often the qualities of 
either parent or of both recur in the children. As a hypothesis for the 
explanation of heredity, it is only necessary to assume that the peculiar 
quality under consideration represents not merely a somatic change 
accidentally acquired during the life of the ancestor, but rather a quality 
of the ancestor developed on a congenital basis. Diseases which in a 
normal individual arise only under the influence of some external in- 
jurious agency are never in a true sense inherited (compare § 17), but 
only those pathological conditions existing in the germ are to be regarded 
as examples of true inheritance. If a certain disease, as, for example, 
mental disease or myopia, is the product of a special inherited predisposi- 
tion plus the effect of injurious influences which have acted on the body 
during life, only that part can be transmitted which has its seat in some 
peculiar congenital arrangement, but not that caused by external in- 
fluences —• the acquired condition cannot be inherited. 
In direct inheritance — i.e., in that form of inheritance in which 
parental qualities are transmitted to the child — the transmission of nor- 
mal as well as of pathological qualities is possible only when both sexual 
cells, in the condition in which they combine, contain the potential char- 
acteristics of both parents, in so far as these are transmissible. The 
product of the union of the sexual cells — the segmentation-cell — must, 
therefore, contain within itself both the paternal and maternal qualities. 
Since the sexual cells do not represent a product of the body developing 
during the course of life, but are rather to be regarded as independent 
structures, which at an early period of development are separated from 
the other parts of the body (that is, from the somatic cells) into special 
organs, where, protected and nourished by the body to which they belong, 
they lead an independent existence; the only possible explanation for the 
phenomenon of inheritance is found in the hypothesis that the idividual 
sexual cells contain, from the time of their origin onward, the poten- 
tialities which appear in the body in which they dwell. Both the sexual 
cells and the body itself, therefore, inherit in general the same qualities 
from the ancestors. Since in the act of frutification only the nuclei of the 
sexual cells — that is, parts of the same — come to copulation, we are 
compelled to assume that the nuclei are the bearers of inheritable quali- 
ties, and the peculiarities of the individual arising from the combination 
of sexual nuclei have their foundation in the organization of the nuclei. 
The appearance in the descendants of normal or pathological char- 
acters belonging to the collateral relatives (uncle, great-aunt, or cousin), 
but which are not present in the parents, is known as collateral inheri- 
tance. This phenomenon is explained by the hypothesis that the sexual 
cells, in their origin, received characteristics which the bodies of the INHERITANCE OF DISEASE. 
41 
parents did not receive, or which, at least, did not undergo development 
or were submerged in the parental bodies, whereas in certain relatives 
they did develop and become manifest. 
The appearance in an individual of normal or pathological character- 
istics which were wanting in the parents, but were present in the grand- 
parents or great-grandparents, is known as atavistic inheritance. This 
phenomenon is explained by the hypothesis that given characteristics of 
the grandparents or great-grandparents were transmitted to the sexual 
cells of the son, or of the son and grandson, without developing in the 
body of the first, while the quality thus remaining latent was re-awakened 
in the grandson or great-grandson. 
The attempt has been made to give to the atavistic mode of transmis- 
sion — which is of frequent occurrence and is usually confined to the 
immediate generations of ancestors — a wider significance in pathology. 
Thus it has been proposed to explain the occurrence of many newly aris- 
ing pathological conditions, which appear similar to certain somatic 
qualities possessed by remote animal species in the ancestry of man, as a 
reversion to the type of these ancestors. For example, microcephalus 
and micrencephalus have been explained as a reversion to the ape type; 
and Lombroso is inclined to regard the homo delinquens as an atavistic 
phenomenon. There can be no doubt that certain writers have gone too 
far in this respect and have mistaken certain acquired pathological for- 
mations or new germ-variations (compare § 17) for atavistic conditions. 
Aside from the question of reversion to the type of the nearest genera- 
tions of ancestors, atavism plays but an insignificant part in pathology, 
and it can really be employed only in the explanation of pathological 
formations in which the tissues show a certain fluctuation of behavior, 
so that not rarely formations arise which in phylogeny or ontogeny rep- 
resent stages of the then normal conditions. In this category belong, for 
example, the occurrence of certain forms of the ear, supernumerary ribs, 
nipples, or mammary glands, and the development of certain muscles 
which are found in the closely related mammals. 
It is held by many writers that in individual cases, acquired pathological conditions 
may, under certain circumstances, be transmitted to the descendants. Some even 
affirm hereditary transmission of deformities caused by injury. In support of their 
view they refer to the hereditary transmission of birth-marks, malformations of 
the fingers, myopia, mental diseases, predisposition to tuberculosis, etc., as examples 
which appeared in the first instance as acquired, and were then transmitted to the 
descendants. Further, they hold that they can point to observations on animals as 
giving evidence that injuries may cause deformities which are later transmitted to 
the offspring. 
An unprejudiced examination, however, of the material collected in support of 
this view shows that the hereditary transmission of acquired pathological character- 
istics does not occur. The alleged proofs are found in part to be based on inac- 
curate observations, in part on incorrect inferences drawn from accurate observa- 
tions. For example, the assumption that the occurrence of a birth-mark in a child 
in the same region of the skin as that in which the mother has a scar is proof of 
inherited deformity is wrong, inasmuch as birthmarks and scars represent two 
entirely different pathological processes. If, among the descendants of a man who 
suffered from some form of mental disease and who showed this disease only after 
a certain age, there appears an inheritable disease of the central nervous system, or 
if we note a similar occurrence in the case of myopia, we cannot conclude from such 
observations that the disease of the ancestor was an acquired condition. The term 
acquired, in the biological sense, can be applied only to that which in the course 
of the life of an individual arises exclusively from extrinsic influences, but not to 
a quality, the basis of which existed in the germ-cell, although this quality did not 
become manifest until excited by extrinsic influences. Should there appear in a 42 
THE INTRINSIC CAUSES OF DISEASE. 
family inheritable mental diseases or hereditary myopia, the first case of such 
diseases may have been due to some pathological alteration of the germ, although 
no manifestations of the disease occurred until some of the outside influences of 
life excited it to activity, and so rendered possible the recognition of the pathologi- 
cal condition. The pathological condition in this case cannot, therefore, be re- 
garded as acquired. 
As opposed to the theory of the inheritance of acquired pathological condi- 
tions is the consideration that the human race, which is exposed to so many in- 
jurious influences, and whose individual members suffer so frequently from disease 
and mutilations, would soon deteriorate and eventually perish were only a small 
part of the acquired diseases transmitted to descendants. Further, the reproduction 
of man and animal forms through germinal cells is in itself an argument against 
the transmission of qualities accidentally or incidentally acquired by the individual. 
Darwin represented the view that acquired characteristics could be transmitted 
to the descendants, and endeavored to make it intelligible on the theory that mole- 
cules from all the cells of the body contribute to the formation of the germ-cells, 
and that, consequently, alterations of the organism can be transmitted to the germ- 
cell. Nevertheless, there occur in the writings of Darwin statements which not 
only do not agree with this opinion, but contradict it. 
The act of fructification—that is, the first step leading to the production of a 
new individual—is accomplished by copulation of the sexual nuclei—that is, of the 
nuclei of the ovum and spermatozoon. According to the researches of the last 
decades, there can be no doubt that these nuclei are the hearers of the hereditary 
characteristics of the parents, and that the individuality of the copulating nuclei is 
inherent in the organization of the same. It is impossible to conceive in what man- 
ner processes taking place in the body cells can produce in the sexual nuclei, which 
lie within special cells in the sexual glands, such alterations of organization that 
they shall contain in potential form the acquired characteristics of the body and 
transmit them, after copulation has occurred, to the descendants. 
At the present time the views with regard to the inheritance of disease generally 
accepted are that there is no true inheritance of infections and that gross struc- 
tural disturbances cannot be inherited. The only possible inheritance of conditions 
acquired by the parents is that of conditions acting both on the somatic tissues and 
germ-cells of the parents. Chemical and physical conditions acting within the body 
or from without may cause changes in the constitution of somatic and germ-cells. 
The occurrence of such changes in the germ-cells is clearly shown in the effects on 
the progeny of paternal or maternal alcholism, plumbism, and experimentally with 
abrin. It is a well-known fact that in the production of monsters there is often 
obtainable a history of some infection in one of the parents before conception took 
place. Bardeen’s experiments regarding the changes in embryos arising from ova 
fertilized by spermatozoa that had been injured by Roentgen irradiation are very 
suggestive. 
Recently much discussion has been waged over the principles of heredity in- 
volved in Mendel’s law, Galton’s law, and De Vries’ theory of mutations (see 
literature). 
Literature. 
{Inheritance of Pathological Conditions.) 
Bateson: Mendel’s Principles of Heredity, London, 1902. 
Bulloch, Hemophila, Albutt and Rolleston’s System of Medicine. 
Darwin, C. H.: Die Ehe zwischen Geschwisterkindern und ihre Folgen, Leip- 
zig, 1876. 
Galton: Natural Inheritance, London, 1889; Proc. Roy. Soc., 1897. 
Israel: Angeb. Spalten der Ohrlappchen. Virch. Arch., 119 Bd., 1890. 
Mayer: Spalthand u. Spaltfuss (durch 4 Generat. vererbt.). Beitr. v. Ziegler, 
xiii., 1898. 
Pearson: Law of Ancestral Heredity. Proc. Roy. Soc., 1898; Law of Re- 
version. Ibid., 1900. 
De Vries: Die Mutationstheorie, Jena, 1901. 
Ziegler: Konnen erworbene pathologische Eigenschaften verebt werden u. wie 
entstehen erbliche Krankheiten u. Missbildungen? Beitr. v. Ziegler, i., 
1886; Die neuesten Arbeiten uber Vererbungs- u. Abstammungslehre u. 
ihre Bedeutung f. d. Pathologie, ib., iv., 1888. 
See also § 15 and § 17. THEORIES OF INHERITANCE. 
43 
§ 17. As has been explained in § 16, inherited diseases are such as 
have developed from intrinsic causes, that is, from certain peculiarities 
in the germ-cells; or at least are diseases in which the predisposition 
thereto is a congenital characteristic. Conversely, the statement may be 
made that all normal or pathological qualities in the germ-cells are in- 
heritable. 
The appearance of new pathological characteristics which are in- 
heritable may be dependent on the fact that as a result of the union of 
two sexual nuclei, one of which is the bearer of the transmissible qualities 
of the father, the other of those of the mother — variations are con- 
stantly arising, so that the child is never exactly like one parent; but, in 
addition to the qualities which the parents offer, it possesses new quali- 
ties. Even if we assume that the sexual nuclei at times contain in poten- 
tial form exactly the same characteristics as those of the parents, the 
product resulting from the union of these nuclei would present a certain 
degree of variation. However, the differences between the children of 
such parents would be but slight. As a matter of fact, different products 
of the same parents may show an infinite variety, by reason of the fact 
that the germ-cells themselves contain a mixture of the transmissible 
characteristics of the paternal and maternal ancestors, and this mixture 
is never the same. 
In accord with this is the fact that the children of a certain family 
always present important differences in both physical and mental quali- 
ties. A marked resemblance occurs only in the case of twins arising from 
one egg — i.e., when the process of development of both children has 
started from the same act of copulation. 
The embryonal variations resulting from the mixture of two indi- 
vidually different hereditary tendencies find their expression in varied 
qualities of body and mind of the developing child. If these do not 
deviate in marked degree from the characteristics which other members 
of the family show, the conditions are regarded as normal and ordinarily 
receive no special attention. If, on the contrary, important differences 
are produced, the fact attracts attention; and, according to the value 
which it has for the individual concerned, is regarded at one time as 
something favorable, at another time as something unfavorable, some- 
thing pathological. When small, weak parents produce children who 
develop into large and strong individuals, or when the intellectual ca- 
pacity of the children surpasses that of the parents, the occurrence is re- 
garded as favorable. If, as happens, a genius suddenly appears in a 
family, without any evidence of extraordinary mental development in the 
ancestors, the phenomenon attracts attention and is regarded as a for- 
tunate event. But if, on the other hand, strong parents beget children 
who are weak or defective, or if they show a mental development in- 
ferior to that of their parents, or stunting of their mental faculties, the 
newly appearing variation is regarded as abnormal, pathological. 
The assumption seems warranted that of transmissible pathological 
conditions and predispositions, many, perhaps the majority, are refer- 
able to a variation of the germ based on the amphimixis.. For ex- 
ample, the group of hereditary pathological conditions and predispositions 
of the central nervous system, hereditary myopia, haemophilia, pigmenta- 
tion of the retina, and polydactylism may arise in this manner. If such 
abnormal characteristics show themselves repeatedly in the children of 
parents who are themselves normal and have healthy ancestors, it may 44 
THE INTRINSIC CAUSES OF DISEASE. 
be assumed that the germ-cells of the parents, though individually 
normal, have through their union given rise to pathological variation. 
This hypothesis becomes substantiated when one or both parents produce 
normal offspring through copulation with other individuals. 
Besides those variations which are the result of normal sexual repro- 
duction, it is probable that pathological germ-variations which lead to 
the development of transmissible pathological qualities may also arise 
through the action of injurious influences on the sexual nuclei or the 
segmentation nucleus; or that the union of the sexual nuclei has been 
disturbed. The injurious substance may be a body-product, or it may 
come from without, and at the same time produce its harmful effects. 
Consequently, in these cases we may speak of the germinal acquisition 
of a transmissible pathological characteristic through the action of an 
extrinsic injurious influence. This does not mean, however, as has been 
accepted by many, that the tissues of the body, under the influence of 
extrinsic harmful influences, suffer changes in themselves, and then 
transfer these changes to the germ-cells. It is to be believed, rather, that 
the harmful influence acts directly on the sexual nuclei or on the seg- 
mentation-nucleus, producing in these a change which later leads to 
pathological development in the individual developing from the im- 
pregnated egg. It is a matter of no importance, so far as the nature of 
the resulting pathological variation is concerned, whether the somatic 
tissues also suffer changes, or what the character of these may be. 
If a transmissible pathological characteristic arise, it may, if it does 
not affect life or prevent reproduction, be transmitted, although this 
does not necessarily follow. The chances that a particular characteristic 
will be transmitted are greatest when both parents possess the same 
quality, as, for example, when both parents are affected with hereditary 
deaf-mutism or with near-sightedness. If the characteristic is wanting 
in one parent, there is produced most frequently a new germ-variation, 
in which the pathological characteristic fails entirely to manifest itself, 
and in following generations may completely disappear. If several 
descendants are begotten, the pathological characteristic, if it be not 
wholly lost, may show itself in only a few of the descendants, and in 
either modified or aggravated form. Not rarely it happens that the 
characteristic remains latent in one generation — that is, confined to the 
sexual cells, and appears again in the second. 
§ 18. Besides the inheritable pathological conditions mentioned above, 
hereditary transmission of infectious diseases sometimes occurs. 
This is not a true form of inheritance, but is more properly designated 
as postconceptional intra-uterine infection. 
If pathogenic micro-organisms enter the blood-stream of a pregnant 
woman they may be carried into the vessels of the maternal placenta, and 
may pass through the foetal placenta into the body of the foetus. Such 
transmission has been demonstrated in many infections (staphylococcus, 
streptococcus, pneumococcus, typhoid fever, anthrax, smallpox, syphilis, 
and others) through the presence of the micro-organisms or of charac- 
teristic changes in the tissues of the foetal organism. In certain cases, 
for example, in anthrax, the path which they have taken may be demon- 
strated since the placenta shows characteristic pathological changes. 
It was once assumed that besides placental transmission there 
might also occur germinal transmission, that is, infection of the sexual 
cells before or during fructification. Further, it has been taken for THEORIES OF INHERITANCE. 
45 
granted, that, through infection of the fructifying spermatosome, infec- 
tion of the ovum without that of the maternal organism may occur, and 
such a mode of infection has been regarded as established, particularly 
in syphilis. Up to the present time, however, this mode of transmission 
has not been proved by unquestioned observations to occur in man and 
the mammals, and its occurrence even in syphilis has also been thrown 
into doubt (Matzenauer). According to our present knowledge we may 
say definitely that the transmission of infections through the placenta 
to the foetus in utero has been positively demonstrated and occurs in 
different infectious diseases. Infections of the ovum or of the sperm 
before or during fructification are indeed possible, but it has not yet 
been positively demonstrated in the case of man and the other mammals 
that a further development into a viable foetus is possible in the case of 
an ovum in which the agents of infection have produced characteristic 
changes. This is true not only in the case of acute infections, but also 
in such chronic ones as tuberculosis and syphilis. 
According to the views of Matzenauer, in no case of hereditary syphilis can 
maternal transmission be excluded; and there are no clinical observations that speak 
for a pure paternal spermatic infection of syphilis. The fact that the mothers of 
children showing hereditary lues are immune toward syphilis (Colles’ law) cannot 
be explained by the hypothesis that the mother has received syphilis toxins from 
the child syphilized from the father and in consequence has produced antitoxins 
(Finger), but can be explained only on the ground that she herself was infected 
with syphilis. That the mother often shows no syphilitic changes cannot be taken 
as an argument against the latter view, since syphilis may often be present with 
complete absence of symptoms. 
Literature. 
(Transmission of Infectious Diseases to the Foetus.) 
Blumer: Congenital Typhoid. Jour. Amer. Med. Assn., xxxv. 
v. During: Hereditare Syphilis. Eulenb. encyklop. Jahrb., v. 1895 (Lit.). 
Eberth: Geht der Typhusorganismus auf den Fbtus iiber? Fortschr. d. Med., 
vii., 1889. 
Finger: Die Vererbung der Syphilis, Wien, 1898 (Lit). 
Kockel u. Lungwitz: Placentartuberkulose beim Rin'd1. Beit v. Ziegler, xvi., 
1894. 
Latis: Uebergang des Milzbrandes von der Mutter auf den Fotus. Beit v. 
Ziegler, x., 1891. 
Lubarsch: Ueber die intrauterine Uebertragung pathogener Bakterien. Virch. 
Arch., 124 Bd., 1891. 
Malvoz: Transmission interplacentaire des microorganismes. Ann. de l’lnst. 
Past., 1888 and 1889. 
Morse: Fcetal and Infantile Typhoid. Arch, of Ped., 1900. 
Schmorl u. Geipel: Tuberkulose der mensch. Placenta. Munch, med. Woch., 
1904. 
Warthin: Tuberculosis of the Placenta. Journal of Infectious Diseases, 1907. 
Warthin and Cowie: Tuberculosis of the Placenta. Journal of Infectious Dis- 
eases, 1904. , CHAPTER II. 
The Spread and Generalization of Disease Through the Body. 
Autointoxications and Secondary Diseases. 
§ 19. Primary local disease is accompanied by disturbance of func- 
tion of the affected part. If the causative agent passes into the lymph 
stream or blood without causing noticeable changes at the point of en- 
trance, while within the body it gives rise to solitary or multiple foci, 
the disease thus resulting is designated lymphogenous or haematogenous, 
as the case may be. 
Local diseases may remain confined to the organ originally affected; 
frequently they lead to secondary diseases of organs or to general 
disease. 
One method by which disease spreads through the body is by the 
process of metastasis, by means of which not only solitary, but innumer- 
able foci arise in different parts. Not infrequently dissemination of 
disease by the blood and lymph-channels (tuberculosis, suppuration, and 
malignant growths) may proceed to such an extent that the majority 
of the organs are thus secondarily involved. 
A second method occurs in which at the primary focus toxic pro- 
ducts are formed, and these, when taken into the lymph and blood, 
produce local changes due to the effects of poisoning. Such intoxica- 
tion is of common occurrence in the infectious diseases, and leads not 
only to secondary degeneration of organs, but even to general disease, 
as shown by constitutional reactions characterized by disturbances of 
metabolism and fever. 
A third form of the spread of disease through the body becomes 
possible by reason of the fact that the integrity and normal functional 
capacity of many organs are in great measure dependent on the func- 
tion of other organs; and, further, on the fact that the organism needs, 
for the preservation of its normal condition, the perfect functional work- 
ing of its organs. There is, therefore, a large group of local and general 
diseases which arise as the result of the imperfect functional activity of 
individual organs. 
A fourth mode of origin of secondary diseases is through autointoxi- 
cation— that is, through poisoning of the organism by substances which 
arise in the body itself (metabolic poisons). These substances may arise 
in the intestinal tract (enterogenous poisons), or in the tissues (histo- 
genous poisons). The poisonous action of these products of metabolism 
lies partly in the fact that they are produced in increased amount or 
are retained in the body as a result of disease of certain glands; or 
because they are not transformed to non-poisonous bodies, as in normal 
circumstances. In conditions of disturbed metabolism poisons foreign 
to the normal body may be produced. METASTASIS AND EMBOLISM. 
47 
A fifth method by which the body may be injured is through loss 
of function of those glands producing an internal secretion. In this 
category belong the thyroid, hypophysis, pancreas, adrenals, and sexual 
glands. Since in disease of the glands just named intoxication plays an 
important role, this group of processes is closely connected with that of 
the fourth mode of generalization of disease. 
I. Metastasis and Embolism and their Significance in the Etiology 
of Lymphogenous and Haematogenous Diseases. 
§ 20. The transportation, through the blood or lymph-stream, of a 
disease-producing agent, and the production of disease at the point of 
deposit, is termed metastasis. This is one of the common modes of the 
spread of disease through the body. Ordinarily the term metastasis is 
applied to those cases in which the transportation of a given substance 
is followed by easily recognizable clinical and anatomical manifesta- 
tions of disease, especially those of inflammation or tumor-formation, 
so that we are accustomed to speak of 
metastatic inflammations and metas- 
tatic tumors. There is, however, no 
good reason for not including under 
metastasis those cases of transporta- 
tion of corpuscular elements through 
the lymph or blood stream in which 
the changes produced by the trans- 
portation are less striking, and are 
recognizable only through careful 
anatomical or microscopical investiga- 
tion. 
The term metastasis indicates that 
the substance deposited has arisen 
from some other place in the body, 
and we are accustomed to speak of lymphogenous or haematogenous 
metastasis, depending on the mode of transmission. 
The significance of metastasis is dependent on the properties of 
the transported body. Insoluble bland foreign bodies of small size 
may have little effect on the tissue; soluble and chemically active sub- 
stances may, on the other hand, produce important tissue changes. Bac- 
teria capable of reproduction may give rise to disease which corre- 
sponds to that produced at the primary focus of infection. Tumor-cells 
may develop a secondary tumor. The size of the transported body is 
of importance in haematogenous metastasis, in that small bodies may pass 
all the blood-vessels, even the capillaries, while larger ones are carried 
only through those vessels whose lumen is sufficiently large to admit 
them. When the latter obtain entrance to the arteries and are carried 
along by the blood-stream, they become lodged at those divisions of the 
vessels where the lumen is too small to admit them, and more or less com- 
pletely obstruct the lumen. This occurrence is designated embolism; 
the body blocking the vessel is the embolus (Fig 1). The effect of 
embolism is more or less complete obstruction of the vessel, partly 
through the presence of the embolus itself, partly through associated 
coagulation of the blood. As a result of such obstruction there is in- 
Fig. i.—Multiple emboli in the branches 
of the pulmonary artery, after thrombosis 
of the right auricle, a, Arterial branch; 
b, embolus; c, embolus with secondary 
thrombosis. 48 
THE GENERALIZATION OF DISEASES. 
terference with the circulation, which may vary greatly in different 
cases; behind the point of obstruction there may be established either 
complete or partial collateral circulation, in other cases such compen- 
sation may be wanting. When compensation is incomplete or absent, 
the tissue supplied by the obstructed vessel undergoes degeneration or 
dies. 
Both lymphogenous and hsematogenous metastasis usually occur in 
the direction of the normal current, but transportation in the opposite 
direction may take place—retrograde metastasis. Such a change of 
current in the lymph-vessels occurs when the escape of lymph from the 
region involved is hindered through stoppage of the lymphatics, and the 
lymph is forced to seek other outlets. A similar condition may occur in 
circumscribed areas supplied by the peripheral blood-vessels. In this 
way clots arising in the right heart or in the large veins of the body 
may be transported to the peripheral veins, particularly under conditions 
in which backward waves of blood gradually force the clots into the 
smaller veins. According to the investigations of Arnold on dogs, for- 
eign bodies (wheaten grits), which were too large to pass the capillaries, 
when introduced into the jugular or crural veins, as well as into the 
longitudinal sinus of the dura mater, were carried by retrograde metas- 
tasis not only into the main trunks, but into the smallest branches of 
the veins of the liver, kidneys, heart, extremities, dura mater, pia mater, 
and orbit, and into the posterior bronchial veins. 
In the case of a defect in the septum of the heart, bodies circulating 
in the blood may pass directly from one side of the heart to the other, 
and thereby give rise to crossed or paradoxical embolism. 
§ 21. The substances which are transported in the process of 
metastasis may be divided into six groups, this classification being 
based partly on the origin and character of the transported body, and 
partly on the effects of its lodgment. 
In the first group are placed insoluble lifeless substances composed of 
small particles, which enter the body from without, and may be desig- 
nated collectively as dust. The majority of'these substances enter the 
body in the respired air, and pass from the lungs into other tissues. 
Others enter the tisues through accidental or intentional wounds 
(tattoo). Most frequently these substances are particles of soot, coal- 
and stone-dust, more rarely metal, porcelain, tobacco, hair or other kinds 
of dust. In tattooing of the skin, lampblack, india-ink, ultramarine, and 
similar granular pigments are used. 
The behavior of the tissues toward such substances will be treated 
of elsewhere; it is only necessary to mention here that these forms of 
dust, sometimes in a free state, sometimes enclosed within cells, are first 
deposited in the tissues nearest the point of entrance, later in the lymph- 
vessels and lymph nodes. In the latter location they may remain for a 
life-time; but in cases of excessive deposit they may be carried beyond 
the lymph nodes, especially in those instances in which the nodes, be- 
cause of the great deposit, undergo softening and give rise to inflamma- 
tion and proliferation of the tissues in the neighborhood. Often as a 
result of such changes the affected nodes become confluent with and 
break into neighboring veins. This event is especially likely to happen at 
the hilum of the lungs, whereby the contents of the node ultimately, 
sometimes slowly, at other times more rapidly, gain entrance to the 
vessel-lumen and are carried away by the blood-stream. In the lungs, METASTASIS AND EMBOLISM. 
49 
dust may be deposited directly in the vessel-walls and gradually pene- 
trate as far as the intima. Further, the particles from a broken-down 
lymph node can enter the lymph-stream, and, if not arrested by some 
other lymph node, may reach the blood-stream. It is also conceivable 
that softened lymph nodes may break directly into the thoracic duct. 
In fact, rupture of a tuberculous node into the receptaculum chyli is a 
recognized mode of origin for the rapid dissemination of tubercle bacilli 
through the body (acute miliary tuberculosis). 
As numerous experiments have shown, dust gaining entrance to a 
blood-vessel remains but a short time in the circulation. Large amounts 
artificially introduced into a vein disappear in a few hours from the 
circulating blood. The greater part collects in the capillaries of the liver, 
spleen, and bone-marrow, partly free and partly within leucocytes, in 
the former case adhering to the surface of the endothelium. After a 
short time the leucocytes containing the dust particles wander out from 
Fig. 2.—Fat-embolism of the lungs (Flemming’s solution, safranin). _ a, Arteries filled with 
blackened masses of fat; b, fat-droplets in capillaries; c, veins; d, cells in the alveoli, x ioo. 
the vessels and the dust collects in the tissues, where it is held for a 
long time, in wandering or in fixed cells, or free. It may remain here 
during the lifetime of the individual, or be carried in the lymphatics to 
other regions and deposited, particularly in the portal and coeliac lymph 
nodes. According to the researches of Kunkel and Siebel, still other cells 
containing dust-particles may reach the surface of the body-cavities, either 
through the lungs, the parenchyma of the tonsils, and probably also from 
the lymphoid tissue of the intestines, and in this way be discharged 
externally. From the liver the dust-particles may be discharged in the 
bile. According to observations made on inflamed organs, wandering 
leucocytes are able to take up a great number of the particles lying in the 
tissues and transport them from the lungs, intestinal tract, and other 
organs to the surface, and in this way clear the tissues. 
The second group is composed of portions of the body itself, namely, 
tissue-detritus, parenchyma cells, and dead, coagulated, and broken-up 
constituents of the blood. Of the elements arising from the destruction 50 
THE GENERALIZATION OF DISEASES. 
of tissue, fat-droplets (Fig. 2, a, b, and Fig. 3, a, b) often find their way 
into the circulation; particularly when through trauma or some other 
pathological process, as, for example, haemorrhage, the tissues are de- 
stroyed. This occurs most frequently in cases of crushing, destruction, 
and violent agitation of fat-tissue, as may happen in the different 
panniculi adiposi and the bone-marrow; fat may also enter the circu- 
lating blood through destruction of liver-tissue. The parenchyma 
cells most frequently entering the circulation are liver-cells, syncytial 
placenta-cells, portions of chorionic villi, and bone-marrozv cells. Ordi- 
narily these are carried into the pulmonary arteries and capillaries, but 
through retrograde metastasis they may be carried into the veins, and 
through paradoxical embolism into the arteries and capillaries of the 
systemic circulation. Embolism of liver-cells and bone-marrow giant- 
cells is caused by traumatic and toxic injuries and haemorrhages of the 
affected tissues. Placental-cell emboli, in the form of syncytial giant- 
cells, have been observed in puer- 
peral eclampsia, but occur also in 
the course of normal pregnancies. 
Pulmonary emboli composed of 
small portions of the chorionic villi 
have been observed. In diseased 
conditions of the intima of the 
heart or blood-vessels, degenerated 
endothelium, broken-down arid de- 
generate masses of intima, portions 
of the valves, and material of 
similar nature may gain entrance to 
the blood-stream. Fragments of 
blood-corpusles may enter the cir- 
culation from haemorrhagic foci or 
may arise within the vessels them- 
selves, in degenerative changes produced in the blood through the in- 
fluence of the various harmful agents. Coagulated masses of blood enter 
the circulation when a thrombus—i. e., blood coagulated in the vessels 
(see Chapter IV)—breaks loose, either in toto or in fragments. 
The fate of the last-named substances is for the chief part dependent 
on their size and physical properties. All fragments of greater diameter 
than the lumen of the capillaries become lodged in the bifurcations 
of the arteries (Fig. 1, a, b) and usually occlude the same. This occurs 
most frequently in the case of dislodged thrombi or of fragments of such; 
on the other hand, fat-droplets usually pass into the capillaries, where 
part remain, while others pass through and become lodged in some other 
place. Since the fat occasionally passes first into the veins of the body 
and thence to the heart, the fat-droplets collect especially in the capil- 
laries of the lungs (Fig. 2, b) ; but they may also pass through the 
lungs into the capillaries of the greater circulation, and are then found 
in the intertubular and glomerular capillaries of the kidneys (Fig. 3, a, b), 
and to some extent in the capillaries of other organs. Capillary fat- 
embolism causes noticeable disturbances of the circulation only when of 
extensive occurrence; in this case it may lead to the production of oedema 
of the lungs. Furthermore, the fat disappears in the progress of metabo- 
lism, or is conveyed into the neighboring tissues. 
Fig. 3.—Fat-embolism of the kidney (Flem- 
ming’s solution, safranin). a, Glomeruli with 
fat in the capillaries; b, fat-droplets in the in- 
tertubular capillaries, x ioo. METASTASIS AND EMBOLISM. 
51 
Parenchyma cells become lodged in the capillaries or smaller arteries 
in the case of arterial metastasis. The latter is especially true of liver- 
cells when entering the circulation en masse. At the place of lodgment 
their presence may lead to heaping-up of blood-plates and hyaline coagu- 
lation. The cells themselves do not multiply, but may remain unchanged 
for a time, according to Lubarsch, as long as three weeks. They then 
gradually die, the protoplasm dissolves, the nuclei swell or shrink, and 
finally lose their chromatin. 
The point of lodgment of loosened thrombi or fragments of thrombi 
depends on the path which they take, as well as on their size. Since 
thrombi may be formed in the systemic veins, right heart, and pulmonary 
arteries, as well as in the pulmonary veins, left heart, and systemic 
arteries (see Chapter IV.), it is possible for embolism to occur in any 
of the arteries of the greater or lesser circulation. Often emboli lodge at 
the bifurcation of arteries, forming the so-called riding or straddling 
emboli (Fig. 1, c). Through retrograde metastasis emboli may be 
carried from the venae cavae or larger veins into the smaller veins. 
Defects in the septum of the heart may lead to the production of para- 
doxical embolism. 
Small fragments of thrombi, dead red blood-cells or fragments of 
such, endothelial cells undergoing disintegration or fatty degeneration, 
etc., meet the same fate as dust-particles. They may remain free or be 
taken up by cells; but are soon removed from the circulation and collect 
in the spleen, liver, and bone-marrow, where they undergo further 
changes and are destroyed. The products resulting from the destruc- 
tion of red blood-cells may persist for a long time in the organs named, 
as pigment deposits. 
The third group of substances producing metastases is composed of 
living cells, which, originating from proliferating tissue-foci and hav- 
ing gained entrance to the circulation through rupture into the blood- 
vessels, or having entered the lymphatics, are carried to other organs. 
This process may be observed in the case of tumors growing by infiltra- 
tion. The metastasis of living cells from a tumor leads through prolifera- 
tion of the transported cells to the production of metastatic secondary 
tumors, which in lymphogenous metastasis develop first in the lymph- 
vessels and lymph nodes, but in the event of direct rupture into the 
blood-vessels arise in that part of the vascular system to which the 
tumor-cells are carried by the blood. The metastasis usually occurs in 
the normal direction of the blood- and lymph-streams, but retrograde 
transportation may occur, so that a tumor which has broken into one of 
the systemic veins may give rise to metastases in the region drained by 
smaller branches of other systemic veins. Retrograde metastasis is not 
infrequently observed in the lymphatic system, when closure of the ef- 
ferent lymph-channels has produced a change in the direction of the 
lymph-current. 
In the fourth group may be placed all those processes characterized 
by the entrance of vegetable or animal parasites into the circulation. 
If in such circumstances these organisms do not find conditions suit- 
able for their development, they are eliminated from the blood-stream and 
destroyed. But if they are able to reproduce themselves, they give rise 
to metastatic foci of infection, partly in the vascular system, but also 
extending thence into neighboring tissues. The secondary foci produced 
by bacterial invasion have in general the same character as that of the 52 
THE GENERALIZATION OF DISEASES. 
primary. If an embolus contains organisms capable of producing tissue- 
necrosis, inflammation, and putrid decomposition, repetition of the same 
processes will occur at the place of lodgment. 
In the fifth group of metastatic processes may be classed those cases 
in which constituents of the human body having undergone solution 
are transported in the soluble state and deposited in a solid form; 
and also those in which extrinsic substances are taken up by the body 
in a soluble form and are deposited in the tissues in a solid state. 
Frequently bile-pigment enters the circulation within the liver, and 
permeates the tissues, giving to them a yellowish color (icterus). Not 
infrequently iron-containing derivatives arising from the destruction of 
red blood-cells in the circulation are carried to the spleen, bone-marrow, 
liver, and kidneys and form pathological deposits of iron (hsematogenous 
siderosis). Fat can be split from the fat-depots in the form of soluble 
soaps and carried through the blood to different organs where it is taken 
up by the cells and changed into neutral fat. 
When preparations of silver are, for medicinal purposes, introduced 
into the body through the gastro-intestinal tract for long periods of time, 
there may occur a deposit of fine granules of silver in the connective tis- 
sue of the skin, in the glomeruli, medullary pyramids of the kidneys, 
intima of the large arteries, adventitia of the small arteries, in the neigh- 
borhood of mucous glands, connective tissue of the intestinal villi, in the 
choroid plexus of the cerebral ventricles, and in the serous membranes. 
Tissues showing such a deposit have a grayish color. 
The fact that epithelial tissues and the brain are not affected shows 
that there is a selective action on the part of the tissues, and that this 
selective action differs essentially from that which is seen in the metastatic 
deposit of corpuscular elements. It may be assumed that the chemico- 
physical character and the functional activity of the tissues coming into 
contact with substances in solution exert a determining influence on the 
separation and precipitation of such substances. 
In a sixth group of metastatic processes may be classed the entrance 
of air into the circulation. If a large amount of air gains entrance 
to the right heart, an event which occurs especially in case of injury 
to the large veins lying in the neighborhood of the thoracic cavity, or 
more rarely from the opening of a vein, for example, in the stomach, 
through ulcerative processes, the air mingling with the blood forms a 
foamy mass, which the contractions of the heart are not able to drive 
onward. As a result the left heart receives little or no blood, the 
aortic pressure falls, and the individual quickly dies. Should the air 
enter the circulation in small amounts or intermittently, it may be 
carried by the blood-stream in the form of bubbles and circulate through 
the body. Larger amounts may lodge for a time in the vessels of the 
major or minor circulation, obstruct their lumen, and cause disturbances 
of the circulation, which give rise to functional disturbances of the brain 
and respiration. If these conditions do not cause death, the air is after a 
time absorbed. 
If the lung-tissue be ruptured through trauma or violent coughing, 
screaming, or vomiting, etc., air may be forced into the connective- 
tissue spaces and lymphatics, and may extend through these into all 
parts of the lungs, pleurae, and the mediastinum, as well as into the 
skin. The- condition thus produced is termed emphysema of the skin, of 
the subcutaneous tissue, of the mediastinum, etc. In certain circum- METASTASIS AND EMBOLISM. 
53 
stances the air may spread through a large area of the subcutaneous 
lymph-vessels and connective-tissue spaces, and the skin presents an 
inflated appearance and when pressed upon produces a crackling sound. 
According to Siebel and Kunkel, granules of cinnabar and indigo injected into the 
blood-stream of a frog are quickly taken up by leucocytes, and after one to two 
hours no free granules are to be found. After twenty-four hours the leucocytes 
containing pigment-granules have disappeared from the circulation, and lie clumped 
in the capillaries, the greatest number being found in the spleen, liver, bone-marrow, 
and lungs, while they occur in smaller numbers in the kidneys, and in still smaller 
numbers in the capillaries of the heart-muscle. 
Even after two hours free pigment and cells containing granules are found out- 
side the vessels, and after a few days they have almost wholly disappeared from 
the vessels. The granules lie partly in wandering-cells, partly in fixed cells, and 
in the free cells of the splenic pulp (Ponfick) and bone-marrow. They may be 
found in these organs for weeks afterward (Hoffmann, Langerhans). In both 
frogs and dogs some of the granule-containing cells find their way into the lumen 
of the alveoli and bronchioles and so pass out of the body. In the liver the pigment- 
particles adhere for a short time to the endothelium of the capillaries and may be 
taken up by the endothelial cells (Browicz, Heinz) ; another part is found in 
leucocytes, which later wander out from the vessels into the tissues. Thence they 
are in part taken up into the lymphatics of the liver and ultimately reach the lymph- 
nodes. A part of the granules finally passes out with the bile, but by what course 
they reach the bile-vessels is not known. In dogs the pigment-granules also collect 
in the tonsils and are carried to the surface through the epithelium by the leucocytes 
which have taken them up. 
According to the observations of Jadassohn (“ Pigmentverschleppung aus der 
Haut,” Arch. f. Derm., 24 Bd., 1892) and Schmorl (“ Pigmentverschleppung aus der 
Haut,” Centralbl. f. allg. Path., 4 Bd., 1893), both normal and pathological pigment 
may be transported from the skin to the lymph-nodes — in other words, pigment- 
metastasis takes place. 
According to Lewin (Arch. f. exp. Path., 40 Bd., 1897), if the outflow of urine 
from the bladder be hindered, small foreign bodies can pass into the kidney-pelves, 
and thence into the urinary tubules, lymph-vessels, and veins, and into the general 
circulation. 
Literature. 
{Metastasis of Dust.) 
Arnold, J.: Staubinhalation u. Staubmetastasen, Leipzig, 1885; Die Geschicke 
des eingeathmeten Metallstaubes im Korper. Beitr. v. Ziegler, viii., 1890. 
Browicz: Phagocytose der Lebergefassendothelien. A. f. mikr. Anat., 58 Bd., 
1902. 
Buxton: Absorption from the Peritoneal Cavity. Journal of Medical Research, 
.1907* 
Heinz: Phagocytose der Lebergefassendothelien. A. f. mikr. Anat., 58 Bd., 
1901. 
v. Kupffer: Sternzellen, der Leber. Munch, med. W'och., 1899. 
MacCallum: Absorption from the Peritoneum. Johns Hopkins Hospital Bulle- 
tin, xiv., 1903. 
Ponfick: Ueber die Shicksale korniger Farbstoffe im Organismus. Virch 
Arch., 48 Bd., 1869. 
Siebel: Ue'ber das Schicksal von Fremdkorpern in der Blutbahn. Virch. Arch., 
104 Bd., 1886. 
Sulzer: Durchtritt corpuscul. Gebilde durch d. Zwerchfell. Virch. Arch., 143 
Bd., 1896. 
{Embolism of Fat and of Parenchyma Cells.) 
Aschoff: Capillare Embolie von riesenkernhaltigen Zellen. Virch. Arch., 134 
Bd., 1*93. 
Beneke: Fettembolie. Beitr. v. Ziegler, xxii., 1897. 54 
THE GENERALIZATION OF DISEASES. 
Colley: Fettembolie nach gewaltsamer Gelenkbeugung. Zeitschr. f. Chir., 36 
Bd., 1893. 
Ebstein: Lipamie u. Fettembolie bei Diabetes. Virch. Arch., 155 Bd., 1899. 
Graham: Fat Embolism. Jour, of Med. Research, 1907. 
Hamilton: Lipeemia and Fat Embolism. Edinburgh Med. Journal, 1879. 
Hess: Beitr. z. d. Lehre v. d. traumatischen Lebterrupturen. Virch. Arch., 121 
Bd., 1890. 
Jurgens: Fettembolie u. Metastase v. Leberzellen. Tagebl. d. Naturf.-Vers. in 
Berlin, 1886. 
Klebs: Multiple Leberzellenthrombose. Beitrage v. Ziegler, iii., 1888. 
Leusden: Puerperale Eklampsie. Virch. Arch., 142 Bd., 1895. 
Lubarsch: Parenchymzellenembolie. Fortschr. d. Med., xi., 1893; Zur Lehre 
yon den Geschwulsten u. Infectionskrankheiten, Wiesbaden, 1899. 
Maximow: Parenchymzellenembolie. Virch. Arch., 151 Bd., 1898. 
Ribbert: Fettembolie. Correspbl. f. Schweizer Aerzte, 1894. 
Schmorl: Embol. Verschleppung v. Lebergewebe. Deut. Arch. f. klin. Med., 
42 Bd., 1888; Organbefunde bei Eklampsie. Cent. f. allg. Path., ii.; Enters, 
iib. Puerperaleklampsie, Leipzig, 1893. 
Turner: Hepatic Cells in the Blood. Trans, of the Path. Soc. of London, 1884. 
Warthin: Pulmonary Emboli of Liver-cells and Bone-marrow Giant-cells. Med. 
News, 1900. 
{Air Embolism.) 
Hare: Entrance of Air into Veins. Therapeutic Gaz., 1889; Amer. Jour, of 
Med. Soc., 1902. 
Senn: Entrance of Air into Veins. Trans. Amer. Surg. Assn., 1885. 
Wolf: Luftembolie. Virch. Arch., 174 Bd., 1903. 
II. The Sequelae of Local Organic Disease. 
§ 22. Secondary diseases occur with great frequency as phenomena 
associated with pathological changes in the blood and circulatory appar- 
atus. 
The circulatory apparatus and the blood bear intimate relations to 
all the body-tissues, and accordingly diminution in amount and patholog- 
ical alterations of the blood, as well as changes in the blood-vessels, 
often give rise to disease conditions. If the haemoglobin-content of the 
blood is decreased through diminution in the number of red blood-cells 
(oligocythaemia), or through a pathological condition of the same, or if 
the haemoglobin through the action of carbon monoxide is rendered in- 
capable of taking up the oxygen of the air, the body-tissues no longer 
receive a normal amount of oxygen; consequently if the degree of 
oxygenation falls below a certain point, disturbances of nutrition arise, 
and are most frequently exhibited in the form of fatty degeneration of 
the heart, kidneys, liver, and other viscera. 
Should an artery become narrowed or closed through thrombosis or 
embolism, or thickening of its walls, as in the disease known as arterio- 
sclerosis, there arise in the region supplied by the affected vessel a local 
deficiency of food and oxygen, local asphyxia, and later degenerative 
processes, which frequently end in death of the specific parenchymatous 
elements, at times also of the connective-tissue framework. 
In the brain and spinal cord the vessel-changes lead to ischaemic soft- 
ening, which frequently results in paralysis, and not rarely in death. In 
the heart diffuse fatty degeneration or local softening of the heart- 
muscle may occur, giving rise to disturbances of cardiac activity or even 
to complete insufficiency. In the kidneys the secreting parenchyma, to- THE SEQUELS OF LOCAL DISEASES. 
55 
gether with a portion of the connective tissue, undergoes necrosis or 
atrophy; and the loss of these substances gives rise to local or widespread 
contractions, which, according to their origin, are designated embolic or 
arteriosclerotic atrophies. 
In the stomach ischaemia of the mucous membrane gives rise to local 
ulcerations; in the liver and muscles to atrophic conditions. No tissue 
can withstand the harmful effects of long-continued anaemia, and con- 
sequently the narrowing and closure of arteries, through the formation 
of clots or changes in the vessel-walls, play an extremely important 
role in pathology; and are not only the causes of anaemic necrosis (see 
Chapter V.) and hocmorrhagic infarction (see Chapter IV.), but also of 
numerous progressive atrophies of organs. In the pathogenesis of the 
last named, arteriosclerosis has an especially important part, since in old 
age it is of common occurrence, and gives rise to tissue-degenerations 
in organs of widely different structure. The majority of the affected 
organs show areas of scar-tissue, in which the specific parenchyma has 
disappeared while the connective tissue has increased. 
The active participation of the vascular apparatus in all inflammatory 
processes (see Chapter VII.), the disturbance of circulation through 
alteration of the vessel-walls, the shifting and changes in the vascular 
channels which result from the closure of vessels by proliferation of en- 
dothelium and connective tissue, or through thrombosis, as well as from 
the formation of new vessels, make easily comprehensible the fact that in 
all chronic inflammations the specific cells dependent on regulated nutri- 
tion undergo degeneration and are frequently replaced by connective 
tissue of a lower grade than normal. 
Profuse watery discharge from the intestines may deprive the body 
of water. If, as a result of stenosis of the oesophagus or pylorus, food is 
prevented from entering the intestinal tract, or if the stomach and intes- 
tine are no longer able to digest food and to prepare it for assimilation, 
the organism as a whole becomes poorer in albumin and fat. 
If the heart is no longer able to propel with normal strength the blood 
coming to it, there arise in various organs changes due to venous stasis. 
If respiration is imperfect, the composition of the blood suffers. Collec- 
tion of fluid in the thoracic cavity causes compression of the lungs; such 
mechanical interference may lead to atrophy. If a part of the lung has 
been rendered useless by chronic inflammation, the inspiratory enlarge- 
ment of the thorax affects only that portion of the lung which is capable 
of functionating, and this part becomes over-distended and finally 
atrophic. 
Disease of the parenchyma of the liver often gives rise to disturbances 
of the circulation of the blood through the organ, and stasis throughout 
the portal circulation with resulting ascites. Should the pancreas be de- 
stroyed or if it is no longer able to produce its ferments (proteolytic 
trypsin, amylolytic diastase, and the fat-splitting and emulsifying steap- 
sin) there results imperfect metabolism of albumin, carbohydrates, and 
fat. 
Hindrance to the outflow from the ureters reacts on the secretion of 
the kidneys and leads to atrophy. The loss of a large portion of the renal 
parenchyma is followed by increased blood-pressure in the aorta, in- 
creased action of the heart, and hypertrophy. 
Increased resistance in the pulmonary circulation due to diseased con- 
ditions of the lungs is often followed by dilatation and hypertrophy of 56 
THE GENERALIZATION OF DISEASES. 
the right heart. Obstruction to the flow of blood through the aortic 
opening is followed by hypertrophy of the left ventricle. Stenosis and 
insufficiency of the mitral valve cause a stasis of blood backward through 
the lungs to the right heart. This may be compensated for through 
hypertrophy of the right ventricle, or the process of stagnation may ex- 
tend into the veins of the systemic circulation. 
An oblique position of the pelvis leads to curvature of the spine. 
Stiffness and immovability of a joint cause atrophy of the muscles which 
normally control the movements of the joint, the atrophy being due to 
inactivity. 
Diseases of the nervous system may give rise to functional dis- 
turbances and anatomical changes in any organ of the body—in glands, 
muscles, skin, bones, lung, heart, intestine, etc. Destruction of the 
ganglion-cells in the anterior horns of the spinal cord leads to atrophy 
of the corresponding peripheral nerves and muscles. Paralyzed extrem- 
ities become atrophic. Injury to certain portions of the medulla ob- 
longata, or the presence of tumors in the brain may be followed by or 
associated with withdrawal of the glycogen of the liver into the blood- 
stream and the excretion of sugar in the urine. Stimulation of periph- 
eral nerves may produce abnormal reflex sensations and movements as 
well as circulatory disturbances in other parts of the body. Paralysis 
of both vagi or of their branches, or the recurrent laryngeal nerves, 
through inflammatory changes or pressure from enlarged lymph nodes, 
etc., may be followed by inflammation of the lungs, in that the accom- 
panying paralysis of the laryngeal muscles favors the entrance of for- 
eign bodies during inspiration. 
The so-called trophoneurotic diseases of the tissues are not mentioned 
above, for the reason that the trophic relations of the nervous system to indi- 
vidual tissues are not clear, and the views of different authors as to the depend- 
ence of the tissues on the nervous system vary greatly. Many authors ascribe 
to the trophic action of the nervous system a far-reaching influence. For 
example, muscular atrophy, glandular atrophy, atrophy of the bones and joints 
(in tabes and syringomyelia), different pathological conditions of the skin char- 
acterized by thinning, exfoliation of the epithelium, loss of hair, inflammation, 
etc., unilateral tissue-atrophies, necroses, hypertrophic proliferation of muscles, 
glands, skin, or bones, etc., are all referred to affections of the nerves. 
It cannot be doubted that both degenerative and hypertrophic tissue-changes 
and inflammation often occur as sequelae to disturbances of innervation, but 
these most probably are not the direct result of removal or change of nerve- 
influences, but are the results of increased or decreased functional activity of 
the tissue, or of injuries, inflammation, or disturbances of circulation, which 
have developed in connection with the disturbances of innervation — for exam- 
ple, in connection with the loss of sensibility. Gols and Ewald, after completely 
destroying the thoracic and lumbar portions of the spinal cord of dogs, were 
able to preserve uninjured the skin of the animals thus operated on; they are, 
therefore, opposed to the theory of trophic centres and nerves. (Pfliiger’s 
Arch., Bd. 63, 1896.) 
III. Autointoxications and Disturbances of Internal Secretion. 
§ 23. Autointoxicaticn may take place in a variety of ways. Pois- 
onous products of metabolism may fail of proper excretion. Secondly, 
the physiological production of poisonous substances may be transcended 
to such an extent as to become pathological. Thirdly, it may happen 
that poisonous products of metabolism, which normally are decomposed 
and rendered harmless, may escape destruction. Finally, it may happen 
that, as the result of pathological changes in, or interference with the AUTOINTOXICATION. 
57 
functional activity of certain organs, poisonous substances appear in the 
blood and are excreted in the urine. According to their origin poisons 
may be classed as enterogenous, arising in the intestine, and histo- 
genous, arising in the tissues. 
If injurious products arising from the decomposition of albumin 
are retained or are formed in excessive amounts in the intestinal canal, 
they may give rise not only to local changes, but to symptoms of general 
intoxication. For example, through the action of bacteria present in 
the intestines, sulphuretted hydrogen may. be formed in such amount as 
to pass into the blood and impart its characteristic odor to the breath, 
and also to be found in the urine. Further, toxic substances which 
arise from the decomposition of albumin through the action of intes- 
tinal bacteria, when taken into the blood are able to produce symptoms of 
poisoning—vomiting, headache, vertigo, stupor, acceleration and weak- 
ening of the heart’s action, etc. This is especially true of those cases 
in which there is faecal retention. 
If the function of the kidneys is disturbed to such a degree that sub- 
stances convertible into urea are excreted in sufficient quantity, symp- 
toms of intoxication manifest themselves. These are characterized by 
coma interrupted by convulsions and by disturbances of respiration— 
the symptoms collectively being designated uraemia. According to von 
Limbeck, the retained substances have a narcotic action, the first effects 
of which are dulling of sensibility and insomnia. It has not been de- 
termined whether the toxic effects are due to a single element or to a 
mixture of substances. 
Disturbed function of the intestines may render it difficult for the 
organism to rid itself of poisons, and in this way leads to autointoxication, 
copraemia. Likewise, excessive accumulation of carbonic acid in the 
blood, through interference with the exchange of gases in the lungs, may 
cause symptoms of poisoning. 
When the excretion of bile is hindered or arrested, through altera- 
tions in the bile-passages or in the liver itself, the elements of the bile are 
taken into the blood, and the condition known as cholaemia is produced. 
Biliary salts and bile-pigment enter the blood, and give rise to lassitude, 
depression, inclination to sleep, slowing of the pulse, itching of the skin, 
a tendency to hemorrhage on slight provocation, and abnormal sensations 
of hearing and taste. The effects on the heart, muscles, and central ner- 
vous system are ascribed to the bile-salts. These also possess a lytic 
action on the red blood-cells. According to Bickel, ammonia-salts, 
leucin, and phenol must also be taken into consideration in the explana- 
tion of the symptoms. 
If the liver has undergone marked pathological changes, not only 
does the production of bile and the synthesis of urea suffer, but sub- 
stances brought to the liver from the intestines and normally decomposed 
by this organ may pass through unchanged. Many believe that the 
severe symptoms (delirium, lethargy, coma), which occur in degenera- 
tions of the liver (icterus gravis) are to be referred in part to the pres- 
ence of such substances in the blood, and base their belief on the fact that 
under such conditions abnormal products of metabolism (ammonium 
carbonate) appear in the urine. In degenerations of the pancreas, large 
amounts of dextrose, acetone, and aceto-acetic acid (see § 25) may ap- 
pear in the blood and urine. The two last-named substances have a 58 
THE GENERALIZATION OF DISEASES. 
toxic action, and many are disposed to ascribe such symptoms to dis- 
turbance of pancreatic function. Finally, after degeneration of the 
thyroid or adrenals (§§ 25 and 26), pathological symptoms arise which 
may be explained in part by the assumption that poisonous products of 
metabolism are no longer destroyed. 
In the constitutional disease known as gout, deposits of urates are 
associated with tissue-degeneration and inflammation. 
The condition of eclampsia is an autointoxication resulting from 
pregnancy, and is possibly due to poisons originating in the placenta. 
The term autointoxication is not used in the same sense by all writers. 
Many give to it a broader meaning than the one above, and even apply the term 
to certain intoxications caused by pathogenic bacteria. Such widening of the 
term appears to me inexpedient, in that the cause of the decomposition lies not 
in the body itself, but comes from without, so that intoxication is the result of 
a preceding infection. It seems to me to be more correct to apply the term 
autointoxication only to those forms of poisoning which are caused by products 
of metabolism, either under the influence of the body-cells or through the 
activity of bacteria constantly present in the intestine. As authorization for 
including the poisoning by products arising from intestinal decomposition 
among the autointoxications, I draw on the fact that the micro-organisms which 
cause this decomposition are constant inhabitants of the intestine, and, accord- 
ing to the investigations of Schottelius, are indispensable factors in the processes 
of nutrition of man and the higher vertebrates. The enterogenous autointoxica- 
tions, which are caused by these intestinal bacteria and which occur especially 
in childhood through retention of the intestinal contents (ileus) or in acute 
digestive disturbances are in their severe forms characterized by disturbance 
of heart-action, small and frequent pulse, cyanosis, coldness of the extremities, 
and lowering of the body temperature. They may owe their origin in part to reten- 
tion of intestinal contents, and in part to changes in the products of decompo- 
sition (formation of toxins) depending either on the character of the material 
taken into the intestines (deficiency of carbohydrates, particularly of sugar, 
favors the extension into the small intestine of processes of decomposition 
normally confined to the colon), or on a change in the virulence of the bacteria, 
or on deficient production of enzymes. It is not always possible in such cases 
to decide whether bacteria, foreign to the intestine, are not also concerned in 
the production of poisons. The appearance of cystin in the urine is to be 
regarded, according to the researches of Baumann and von Udranski, as evi- 
dence of intestinal decomposition resulting in the production of diamins. 
The hypothesis. that puerperal eclampsia is an autointoxication is sup- 
ported by the majority of writers.. Clinically the formation of toxic substances 
during pregnancy may be recognized by the occurrence of nausea, vomiting, 
emotional depression, hasmoglobinuria, albuminuria, and finally by convulsions 
and coma. The anatomical findings in women who have died of eclampsia are 
multiple thromboses in the smaller vessels and capillaries, and focal degenera- 
tions, usually associated with haemorrhages in the liver (hemorrhagic hepatitis). 
In the lungs there may also be found syncytial cells. The fibrin-content of the blood 
is markedly raised. Should the child die (as takes place in about forty per cent, of 
cases) corresponding changes may be found in its liver and blood. 
It was at first thought that the origin of the poison was in the maternal 
organism, and the cause was sought in alterations of proteid metabolism in 
which the disturbances of function were located in the kidneys, or in the liver 
or the thyroid. Recently the view has been advanced that the intoxication is 
to be referred to products of the placenta (cytotoxins). Veit assumes a direct 
intoxication through placental elements which takes place when the placental 
toxin can no longer be rendered inactive through the formation of antitoxin 
(syncytiolysin). On the other hand, Arcoli believes that the mother produces 
an excess of syncytiolysin and thereby poisons herself. Weichart thinks that 
there are formed through, syncytiolysis, that is, the solution of the transported 
placental elements, albumin bodies (syncytiotoxins) which are poisonous to the 
mother. At the present time it cannot be decided which one of these hypothe- 
ses corresponds most fully to the actual conditions. DISTURBANCES OF INTERNAL SECRETIONS. 
59 
§ 24. If a gland produces an internal secretion—that is, if it gives 
to the lymph or blood substances which are necessary for the perform- 
ance of the functions of other organs or of the body as a whole— 
alteration or withdrawal of this secretion is succeeded by more or less 
grave disturbances. Such an internal secretion is ascribed to the pan- 
creas, thyroid, adrenals, pituitary, thymus, and the sexual glands. We 
are able to infer the influence exerted by these glands on metabolism 
and life from the disturbances which arise when the glands in question 
become diseased. Among the more important diseases belonging in 
this category are diabetes mellitus, exophthalmic goitre, the dystrophies 
of pituitary origin, eunuchoidism, myxcedema, cretinism, Addison's dis- 
ease, and the functional and anatomical changes occurring in the body 
after castration. 
Diabetes mellitus is a disease which is characterized by large 
amounts of grape-sugar in the urine (glycosuria), accompanied by great 
increase in the amount of urine secreted (polyuria), and often by 
acetone and the excretion of aceto-acetic acid and /I-oxybutyric acid. 
At the same time grape-sugar and these acids are found in the blood and 
lead to diminution of its alkalinity. When the acid-content of the blood 
is high, headache, delirium, fainting, and finally loss of consciousness 
(coma diabeticum) develop. 
Glycosuria may be caused by too great ingestion of sugar, so 
that part passes into the urine unchanged (alimentary glycosuria). 
Glycosuria may also follow injury to certain portions of the 
medulla oblongata (puncture of Bernard), or as the result of fracture 
of the skull with hemorrhage, epilepsy, severe psychical disturbances, 
tumors, parasites, or of certain forms of poisoning (carbon monoxide, 
curare, morphine, strychnine, amyl nitrite, nitrobenzol), in which the 
liver probably gives its glycogen to the blood more rapidly than normal, 
so that hyperglycsemia is produced. 
Finally, glycosuria may be due to inability on the part of the kidneys 
to hold back the small amounts of glucose normally found in the blood, 
a phenomenon which may be produced experimentally by the administra- 
tion of phloridzin (von Mering) or of caffeine sulphate (Jacobj). 
These alimentary, nervous, and toxic glycosurias are to be sharply 
distinguished from true diabetes. In the latter the cause of the gly- 
cosuria is to be sought, not in an increased conveyance of sugar into 
the blood, or in a pathological excretion of the sugar normally contained 
in the blood, but rather in the fact that the diabetic patient is unable 
to decompose carbohydrates, notably dextrose, although the sugars which 
turn polarized light to the left (levulose and inulin) can be oxidized either 
wholly or at least in greater amounts than dextrose. In most cases the 
power to form fats from carbohydrates is also lessened, yet there are 
instances in which this function is unimpaired and the sugars are stored 
in the body in the form of fat (diabetogenous obesity). 
Accordng to the investigations of von Mering and Minkowski, which 
have been confirmed by others, this loss of power to oxidize the sugars 
brought to or formed in the body, or to store them as glycogen or fat, 
is to be ascribed to insufficiency of pancreatic function. This conclu- 
sion is drawn chiefly from the fact that after total extirpation of the 
pancreas in dogs, diabetes of severe character, usually fatal within a few 
weeks, is produced, this being characterized, as is diabetes in the human 
subject, by polyuria, polydipsia, hyperglycsemia, glycosuria, diminution 60 
THE GENERALIZATION OF DISEASES. 
of the glycogen of the tissues, at times by marked destruction of albumin, 
emaciation, excretion of large amounts of acetone, aceto-acetic acid, 
/3-oxybutyric acid, and ammonia, as well as by the occurrence of diabetic 
coma. In support of the view that there is a definite relation between 
disturbances of pancreatic function and diabetes, it has been found 
that in this disease in man the pancreas has exhibited demonstrable 
changes, of the nature of atrophy or degeneration. Thus it has been 
shown by Opie, and abundantly confirmed by others, that a large per- 
centage of all subjects dead of diabetes mellitus exhibit sclerotic or 
hyaline changes in the islands of Langerhans. In those instances where 
anatomical changes in the pancreas are not found we are forced to con- 
tent ourselves with the hypothesis that our methods of investigation are 
defective or that there is a variety of extra-pancreatic diabetes. 
An exact explanation of the relations between pancreatic disease and 
diabetes cannot be given, yet from the foregoing researches the hy- 
pothesis has been deduced that the pancreas produces an internal secre- 
tion which either gives the body the power to destroy glucose or in- 
creases this glycolytic capacity. Likewise, no explanation can be given 
for the increased destruction of the albumins and the accompanying 
abundant production of /3-oxybutyric acid, aceto-acetic acid, and acetone. 
Since these substances are not always found in experimental pancreatic 
diabetes, their formation probably does not stand in direct relation fi> the 
excretion of sugar, but is to be regarded as a complication of diabetes 
(Minkowski). Their occurrence in human diabetes, moreover, is not 
constant, and they are found in other diseases (intoxications, carcinoma, 
disturbances of digestion, pregnancy, starvation, ether narcosis, etc.). 
The occurrence of diabetes after total extirpation of the pancreas is evidence 
that this organ possesses a special function which is of the greatest importance in 
the normal consumption of sugar in the organism. Lepine is of the opinion that 
there is in the blood a glycolytic ferment, which is formed by the pancreas and 
passed from this organ into the blood; and that the cause of the mellituria in 
diabetic patients and in dogs from which the pancreas has been removed is to be 
sought in decrease in the amount of this ferment. According to Cohnheim, Ralicl 
Hirsch, Arnheim, Blumenthal, and others the pancreas has the power, in a way 
not explained, of exciting to action the glycolytic ferments found in the different 
organs. The addition of pancreatic emulsion (Cohnheim) to the expressed juice 
of muscle increases its glycolytic capacity. At the present time it is impossible to 
offer a satisfactory explanation of the pathogenesis of pancreatic diabetes. Accord- 
ing to Stoklasa the anaerobic respiration of the animal organs is an alcoholic fer- 
mentation caused by enzymes which may be separated from the cells and obtained 
in the form of powder. They will produce an alcoholic fermentation as long as 
they are not subjected to the action of lactic acid and thereby inhibited. In 
diabetes such an inhibition of the splitting of glucose into alcohol and carbonic 
acid occurs through the formation of lactic acid. 
If only a portion of the pancreas of a dog be removed, no diabetes occurs, or 
at least the excretion of sugar is much less than after total extirpation (1Minkow- 
ski). If in dogs from which the pancreas has been totally removed a portion of 
pancreas is transplanted subcutaneously, diabetes does not follow (Minkowski, 
Hedon), but occurs if the transplanted piece be excised. 
According to Minkowski, there is no direct communication between the secre- 
tory function of the pancreas and that function of the organ concerned in the 
metabolism of sugar. 
Poisoning with phloridzin produces, according to von Mering and Minkowski, 
a marked glycosuria in most animals and in man, and the same symptoms as those 
seen in diabetes, may be produced by continuous administration of the poison. 
Since in this case the cause of the pathological excretion of sugar lies in the kidneys 
and represents a flushing-out of sugar from the organism, phloridzin diabetes can- 
not be identified with the ordinary form of diabetes found in man — that is with CACHEXIA THYREOPRIVA. 
61 
pancreatic diabetes. In dogs in which diabetes has been produced by the extirpation 
of the pancreas, phloridzin produces an increase in the amount of sugar excreted 
(Minkowski). 
Literature. 
{Diabetes Mellitus.) 
v. Mering: Ueber experimentellen Diabetes. Verhandl. d. V. u. VI. Congr. 
f. inn. Med., Wiesbaden, 1886, 1887; Zeitschr. f. klin. Med., xiv., 1888, and 
xvi., 1889. 
v. Mering u. Minkowski: Diabetes mellitus nach Pankreasexstirpation. Arch, 
f. exper. Pathol., 26 Bd., 1890; Zeitschr. f. Biol., 29 Bd., 1892. 
Michael: Diabetes (Cysticercus im IV. Ventrikel). Deut. Arch. f. klin. Med., 
44 Bd., 1889. 
Minkowski: Diabetes nach Pankreasextirpation. Arch. f. exp. Path., 31 Bd., 
1893 (Lit.). 
Moritz u. Prausnitz: Phloridzindiabetes. Zeitschr. f. Biol., 27 Bd. 
v. Noorden: Pathologie des Stoffwechsels, Berlin, 1893 (Lit.). 
Opie: The Relations of Diabetes Mellitus to Lesions of the Pancreas. Journ. 
of Exp. Med., vol. v., 1901. 
Sauerbeck: Die Langerhansschen Inseln d. Pankreas. Ergebn. d. a. P., viii., 
1904. 
Seegen: La glycogenie animale, Paris, 1890; Der Diabetes mellitus, Berlin, 
1893. 
Stoklasa: Die glykolytische Enzyma im tier. Gewebe. D. med. Woch., 1904. 
Tiroloix: Le diabete pancreatique, Paris, 1892. 
§ 25. Cachexia thyreopriva is a disease caused by deficient or 
arrested function of the thyroid, resulting either from defective de- 
velopment or from pathological changes in the gland. Kocher was the 
first to observe that it followed extirpation of the thyroid, and his re- 
sults have been substantiated by many others. Numerous clinical 
observations and experimental researches have confirmed the fact that 
the presence of thyroid tissue is essential to the integrity of the organ- 
ism, especially during its period of growth. The gland produces a sub- 
stance known as thyroiodine which is the active ingredient of the colloid 
and which probably neutralizes or destroys certain poisons and at the 
same time exerts a complementary action on intracellular metabolism. 
According to older experimental observations, total extirpation of 
the thyroid gland produces in man and in animals severe symptoms 
characterized by muscular twitchings, convulsions, and paralysis, so- 
called tetany. It is now known, however, that the production of tetany 
is due, not to removal of the thyroid itself, but of the parathyroid 
glands (parathyreoprival tetany). 
If loss of the thyroid gland is at first well borne, there arise in man 
in the course of months or years peculiar disturbances of nutrition, be- 
ginning with weakness and heaviness of the limbs, feeling of coldness, 
pain and transient swelling, loss of mental activity, leading to cachexia 
associated with anaemia, by pale swellings of the skin, especially of the 
face, and diminution of mental powers, together with loss of muscular 
strength, these symptoms terminating in death. Removal of the thyroid 
gland in childhood causes disturbances of growth, the increase in length 
of the bones falling below the normal or ceasing altogether. Animals 
(rabbits and goats) that have had their thyroid glands removed soon 
after birth do not reach full growth and acquire an expression of stupidity. 
Disturbances of thyroid function, as well as total extirpation, lead 62 
THE GENERALIZATION OF DISEASES. 
to pathological conditions of the body. Both clinical observations and 
experimental investigations show that the disease known as myxoedema 
(Ord) is due to changes in the thyroid. Myxoedema is a condition in 
which the external appearance of the patient is indicative of thyreoprival 
cachexia, in that the same characteristic pale and elastic swellings of the 
skin of the face, are associated with similar changes in the skin of other 
parts of the body. Further, there is loss of intellectual power, which 
finds expression in increasing difficulty in thinking and acting, dullness 
of the tactile sense, retardation of muscular action, and a monotonous 
nasal voice. Finally, general weakness and pronounced symptoms of 
mental derangement occur, and death follows after gradually increasing 
cachexia associated with anzemia and coma. 
Cretinism is dependent on disturbances of thyroid function. In 
cretins there is always present some degenerative condition of the thyroid, 
the organ being either enlarged (goitre) and changed in structure 
(endemic cretinism), or imperfectly developed or absent (sporadic 
cretinism). The general appearance of cretins is similar to that of those 
individuals who as a result of thyroidectomy in early childhood have 
become stunted in development. The longitudinal growth of the long 
bones is below the normal, while the soft parts are well developed. Indi- 
vidual parts of the body are unequally developed; the head is relatively 
large, the abdomen and neck are thick, the bridge of the nose is depressed, 
while the nose itself is broad and stumpy; the skin is pale, flabby, 
wrinkled, or puffed, as if cedematous, particularly over the face, and the 
belly is protuberant. The mental faculties are feeble, sometimes markedly 
so. The power of speech and of understanding may be absent, and only 
in the less-marked cases of cretinism are the subjects capable of work of 
any kind. The cause of endemic cretinism is unknown. 
The importance of the thyroid gland in nutrition and development has been 
placed beyond doubt by clinical observations and experimental investigations. As 
to the mode of action of the thyroid, there are, however, different opinions. If an 
animal, after thyroidectomy, is fed with the thyroid of some other animal — for 
instance, that of the sheep — the injurious effects usually observed after removal 
of the thyroid do not appear and occur only when the feeding is stopped. In man 
the administration of fresh thyroid tissue or of thyroid extracts exerts a healing 
influence on the thyreoprival cachexia and myxoedema; and reports have been 
published of favorable results in the treatment in children suffering from cretin- 
like disturbances. 
According to the investigations of Baumann, the thyroid contains an iodine 
substance, thyroiodine or iodothyrin, which is present in greatest quantity in old 
individuals, and in the smallest quantity in young children. The normal thyroid is 
able to store the extremely small amounts of iodine brought to the body in vegetable 
foods or in drinking-water, and to convert it into thyroiodine. The internal 
administration of preparations of iodine leads to accumulation of iodine in the 
thyroid. 
According to Baumann, iodothyrin is the active element of the gland. Its 
employment in the treatment of goitres, myxoedema, and strumiprival cachexia, etc., 
has the same effect as feeding with fresh thyroid tissue. It would appear that the 
organism requires iodine for its maintenance, and that the thyroid supplies it with 
the necessary combination. In regions where goitres are not commonly found 
(North Germany), the thyroid glands are, on the average, smaller (from 30-40 gm.) 
and contain more iodine (on the average about 3T4 mgm. instead of 2 mgm.) than 
in regions where goitres are numerous (Switzerland, South Germany). Whether 
lack of iodine in the food and drinking-water is the cause of the hypertrophied 
condition of the thyroid in goitre, or whether some injurious agent, perhaps some 
lower organism, interferes with the specific function of the gland, cannot be said. 
Among domestic animals having a large amount of iodine in the thyroid are the 
sheep, cow, and calf, while in hogs the iodine-content is small. EXOPHTHALMIC GOITRE; ACROMEGALY. 
63 
Anatomical investigations have failed to throw definite light on the question 
of the internal secretion of the thyroid. It has been proved that the colloid pro- 
duced by the thyroid cells passes into the lymph-vessels. It is probable that 
iodothyrin is obtained in this colloid substance. During intra-uterine life the 
thyroid appears to be destitute of that function, which in later life is so important. 
Graves’ disease, or exophthalmic goitre, which is characterized by goitre, 
exophthalmos, rapid heart, tremor and great excitability on the part of the patient, 
is dependent on disease of the thyroid characterized by hypersecretion (hyper- 
thyreosis). According to Beebe the experimental feeding of thyroid glands pro- 
duces symptoms and metabolic changes similar to those of Graves’ disease. Removal 
of a considerable portion of the gland will in many cases effect a cure; and recur- 
rence of the disease after operation is in most cases accompanied by recurrence of 
the tumor. Oswald has shown that the colloid of the glands from cases of 
exophthalmic goitre is, in the majority of cases, deficient in iodine. He believes 
that the symptoms are due to flooding of the body by altered secretion. Ewing 
Fig. 4.—(Bellevue Hospital,) Acromeyaly, showing the enlargement and spade-like char- 
acter of the hands. 
has studied the histological changes in the glands of forty cases of exophthalmic 
goitre, and believes, in common with other writers, that the findings are to a certain 
extent specific. In many instances of exophthalmic goitre, however, the histological 
changes in the thyroid present no essential differences from those of ordinary forms 
of goitre. Symmers has shown that the so-called idiopathic cardiopathy is asso- 
ciated with sclerotic and hyperplastic changes in the thyroid gland, and suggests 
that this variety of cardiac enlargement is part of an ill-developed variety of Graves' 
disease (thyro-toxic cardiopathy). Some writers regard the thymus as associated 
in some way with the pathogenesis of exophthalmic goitre, but no definite, proof of 
this is at hand. Preliminary removal of thymic tissue has been practiced with 
beneficial results in the operative treatment of Graves’ disease (Halstead). 
Acromegaly may be defined as a dystrophy characterized by increase in size of 
the bones of the face and extremities, associated with perverted secretion of the 
pituitary body. Hyperactivity of the anterior lobe of the pituitary coming on 
before completion of epiphysial ossification results in giantism; that is to say, the 
individual is overgrown, but well proportioned. If epiphysial ossification is com- 
plete, however, hyperactivity of the pituitary results in acromegaly with or with- 
out giantism. That the relationship between acromegaly and giantism is close, is 
shown by the fact that a considerable percentage of acromegalics are giants and 
that a still larger percentage of giants eventually develop acromegaly. Clinically, 64 
THE GENERALIZATION OF DISEASES. 
acromegaly is characterized by increase in the size of the bones of the head, par- 
ticularly those of the face. Thus, hypertrophy of the cranial bosses, the supra- 
orbital ridges, the malar bones, both maxillae, and the nasal bones gives rise to 
profound changes in facial expression. In addition, enlargement of the bones of 
the hands produces a spade-like appearance. The nails are usually broad, but 
there is no curving and the terminal phalanges are not bulbous. The feet are uni- 
formly enlarged. Later the spine may be affected. In acromegalic giantism, in 
addition to changes in the osseous system, there is enormous increase in the size 
of the viscera, notably the heart, lungs, liver and spleen (the so-called 
splanehnomegaly) and atrophy of the genitals. Acromegaly and acromegalic 
giantism both depend on disease of the pituitary, such as adenomata and other 
tumors, or replacement by syphilitic or tuberculous granulomata, cysts, etc. Both 
commonly are attended by changes in other of the ductless glands. For example, 
the association of status lymphaticus is common, and changes in the thyroid occur 
so frequently in conjunction with enlargement of the pituitary, that certain observers 
have been led to the conclusion that interference with the interaction of these 
glands is a formidable factor in the production of the disease in question. More- 
over glycosuria is of frequent occurrence in acromegaly and acromegalic giantism. 
Sometimes it is a symptom of genuine diabetes and is associated with sclerotic 
or hyaline changes in the islands of Langerhans. At other times it is an expression 
of diminished tolerance for carbohydrates, brought about by increased activity of 
the pituitary. In still other instances, subjects of acromegaly develop signs of 
pituitary insufficiency, marked by greatly increased tolerance of carbohydrates, 
adiposity, impotence, etc. Acromegaly usually begins in the third or fourth decade 
and is rather more frequent among men than women. Heredity appears to play 
an important role. For example, the disease has been observed in both parents 
and a child, in father and son, in father and daughter, in mother and daughter, and 
in a case of acromegalic giantism that I investigated postmortem at the Willard 
Parker Hospital in New York, tlhe disease occurred in two brothers. 
Literature. 
(Cachexia Thyreopriva, Myxoedema, Acromegaly, Cretinism, and 
Graves' Disease.) 
Baumann: Jod im Thierkorper. Zeitschr. f. phys. Chem., 21, 22 Bd., 1895-1896; 
Jodothyrin. Munch, med. Woch., 1896. 
Bayon: Beitr. z. Diagnose und Lehre vom Kretinismus, Wurzburg, 1903 (Lit.), 
Beadles: The Treatment of Myxoedema and Cretinism. Journ. of Med. Sc., 
1893. 
Blumreich u. Jacoby: Bedeutung der Schilddriise. Arch. f. d. ges. Phys., 64 
Bd., 1896. 
Buschan: Myxodem. Eulenburg’s Realencyklop., xvi., 1898. 
De Coulon: Thyreoidea u. Hypophysis der Kretinen. Virch. Arch., 147 Bd., 
1897. 
Edmunds: Observ. and Exper. on the Thyroid. J. of Path., vii., 1900. 
Ewald: Die Erkrankungen der Schilddriise, Myxodem und Kretinismus, Wien, 
1896 (Lit.). 
Ewing: Exophthalmic Goitre from the Standpoint of Serum Therapy. New 
York Med. Jour., lxxxiv., 1906. 
Gley: Effets de la thyroidectomie. Arch, de phys., iv., 1892; vii., 1895. 
Gull: Cretinoid State Supervening in Adult Life in Women. Trans, of the Clin. 
Soc., London, 1893. 
Halsted: Hyipoparathyreosis. Amer. Jour, of Med. Sc., 1907. 
Horsley: Function d. Schilddriise. lnternat. Beitr. Festschr, f. Virchow, i., 
Berlin, 1891 (Lit.). _ 
Kocher: Kropfexstirpation u. ihre Folgen. Arch. f. klin. Chir., 27 Bd., 1883; 
Verhutung des Kretinismus. Deut. Zeit. f. Chir., 34 Bd., 1892; Schilddriisen- 
function. Correspbl. f. Schweizer Aerzte, 1895. 
Lannois: De la cachexie pachydermique (myxoedeme). Arch, de med. exp., i., 
1889. 
MacCallum: J. Exp. Med., xx., 1914. 
Ord: On Myxoedema. Med.-Chir. Trans., lxi. and Bri. Med. Journ., 1877. 
Osier: Sporadic Cretinism in America. Trans. Assn, of Amer. Phys., 1893, 
vol. viii. ADDISON’S DISEASE. 
65 
Oswald: Jodgehalt d. Schilddriisen. Zeit. f. phys. Chem. xxiii., 1897; Function. 
Munch, med. Woch., 1899. 
Ponfick: Myxodem u. Akromegalie. Cbl. f. allg. Path., ix., 1898; Zeit. f. klin. 
Med., 38 Bd„ 1899. 
Seligmann: Cretinism in Calves. Jour, of Path., ix., 1904; Symmers and Wal- 
lace, Fetal Chondrodystrophy. Arch. Int. Med., xii., 1913. 
Stewart: T/he Treatment of Myxoedema by Thyroid Feeding. Fortschr. d. Med., 
1894. 
Stieda: Hypophyse d. Kaninchens nach Entfernung d. Schilddriise. Beitr. v. 
Ziegler, vii., 1890. 
Symmers: Idiopathic Cardiopathy. Arch. Int. Med., 1918. 
§ 26. Addison’s Disease is to be regarded as the result of functional 
disturbance of the suprarenals. It is characterized by the appearance 
of a light-yellow-brown to dark-brown, diffuse, and spotted pigmenta- 
tion (melasma suprarenale), which shows itself first in the portions of 
the skin normally exposed, later in other parts, notably in those cutane- 
ous surfaces which are subject to irritation, such as the neck, waist, 
wrists and ankles; and in the more exposed mucous membranes, such as 
those of the mouth and lips, occasionally the penis or vagina. Even 
at the beginning of the disease, or before the pigmentation of the skin, 
there occur loss of appetite, nausea, diarrhoea or constipation, and 
vomiting — all symptoms of disturbed intestinal and gastric function; 
later, muscular weakness: asthenia, fatigue on slight exertion; headache, 
vertigo, fainting, epileptiform attacks, and coma. Occasionally recogniz- 
able increase of the pigment of the skin does not occur and the disease 
is characterized only by gastro-intestinal symptoms, progressive weak- 
ness, and anaemia. 
In about eighty-eight per cent of all cases of Addison’s disease the 
suprarenals are found to be diseased, the majority being changed into 
caseous or fibro-caseous masses of tuberculous nature. More rarely 
there are found tumors in the adrenals or simple atrophy, agenesia, or 
hypoplasia. Alterations in the suprarenals bear a causal relation to the 
symptoms described above; the disease may, therefore, be designated as 
suprarenal cachexia. It is not improbable that the suprarenal bodies, 
like the thyroid, produce a substance which is necessary for the preserva- 
tion of the organism; that poisonous substances are destroyed by them is 
known, since epinephrin, which is the active principle of the adrenal 
mudulla, has been shown to neutralize diphtheria toxin (Marie, Stutzer). 
The suprarenal capsule represents, developmentally, two sets of organs which, in 
higher forms, are fused, the cortex originating in the mesoderm and the medulla 
in the neuroectoderm. The cortex, which is of companion origin with the testicle 
in the male and the ovary in the female, is in some way connected with sexual 
activities. For example, there is a tumor of the adrenal cortex which, when it 
develops before the onset of puberty, brings about certain changes in bodily growth 
and in the development of the genitals and secondary characteristics that can be 
attributed only to interference with the normal function of the cortical cells. The 
medulla, on the contrary, is composed largely of nervous elements and of 
polymorphous cells which, when treated with chrome salts, take on a brownish 
appearance and are known as chromaffine cells. Identical cells are encountered in 
situations beyond the suprarenal capsule, mainly in the tissues along the course of the 
abdominal aorta — the so-called Zuckerhandl’s paraganglia. It is held by many 
that the specific function of the suprarenal and other chromaffine cells is to furnish 
an internal secretion which maintains the vascular and muscle tone and controls 
the amount and distribution of certain pigment in the skin and mucous membranes. 
Interference with the function of the chromaffine system, particularly with those 66 
THE GENERALIZATION OF DISEASES. 
elements which reside ini the suprarenal medulla, is followed by changes of profound 
importance, notably by the disease described by Addison. In other cases, however, 
it is possible for extensive changes to arise in both suprarenal capsules without 
Addison’s disease. In these circumstances it is held that islands of functionating 
suprarenal tissue are still intact and, in addition, that the extra-capsular chromaffine 
cells are called on to compensate for those lost by destruction of the suprarenals. 
Conversely, Addison’s disease may arise without detectable changes in the supra- 
renal capsules, in which case it is argued that the extra-capsular chromaffine system 
is the seat of disturbance, the supply of chromaffine cells in the suprarenal bodies 
being inadequate to balance the loss. 
Of over 5,600 autopsies at Bellevue Hospital destructive lesions of the supra- 
renal capsules were encountered 48 times. In 23 cases the lesion was unilateral, in 
25 bilateral. Of the 48 cases both suprarenal capsules were completely or almost 
completely destroyed in 18 cases of long standing, but in not one of the number 
were signs of Addison’s disease detected. In two other cases, however, both supra- 
renals were completely replaced — once by tumor metastases and once by caseating 
tuberculosis, and in both instances the patients during life presented diffuse, dirty 
yellowish pigmentation of the skin, low blood pressure and asthenia. Similar cases 
of “ suprarenal insufficiency ” attended by symptoms comparable to those of Addi- 
son’s disease have been recorded by Osborne. It appears from such observations 
that typical and fully developed Addison’s disease depends on more complete 
changes than destruction of the adrenals alone. It is probable that involvment 
of the coeliac ganglia plays an important part in completing the pathological 
picture. 
The view is widely prevalent that the epinephrin of the suprarenal capsule is 
indispensable to life, that it is an important factor in the maintenance of muscle 
and vascular tone, and that in certain circumstances it acts as a detoxicating agent, 
notably in diphtheria (Marie, Ann. de l’lnstit. Pasteur, 1918). Recently Cannon 
and his coworkers (Am. Journ. Physiol., 1919) have advanced the view that the 
suprarenal medulla is stimulated to secrete epinephrin by emotional excitement, pain 
and asphyxia—'Conditions which are known to be accompanied by activity on the 
part of the sympathetic nervous system — in other words, that the physiological 
reaction to fear and related emotional states depends on hypersecretion of epinephrin 
into the circulation. This view has been combated by Stewart and Rogoff, who 
insist that there is no increase of suprarenal secretion in the emotional states 
mentioned. The same investigators have demonstrated (Am. Journ. of Physiol., 
1919) that it is possible for animals to live indefinitely in good health after one 
suprarenal capsule has been excised and the nerve of the other sectioned, an opera- 
tion which either abolishes the output of epinephrin or reduces it to a minimum, 
in other words, that epinephrin is not essential to muscle and vascular tone. 
§ 27. As a pathological condition due to loss of a specific glandular 
function should be classed those changes in the body resulting from 
castration — that is, the removal of the sexual glands. If the ovaries 
are removed after puberty, menstruation ceases at once, rarely after 
some time. Sexual desire and the erethism accompanying the sexual act 
are usually diminished in intensity, but may be unchanged. The re- 
maining portions of the genital apparatus undergo atrophy; this is 
marked in the case of the uterus. Certain nervous manifestations may 
follow, the most common of which are excitement, with flushing of the 
skin, especially of the face, associated with attacks of sweating; these 
symptoms are of most frequent occurrence in the period immediately 
following the castration. The disposition remains unchanged or even 
becomes more cheerful, especially in those cases in which the woman 
by castration is relieved of pain. At times depression or melancholia 
may follow. If the ovaries are removed or destroyed during childhood, 
the secondary sexual characters are not clearly defined; the muscles are 
more strongly developed, the configuration of the pelvis is changed, and 
the breasts do not increase in size. 
Castration in an adult male produces no marked change in build. 
On the other hand, if boys are castrated, the body loses in masculine EUNUCHOIDISM; STATUS LYMPHATICUS. 
67 
character. There is increased deposit of fat, particularly the abdomen, 
while the musculature is feebly developed. The external genitals remain 
small, the prostate is diminished in size, and there is little or no growth 
of beard or pubic hair. The larynx is infantile, the voice child-like. 
The mental powers are lacking in energy and strength. 
A type of physical degeneracy is described under the title of eunuchoidism 
or dystrophia adiposo-genitalis. The male eunuchoid is an individual whose 
bodily configuration is characterized by abnormal length of the extremities and 
in whom the distance from the umbilicus to the soles of the feet is noticeably 
greater than that from the umbilicus to the crown of the head. There are marked 
accumulations of fat in the region of the breasts and mons veneris while the abdo- 
men is protuberant and the waistline narrow. The penis, testicles and scrotum are 
extraordinarily small, the pubic hair scanty and of the feminine type, the voice is 
high and shrill, the skin pale and satiny. Most of these individuals are sterile. In 
female eunuchoids the breasts are poorly developed or fatty and contain few 
glandular elements. A male subject of eunuchoidism, age 22 years, was investi- 
gated postmortem at Bellevue Hospital. In addition to the peculiarities of con- 
figuration, it was found that the seminal vesicles contained only a thin, milky fluid. 
Both testicles were extremely small, measuring 1x1*4 cm. They were dark brown 
in color and firm. The prostate, on the contrary, was apparently normal in size and 
consistence. 
According to White, Kirby, Kummel, Bruns, and others, castration in fully 
developed animals causes decrease in the size of the prostate; and castration of old 
men suffering from prostatic enlargement was at one time practiced as a surgical 
procedure; even now castration is a religious rite among certain fanatics, notably 
among Russian peasants. 
In what way extirpation of the sexual glands affects the body has not been 
determined. By many it has been assumed that, as a result of castration, the 
trophic influence exerted on the tissues by the sexual glands is withdrawn; but it 
is more likely that chemical substances, which exert a certain influence on functions, 
growth, and development, are formed in the sexual glands. 
According to the investigations of Loewy and Richter, after castration of female 
dogs there occurs lowering of the oxidation-power of the cells and decrease in the 
amount of oxygen used by about twenty per cent. According to Breuer and von 
Seiller, the total mass of haemoglobin and red blood-cells is diminished. The admin- 
istration of dried ovarian substance or of oophorin from the ovaries of the cow 
or hog to the animal operated on causes an increase in the amount of oxygen con- 
sumed even greater than the average observed before castration. Preparations of 
testicles showed no such influence. In male dogs the same conditions prevailed; 
spermin caused only slight increase in the gaseous interchange, oophorin gave a 
marked increase (as much as forty-four per cent.). 
According to the investigations of Born and L. Fraenkel the corpus luteum 
appears to possess an internal secretion. On the one hand, it is thought to govern 
the metabolism of the uterus and to make possible the insertion of the impregnated 
ovum, and, on the other hand, to excite menstruation. 
The thymus has often been credited with' an internal secretion. Most investi- 
gators are now convinced that this is not true and that the thymus is not essential 
to life. In animals extirpation produces no noteworthy detectable alterations, 
although it cannot be denied that it may have some influence in delaying closure 
of the epiphyses, thus retarding development. 
Chief interest in the thymus centers in its association with sudden death 
in the condition known as status lymphaticus. Status lymphaticus is not a disease. 
On the contrary, it is to be defined as a combination of hereditary constitutional 
anomalies, entering into which are certain peculiarities of configuration (Norris), 
with preservation or hyperplasia of the thymus gland at an age when involution 
is to be expected, hyperplasia of the lymphoid cells in the spleen and intestine, and, 
to a less extent, in the lymph nodes, hypoplasia of the cardio-vascular system, 
developmental deficiencies in the genitalia and incidental, visceral anomalies of 
uncertain occurrence and irregular distribution. The condition sometimes is termi- 
nated by sudden death, usually in children, but occasionally in young adults. 
Although status lymphaticus is compatible with life, it is, nevertheless, a menace, 
and for at least three reasons: (1) Because it is attended by certain necrotic 
changes in the lymphoid tissues, providing a mechanism which, when once set in 68 
THE GENERALIZATION OF DISEASES. 
motion, is capable of so sensitizing the body as to produce anaphylactic phenomena 
varying, from simple urticarial rashes to convulsive seizures or sudden death. 
The theory that sudden death in status lymphaticus may be due to pressure of 
the enlarged thymus on the trachea is not tenable. In the Bellevue Hospital 
autopsies not a single incidence of death from this cause was found. (2) The 
same instability of the lymphoid tissues is apparently responsible for lowering the 
threshold of infection, particularly those infections which gain entrance through 
the pharyngeal and faucial tonsils and the lymphoid structures of the intestinal 
tract. (3) It is attended by defective development of the muscular coat of the 
arteries and renders them incapable of withstanding increased blood pressure of a 
degree ordinarily well borne. Status lymphaticus is easily recognized clinically. The 
angelic child of the elder Gross is of this category. In male adults there are two 
types of configuration — the rectangular and the Appoline. In the first the 
shoulders are squared and the chest somewhat flattened antero-posteriorly. In the 
second the muscular development often attains magnificent proportions. In both 
varieties the skin is of unusually delicate texture; the facial, axillary and pubic hairs 
are scanty, the latter being more or less sharply defined in a transverse direction; 
the waistline is narrowed and the thighs are rotund and arching. In the female 
the delicate texture of the skin, the accentuation of the graceful outlines of the 
body and the presence of small axillary fat pads with the scanty growth of hair on 
them, combine to render recognition easy. Status lymphaticus is fairly common. 
It was recognized in about eight per cent, of six thousand autopsies at Bellevue 
Hospital. The average weight of the thymus gland was about twenty-five grams. 
In status lymphaticus the aorta and the cerebral vessels are hypoplastic in about 
forty per cent, of cases. Rupture of the cerebral blood vessels with fatal 
haemorrhage into the pia arachnoid or into the substance of the brain not infre- 
quently occurs, spontaneously or under the influence of such trivial causes as 
argument, fighting, etc. Status lymphaticus is a distinct contraindication to the 
acceptance of a workman for duty in an atmosphere of compressed air, since decom- 
pression is apt to be followed by sudden death. Status lymphaticus is common 
among the emotionally unstable — drug habitues, neurasthenics and the insane, 
suicides, degenerates and criminals. Its association with exophthalmic goitre is 
exceedingly common and the same is true of chlorosis, Addison’s disease, acrome- 
galy, and the like. Finally, it has been shown by Daut, Elser and Symmers that 
diphtheria, cerebro-spinal meningitis, typhoid fever and acute infective endocarditis 
occur with noticeable frequency in subjects of status lymphaticus and that these 
and other infections in such individuals are apt to pursue a rapidly fatal course. 
Literature. 
(Function of Adrenals and Addison’s Disease.) 
Abel: Epinephrin. Zeitschr. f. phys. Chem., 28 Bd., 1899. 
Addison: On the Constitutional and Local Effects of Disease of the Suprarenal 
Capsules, London, 1855. 
Alezais et Arnaud: fitudes sur la tuberculose des capsules surrenales et ses 
rapports avec la maladie d’Addison. Rev. de med., xi., 1891. 
Bulloch and Sequeira: The Relation of the Suprarenal Capsules to the Sexual 
Organs, Transactions of the Path. Soc., London, 1905. 
Fraser: The Origin of Hypernephroma of the Kidney, Surg., Gynecology and 
Obstet., 1916. 
Karakascheff: Z. path. Anat. d. Nebennieren. Beitr. v. Ziegler, xxvi., 1904. 
Linser: Nebennieren u. Korperwachstum. Beitr. v. Bruns, 37 Bd., 1903 (Lit.). 
Oliver: On the Therap. Employ, of the Suprarenal Glands. Brit. Med. Journ., 
ii., 1895. 
Osborne: Two Cases of Suprarenal Disease. Am. J. Med. Sc., 1918. 
Philips: Addison’s Disease with Simple Atrophy of the Adrenals. Jour, of 
Ex.p. Med., 1899. 
Rolleston: The Suprarenal Bodies. Brit. Med. Journ., 1895. 
Symmers: Addison’s Disease, Interstate Med. Journ., 1917; Neuroblastoma, 
Journ. Am. Med. Assn., 1913. 
Tizzoni: Ueber die Wirkungen der Exstirpation der Nebennieren. Beitr. v. 
Ziegler, vi., 1889. FEVER. 
69 
(Results of Castration; Internal Secretion of Sexual Glands; Status 
Lymphaticus.) 
Breuer u. von Seiller: Einfl. d. Kastration auf d. Blu>tbefund. A. £. exp. Path., 
SO Bd., 1903. 
Loewy u. Richter: Sexualfunction u. Stoffwechsel. Arch. f. Anat., Suppl., 1899. 
Metschnikoff: Spermatoxine et Antispermatoxine. Ann. de l’lnst. Pasteur. 
1900. 
Mobius: Die Wirkungen der Kastration. Halle, 1903. 
Norris: Status Lymphaticus. Johnson’s “Surgical Diagnosis,” iii., 1910; Sym- 
mers, Am. J. of the Med. Sc., 1918; Am. J. Dis. Children, 1917; Blumer, 
Johns Hop. Hosp. Bull., 1903. 
IV. Fever and Its Significance. 
§ 28. When a local organic disease takes on the character of a gen- 
eral disease, or when a disease at its inception manifests such a char- 
acter, there frequently is seen the symptom-complex known as fever. 
Particularly in infectious diseases associated with symptoms of intoxi- 
Fig. 5.—Temperature-curve of a continued remittent fever, with slowly risin'g and gradually 
falling curve (typhoid fever). 
cation does the appearance of fever play an important role. The char- 
acteristic sign of fever is increase of bodily temperature; but accompany- 
ing this are other symptoms, especially increase of the pulse-rate, disturb- 
ances in the distribution of the blood, changes in the gaseous interchange 
within the lungs, and changes in the urinary secretion. There is usually 
a subjective feeling of illness, but this is not a necessary part of the 
symptomatology of fever, but the effect of poisoning associated with 
infection. 
Observation has taught us that, in spite of changes of temperature 
externally, the body-temperature is maintained at an average height of 
37.2-37.4° C. (98.96—99.32° F.). The absolute variation between morn- 
ing and evening is 1—1.5° C. (1.8—2.7° F.), the maximum occurring at 
evening. 
The elevation of temperature of the body above that of its surround- 
ings is due to the fact that through chemical changes, particularly in the 
muscles and glands, heat is produced, and to such an extent that the 
temperature may be raised one degree Centigrade (1.8° F.) in half an 
hour. This phenomenon of heat-production is offset by one of heat- 
dispersion, occurring chiefly through the skin, lungs, and the excreta. 
Both heat-production and heat-dispersion are under the influence of the 
nervous system, and through its regulation of both processes a constant 
temperature is maintained. 70 
THE GENERALIZATION OF DISEASES. 
On exposure to lower temperatures heat-production is increased 
(chiefly through the agency of the muscles), while heat-dispersion is 
lessened through contraction of the cutaneous vessels and inhibition of 
perspiration. 
On exposure to higher temperatures heat-dispersion is increased 
through increased frequency of respiration, dilatation of the arteries of 
the skin, and increased secretion of sweat. 
In that condition which we call fever there is disturbance of the 
regulation of heat-production and heat-dispersion, in favor of heat- 
production, so that the temperature of the body is elevated above the 
normal (Figs. 5—7). Elevations of temperature (rectal measurements) 
to 38° C. (100.4° F.) are called hypernormal; from 38° to 38.5° C. 
(100.4-101.3° F.), light fever; from 38.5° to 39.5° C. (101.3-103.1° F.), 
moderate fever; 39.5-40.5° C. (103.1-104.9° F.), marked fever; over 
40.5° C. (104.9° F.) (evening temperature), high fever; and over 
41° C. (105.8° F.), as hyperpyrexia. 
Four periods may be distinguished in fever. The first, which is 
known as the pyrogenetic or initial stage, corresponds to that time dur- 
Fig. 6.—Temperature curve of a 
continued fever with rapidly ascend- 
ing and rapidly falling curve (pneu- 
monia). 
Fig. 7.—Temperature-curve of an in- 
termittent tertian fever (malaria). 
ing which the previously normal temperature reaches the average 
height characteristic of the disease. This period is sometimes short 
(Fig. 6), half an hour to two hours long and is usually accompanied 
by a chill; sometimes longer (Fig. 5), one to several days, and usually 
runs its course without a chill, though chilly sensations may repeatedly 
occur. 
In the second period, known as the fastigium, whose duration varies 
according to the disease from a few hours to several weeks, the 
temperature reaches one or several high points, between which there 
are more or less marked remissions. 
In the stage of decline or defervescence, the body-temperature 
returns to the normal. If this takes place through a rapid fall (Fig. 
6), it is called crisis; if slowly it is termed lysis (Fig. 5). The 
former is usually accompanied by profuse sweating, and in a few hours, 
or at most in one to one and a half days, the temperature falls two or 
three degrees, occasionally as much as five or six degrees Centigrade. 
In lysis the temperature falls gradually for three to four or more days; 
the decline may be either continuous or intermittent. FEVER, 
71 
The boundary line between fastigium and defervescence is not al- 
ways sharply defined, and before the latter sets in there may occur 
elevations of temperature. Between fastigium and defervescence there 
may be several days of uncertainty with striking fluctuations upward 
or downward. Occasionally there is a short period in which the 
temperature is somewhat lowered, but yet remains high above the 
normal, to sink after a few days to the normal, either rapidly or by 
gradual decline. 
In the stage of convalescence the temperature returns to the normal. 
The heat-regulation during this time is still imperfect, so that often 
slight elevations and not infrequently subnormal temperatures occur. 
If during the course of a fever the daily variation is slight, and 
the difference between maximum and minimum is not more than that 
under normal conditions, the fever is called continuous (febris con- 
tinua) (Fig. 6). If the differences are greater, the fever is termed 
subcontinuous (febris subcontinua), remittent (febris remittens) 
(Fig. 5), or intermittent (febris intermittens) (Fig. 7). 
In the last-named, afebrile periods (apyrexia) alternate with periods 
of fever, each paroxysm having an initial period, a fastigium, and a 
defervescence. In the infectious disease known as febris recurrens there 
is first continuous fever, which after a few days falls by crisis; after 
a week or so a second rise of temperature occurs, which may be followed 
by a second stage of apyrexia, and this by a third period of fever, and 
so on. 
Many diseases — such as typhoid fever, pneumonia, measles, re- 
lapsing fever, etc.— are characterized by a typical temperature-curve; 
others — as the fevers of pleuritis, endocarditis, diphtheria, tuberculosis, 
phlegmon, etc.— have no typical course. 
The elevation of the body-temperature in fever is dependent, first, 
on increase in heat-production through increase of chemical changes in 
the tissues. The respiratory interchange of gases — the excretion of 
carbonic acid and the taking-up of oxygen — and the excretion of 
nitrogenous elements in the urine, (urea, uric acid, creatinin) are in- 
creased— the latter from seventy to one hundred per cent, under certain 
conditions as much as threefold. There is also increased destruction of 
the albuminoid substances of the body, even in the latent period of the 
fever. 
The increase of heat-production varies in different fevers, and reaches 
its highest point during the violent muscular contractions at the time 
of the initial chill. 
The second cause of elevation of the body-temperature is deficient 
heat-dispersion. At the height of the fever the patient as a rule gives 
off more heat than the normal individual, but this dispersion is not suffi- 
cient to offset the excessive heat-production. Heat-production is con- 
stantly increased; heat-dispersion is irregular. 
In the initial stage the cutaneous vessels are contracted as a result of 
stimulation of the vasomotor mechanism, the skin is pale, the heat-dis- 
persion slight, under certain conditions even less than normal. 
Chills occur when, through contraction of the peripheral arteries, the 
supply of blood, and consequently the heat-supply, to the skin, is sud- 
denly diminished, while in the interior of the body the temperature is 
rising. 72 
THE GENERALIZATION OF DISEASES. 
In the second stage of fever the skin is often hot and reddened, and 
in certain diseases sweating occurs; but the increased heat-dispersion 
thus produced is not sufficient to lower the temperature to the normal. 
The increased excitability of the vasomotors or the deficient irritability 
of the vaso-dilators is also present during this period, and as a result 
the skin-temperature, as well as the heat-dispersion, varies greatly. The 
skin is at times pale and cold, at other times red and hot, or the hands 
may be cold while the trunk is hot. The centres governing heat-disper- 
sion are therefore acting faultily. 
In the period of defervescence the relations of heat-dispersion and 
heat-production are changed in favor of the former. The cutaneous 
vessels become dilated, the skin gives out a great amount of heat from 
the abundance of blood circulating through it, and when the critical 
fall of temperature occurs there is usually profuse sweating. 
The cause of fever is not known with certainty, yet this much can be 
said, that fever is most frequently the result of the entrance of a harmful 
agent into the fluids of the body. In many cases this harmful agent 
arises from a local focus—for example, from erysipelatous and phleg- 
monous inflammations of the skin. In man, the infectious diseases, 
which are due to specific micro-organisms multiplying in the body, are 
characterized, among other things, by all the phenomena of fever. 
Parasites multiplying within the body cause increased tissue-destruc- 
tion, and at the same time substances are probably produced which act 
as poisons to the central nervous system. The action of the latter may 
be assumed to be of such a nature that, on one side, the activity of the 
muscles and glands, and consequently the heat-producing metabolism, is 
increased; while, on the other hand, through the diminished and dis- 
turbed functions of the nerves governing sweating, as well as of the 
vasomotors, the processes of heat-dispersion fall behind those of heat- 
production. Though the organism makes an effort to regulate the 
temperature, it is no longer able to maintain it at the normal level, 
because of the disturbances of the regulating apparatus. What share in 
the increase of body-temperature is due to the direct action of bacteria 
and of the ferments formed by them, or what share is due to the in- 
crease of metabolism, or through disturbance of heat-dispersion, cannot 
at present be determined. It is, however, certain that the factors vary 
in different cases. That certain changes in the nervous system are suffi- 
cient to cause increase of temperature, is shown by the fact that such 
increase occurs in epileptic attacks, in the periods of excitation in pro- 
gressive paralysis, after severe frights, after the passage of a catheter 
into the bladder, etc. In this connection, however, it is to be empha- 
sized that fever is a far more complex affair than mere elevation of 
temperature. According to the investigations of Richet, Aronsohn, 
and Sachs, marked increase in body-temperature with increase of 
the respiratory interchanges of gases and increased excretion of 
nitrogen (Aronsohn and Sachs) may be produced in animals by puncture 
through the cerebral cortex and into the corpus striatum. The same 
phenomenon may be produced by electrical stimulation of the same 
portion of the brain. Nevertheless, fevers dependent on nervous dis- 
turbance are rare, and are overshadowed in importance by those caused 
by infection. FEVER, 
73 
The rise of temperature in fever is usually accompanied by in- 
crease in the frequency of the pulse; but in some cases this effect of 
the elevation of temperature may be so modified by stimulation of the 
vagus — as, for example, in basilar meningitis — that the pulse-rate is 
lowered. 
In diseases attended by fever, the patient may or may not be appre- 
ciative of the fact that he is ill, according to the extent to which his 
senses are benumbed. In anthrax, for example, clarity is frequently 
maintained until the moment of death. In the majority of fevers, how- 
ever, there are symptoms of excitation or depression, delirium, apathy, 
involuntary evacuations, convulsions (in children), etc. The muscles 
of the body become weak and not infrequently painful. Digestion is 
impaired; the appetite for food is slight, but on the contrary there is 
great thirst; the mouth is dry. There is increased frequency of respira- 
tion ; after the appearance of muscular weakness the respiratory move- 
ments are superficial. The excretion of urine is usually diminished; 
the amount of urea is increased, while that of sodium chloride is apt 
to be diminished. 
In prolonged fevers there is marked wasting of the body, in that a 
large portion of the albuminous material and fat is destroyed. 
To what extent these symptoms in individual cases are dependent 
on the increase of temperature or to what extent on the damage caused 
by the specific morbid process, it is difficult to say. The marked effects 
on the nervous system must in part be regarded as a result of infection 
and co-incident intoxication. 
The direct cause of death in febrile diseases is most often to be 
ascribed to degenerative changes in the heart muscle resulting in dilata- 
tion of its chambers with or without congestion and oedema of the lungs. 
Contributing factors are to be found in degenerative lesions in such 
important viscera as the liver and kidneys and in the central nervous 
system. The effects so produced are not attributable alone to elevation 
of temperature, but to attendant intoxication. Indeed, it should be 
remarked that high temperatures may be borne for a length of time 
without fatal results (see § 3). CHAPTER III. 
The Protective and Healing Forces of the Human Body. 
The Acquisition of Immunity. 
§ 29. The body is by no means defenceless against the many harmful 
influences to which man in the course of his life is exposed. It possesses 
various protective contrivances by which it is able to ward off injury, 
or to counteract its influence, so that disease may be prevented or con- 
fined to a local lesion. The mode of action of different injurious agents 
varies greatly, so does the manner of defense vary. The protective 
forces may act at different times — sometimes before the tissues have 
been damaged, at other times after the injury has reached a certain 
stage, and threatens, through direct extension or metastasis of its pro- 
vocative agent, to spread through the body. 
When the surroundings become relatively cold or relatively warm, 
regulating functions are brought into play through which the organism 
can increase or diminish heat-production and heat-dispersion, and in this 
manner protect itself within limits against the external temperature. If 
these regulating functions are imperfectly performed, as in alcoholic in- 
toxication, the individual may succumb more easily to the effects of cold 
than in normal circumstances. 
We cannot speak of special protecting contrivances against the cruder 
forms of mechanical injury; yet it is to be noted that the tissues are 
fitted to offer resistance to the more subtle varieties of traumatism. If 
small, firm bodies, such as dust-particles, reach the mucous membrane of 
the respiratory or intestinal tracts, the epithelium forms a barrier against 
their entrance. If cilated epithelium be present, the dust-particles may 
be carried away by the movements of the cilia, or become surrounded 
by the mucus produced by the epithelium of the mucous glands, and in 
this way are transported out of the body. 
Not infrequently cells appear on the surface of the mucous mem- 
brane that encompass the dust-particles, and, taking these into their 
substance, are carried away with the secretions. This phenomenon is 
known as phagocytosis. The active agents participating in it are cells 
which pass from the tissues to the surface, and are derived from the 
blood, from the lymphadenoid tissue of the mucous membrane, and from 
the epithelium. The phenomenon of phagocytosis depends on the fact 
that the cells, by movements of their protoplasm, take up particles, 
which, like insoluble dust, exert no harmful influence on their pro- 
toplasm. If these cells pass outside the body, the taking-up of the dust 
is useful in cleansing the organs of dust. If the dust-laden cells, as 
happens particularly in the lungs, pass into the lymph-channels and are 
deposited in or carried to the lymph-nodes — that is, if metastasis takes 
place — we can regard this act as useful only in the sense that infiltra- 
tion of the pulmonary connective tissue and lymph-nodes is less harm- 
ful than the deposit of dust in the alveoli. NATURAL IMMUNITY. 
7 5 
When dust-particles, free or enclosed in cells, reach the lymph-nodes, 
they are arrested, so that the lymph-nodes are to be regarded as filters, 
which guard the blood and organs from the entrance of dust, and, in- 
deed, from many other foreign substances. 
Against the action of poisons the body is able to protect itself in 
various ways. Against corrosive poisons the horny layer of the epi- 
dermis and the mucus of the mucous membranes offer a certain pro- 
tection ; for example, increase in the production of mucus in the stomach, 
may diminish the harmful effects of a corrosive fluid. Through transu- 
dation of fluid from the blood-vessels to the surface of the mucous mem- 
brane a caustic fluid may be so diluted as to modify its action. On the 
other hand, the injurious substance may thus be spread over a greater 
surface, and cause more widespread damage. 
On many poisons, abrin, ricin, the toxins of cholera, tetanus, and 
diphtheria, and snake-venom, the digestive juices have such an influence 
that doses invariably fatal when injected under the skin are borne with 
impunity when taken by the mouth. According to Ransom, guinea-pigs 
are able to withstand, by the mouth, an amount of tetanotoxin equivalent 
to three hundred thousand times the minimal fatal dose. According 
to Nencki and others, this neutralisation is produced by the digestive 
enzymes. It is probable (Nencki) that the digestive enzymes cause a 
slight change in the molecules of the toxin, and the products thus aris- 
ing may accordingly be termed toxoses or toxoids. The intestinal 
enzymes have no neutralizing influence in the poisoning produced by 
Bacillus botulinus and, after the eating of infected foods fatal intoxica- 
tions may occur. 
Those poisons which act injuriously on the blood or nervous system, 
may be counter-acted by rapid excretion through the kidneys, intestine, 
salivary glands, mammary glands, sweat glands, and lungs; by trans- 
formation into combinations soluble with difficulty, which are then stored 
in different organs (liver), by change of the poisons into combinations 
that are relatively harmless and easily soluble, and which are taken into 
the circulation and excreted, and by chemical change of the poison. 
Of natural immunity or resistance to poisons we know but little, yet 
there is no doubt that many substances are poisonous only for certain 
organisms, that man is resistant to poisons which are injurious to certain 
lower animals. The same holds true of toxins (§ 11) , such as are formed 
by bacteria or by animals (snakes) and plants (ricin and abrin). If 
we consider that many animals are only slightly or not at all susceptible 
to poisons which have marked action on the human body — the hedge- 
hog is immune or resistant to cantharidin and to the bite of poisonous 
snakes; birds are immune to atropine and opium; goats to lead and 
nicotine; while dogs, rats, or other animals used for experiment show a 
disproportionately greater resistance to bacterial poisons or plant-al- 
kaloids than does man — it is probable that the reverse is true. The 
natural immunity of man to many of the infectious diseases of animals 
must depend on resistance to the toxins produced by the particular 
bacteria. According to Ehrlich, this resistance may be explained on the 
ground that the particular toxin possesses no chemical relationship to any 
one of the body elements. Relative immunity may therefore depend on 
the fact that the healthy individual possesses a certain amount of anti- 
toxin (for example, against diptheria toxin). 76 
THE PROTECTIVE FORCES OF THE BODY. 
§ 30. Against the infections and intoxications caused by parasites 
the body also possesses protective contrivances and powers of defence; 
and these play an important role in the diseases caused by bacteria. In 
the first place, man possesses a natural immunity to many of the micro- 
organisms which are pathogenic for animals (for example, swine plague, 
swine erysipelas, cattle plague, symptomatic anthrax), so that the given 
micro-organisms are not able to reproduce within the body, either be- 
cause they do not find in human tissues the necessary conditions of life, 
or because the presence of certain chemically active substances hinders 
their increase or kills them directly. Further, immunity may rest on the 
fact that poisons produced by given bacteria in a given organism are in- 
effective because no chemical affinity exists between the poisons and 
any of the body elements. For the protection of the body against the 
pathogenic micro-organisms there are available certain forces, which, 
according to their action, may be divided into four groups: the first 
hindering the entrance of bacteria into the tissues; the second opposing 
local dissemination of those bacteria which have gained entrance and 
have begun to multiply; the third preventing the entrance of bacteria into 
the blood; the fourth tending to neutralize the effects of intoxication. 
For the prevention of the entrance of pathogenic bacteria into 
the tissues the same properties of tissues are effective as those hinder- 
ing the entrance of dust; and in such capacity epithelium and mucus play 
an important role. In the respiratory tract the movements of ciliated 
epithelium furnish protection, and in the stomach the destructive action 
of the gastric juice on pathogenic bacteria is an efficient means of de- 
fence, notably against the cholera vibrio. 
It appears that mucus not only can envelop bacteria, hinder their 
entrance into the tissue, and favor their removal, but that — what is 
of greater importance — the mucus acts on the bacteria, causing them to 
degenerate, either because it contains substances which are injurious or 
because it offers an unfavorable medium for growth. 
In the intestine bacteria normally present (B. coli communis, B. 
lactis aerogenes) afford protection against multiplication of pathogenic 
bacteria that may have entered; for example, against cholera-spirilla, 
while, on the other hand, the development of staphylococci and strep- 
tococci does not appear to be hindered. 
Not every pathogenic micro-organism, therefore, which gains a foot- 
hold on the skin or mucous membranes or effects entrance into the in- 
testines or lungs produces infection. It has been shown that in normal 
individuals there frequently occur in the upper respiratory passages and 
mouth not only harmless bacteria, but also those which produce disease, 
as, for example, pneumococci and the bacillus of influenza. It must, 
therefore, be granted that bacteria which are found on mucous membranes 
and perhaps multiply there often are carried off or destroyed without 
having produced infection. This occurs not only to the bacteria just 
mentioned, but to many others, including tubercle bacilli, as well as to 
cholera spirilla that have been brought into contact with the acid secre- 
tions of the stomach. Of the pathogenic bacteria entering the alveoli of 
the lung in the inspired air, many do not reproduce, but die. 
When bacteria succeed in gaining entrance and have begun to 
multiply— no matter whether they have passed through the epithelium 
without the aid of others (typhoid-bacilli, cholera-spirilla), or have PROTECTION AGAINST INFECTION. 
77 
passed into the tissues through wounds (tetanus-bacilli, pus-cocci, 
tubercle-bacilli)—if they produce destruction of tissue or poison the 
fluids of the body, there may be brought into action counter-influences 
which hinder their development or weaken or destroy the poisons pro- 
duced by them. 
Many writers ascribe the prevention of the spread of infection 
and the destruction of bacteria, in local foci of growth, to the activity 
of cells which collect at the seat of infection and take up the bacteria 
into their protoplasm — that is, to phagocytosis. According to Met- 
schnikoff and others the amoeboid cells of the body carry on a fight 
against invaders and endeavor to overcome and destroy them. Such 
characterization of the phenomena of phagocytosis is not supported by 
facts, but is to be regarded as a poetical expression by which conscious- 
ness and will-power are attributed to amoeboid cells (leucocytes and pro- 
liferating tissue-cells). It is self-evident that such attributes do not 
exist in cells. Scientifically considered, the gathering of the cells at the 
infected focus and the resulting phagocytosis represent simply an ex- 
pression of certain processes which are natural to amoeboid cells, and 
which are dependent on the fact that such cells under the influence of 
mechanical, chemical, and thermal influences perform certain movements. 
We know that the motile cells of the body are in part attracted, in part 
repelled or paralyzed by chemical substances in certain concentrations 
(see the Chapter on Inflammation) ; and, further, that contact with hard 
bodies can stimulate them to send out protoplasmic processes. 
Such phenomena are designated negative and positive chemo- 
tropismus or chemotaxis and tactile irritability. We must assume 
that bacteria multiplying in the tissues act on the amoeboid cells through 
the chemical substances which they produce, sometimes repelling or 
paralyzing, sometimes attracting, in the latter case affording conditions 
favorable for phagocytosis. The bacterial proteins arising from the 
bodies of dead or dying bacteria and passing into solution in the body 
juices have, in particular, a positive chemotactic action on the phagocytes. 
The result of the taking-up of bacteria into cells depends partly on 
the properties of the devouring cells, partly on the properties of the 
microparasites, and can result as well in the death and dissolution of the 
parasite, as in the death of the cells; or in symbiosis of the cells with 
the parasites, the latter living within the cells unchanged and giving rise 
to no disturbance. If the parasite be destroyed phagocytosis may be 
regarded as a curative process. If the cell be killed by the parasite, 
or if the parasite continue to live in the body of its host, the process of 
phagocytosis is useless in preventing the spread of infection; there are 
cases (leprosy and to some extent tuberculosis) in which parasites find 
favorable conditions for development inside the cells, and finally cause 
their destruction. If the cells containing bacteria remain preserved for 
a length of time, they may wander with the enclosed bacteria to other 
parts of the body, in this way actually promoting infection. 
Phagocytosis is therefore only of slight protective value in certain 
cases; yet it cannot be doubted that the phagocytes in other infections 
take up, not only dead or dying, but also living bacteria, and cause their 
death. The collection of great numbers of cells in the infected tissue 
may, through close packing of the lymphatics, offer mechanical hindrance 
to the spread of bacteria, yet the protection so afforded is frequently 
inadequate 78 
THE PROTECTIVE FORCES OF THE BODY. 
If bacteria, either free or enclosed in cells, pass from the lymph- 
vessels into the lymph-nodes, the latter act as filters, as in the case of 
dust, and retain the bacteria; but the protection which they offer is 
sufficient only when the bacteria so collected are hindered in their repro- 
duction or are killed by the influence of their surroundings. The destruc- 
tion may be accomplished by phagocytosis, but in many cases phago- 
cytosis is possible only when the bacteria are weakened or have already 
been killed. Further, the ingestion of living bacteria by the cells is not 
always followed by destruction, on the contrary, intracellular multipli- 
cation may occur. 
More important than phagocytosis for the prevention of the spread 
of bacteria and other microparasites is the influence exerted by certain 
chemical substances in solution in the tissues. Since saprophytic, non- 
pathogenic bacteria, when injected into living tissue, are killed within a 
short time, we must assume that in the tissues there are chemically active 
substances which are poisonous for many bacteria and cause their de- 
struction. Further, since some pathogenic bacteria increase only locally 
(tetanus-bacilli, diphtheria-bacilli, cholera-spirilla) and after a time 
perish within the infected area, without spreading through the body, it 
is probable that the tissues contain substances which are likewise 
poisonous for pathogenic bacteria and prevent their spread. The phe- 
nomena observed in local infections speak also for the fact that such 
substances at times are formed in increased amounts or are aided in their 
action by newly-formed substances. It is, furthermore, probable that the 
crowding of cells which takes place in the infected area or in its neigh- 
borhood contributes to such increase; nevertheless, attention should be 
drawn to the fact that in many infections the spread of bacteria comes 
to a standstill in places where there has been no crowding of cells. It 
is also a fact that in many infections the spread of bacteria is either 
wholly wanting (tetanus, diphtheria) or is insignificant. The explanation 
of this fact is to be sought, not so much in the assumption that local 
tissue-changes, through chemical substances or mechanical barriers 
hinder the entrance of bacteria into the lymph and blood, but that there 
are present in the lymph and blood certain forces which are able to in- 
jure bacteria actually taken into these fluids or to destroy them. (See 
paragraph on opsonins). 
The hostile action of the blood on bacteria has been ascribed to the 
phagocytic action of the leucocytes; this theory is supported by the fact 
that such phagocytosis can be demonstrated in acquired infections or 
after the artificial introduction of bacteria into the blood; and by the 
fact that bacteria in the blood, enclosed in cells, may often be carried out 
of the vessels and deposited in different organs—the spleen, liver, bone- 
marrow, and kidneys—and destroyed or excreted. These observations 
do not warrant the conclusion that phagocytosis constitutes a protection 
against the spread of bacteria in the lymph and blood. Here, again, it 
is a secondary phenomenon which occurs when there are present in 
the blood bacteria or protozoa, that are not able to prevent themselves 
from being taken into the bodies of the leucocytes — that is, they exert 
a positive attraction on the phagocytes. 
The forces which are able to hinder the development of bacteria in 
the blood are believed to depend on antibacterial chemical substances, 
which are designated alexins (Buchner). According to Buchner, with PROTECTION AGAINST INFECTION. 
79 
whom the majority are in harmony, there is formed a ferment-like 
body, an enzyme (cytase) [Metschnikoff ]), which, through the aid of 
an intermediate body (amboceptor), exerts its destructive action on the 
bacteria. The leucocytes are probably the chief producers of this pro- 
tective body, and the leucocytosis observed in the course of many in- 
fections may therefore increase the protective power (see opsonins 
below). 
So far as conclusions can be drawn from the behavior of the human 
and animal organisms in infectious diseases, we may assume that in the 
blood of man there are always present protective chemical substances, 
that is, alexins, particularly against bacteria which never or only excep- 
tionally enter the blood; and that others are produced only during the 
course of infection, so that not until a certain stage of infection does 
inhibition of the development of the bacteria, through the formation of 
antibacterial substances, occur. In favor of such hypothesis is the fact 
that many bacteria (typhoid-bacilli, cholera-spirilla, pus-cocci) possess 
their full virulence when distributed through the body by the blood, but 
later suffer loss of virulence and finally die. 
The means of protection against the poisons produced in the 
tissues by bacteria are to be found, first in rapid excretion by the kid- 
neys, or by the stomach, intestine, and skin; this action may suffice to 
prevent fatal poisoning. Further, in certain infections in which true 
toxins are formed there is an antagonistic action in that the poisons are 
made ineffective through the action of counter poisons, so-called anti- 
toxins. (See § 31 and § 32.) 
The antagonistic properties of blood and lymph against certain bacteria have 
been demonstrated conclusively by experimental investigations. These experiments 
have shown that the bactericidal action of the blood of a given animal is exerted 
only on certain forms of bacteria and never on all; and that this action is subject 
to individual variations. 
According to the investigations of Fodor, Petruschky, Nuttal, Ogata, Buchner, 
Behring, Nissen, Pansini, and others, the blood and the serum from dogs, rabbits, 
and white rats are capable of rendering the aruthrax-bacillus harmless, and even 
of killing it; but this action is a limited one, so that after the introduction of a 
large number of bacilli into the blood taken from the vessels, the bacilli after a time 
begin to multiply. Defibrinated blood of dogs and rabbits can destroy the cholera- 
spirillum and typhoid bacillus; but, on the other hand, has no effect on the different 
pus-cocci, and against proteus; the same is also true with regard to the blood-serum. 
Human blood or blood-serum can kill typhoid-bacilli, diphtheria-bacilli, and the 
bacilli of glanders. 
Von Baumgarten and Walz, as well as A. Fischer, oppose the view that.there 
are chemically active substances in the blood, and explain the natural immunity of 
the tissues and the blood against certain bacteria as due to the inability of the bac- 
teria to find there the necessary chemical conditions for growth and multiplication. 
They regard the fact that different bacteria which have passed into the blood or 
blood-serum do not develop at all, or show but partial or delayed growth and great 
diminution in numbers when cultivated on plates, as in no manner speaking for the 
presence of bactericidal substances in the blood. According to their view, the sec- 
ond transplantation into another culture-medium causes disturbance of the processes 
of assimilation and osmosis. There arise in consequence plasmolytic changes in the 
bacteria present in the serum; during the pouring of the plates the already injured 
cells die from disturbances of assimilation. On the other hand, it is to be noted 
that A. and H. Kosscl have demonstrated that certain products of animal cells 
(nucleinic acid, protamine) possess bactericidal properties. 
The alexins of the blood serum are made inactive through heating to 55° C., 
and are susceptible to the action of sunlight (Buchner), and can also be destroyed 
by living bacteria and their decomposition products. They resist pepsin. The 
addition of salt to the serum lowers their sensibility to heat. By means of a 90- 80 
THE PROTECTIVE FORCES OF THE BODY. 
per-cent, sodium sulphate solution there may be obtained from dog serum a precipi- 
tate which remains active when dried at 70° C. 
. The bactericidal action finds its analogy in the globulicidal and haemolytic 
action of the serum; that is, its capacity to destroy and dissolve the red blood- 
cells of an animal of a different species. 
According to the investigations of Ehrlich and his students the bactericidal 
and globulicidal antibodies contain two components, one thermolabile, which is 
destroyed by heating to 55-60° C., and a thcrmastabile, which resists heating. Both 
must act together in order to bring about the death of bacteria or the solution of 
red blood-cells. 
Ehrlich designates the thermostabile component as the immune body or inter- 
mediate body (Bordet “as the substance sensibilatrice”), the thermolabile as the 
complement. To the immune body he ascribes two haptophorous side-chains, one 
the cytophile, which unites with the cell (bacterial cell, red blood-cell), for which 
it possesses a chemical affinity, and a complementophile, which combines with the 
complement. It is therefore an amboceptor, which carries over the action of the 
complement to the cell. Buchner’s alexin is identical with the thermolabile com- 
ponent, the complement of Ehrlich (Bordet). That a union of the immune body 
with red blood-cells and bacteria, respectively, does take place has been demon- 
strated by the investigations of Ehrlich, Morgenroth, Hahn, Trommsdorff, von Dun- 
gem, and others. 
Hankin, Kanthack, Denys, Hahn, Lowit, and others assume, on the ground of 
experimental investigations, that the alexins are produced by the leucocytes. Kossel 
holds it as possible that the nucleinic acid present in the leucocytes in relatively rich 
amounts plays a role in the destruction of the bacteria. Noesske believes that the 
eosinophile cells of the bone-marrow in particular produce bactericidal substances. 
It is not possible at the present time to draw a definite conclusion as to the part 
played by the colorless cells of the blood in the defence against infections. 
According to Bitter, the bactericidal substance found in organs — that derived 
from the lymph-nodes, spleen, and thymus — is to a certain extent different from 
that of the blood and the blood-serum, and therefore does not originate wholly in 
the blood. It is certain that the bactericidal action of the blood is not the only 
protective influence which can oppose the spread of an infection, or wholly prevent 
it, and confer immunity. 
According to observations of Czaplewski, anthrax-bacilli in an infected organ- 
ism, which have been taken into leucocytes, degenerate as a rule more slowly than 
those lying free in the blood and tissue-juices. It appears, therefore, as if under 
certain conditions the cells afford to the bacteria which they enclose a certain degree 
of protection from the bactericidal substances of the tissue-fluids. 
The antitoxins which render the bacterial poisons harmless are usually formed 
during the course of the infection; but, according to the investigations of IVasser- 
mann, Abel, Fischl, von Wunschheim, and others, the serum of healthy men also con- 
tains such substances. Serum which contains the antitoxin against a certain toxin — 
for example, that against the diphtheria-toxin — can be a good culture-medium for 
the given bacteria; the antitoxin does not destroy the bacteria. 
Animals refractory to diphtheria contain in the blood serum no diphtheria anti- 
toxin, but according to Wassermann about 80 per cent, of human individuals have 
in their blood a not insignificant amount of antitoxin. The immunity of the animals 
depends therefore not on the presence of the antitoxin, but on a lack of affinity 
between the poison and the tissue-cells (Ehrlich and Wassermann). It is possible 
to produce in mice a fatal intoxication with the blood of apparently healthy fowls 
that have been injected with large doses of tetanus toxin. 
Opsonins. The protective function of phagocytosis has been accorded a 
position of importance through the discovery by Wright and Douglas (1902) of 
the presence in the blood and other fluids of the body of certain substances, called 
opsonins, which render various bacteria susceptible to the phagocytic action of leu- 
cocytes. It is now an established fact that certain special substances, normal and 
immune, act on the bacteria and change them in such a manner that they are readily 
taken up by polynuclear leucocytes in vitro. Opsonins capable of acting on a variety 
of bacteria occur in normal blood. They appear to be important antibodies in 
infections with streptococci, staphylococci, pneumococci, micrococcus melitensis, 
gonococci, meningococci, the bacilli of plague, dysentery, anthrax, tuberculosis, 
typhoid fever, the colon bacillus, cholera spirillum, etc. Whether this wide range 
of opsonic action is dependent on a common opsonin or on a variety of specific 
opsonins is not yet determined. Specificity of the opsonins probably does not exist. 
Various researches suggest that they may be a constant quantity. They are to a OPSONINS. 
81 
certain extent thermolabile, being partly destroyed at 60-65° C. Bacteria first 
treated with normal serum and then exposed to this temperature are taken up as 
under normal conditions. The opsonic power of the blood is increased in recovery 
from infection, and it can also be artificially increased by immunization with living 
attenuated bacteria, dead bacteria, or proteid constituents of the bacterial cells. The 
opsonic index is the relative influence of a patient’s blood on phagocytosis as 
compared with that of normal individuals. It is determined by mixing in a 
capillary tube equal parts of the patient's serum, a suspension of leucocytes, 
and an emulsion of the bacteria against which the index is taken. Control tests 
are made in the same way with normal serum. The mixtures are incubated for 
a time, thin smears are made, dried, and stained, and the average number of 
bacteria taken up by the leucocytes is estimated. Regarding the index of the 
normal blood as unity, the average number of bacteria in the leucocytes of the 
patient’s serum divided by it will be the opsonic index. 75_100 leucocytes are 
usually counted. A low opsonic index is taken as indicating the presence of an 
infection or of a low degree of resistance to it, while a high index indicates a 
high degree of resistance to a recovery from infection. 
Literature. 
(The Protective Power of the Body against Infection.) 
Baumgarten; Der gegenwartige Stand der Bakteriologie. Berl. klin. Woch., 
1900; Die natiirl. Schutzmittel geg. Infection, ib., 1900; Verhandl. d. D. 
path. Ges., ii., Berlin, 1900. 
Behring: Infection und Desinfection, Leipzig, 1894; Infectionsschutz u. Im- 
munitat. Eulenb. Jahrb., ix., 1900. 
Behring u. Nissen: Bakterienfeindl. Eigenschaften verchied. Blutserumarten, 
Zeit. f. Hyg., viii., 1890. 
Besredka: Pouvoir bactericide des leucocytes. Ann. de l’lnst. Pasteur, xii., 
1898. 
Bitter: Ueb. d. bakterienfeindlichen Stoffe thierischer Orgame. Zeit f. Hyg., 
xii., 1891. 
Bordet: Rech. sur la phagocytose. Ann. de l’lnst. Pasteur, 1896. 
Buchner: Ueber die bakterientodtende Wirkung des freien Blutserums. Centbl. 
f. Bakt., v., vi., -1889; Ueber die bakterientodtende Wirkungen d. Blutes u. 
Blutserums. Arch. f. Hyg., x., 1890, ref. Cbl. f. Bakt., ix.; Hiilfskrafte d. 
Organismus gegen Krankheitserreger. Miinch. med. Woch., 1894; Bakter- 
iengifte und Gegengifte, ib., 1893; Natiirl. Schutzeinrichtungen, ib., 1899. 
Charrin: JLes defenses naturelles de l’organisme, Paris, 1898. 
Czaplewsi: Unters. iib. d. Immunitat der Tauben gegen Milzbrand. Zeit. f. 
Hyg., xii., 1892. 
Fischer, A.; Die Empfindlichkeit d. Bakterienzelle u. d. baktericide Serum. 
Zeit. f. Hyg., 35 Bd., 1900. 
Fischl u. v. Wunschheim: Schutzkrafte im Blute d. Neugeborenen. Zeit. f. 
Heilk., 1895 (Lit.). 
v. Foder: Die Fahigkeit d. Blutes, Bakterien zu vernichten. Cbl. f. Bakt., vii., 
1890. 
Hahn: Naturliche Immunitat. Handlb. d. path. Organismen, iv., Jena, 1904 
(Lit.). 
Hankin: Ueber den schiitzenden Eiweisskorper der Ratte. Cbl. f. Bakt., ix., x., 
1891; Ueber den Ursprung und das Vorkommen von Alexinen im Organis- 
mus, ib., xii., 1892. 
Kossel: Lymphzellen. Deut. med. Woch., 1894; Baktericide Zellbestandtheile. 
Zeit. f. Hyg., 27 Bd., 1898. 
Lowit: Bezieh. d. Leukocyten zur baktericiden Wirking. Beitr. v. Ziegler, 
xxii., 1897. 
Metschnikoff: Die Lehre v. d. Phagocyten. Handb. d. pathog. Organismen, iv., 
Jena, 1904. 
Nuttal: Bacillenfeindl. Einfliisse des thier. Korpers. Zeit. f. Hyg., iv., 1888; 
Bakterienvernidhtende Eigenschaften des Blutes. Cbl. Bakt., iv., 1889. 
Ogata: Ueber die bakterienfeindliche Substanz des Blutes. Cbl. f. Bakt., ix., 
1891. 82 
THE PROTECTIVE FORCES OF THE BODY. 
Petruschky: Der Verlauf der Phagocytencontroverse. Fortsch. d. Med., viii., 
1890; Einwirkung des lebenden Froschkorpers auf den Milzbrandbacillus. 
Zeit. f. Hyg., vii., 1899. 
Walz: Baktericide Eigenschaften des Blutes, Braunschweig, 1899. 
Wassermann: Personl. Disposition gegen Diphtherie. Zeitschr. f. Hyg., xix., 
1895. 
(Opsonins.) 
Bulloch: Lancet, 1905; Practitioner, 1905. 
Hektoen: Jour. Amer. Med. Ass., 1906; Jour, of Infect. Dis., 1906, 1907. 
Wright: Med. Chir. Trans., 1905; Lancet, 1905; Jour. Amer. Med. Ass., 1907; 
Practitioner, 1908. 
Wright and Douglas: Proc. Roy. Soc., 1903, 1904; Lancet, 1904. 
§ 31. The healing-powers of the body are those processes which 
are able to compensate for the changes caused by disease, and to render 
harmless or to remove any harmful agent that may still be present in 
the body. If portions of tissue have been destroyed, healing consists in 
removal of the dead tissue, and its replacement by new tissue. 
When the temperature of the body becomes abnormally low or high, 
compensation may be effected in such way that through regulation of 
heat-production and heat-dispersion the temperature is brought back to 
normal. If through trauma tissue is destroyed, the organism may repair 
the defect through the production of new tissue (regeneration) or by 
corresponding increase in similar tissues (compensatory hypertrophy). 
If poisons enter the body and produce intoxication, healing follows 
only through rapid excretion of the poison, or its destruction or neu- 
tralisation in the body; while at the same time the damaged tissues 
return to their normal state, existing defects being properly compen- 
sated. 
In infections the healing processes follow directly on the action of 
the protective forces; indeed, the latter constitutes the first stage of 
healing; the protective and healing processes are integral factors in 
repair. 
In many infectious diseases the influence of protective substances 
already present is supplemented by the appearance of new substances 
foreign to the normal organism, which as bactericidal substances and as 
antitoxins, respectively, antagonize infection and intoxication. The bac- 
tericidal antibodies are formed by the tissue-cells which through the 
infection have been placed under altered conditions of life; they spread 
through the tissues, and thus hinder the extension and multiplication of 
the bacteria. They are formed particularly in typhoid fever, cholera, 
and plague, and shozv a certain specificity in that they influence pri- 
marily those bacteria through whose vital activities they have arisen. 
This specificity is, however, not absolute, inasmuch as they can act on 
closely related species. 
Antitoxins are formed in those infections in which toxins are pro- 
duced. The action of the toxin takes place in this manner (Ehrlich) : 
the poison molecule combines through a haptophorous side-chain with 
the haptophorous group of certain cells, while the toxophorous side- 
chain of the poison exerts its influence in a specific manner on the 
affected cells, so that we may regard the antitoxins as representing an 
excess of haptophorous side-chains of the cell-substance susceptible to the ANTITOXINS; WIDAL’S REACTION. 
83 
poison, that are given off into the blood-serum, and combine the corres- 
ponding haptophorous side-chains of the toxins. The haptophorous 
group of the toxin is thus prevented from carrying over its toxophorous 
group to the cells and becoming active. 
Toxin and antitoxin combine according to fixed quantitative relations. 
Antitoxins are formed against the toxins of diphtheria and tetanus, pyo- 
cyaneus, ricin, and poisonous snakes, eels and mushrooms. 
Since the antitoxins of snake-venom (Calmette) and that of the pyocyaneus 
toxin (Wassermann) are more easily destroyed than the poisons themselves, it is 
possible in a mixture of the two, when the combination has lasted but a short time, 
to destroy by heating to a certain degree the antitoxin alone, so that the toxin 
again becomes active. 
The virulence of the toxin of diphtheria is weakened with age, through the fact 
that the toxophorous group in part becomes inactive. 
According to investigations by R. Pfeiffer, confirmed by Sobernheim, Dunbar, 
Loeffler, and others, there is found in the blood-serum of animals made immune 
against typhoid-bacilli or cholera-spirilla, or of individuals suffering or convalescing 
from typhoid fever and cholera, a specific bactericidal substance. The addition of 
such serum to a virulent bouillon-culture of these bacteria so changes the latter 
that the bacteria when inoculated into the peritoneal cavity of an experimental 
animal rapidly disintegrate and are finally dissolved. 
Bordet has shown that fresh human serum is also active in the test-tube outside 
of the human body. When heated to 56° C. this activity is lost (inactivation) but 
it may be restored through the addition of normal serum (reactivation). 
Acording to the investigations of Gruber, Durham, Pfeiffer, Kolle, Sobernheim, 
Widal, C. Fraenkel, and others, the blood-serum of individuals ill, convalescing, or 
recovered from typhoid or cholera exerts a damaging influence on typhoid-bacilli or 
cholera-spirilla respectively; this influence being of such nature that in bouillon- 
cultures the bacteria so affected become motionless, clump, and are destroyed. 
When the serum is added to a hanging drop of bouillon-culture, the rapidly moving 
vibrios at once become motionless and collect in little heaps. Gruber believes that 
this phenomenon is to be explained by a swelling and bursting of the membrane of 
the bacterial cell, and assumes that this change enables the alexins to destroy the 
bacteria present in the body. He therefore designates the active substances in the 
serum agglutinins, and believes that to these may be attributed the chief agency 
in the healing of infectious diseases and in the production of immunity against the 
same. Pfeiffer, on the contrary, denies the occurrence of any swelling of the cell- 
membrane, and explains the phenomenon as the inhibition of development, and 
designates the active substances, the nature of which is wholly unknown, as specific 
paralysins. After Gruber had demonstrated the peculiar action of the blood-serum 
of typhoid-fever patients, Widal (Sem. medicate, Paris, 1896) proposed that this 
action of the blood-serum on cholera-spirilla and typhoid-bacilli respectively be 
utilized as a diagnostic aid. Numerous investigations have demonstrated that it is 
possible to make a diagnosis of typhoid from the action of the blood-serum on 
cultures of typhoid bacilli (Widal's reaction). (See § 33.) In fact the procedure is 
now carried out as a part of the routine diagnosis. It is to be remarked, however, 
that not every individual whose blood serum affects typhoid bacilli in this manner 
is suffering from typhoid fever, since the phenomenon may occur months or years 
after typhoid, and in those who have been vaccinated against the disease. 
According to Kraus, there is present in the blood of animals artificially im- 
munized against cholera and typhoid fever a body, which, on the addition of such 
a serum to a clear bacteria-free filtrate of cultures of cholera or typhoid bacilli, 
produces in the latter clouding and later precipitation, thus acting as a precipitin. 
(See § 33.) 
The protective substances which appear in the blood in the course of infec- 
tious diseases are not always formed at the same place; in pneumonia they are said 
to be produced in the bone-marrow (Wassermann) ; in cholera and typhoid fever in 
the spleen (Pfeiffer and Marx) ; in “Rinderpest” in the liver (Koch). They are 
to be regarded as specific secretory products arising in response to specific stimuli. 
The bactericidal immune-bodies are, according to their physical and chemical 
properties, to be regarded as ferments (they are neither globulins nor albumins), 
immune-bodies combined with the bacterial cells during bacteriolysis may be set 
free after the solution of the bacterial protoplasm, and again become capable .of 
action. 84 
THE PROTECTIVE FORCES OF THE BODY. 
It has often been assumed that the fever occurring in infectious diseases is a 
protective process favoring the destruction of bacteria; and it is not impossible that 
in individual cases it may exert such a favorable influence. For example, it is con- 
ceivable that a parasitic micro-organism, growing well at a temperature of 37~38° C. 
will not thrive at a temperature of 4(L41° C., so that high temperatures in the 
course of fever may hinder its power of reproduction. The conclusion should not, 
however, be drawn from this that fever is a useful phenomenon which always 
favors the counterbalancing of pathological disturbances. Even in those cases in 
which the metabolic processes occurring during the fever exert an injurious influ- 
ence on the bacteria, this is not to be taken as proving the usefulness of fever. 
We can only say that a part of the morbid processes occurring during an infectious 
fever leads to the formation of decomposition-products which may possess anti- 
bacterial or antitoxic properties. 
Literature. 
(Bactericidal Substances and Antitoxins.) 
Biedl u. Kraus: Ausscheidung d. Mikroorganis'men durch Driisen. Zeit. f. 
Hyg., xxvi., 1897. 
Bitter: Metschnikoff’s Phagocytenlehre. Zeit. f. Hyg., iv., 1888; Bakterien- 
feindl. Stoffe thier Organe, ib., xii., 1892. 
Bordet: Action des serums preventifs. Ann. de l’lnst. Past., 1896; Mecanisme 
de l’agglutination, ib., 1899. 
Bordet et Genon: Substances sensibilatrices des serums antimicrobiens. A. d. 
l’lnst. Past., 1901. 
Bouchard: Les microbes pathogenes, Paris, 1892. 
Brieger: Antitoxine und Toxine. Zeit. f. Hyg., xxi., 1896. 
Conradi: Bildung baktericider Stoffe bei der Autolyse. B. v. Hofmeister, i., 
1901. 
Denys et Havel: La part des leucocytes dans le pouvoir bactericide du sang. 
La Cellulfc, x., 1893. 
Durham: On a Special Action of the Serum. Journ. of Path., iv., 1896. 
Foerster: Die Serodiagnostik d. Abdominaltyphus. Fortschr. v. Med., 1897 
(Sammelref.). 
Fraenkel, C.: Agglutinine bei Typhus abdom. (Widal’sche Probe.) Deut. med. 
Woch., 1897 (Lit.). 
Gruber: Immunitat geg. Cholera u. Typhus. Wien. med. Woch., 1896; Theorie 
der Immun. (Agglutinine). Miinch. med. Woch., 1897; Serumdiagnostik d. 
Typhus, ib.; Theorie der Agglutination, ib., 1899. 
v. Klecki: Ausscheidung d. Bakt. durch d. Nieren. Arch. f. exp. Path., 39 Bd., 
1897 (Lit.). 
Melnikow: Bedeutung der Milz bei Infectionen. Zeit. f. Hyg., xxi., 1896 (Lit.). 
Pawlowsky: Heilung des Milzbrandes durch Bakterien u. das Verhalten der 
Milzbrandbacillen im Organismus. Virch. Arch., 108 Bd., 1887; Bemerk. 
iib. d. Mittheilung v. Emmerich u. di Mattei: Ueber Vernichtun g' der 
Milzbrandbacillen im Organismus. Fortschr. d. Med., vi.; Infection u. Im- 
munitat. Zeit. f. Hyg., 33 Bd., 1900. 
Pfeiffer (Kolle, Vagedes): Ein neues Grundgesetz d. Immunitat, etc. Deut. 
med. Woch., 1896; Specifische Immunitatsreaction der Typhusbacillen. 
Zeit. f. Hyg., xxi., 1896 (Lit.); Weitere Untersuchungen iib. specifische Im- 
munitatsreaction. Gbl. f. Bakt., xx., 1896 (Lit.); Wirkung und Art. d. 
aktiven Substanz d. praventiven u. toxischen sera. Ibid., xxxv., 1904. 
Ruffer: Destruc. des microbes par les cellules amoeboides. Ann de l’lnst., 
Past., v. 1891. 
Sherrington: Exper. on the Escape of Bacteria with the Secretions. Journ. of 
Path., i., 1893 (Lit.). 
Wassermann: Pneumokokkenschutzstoffe. Deut. med. Woch., 1899. 
Williamson: Leukocyten bei Pneumokokkeninfektion. B. v. Zeigler, xxix., 
1901. 
Widal et Sicard: Le serodiagnostic. Ann. d. l’lnst. Past., 1897 (Lit,). 
Ziegler: Die Ursachen d. pathol. Gewebsneubildungen. Internat. Beitr., ii., 
Festr. f. Virchow, Berlin, 1891; Ueb. d. Zweckmassigk. d. pathol. Lebens- 
vorgange. Miinch. med. Woch., 1896. 
See also § 30, § 32, and § 33. ACQUIRED IMMUNITY. 
85 
II. The Acquisition of Immunity against Infection and Intoxication. 
Protection through Inoculation. 
§ 32. The acquisition of immunity against a particular infectious 
disease is a phenomenon whose frequent occurrence has long been known 
through clinical observations. This fact has been established chiefly by 
the observation that the great majority of men suffer but one attack of 
such widespread infections as measles, smallpox, whooping-cough, scar- 
let fever, and diphtheria, and that after such attack they are spared by 
the disease, even- when they are again exposed to the danger of infec- 
tion. The knowledge of this fact is old, and early in the eighteenth 
century it led, in the Orient, to attempts to obtain immunity against the 
natural contagion of smallpox by the inoculation of material from small- 
pox pustules. In the latter part of the eighteenth century Jenner dis- 
covered that the disease known as cowpox—i. e., a milder form of pox, 
which is an attenuated form of human smallpox—afforded protection 
against the true smallpox. As a result of this observation, since the be- 
ginning of the year 1796, at first by Jenner himself, afterward by the 
physicians of all civilized countries, artificial inoculations of cowpox have 
been carried out on millions of human beings, with the result that 
through such inoculation a high degree of immunity against the true 
smallpox has been secured to the inoculated; so that at the present time, 
in all countires where vaccination is universally practised, the occur- 
rence of widespread epidemics of smallpox, once so frequent, is rare, and 
the disease no longer assumes the character of a pestilence. - 
The investigations of the cause and origin of infectious diseases have 
shown that the acquisition of immunity against a certain infectious 
disease through one attack occurs in numerous infections, especially in 
those running an acute course; and represents sometimes a transitory, 
at other times a permanent peculiarity of the individual concerned; in 
pregnant women it may be transmitted to the foetus in utero. Observa- 
tions have also shown that the single or repeated inoculation of attenu- 
ated pathogenic bacteria—that is, of bacteria which on account of slight 
virulence produce a disease that, in contrast to the infection with bac- 
teria of full virulence, is relatively insignificant, often confined to a 
limited area—can also confer immunity against the corresponding dis- 
ease. Further, it has been demonstrated that the injection of certain 
chemical substances produced by the bacteria is sufficient to confer 
immunity against certain infections. 
Immunity through the inoculation of attenuated specific disease- 
germs may be produced, for example, against anthrax, symptomatic 
anthrax, chicken-cholera, diphtheria, and swine-erysipelas. The weak- 
ening of the virulence of bacteria may be produced either by the action 
of high temperatures or chemical agents, or by the action of the air alone; 
further, it may be produced by the inoculation of the bacteria into 
certain animals or through their long-continued cultivation on artificial 
media. Inoculation is, in general, carried out by injecting subcutane- 
ously first markedly attenuated, then less attenuated, and finally fully 
virulent bacteria together with their products. 
According to the investigations of numerous authors, immunity in 
animals may also be produced by the injection of sterilized cultures 86 
THE PROTECTIVE FORCES OF THE BODY. 
of bacteria—as, for example, against American hog-cholera, sympto- 
matic anthrax, diphtheria, the infectious disease produced experiment- 
ally in rabbits by the injection of the Bacillus pyocyaneus, and the in- 
fection produced in guinea-pigs by cholera-spirilla. 
A third form of artificial immunization, which Raynaud attempted as 
early as 1877, but was first securely established by Behring in 1890, can 
be produced by the injection into man or an experimental animal of 
blood-serum taken from animals which were previously susceptible, 
but have been rendered immune by means of inoculations. The most 
extensive and at the same time the most successful attempts thus far 
made have been carried out with diphtheria and tetanus; that is, in dis- 
eases in which intoxication through toxins forms the most striking fea- 
ture. Moreover, successful experiments with the blood-serum of immu- 
nized animals, in cholera, swine-erysipelas, anthrax and typhoid fever, 
have been reported. 
The specific protection which the blood-serum affords may be secured, 
not only by injection before infection occurs, but also after infection 
has taken place; so that the serum may be designated not only protective, 
but healing. For both protection against and for the cure of a certain 
infection a definite amount of serum is necessary, depending on the se- 
verity of the infection, and on the activity of the serum itself, the latter 
increasing with the completeness of the immunization of the originally 
susceptible animal furnishing the serum. If the serum is not injected 
until after infection has occurred, the amount must be greater in pro- 
portion to the lapse of time after the beginning of the infection. 
In diphtheria, the injection of curative serum has been carried out in 
thousands of cases and its value has been shown beyond all doubt. In 
tetanus curative action of serum has been demonstrated in the case of 
experimental animals, guinea-pigs, and mice; but the results in man have 
not been altogether satisfactory. As a protective measure its injection 
before the actual onset of symptoms is of unquestioned value. 
The blood-serum of immunized animals exerts its beneficial action, 
without doubt, through the presence of a counter-poison, an antitoxin, 
which neutralizes the poisons produced by the bacteria. In patients 
treated by a given antitoxin, there is produced an immunity against the 
corresponding bacterial poison—for example, against the poison pro- 
duced by the diphtheria-bacilli, in patients injected with diphtheria- 
antitoxin. 
Besides the antitoxins, the blood-serum of immunized animals or 
human beings may also contain bactericidal substances, which injure or 
kill the bacteria themselves; this is held to occur especially in cholera 
and typhoid fever. 
In immunization by means of attenuated cultures or by sterilized 
bacterial products, the antibodies are produced as new substances in the 
organism; this process has been designated active immunization 
(Ehrlich); in the injection of immunizing, serum the formed antitoxin 
is introduced from without; this is spoken of as passive immunization. 
It is probable that in the last case no new-formation of antitoxin occurs 
after the injection. 
For the pioneer work in inoculation with attenuated cultures of bacilli culti- 
vated outside the body, we are indebted to Pasteur, who, in 1880 demonstrated 
that chickens could be immunized against chicken-cholera through the inoculation IMMUNITY. 
87 
of cultures of chicken-cholera bacilli, that had been weakened through long ex- 
posure to the air. 
Since that time numerous experiments have been carried out with other forms 
of bacteria, especially with attenuated cultures of the bacilli of anthrax and symp- 
tomatic anthrax. Good results have been obtained from inoculations against the 
symptomatic anthrax of cattle. Less favorable are the results in inoculations 
against anthrax, in that some of the animals die from the effects of the protective 
inoculation, while others are not rendered absolutely immune against a new anthrax 
infection. 
Sheep and cattle may be made immune against anthrax; most expediently 
{Koch) by first inoculating them with attenuated cultures of anthrax-bacilli, which 
will kill mice but not guinea-pigs, and then with those which will kill guinea-pigs 
but not large rabbits. 
As vaccine against symptomatic anthrax, there may be used cultures of the 
bacillus attenuated through heat or such chemical agents as sublimate solutions, 
thymol, eucalyptol, and silver nitrate; and by such inoculations cattle may be ren- 
dered immune. At the present time heat {Hess, Kitt) is most commonly used in 
the preparation of the vaccine. The infected muscle of an animal dying with 
symptomatic anthrax is chopped fine, triturated with one-half its weight of water, 
and pressed through a piece of linen cloth. Finally, the fluid is again filtered 
through a moistened piece of fine linen. The virulent material is then spread in thin 
layers on glass plates or flat dishes, and transferred to a dry chamber at a tempera- 
ture of 32-35° C. When thoroughly dry the virus is scraped off and removed in 
the form of powder. When it is desired to give inoculations, the virus is triturated 
with double its weight of water and the fluid evaporated in a thermostat. By 
raising the temperature to 100° C. for six hours a weak vaccine is obtained; at a 
temperature of 85° C. for six hours a stronger one. For the immunization of cattle, 
about 0.5 gm. of the weaker virus in a dilute water solution is injected into the 
subcutaneous tissue of the animal’s tail, and after eight to twelve days the stronger 
solution is similarly injected. 
According to observations of Chanveau and others, protective inoculations may 
also be made by the injection of virulent bacteria in small quantities, or in such 
manner that the life of the animal shall not be endangered. In symptomatic anthrax 
this may be accomplished by the injection of small doses into the extremity of the 
animal’s tail; such injections not causing fatal illness, but merely a local dis- 
turbance. 
Cattle may also be immunized against contagious pleuropneumonia (Schiitz) 
by injecting the tissue-juices from the lung of an animal dying from this disease 
into the tip of the tail. There is produced in this way a curcumscribed inflammation, 
or, at least, one which is confined to the tail; after recovery the animal is immune 
to both natural and artificial infection with this disease. 
Hogs may be rendered immune against virulent bacilli of szvine-erysipelas 
{Pasteur), by using, as vaccine, cultures attenuated by successive inoculations in 
rabbits. According to Emmerich, rabbits may also be made immune against the 
bacilli of swine-erysipelas through the injection into the ear-vein of a small quan- 
tity of a virulent bouillon-culture diluted with fifty times its volume of water. 
Animals susceptible to diphtheria may be rendered immune against this disease, 
according to Behring, by the injection of cultures of diphtheria-bacilli which have 
been weakened in virulence by exposure for sixteen hours to iodine trichloride 
(1:500). Two cubic centimetres of such a culture are injected into the peritoneal 
cavity; after three weeks this injection is repeated with a diphtheria-culture (0.2 
c.c.) which has been washed four days in bouillon containing iodine trichloride 
(Lfij500). After this, fully-virulent cultures are injected in increasing doses. 
Protective inoculations against rabies were first carried out in cases resulting 
from bites by rabid animals, particularly in France (Pasteur Institute), Russia, 
and Italy. As inoculation-material, the spinal cord from rabbits which have been 
infected with rabies is used after it has been dried in air at a temperature of 23-25° 
C.; the virulence of the cord being gradually lost after about fifteen days. Small 
portions of a rabbit’s cord thus treated are triturated in sterilized chicken-broth 
and injected subcutaneously into the bitten individual; at .first pieces of cord greatly 
reduced in virulence are used, then those of gradually increasing virulence. Ac- 
cording to the view held by Pasteur, the spinal cord contains both the microbes of 
the disease and the specific poison formed by them; if the latter spreads through 
the body more rapidly than the microbes, it confers an immunity against a 
subsequent spread of the microbes and affords protection to the nervous 
system in particular. In order to confer immunity it is, therefore, necessary to 88 
THE PROTECTIVE FORCES OF THE BODY. 
introduce as large a quantity as possible of the chemical poison. According to the 
reports of the Institutes in which the Pasteur inoculations against hydrophobia have 
been carried out, it must be acknowledged that these inoculations have been success- 
ful in preventing cases of hydrophobia. 
Immunity against cholera may be produced, in both man and animals (Haffkine, 
Pfeiffer, Kolle, Voges, and others) by the injection of sterilized or attenuated cul- 
tures of cholera-spirilla; this immunity (which is of short duration) depends on the 
formation of specific bactericidal anti-bodies in the blood (see Voges, 1. c.). On 
the other hand, we do not yet possess a specific remedy by which the life of any 
animal or man infected with cholera may be saved. 
Immunity against typhoid fever may be secured in man by the subcutaneous 
injection of sterilized cultures of typhoid-bacilli (Pfeiffer, Kolle) ; and the estab- 
lishment of the immunity may be recognized by the fact that the blood-serum of 
the individual so inoculated is found, after a few days, to contain bactericidal sub- 
stances. Attempts at immunization in cases already ill with typhoid (Brieger, Was- 
sermann, C. Fraenkel) have up to the present time been unsuccessful. 
According to the reports published by Koch (British Medical Journal, 1897; 
Deut. med. Wochen., 1897, No. 16; Centralbatt f. Bakt., xii., p. 526) of the inves- 
tigations which were carried out during the winter of 1896-1897 with regard to the 
cattle-plague in Cape Colony, cattle may be immunized against “Rinderpest” 
by subcutaneous injections of 10 c.c. of the bile taken from animals dying of the 
disease; the condition of immunity becoming established at the latest by the tenth 
day. According to the report of Winkler (“ Landwirthschaftl. Bezirks-Verein 
Giessen,” August, 1900) hogs and cattle may be immunized against foot-and-mouth 
disease through feeding with milk of animals which are affected by the disease or 
have recently recovered from it. Loeffler and Uhlenhuth (Centralblatt f. Bakt., 
xxix., 1901) have also reported successful protective inoculations with serum 
against the foot-and-mouth disease. 
In the year 1890 Koch made the discovery that cultures of tubercle-bacilli com 
tain an active substance, “tuberculin” which, when injected into tuberculous in- 
dividuals, causes a rise of temperature and to some extent local inflammatory 
changes in the tuberculous foci. It was at first hoped that in tuberculin a remedy 
for tuberculosis had been found, but the many trials made with it on human beings 
and animals have shown that it indeed produces after repeated injections an im- 
munity against the toxic action of tuberculin, but does not hinder the multiplication 
of tubercule-bacilli and the consequent spread of the disease. Further, the local 
inflammation caused by the tuberculin leads to favorable results only under special 
conditions, but, on the other hand, often causes actual harm (through the meta- 
stasis of bacilli). Nevertheless, Koch’s discovery has proved of great importance. 
In the first place, tuberculin is of practical value in the diagnosis of tuberculosis, 
in that injections excite fever. Inoculations for diagnostic purposes are now used 
extensively in cases of suspected tuberculosis in domestic animals. Moreover, 
the reports published by Koch gave a great stimulus to further investigations with 
regard to immunization by means of inoculation with bacterial toxins; and these 
investigations have led to the discovery of the antibodies of diphtheria, tetanus, 
cholera, and typhoid fever. 
In 1897 Koch (“Ueber neue Tuberculinpraparate,” Deut. med. Woch., 1897) 
succeeded in obtaining from highly virulent cultures of tubercle-bacilli a substance 
which he claims is able to immunize against all of the constituents of the tubercle- 
bacillus. To obtain this substance young cultures of tubercle-bacilli are dried in a 
vacuum-exsiccator and then triturated. The product obtained by trituration is 
mixed with distilled water and centrifugated. The active substance is contained in 
the muddy precipitate thus obtained (designated by Koch as T. R.). This is again 
dried and triturated, dissolved in water to which twenty per cent of glycerin is 
added for the purpose of preservation. The fluid preparation contains 10 mgm. of 
solid substance in every cubic centimetre, and when it is to be used should be 
diluted with physiological salt solution. Through the use of large doses animals 
are said to become immunized in from two to three weeks. In the treatment of 
tuberculosis in man the dose should begin at %oo mgm. and gradually be increased 
up to 20 mgm., the injections being given every other day. According to the 
observations so far published, the T. R. preparation does not appear to exert a 
curative action on tuberculosis in man.. 
The blood-serum treatment of diphtheria, i.e., the employment of the anti- 
toxins contained in the blood of an animal immunized against diphtheria as a means 
of curing that disease when it is already contracted, or as a protection against such 
infection, is a discovery which we owe to Behring. The favorable effects of the 
method have been affirmed by thousands of observations. VACCINES. 
89 
If culture-filtrates of the tetanus-bacillus are weakened by the action of chemi- 
cal agents (iodine trichloride or iodine combined with potassium iodide), it is 
possible through repeated injections of such filtrates of increasing virulence to pro- 
duce immunity in animals against tetanus (Kitasato, Behring, Tizzoni, Buchner). 
The blood of such immunized animals contains an antitoxin which affords a sure 
protection to experimental animals against tetanus. The antitoxin treatment of 
human beings suffering from tetanus has not given satisfactory results (see Kohler 
and Schlesinger, l.c.), not even in cases of relatively early injection of the antitoxin, 
though it is highly effective as a preventive measure. 
Susceptible animals and human beings may be immunized against bubonic 
plague by means of sterilized cultures of the pest-bacillus (Yersin, Haffkine, 
Kolle); and it appears that in the blood-serum of immunized animals (the horse, 
for example) there are present anti-bodies which render the serum utilizable for 
both protective and curative purposes. 
Animals may be made immune against snake-poisons by inoculations of small 
doses of such poison continued for some length of time (Calmette, Tschistowitsch) ; 
the blood-serum of such immunized animals is also found to possess an antitoxic 
action against the given poison, so that it may be used as a healing-serum. In 
Brazil, Mexico, Africa, etc., various methods involving the use of snake-poison 
itself are employed for the immunization of individuals against snake-bite, or for 
curing them after they have been bitten (Brenning). 
According to investigations by Ehrlich, mice may be made immune against 
ricin, to which they are extremely susceptible, by mixing small doses of ricin 
with their food and injecting additional small doses subcutaneously. The appear- 
ance of the immunity occurs on the sixth day after the administration of the ricin, 
so on this day the animal can withstand a dose thirteen times as great as at the 
beginning. Through continued systematic inoculations the animal becomes immune 
to a dose eight hundredfold as strong. The immunity is produced by an anti- 
toxic body, antiricin, which neutralizes the poison'. 
Vaccines. Since Wright’s discovery of the opsonins, bacterial vaccines have 
been extensively employed in the treatment of certain infections. The vaccines are 
prepared by cultivating the given micro-organism on agar, suspending the growth 
in salt-solution, and heating to 65°-80° C. for an hour to kill the bacteria. The 
emulsion of dead bacteria is then injected. Immediately following the injection 
the opsonic index falls for a time, the so-called negative phase. This is followed 
in a day or two by a rise in the index to or above its original height, the positive 
phase. Considerable doubt has been thrown on the opsonic index as a guide in the 
progress of an infection; but many clinicians have obtained gratifying results 
in the treatment with bacterial vaccines. The conditions most amenable to this 
treatment are localized inflammations, notably acne, furunculosis, etc. As a 
method of treatment, its successful application is limited. 
Attempts have been made to treat hyper-thyroidism with a specific serum 
(Rogers, Beebe). Experimental immunity to Spirillum obermeieri can be produced 
by the injection of filtered blood in which the spirilla have died out (Novy). 
Experimental immunity can be obtained in cerebrospinal meningitis (Flexner), 
and the therapeutic use of anti-meningococcic serum is a recognized procedure. 
Literature. 
(.Acquired Immunity against Infections and Intoxications.) 
Beebe: Nucleo-proteid Immunity. Brit. Med. Jour., 1906; Serum-treatment of 
Exophthalmic Goitre. Trans. Ass. Amer. Phy., 1906. 
Behring: Die Ursachen der Immunitat von Rattan gegen Milzbrand. Cent. f„ 
klin. Med., 1888; (and Kitasato) Diphtherie-Immunitat u. Tetanus. Deut. 
med. Woch., 1890; Die Blutserumtherapie, i., ii., Leipzig, 1892; Die Blut- 
serumtherapie bei Diphtherie u. Tetanus. Zeit f. Hyg., xii., 1892; Immunis. 
u. Heilung bei Tetanus, ib., xii., 1892; Die Geschichte der Diphtherie, 1893; 
Gesamm. Abhandlungen z. atiol. Therapie, Leipzig, 1893; Infection u. Des- 
infection, Leipzig, 1894; Leistungen u. Ziele der Serumtherapie. Deut. 
med Woch., 1895; Immunitat. Euleriburg’s Realencyklop., 1896; Anti- 
toxintherapeutische Probleme. Fortschr. d. Med., 1897; Heilprincipen 
Deut. med. Woch., 1898. 
Bordet: Serum antistreptococcique. Ann. de. l’lnst. Past., 1897. 90 
THE PROTECTIVE FORCES OF THE BODY. 
Brieger, Kitasato u. Wassermann: Immunitat und Giftfestigung. Zeit f. Hyg, 
_ xii., 1892. 
Brieger u. Ehrlich: Die Milch immunisirter, Thiere. Zeit. f. Hyg., xiii, 
1893. 
Buchner: Immunitat u. Immunisirung. Munch, med. Woch., 1889, 1897, 1899; 
Bakteriengifte u. Gegengifte, ib., 1893; Schutzimpfung. Handb. d. spec. 
Ther., i., Jena, 1894. 
Calmette: Venins, toxines et antitoxines. Ann. de l’lnst. Past., 1895; Venins 
des serpents et serum antivenimeux, ib., 1897. 
Calmus et Gley: Immunite contre le serum d’anguille. Ann. de l’lnst. Past., 
1899. 
Charrin: L’immunite. Arch, de phys., v., 1893; Traite de path, gen., ii., Paris, 
1896. 
Chauveau: Theorie des inoculations preventives. Rev. de med., 1887; Mecanisme 
de l’immunite. Ann. de l’lnst. Past., ii., 1888; Proprietes vaccinales des 
microbes ci-devant pathogenes transformes en microbes d’apparence sapro- 
gene. A. de med. exp., i., 1889. 
Corbette: The Action of Antitoxins. Journ. of Path., vi., 1899. 
Ehrlich: Ueber Ricin u. Antiricin. Deut. med. Woch., 1891; Fortschr. d. Med., 
xv., 1897; Die Werthbemessung d. Diphtherieheilserums. Klin. Jahr., 1897; 
Immunitat durch Vererbung u. Saugung. Zeit. f. Hyg., xii., 1892; Zur 
Kenntniss d. Antitoxinwirkung. Fortschr. d. Med., 1897. 
Emmerich: GTrsache der Immunitat, Heilung von Infectionskrankheiten. 
Munch, med. Woch., 1891; Infection, Immunisirung u. Heilung bei krup. 
Pneumonie. Zeit. f. Hyg., xvii., 1894. 
Emmerich and Low: Bakteriolytische Enzyme als Ursache d. erworb. Immuni- 
tat u. Heilung von Infectionkrankheiten. Zeit. f. Hyg., 31 Bd., 1899. 
Engelmann: Serumtherapie des Tetanus. Munch, med. Woch., 1897 (Lit.). 
Flexner: Exper. Cerebrospinal Meningitis and Its Serum Treatment. Jour, of 
Exp. Med, 1907. 
Fraser: Immunization against Serpents’ Venom. Brit. Med. Journ, i, 1896. 
Galeotti: Immunit. u. Bakteriotherapie gegen Cholera. Cbl. f. allg .Path, vi, 
1895 (Lit.). 
Gay: Vaccination and Serum Therapy against the Bac. of Dysentery, Univ. of 
Penn. Med. Bull, 1902. 
Kitasato: Heilversuche an tetanuskranken Thieren. Zeitschr. f. Hyg, xii, 1892. 
Klemperer: Immunisirung u. Heilung bei Pneumokokkeninfection. Berl. klin. 
Woch, 1891. 
Knorr: Entstehung d. Tetanusantitoxins. Fortschr. d. Med, xv, 1897. 
Koch: Milzbrandimpfung, Berlin, 1882; Mittheil. a. d. K. Gesundheitsamte, 
Berlin, 1884; Neue Tuberkulinpraparate. Deut. med. Woch, 1897, No. 14. 
Kohler: Serumtherapie des Tetanus (Statistik). Munch, med. Woch, 1898. 
Kolle: Active Immunisirung gegen Cholera. Cbl. f. Bakt, xix, 1896 (Lit.); 
Bakteriologie der Beulenpest. Deut. med. Woch, 1897 (Lit.). 
Longcope: A Study of the Bacteriolytic Serum-complements in Disease. Univ. 
of Penn. Med. Bull, 1902. 
Metschnikoff: fitudes sur l’immunite. Ann. de l’lnst. Past, 1890, 1891, 1894, 
and 1895; Rech. sur l’influence de l’organisme sur les toxines. Ib, 1897, 
1898. 
Novy: Studies on Spirillum Obermeieri. Jour, of Infect. Dis., 1906. 
Pasteur: Sur la rage. Ann. de l’lnst. Past., i., 1887; Lettre a M. Duclaux. Ib., 
ii., 1888. 
Pearce and Jackson: Production of Cytotoxic Sera by Inject, of Nucleopro- 
teids. Jour, of Infect. Dis., 1906. 
Petruschky: Immunitat des Frosches gegen Milzbrand. Beitr. v. Ziegler, iii., 
1888; Wissensch. Grundlage d. Serumtherapie. Samml. klin. Vortr., No. 
212, Leipzig, 1898. 
Pfeiffer: Immun. Wirkung m. Choleraambozeptoren belad. Choleravibrionen. 
D. med. Woch., 1903. 
Pfeiffer u. Kolle: Schutzimpfung gegen Typhus. Deut. med. Woch., 1896. 
Raynaud: Role du sang dans la transmission de l’immunite vaccinale. ' Compt. 
Rend., t. 84, 1877. 
Rodet: L’attenuation des virus. Rev. de med., vii., 1887, and viii., 1888; Les 
inoculations vaccinales, L’immunite acquise, ib., viii., 1888, et ix., 1889. 
Roger: Schutzimpfung gegen Rinderpest. Zeit. f. Hyg, 35 Bd., 1900. 
Roux: Immunite contre le charbon symptomatique confere par des substances EHRLICH’S SIDE-CHAIN THEORY. 
91 
solubles. Ann. de l’Inst. Past., 1888; De l’immunite. Ib., 1891; Les serums 
antitoxines. Ib., 1894. 
Roux et Borrel: Tetanus cerebral et immunite. Ann. de l’lnst. Past., 1898. 
Roux et Chamberland: Immunite contre la septicemie confere par des substances 
solubles. Ann. de l’lnst. Past., 1887; Immunite contre le charbon. Ib., 
1888. 
Stephens and Meyers: Action of Cobra Poison on the Blood. Journ. of Path., 
v., 1898. 
Stern: Ergebnisse auf. d. Gebiete der Immunitatslehre. Cbl. f. allg. Path., 
1894; Wirkung d. menschlichen Blutserums auf die exper. Typhus-Infection. 
Zeit. f. Hyg., xvi., 1894. 
Steuer: Serumbehandlung d. Tetanus. Cbl. f. d. Grenzgeb. d. Med., iii., 1900. 
Strong, Crowell and Teague: Studies on Pneumonic Plague and Plague Immun- 
ity. Philippine J. of Sc., 1912. 
Taruffi: Heilung des Tetanus traumaticus durch Antitoxin. Cbl. f. Bakt., xi., 
1892. 
Tavel: Beitr. z. Blutserumetherapie d. Tetanus. Corrbl. f. Schweizer-Aerzte, 
1894. 
Tschistowitsch: L’immunisation contre le serum d’anguille. Ann. de l’lnst. 
Past., 1899. 
Vaughan and Novy: The Cellular Toxins, 1902. 
Voges: Die Choleraimmunitiit. Cbl. f. Bakt., xix., 1896 (Lit.). 
Wasserman: Immunitat. Eulenburg’s Jahr., iv., 1894; Zeit. f. Hyg., xxii., 1896; 
Serumtherapie. Deut. med. Woch., 1897; Kiinstl. Immunitat. Berl. klin. 
Woch., 1898; Seitenkettenimmunitat. Ib., 1898; Neue Versuche auf dem 
Gebiete der Serumtherapie. Deut. med. Woch., 1900; Natiirliche u. kiinst- 
liche Immunitat. Z. f. Hyg., xxxvii., 1901. 
Wechsberg: Natiirl. Immun. u. bakterizide Heilsera. Z. f. Hyg., xxxix., 1902. 
Weigert: Arbeiten zur Theorie der Antitoxinimmunitat Ergebn. d. allg. Path., 
iv., 1899. 
Welch: The Huxley Lecture. Bull, of the Johns Hopkins Hosp., 1902. 
Yabe: Btude sur l’immunite de la tuberculose, Paris, 1900. 
Yersin: La Peste bubonique. Ann. de l’lnst. Past., 1897. 
See also §§ 30, 31, and 33. 
III. The Active Substances of Acquired Immunity. Ehrlich’s Side- 
chain Theory. 
§ 33. Acquired Immunity depends on the presence of specific anti- 
toxic and bactericidal antibodies. The process is seen in its simplest 
form in the production of antitoxins in diphtheria and tetanus. 
According to the views of Ehrlich, only those substances are poisons 
that possess a chemical affinity for some element of the body and act 
through combination with this element. Congenital immunity to poison 
may, therefore, depend on the fact that the poison finds in the body 
no element with which it can react chemically, or if reaction occurs the 
body suffers no damage in a clinical sense. In acquired immunity to 
poison the action of the toxin is prevented through the formation of 
an antitoxin. 
Complex protoplasmic substances, considered as chemical structures, 
consist of a governing-nucleus or central-group (central ring) and of 
various side-chains (Ehrlich). These side-chains combine with the side- 
chains of albuminous nutritive substances, and so bring about assimila- 
tion of the latter. Their significance is that of receptors or of a hapto- 
phore group which combines with a haptophorous group of the albumin- 
ous food-material. In the same way toxins are anchored through their 
haptophorous group to the receptors of the cell-protoplasm, thus enabling 
the toxophorous group of the toxin to exert its action on the cell-pro- 
toplasm and to injure its vital functions. 92 
THE PROTECTIVE FORCES OF THE BODY. 
As the result of the combination of toxins with receptors, portions 
of the protoplasmic albumin-molecule are rendered incapable of func- 
tion. If the life of the cell and its power of compensation are not dam- 
aged, there is produced only transient disturbance of the central group 
without definite injury to it; and the cell may again replace the side- 
chains and even form them in excess — throw them ofif, and give them to 
the blood. Such detached side-chains or receptors constitute an antitoxin. 
The antitoxin is, therefore, no new substance, but one normally present, 
which under certain conditions is produced in increased amount and given 
to the blood, and, circulating there, combines the toxin to form a harm- 
less body, and so prevent action on the cells. The same substance in 
the living body, which as a constituent of the cells renders intoxication 
possible, becomes the cause of healing when set free in the blood-stream 
(von Behring). 
The bactericidal action of the blood-serum, a phenomenon occurring 
in certain infectious diseases (typhoid fever, cholera, plague), is depend- 
ent on the combined action of two substances. One of these is a. ferment- 
like body found particularly in the blood-serum of the normal organism. 
It is labile and is destroyed by heating to 55° C. Buchner has desig- 
nated this substance alexin, Ehrlich complement, and Metschnikofif 
cytase. Alone it is not able to injure the bacteria, but needs for this 
action the cooperation of an intermediate-body, the amboceptor or im- 
mune-body of Ehrlich (substance sensibilatrice of Bordet). 
The amboceptors are formed during the course of an infection, and 
are specific for that disease (specific immune-bodies), that is, they are 
active only in that disease in the course of which they are formed. They 
possess two haptophore groups, one of which (cytophile group) com- 
bines with a receptor of the bacterial protoplasm; the other (comple- 
mentophile group) combines with a haptophore chain of the comple- 
ment, so that the zymotic group of the latter can act on the bacterial 
cells. The amboceptor is less susceptible to heat than the complement 
and is not destroyed by heating to 60° C. 
The bactericidal sera act, in the first place, in such way as to cause 
death and solution of the bacteria, in that the specific immune-body, 
the amboceptor, carries over to the bacteria the digestive action of the 
normal body-juices, in the complement, so that the bacteria are in part 
dissolved. Such sera contain, therefore, bacteriolysins. A second ac-> 
tion is the phenomenon of agglutination, in that specific substances con- 
tained in the serum, agglutinins, combine with the bacterial cells and 
cause clumping. The agglutinins are less susceptible to heat than the 
lysins and are not changed at 56° C. 
Finally, bactericidal immune-sera cause precipitation, in that certain 
substances contained in the serum, precipitins, or coagulins, form chem- 
ical combinations with certain substances given ofif from the disintegrat- 
ing bacterial bodies and coagulate or precipitate them. If an active 
bactericidal serum be added to a clear fluid which contains such albumi- 
nous substances of the bacterial cells, there is produced a flocculent pre- 
cipitate. 
Precipitins withstand heating to 56° C. and may be dried without 
losing their potency 
According to Ehrlich, the receptors for a toxin represent only a hap- 
tophorous group of cells with whose haptophorous chain the toxin has IMMUNITY. 
93 
combined. He designates the same as a receptor of the I order. On the 
other hand, the receptor of the cells for the nutritive albumin-molecules 
contains a haptophorous and a zymophorous group, the latter of which 
causes fermentative disintegretation of the anchored albumin-molecule. 
This is designated as a receptor of the II order. The receptor for bacteri- 
olysin contains a haptophorous group for the anchoring of the ferment- 
like complement and a receptor for the combining of the disintegration 
products of bacteria, so that the former can act on the latter. 
The receptors thrown off by the cells are designated by Ehrlich 
haptins, and he distinguishes: a haptin of the I order, the antitoxin, which 
combines the toxin to form a harmless body; haptins of the II order, the 
agglutinins, precipitins, or coagulins, which, after their union with the 
albumin of the bacteria, cause agglutination, coagulaton, and precipita- 
tion through the action of the zymophorous group; and haptins of the 
III order, or bacteriolysins, which as amboceptors carry over the fer- 
mentative action of the complement to the bacteria. 
Under special conditions there appear, particularly in the blood, substances 
that act on the red blood-cells or tissue-cells or the soluble albumins of the 
human and animal organism in the same manner as the antibodies described 
above. According to their action they are classed as haemolysins (globulicidal 
immune-sera), cytolysins, precipitins, and agglutinins. They arise when into 
the body of an animal there is introduced the blood, lymph, milk, or tissue 
from an animal of a different species (Bordet, Tschistowitsch, Kraus, von Dungern, 
Wassermann, Ehrlich, Morgenroth, Landsteiner, Uhlenhuth, and others). The 
blood-serum of a guinea-pig injected repeatedly with defibrinated rabbit’s blood is 
able to dissolve quickly in vitro the red corpuscles of the rabbit, while normal 
guinea-pig’s blood does not possess such power.. 
The action of haemolysins or of a globulicidal immune-serum corresponds in 
all respects to that of the bacteriolysins, and the researches concerning the nature 
of the haemolysins (Ehrlich, Morgenroth) have aided essentially in the explanation 
of the mechanism of bacteriolysis. 
The immune-body or amboceptor appearing in globulicidal serum shows great 
soecific affinity for the corresponding erythrocytes; it will combine with them at 
0° C. and, when thus separated from the complement left in the serum, is not in 
itself able to dissolve the red blood-cells. The complement will not combine with 
the red cells without the immune-body. When the immune-body or amboceptor 
is present, the complement may, at a higher temperature, be carried by the ambo- 
ceptor over to the red cells and cause their solution. 
After intraperitoneal injections of laked blood of the same species, the so-called 
isolysins may be formed, that is, the blood-serum of the animal injected acquires the 
power of dissolving the red cells of another individual of the same species. 
Cytolysins or cytotoxins arise through the injection of foreign cells into an 
organism, for example, after the injection of ciliated epithelium, spermatozoa, leu- 
cocytes, renal epithelium, adrenal cells, brain-substance, pancreas-cells, placenta- 
cells, and carcinoma-cells. In the case of ciliated epithelial cells and spermatozoa 
the action of the cytolysins contained in the serum can be recognized outside the 
body in the rapid cessation of movement (tricholysin, spermolysin). 
Cytolysins act in the same manner as the haemolysins. 
Precipitins arise in the blood-serum as a specific reaction after the sub- 
cutaneous, intraperitoneal, or intravenous introduction of foreign albuminous 
substances. 
A serum containing precipitins has the power, when added to the albumin solu- 
tion used in the injections, of causing in the latter a precipitate. R. Kraus demon- 
strated this action for cholera-spirilla, that is, for the substance of the bacterial 
cell brought into solution. The serum of goats previously treated with injections 
of cholera-spirilla or with the bacterial substance causes a precipitate in filtrates of 
cholera-cultures that contain no bacilli. This property of the bacterial precipitins 
may be used in diagnosis. 
According to the investigations of Tschistowitsch, Bordet, Wassermann, 
Schutze, Ehrlich, Morgenroth, Myers, Uhlenhuth, von Dungern, and others, such 
precipitins are also formed after the injection of foreign blood, milk, inflammatory 94 
THE PROTECTIVE FORCES OF THE BODY. 
exudates, fresh and dried flesh, etc.; and through the aid of this method it becomes 
possible to distinguish from one another not only the red blood-cells of different 
species, but also flesh, milk, semen, etc.; that is, the precipitating serum of an animal 
A, that has been treated with an albumin of an animal B of another species, will 
precipitate the albumin of B, but not that of a third species. 
This reaction of albumin obtained by biological methods (biological method of 
differentiating albumins, Wassermann and Schiitze) is so extremely sensitive that 
the specific test for albumin is possible even at a dilution of 1:100,000. The pre- 
cipitin reaction has found its most important application in the examination of 
blood-stains, but it is also of use in the differentiation of different kinds of meat, 
milk, etc., and can be applied also to the differentiation of plant-albumins. 
The reaction is specific for the albumin of different species of animals and for 
man; between the albumins of different elements of the body, as, for example, 
between chicken-blood and the white of a chicken-egg, there exist only quantitative 
differences. An antiserum to human blood will precipitate urine containing albumin, 
purulent exudates, ascitic fluid, seminal fluid, etc.; so it may be inferred that the 
various fluids of the body contain the same receptors as those of the blood-serum. 
In the examination of spots, stains, etc., the first thing to be determined is the 
presence of blood (guaiacum test, Teichmann’s test, spectroscopic examination). 
When this is determined, the biological test, properly handled, gives certain results, 
particularly when the animal used for the production of the serum is not closely 
related. An antiserum for human blood gives only a weak reaction with ape’s 
blood (particularly that of anthropoid apes) ; and similar conditions exist between 
the horse and the donkey, and between the chicken and pigeon. 
For the demonstration of the presence of human blood or albumin, the serum 
of rabbits properly treated beforehand may be used to best advantage, but that of 
the horse, sheep, or goat may also be employed (according to von Dungern, cold- 
blooded animals produce no precipitins). To produce the antiserum (Uhlenhuth) 
5-10 c.c. of a dilute solution of albumin derived from human tissues or blood are 
injected into a rabbit at intervals of several days, until a test of blood taken from 
the vein of the ear, made about five days after the last injection, shows the serum 
to be active. It is strange that the time in which this change in the serum occurs 
varies greatly with individual animals. When the serum has attained its full 
strength, the animal is anaesthetized, the thorax opened, and a cut made into the 
heart. The blood is taken up by a pipette and collected in a sterilized glass gradu- 
ate. The serum when separated is filtered through a Berkefeld filter and when 
ready for use must be perfectly clear. The albuminous material to be tested is 
dissolved in physiological salt-solution. 
A serum of high potency may contain precipitins that act not only on homo- 
logous albumins, but also on heterologous. Uhlenhuth recommends, therefore, a 
marked dilution (1:1,000) of the fluid to be examined, which, moreover, must be 
perfectly clear. To 2.0 c.c. of the dilute fluid 0.1 c.c. of the antiserum is added, and 
in the presence of homologous albumin a cloudy precipitate forms at once or after 
one or two minutes. 
Agglutinins that cause clumping through their functional molecule-groups 
may be combined first with bacteria, but also after that with red blood-cells. 
Agglutinable substances and agglutinins possess specific combining haptophore- 
groups (Eisenberg and Volk, Wassermann). In the agglutinable substance the 
functional group is more labile and more easily destroyed than the haptophore- 
group; this is true also of the agglutinin (Wassermann). Through external influ- 
ences the functional group may be lost, and from the agglutinin there is produced 
an agglutinoid, which is no longer able to cause agglutination, and through its 
combination with the agglutinable substance is able to prevent the occurrence of 
agglutination in the presence of agglutinin. As has been mentioned above (§ 31), 
agglutination has been observed chiefly in the case of cholera-spirilla, typhoid- 
bacilli, pyocyaneus, colon, and tubercle bacilli. 
Immune-agglutinins are produced during the process of immunization by 
increased formation and liberation of groups that under certain conditions occur in 
slight amount even in normal serum. 
Agglutination can be applied to the diagnosis of a given disease, but it must be 
remembered that the serum of healthy individuals causes agglutination (in typhoid 
fever even in dilutions of 1:20, while the serum of persons having the disease will 
agglutinate at a dilution of 1:50) ; and that a serum can also agglutinate to a 
greater or less degree other bacteria than the one coming under the influence of its 
agglutination power. The serum of typhoid patients or of those immune to typhoid 
acts on many colon-species even in high dilutions. IMMUNITY. 
95 
The precipitable substance in culture-fluids is, according to Wassermann, identi- 
cal with the agglutinable substance in the bacterial cells; that is, the substance pres- 
ent in the uninjured bacterial cells, combining in agglutination with the agglutinat- 
ing serum, is, in the culture-fluids, dissolved out of the bacteria, set free in the 
same, and gives there a specific precipitate with the serum. 
Agglutination and dissolution of bacteria, according to Wassermann, Ehrlich, 
Morgenroth, etc., are not caused by the same substance, as is believed by von Baum- 
garten and Gruber to be the case. Agglutinins and amboceptors or immune-bodies 
are distinct from each other and do not have the same haptophorous group in com- 
mon. The immune-body needs for its action the complement, the agglutinin does 
not. 
The agglutinin is made up of separate or partial agglutinins, and a bacterial 
agglutinin may, therefore, vary in its constitution according to the biological quali- 
ties of the animals in which it is produced. Two varieties of bacteria (typhoid- 
fever and colon-bacilli) may also possess a number of partial agglutinins in com- 
mon. It, therefore, becomes necessary (Wassermann), when applying agglutination- 
tests for the purpose of diagnosis, to work always with such dilutions as possess a 
limit of action not far from that obtained by titration for the given bacterial species 
(the limits of potency of any serum may vary greatly). A positive agglutination 
is, therefore, decisive as pertaining to that species with which the animal producing 
the serum was previously treated. 
The production of antitoxin plays the most important role in the healing of 
diphtheria and tetanus; the success attending the prophylactic and therapeutic 
use of these antitoxins has already been mentioned in § 32. The toxin is 
not destroyed by the antitoxin. When snake-venom (Calmette) is mixed with 
antitoxin so that the mixture becomes harmless to animals, and if the more thermo- 
labile antitoxin be destroyed by heating to 68° C., the mixture again becomes pois- 
onous. The same thing may be demonstrated in the case of the toxin and anti- 
toxin of the Bac. pyocyaneus. 
According to Wassermann, the substance of the central nervous system chiefly 
affected by tetanus is able to combine with the tetanus toxin after the manner of 
an antitoxin and so render it harmless. Tetanus toxin rubbed up with the brain 
substance of a normal rabbit becomes so weakened that guinea-pigs can bear ten 
times the fatal dose without damage. According to Ransom, the tetanus-poison 
injected in fatal doses into pigeons is demonstrable in all organs except the central 
nervous system, with which it has entered into chemical combination. 
Therapeutic attempts with bactericidal sera have not given such good 
results as those of antitoxic sera. In the first place, the bactericidal sera have 
no influence on an existing intoxication. Further, action on the bacteria 
present is impossible when the injected serum finds no free complement in the 
blood of the patient or when the amboceptor from animal blood (horse blood) 
does not combine with the complement of human blood. 
The agglutinins, precipitins, etc., can in turn produce in the organism anti- 
anti-bodies, antiagglutinins, antipreciptinins, etc. 
Hypersusceptibility or anaphylaxis. Animals may react to certain toxic or 
foreign substances in one of two ways, either by increased resistance or 
immunity or by increased susceptibility (hypersusceptibility or anaphylaxis). 
According to Theobald Smith, Otto, Rosenau and Anderson, Gay and Southard, etc., 
there occurs a remarkable toxic action in guinea-pigs as the result of an injection 
of a small dose of horse-serum (.0001-.1 c.c.), followed after ten days or two 
weeks by a second injection of relatively large amount (5 c.c.), the reaction being 
characterized by severe symptoms and death within one hour. This reaction is 
specific in that guinea-pigs sensitized with horse-serum do not react to the second 
injection of other proteid substances, and vice versa. The reaction following a sec- 
ond injection of the same proteid in guinea-pigs appears to be common to all higher 
forms of albuminous substances (white of egg, haemoglobin, milk, extract of peas, 
bacterial proteids, etc.). Simpler albuminous substances, such as peptone, seem to 
have slight sensitizing and poisonous properties, while lower nitrogenous compounds 
as leucin and tyrosin possess none at all. Hypersusceptibility in the guinea-pig may 
be transmitted by the female to the offspring. The hypersusceptibility may persist 
for a long time (Rosenau and Anderson). The hypersusceptibility produced in 
guinea-pigs to second injections of bacterial proteids resembles that produced by 
second injections of horse-serum. It is significant that the period of incubation in 
a number of infectious diseases corresponds to the ten or fourteen days required 
to sensitize animals to a foreign proteid. (For literature see Anderson and 
Rosenau, Jour, of Med. Res., July, 1908.) 96 
THE PROTECTIVE FORCES OF THE BODY. 
Literature. 
(Acquired Immunity, Ehrlich’s Side-Chain Theory.) 
Aschoff: Ehrlich’s Seitenkettentheorie, Jena, 1902 (Lit.). 
von Baumgarten: Phagocytenlehre. B. v. Zieg., vii., 1896; Jahresber., 1891-1904, 
Die Hamolyse. Festschr. f. Jaffe, Braunschweig, 1900; B. klin. Woch., 1901. 
Bordet: Les serums hemolytiques. Ann. de l'lnst. Past., xiv., 19Q0; Mode 
d’action des serums cytolytiques. Ibid., 1901. 
Charrin: L’immunite. A. de phys., iv., 1893; Traite de path, gen., ii., Paris, 1896. 
Corbette: The Action of Antitoxins. Jour, of Path., vi., 1899. 
von Dungern: Globulicide Wirk. d. tier. Organismus. Munch, med. Woch., 
1899; Immunserum gegen Epithel. Ibid., 1899; Beit. z. Immunitatslehre. 
Ibid., 1900; Die Antikorper, Jena, 1904; Bindungsverhaltnisse b. d. Pracipi- 
tionsreaktion. Cbl. f. B., xxxiv., Orig., 1903. 
Ehrlich: Ueber Toxin und Antitoxin, Berlin, 1901; Munch, med. Woch., 1903; 
Schutzstoffe des Blutes. D. med. Woch., 1901; Verh. d. Ges. d. Naturforsch., 
Leipzig, 1902. 
Ehrlich und Morgenroth: Hamolysine. Berl. klin. Woch., 1900; Wirkung und 
Enstehung d. aktiven Stoffe im Serum nach d. Seitenkettentheorie. Handb. 
d. path. Mikroorg., iv., 1904. 
Emmerich: Bakterolyt. Wirkung d. Nucleasen u. Nucleasenimmunproteide. 
C. f. B., xxxi., 1902, Orig. 
Engel: Leitfaden u. klin. Untersuch. d. Blutes, Berlin, 1902. 
Friedberger: Die baktericiden Sera. Handb. d. path. Mikroorg., iv., Jena, 1904. 
Gruber: Zur Theorie der Antikorper. Munch, med. Woch., 1901. 
Hauser: Serodiagnostische Methode. Munch, med. Woch., 1904. 
Joos: Mechanismus der Agglutination. Z. f. Hyg., 40 Bd., 1902. 
London: Cytolytische Theorie d. Immunitiit. C. f. B., xxxii., Orig., 1902. 
Lowit: Niederschlagsbildung bei d. Agglutination. C. f. B., xxxiv., Orig., 1903. 
Manwaring: The Application of Physical Chemistry to Serum Pathology. 
(Various papers.) Studies from Rockefeller Institute, vi., 1907. 
Marx: Einfuhrung in die Serodiagnostik. Z. f. Tiermed., vi., 1902. 
Metschnikoff: Sur les cytotoxines. Ann. de l’lnst. Past., 1900; Immunitat bei 
Infektionskrankheiten, Jena, 1902; Die Lehre v. d. Phagocyten. Handb. d. 
path. Mikroorg., Jena, 1904. 
Moxter: Immunserum gegen Spermatozoen. D. med. Woch., 1900. 
Muir: The Action of Haemolytic Sera. Lancet, 1903. 
Miiller: Antihamolysine. Cbl. f. Bakt., xxix., 1901. 
Neisser und Wechsberg: Wirkungsart baktericider Sera. Munch, med. Woch., 
190L 
Noguchi: The Thermostabile Anticomplementary Constituents of the Blood. 
Jour, of Exp. Med., 1906. 
Oppenheimer: Toxine und Schutzstoffe. Biol. Cbl., xix., 1899 (Lit.). 
Pfeiffer, L.: Die moderne Immunitatslehre. Z. f. Hyg., 43 Bd., 1903. 
Piorkowski: Die spezifischen Sera. C. f. Bakt., Ref., xxxi., 1902. 
Proscher und Pappenheim; Die theoretischen Grundprinzipien der Immuni- 
tatslehre. Fol. haem., i., 1904. 
Sachs: Die Hamolysine u. ihre Bed. f. d. Immunitatslehre. Ergeb. d. a. Path., 
vii., 1902; Hamolysine d. normalen Blutserums. Munch, med. Woch., 1904. 
Silberschmidt: Ergeb. a. d. Immunitatsforschung. Korr. f. Schw. Aertze, 1902. 
Uhlenhuth: Prazipitine. Eulenb. Jahrb., ii., 1904 (Lit.). 
Vaughan and Wheeler: The Effects of Egg-White and Its Split Products on 
Animals. Jour, of Inf. Dis., 1907. 
Wassermann: Natiirl. u. kiinstl. Immunitat. Z. f. Hyg., 37 Bd., 1901. Ag- 
glutinine u. Prazipitine. Ib., 42 Bd., 1903; Die Grundziige d. Lehre v. d. 
Immunitat u. Serumtherapie. Z. f. arztlich. Fortbildung, i., 1904; Giebt es 
ein biologisches Differenzierungsverfahren f. Menschen- u. Tier blut mittels 
der Prazipitine? Deut. med. Woch., 1904; Entstehung und Wirkung d. 
aktiven Stoffe im Immunserum. C. f. B., xxxv., Ref., 1904; Antitoxische 
Sera. Handb. d. path. Mikro-org., iv., Jena, 1904. 
Weigert: Arbeiten z. Theorie d. Antitoxinimmunitat. Ergebn. d. allg. Path., 
iv., 1899. 
Ziegler, K.; Serumdiagnose verschied. Blutarten. Cbl. f. a. Path., xiii., 1902 
(Lit.). CHAPTER IV. 
Disturbances in the Circulation of the Blood and of the Lymph. 
§ 34. The mass of blood is kept in motion by the rhythmical contrac- 
tions of the heart. The blood, as it is driven into the elastic aorta toward 
the periphery of the body, meets a significant degree of resistance, caused 
by the friction in the innumerable divisions and subdivisons of the 
arterial system. This resistance occasions a relatively high pressure 
throughout the arterial system, which in the human femoral artery equals 
that of about 120 mm. of mercury. After passing through the capillaries 
the blood arrives in the veins with little velocity, and stands in the veins 
under slight pressure, which varies according to the location of the vein, 
and is greatest where a high column of blood rests on the lumen of the 
vein. In the great venous trunks of the thorax the pressure is usually 
negative, especially during inspiration, as the thorax during this stage of 
respiration aspirates the blood from the veins outside the chest. Only 
during forced expiration does the positive pressure in the veins rise some- 
what higher. 
Assuming the mass of the blood to be constant, the degree of pressure 
in the aorta, at any given moment, is dependent on the work of the heart 
and the resistance in the arterial system. The latter in turn is dependent 
on the variations in the total diameter of the combined cross-sections of 
the blood-vessels, brought about by the elasticity and contractility of the 
arteries. In the major circulation the arterial tone is pronounced; in the 
lesser circulation it is slight, the blood-pressure in the pulmonary artery 
being only from one-third to two-fifths that in the aorta. Both the 
heart and the arteries are under the influence of the nervous system, 
which regulates their activity. 
The activity of the heart consists in rhythmical contractions of its 
musculature; and its efficiency presupposes that the heart-muscle, and 
the cardiac ganglia, are sound. Every disease of the heart, therefore, 
in so far as it diminishes the contractile capacity of the heart-muscle and 
lessens the activity of the ganglion-cells, and in so far as lessened func- 
tional activity of the cardiac muscle is not compensated by increased 
activity of other parts, will diminish the functional capacity of the 
heart. 
In many cases in which the functional capacity of the heart-muscle 
is impaired, anatomical changes, such as fatty degeneration and necrosis 
of its cells, can be demonstrated; in other cases no anatomical changes 
can be made out, especially in those cases in which diminution of work- 
ing-capacity follows exhaustion caused by overexertion. This may occur 
when the heart is forced to work for some time slightly above the normal, 
but under unfavorable conditions, as, for example, in elevation of the 
body-temperature; as well as in cases when for a short period it is over- 
worked to an excessive degree. Under certain conditions disturbances 
of nutrition and intoxications, such as occur in the infectious fevers, as 
well as sudden diminution in blood-supply from obstruction of a coronary 
*7 D7 98 
DISTURBANCES OF THE CIRCULATION. 
artery, may cause insufficiency of the heart within so short a time 
that the heart-muscle presents no recognizable anatomical lesion. The 
work of the heart may also be made difficult through the formation of 
adhesions between the epicardium and pericardium, and between the lat- 
ter and the contiguous pleura, in consequence of which the contractions 
of the heart are hindered. 
Through the collection of fluid in the pericardial sac in the course 
of certain diseases, through deformities of the thorax marked by ab- 
normal smallness of the thoracic cavity, and through a high position of 
the diaphragm, the diastolic dilatation of the heart and the free afflux 
of blood from the veins may be hindered to such an extent that the 
ventricles receive too little blood. If, following pathological processes in 
the heart-valves, there result rents or distortions of the flaps or adhe- 
sions between them, or if in case of dilatation of the heart and of the 
valvular orifices the valve-flaps become too short, there may arise those 
conditions of the auricular and ventricular orifices known as insuffi- 
ciency and stenosis. The former condition is characterized by failure of 
a valve to close completely during the diastole of the auricle or ventricle 
lying behind the given valve; the second condition, by the fact that dur- 
ing the contraction of the auricle or ventricle the valvular orifice does 
not suffice for the free passage of blood through the opening. The effect 
of stenosis is that of opposing additional obstacles to the outflow of the 
blood during systole. In aortic and pulmonary insufficiency the blood 
regurgitates, during ventricular diastole, from the great vessels into the 
ventricles; in mitral and tricuspid insufficiency the systole of the ventricle 
causes regurgitation into the corresponding auricle. 
Finally, there are not infrequently formed in the heart masses of 
coagula, which, if they lie near the orifices may interfere with the proper 
closing of the valves, or cause narrowing of the ostium. 
As a result of the above-mentioned pathological conditions, the effi- 
ciency of the heart’s function is impaired, so that in a given time too 
little blood passes into the arterial system, the aortic pressure falls, and 
the velocity of the blood-current is diminished; while in the venous 
system the blood collects, and the venous pressure rises. There is con- 
sequently inadequate filling of the arteries throughout the body, varying, 
indeed, according to the degree of contraction in individual arterial 
systems, while both veins and capillaries are, on the other hand, overfilled 
with blood. There develops, therefore, a condition of general venous 
hyperaemia, which in some parts may become so marked that the tissue, 
because of the engorgement of the capillaries with venous blood, acquires 
a blue-red, cyanotic appearance. When the difference in pressure be- 
tween the arterial and venous systems becomes reduced to a minimum, 
the circulation comes to a standstill, while the right side of the heart be- 
comes distended with blood. 
Should the contractions of the heart from any cause become weak, 
the pulse-wave also becomes small. If the rate of the heart-beat is 
diminished in frequency, the arterial system empties itself to a greater 
extent than normally during the pause between the systoles. 
If the impairment of cardiac efficiency involves the left heart, as is 
the case, for instance, in valvular disease of the left side, the disturbance 
of circulation is manifest first in the systemic arteries, as well as in the 
pulmonary vessels. IMPAIRMENT OF CARDIAC FUNCTION. 
99 
In stenosis of the aortic valves, the arteries, if the heart’s action re- 
main unchanged, fill slowly and incompletely (pulsus tardus). In aortic 
insufficiency a normal or even an increased amount of blood is thrown 
into the arteries during systole (pulsus celer), but a part of this flows 
back during diastole. In both cases the left ventricle becomes distended, 
the emptying of the left auricle is hindered, its cavity becomes dilated, 
and finally the blood is backed into the pulmonary veins. Owing, how- 
ever, to the low pressure in the pulmonary circulation, the blood is readily 
dammed back on the right ventricle, and the blood stasis may finally ex- 
tend into the right auricle and the systemic veins. 
Valvular lesions at the mitral orifice produce similar effects on those 
portions of the circulatory apparatus lying behind the left auricle; in such 
cases there is also produced a condition of pulmonary stasis, with rise 
of pressure in the pulmonary arteries and veins; while the left ventricle 
either receives too little blood (stenosis) or during its contraction drives 
a portion back into the auricle (insufficiency). 
In valvular lesions of the orifices of the right heart the damming back 
of the blood is limited to the veins of the systemic circulation, while in 
the pulmonary circulation both pressure and velocity are diminished. 
Further, the pressure in the aorta falls, since the left side of the heart 
receives too little blood. 
The damming back of blood in the great systemic veins may manifest 
itself by venous pulsations in the neighborhood of the thorax, inasmuch 
as retrograde waves proceeding from the heart pass through the veins 
toward the capillaries, distending the veins to such an extent that the 
valves, particularly those of the jugular bulb, are rendered inadequate. 
In these circumstances, therefore, the essential cause of the transmission 
of venous pulsation is insufficiency of the venous valves. In the event 
of imperfect function of the valve in the jugular bulb, slight pulsation 
may be observed even during normal action of the heart; but when the 
veins are distended, and particularly in the case of tricuspid insufficiency, 
the pulsation becomes much stronger and extends further toward the 
periphery. If the tricuspid is adequate the venous pulsation (presystolic) 
is only the expression of the rhythmical occurrence of a hindrance to 
the outflow of blood from the veins (negative or normal venous pulse). 
In tricuspid insufficiency the contraction of the right ventricle forces 
blood back through the tricuspid opening into the right auricle and into 
the veins beyond, giving rise to systolic venous pulsation (positive venous 
pulse). 
If, in a heart affected with a valvular lesion, the chambers lying be- 
hind the lesion become distended with blood, the muscular walls of these 
chambers, if otherwise normal, may by increased activity compensate 
for the valvular lesion within certain limits. In the course of time there 
results an increase in the volume of the heart-muscle, hypertrophy, 
which enables the heart to carry on its increased work for a prolonged 
period. Such compensation frequently becomes inadequate, with the 
result that the aortic pressure is permanently lowered, while the venous 
pressure, on the other hand, is abnormally high. There is, at the same 
time, the danger that the heart-muscle may in time become exhausted, 
or that even a slight illness may render the heart insufficient. Thus, 
prolonged quickening of the heart’s rate, by shortening the diastolic 
periods of rest, may cause exhaustion and insufficiency. Arrest of the 100 
DISTURBANCES OF THE CIRCULATION. 
heart’s action finally follows, with great accumulation of blood in the 
heart, since the heart is no longer able to drive onward the mass of 
blood entering it. 
Increase of the heart’s action — that is, increase in the frequency of 
its contractions, these at the same time remaining strong and complete — 
causes an increase in arterial pressure and in the velocity of the blood- 
current. When increased demands are frequently made on the left side 
of the heart — as happens in heavy bodily labor, conditions of luxurious 
living, abnormal irritability of the cardiac nerves, etc.— the left ventricle 
may become hypertrophic and act with greater force. Inasmuch as 
quickening of the blood-stream causes the right heart to receive a greater 
amount of blood during diastole, hypertrophy of the right ventricle is 
usually found in connection with the hypertrophy of the left. 
Lessening in the mass of blood or general anaemia from loss of 
blood leads temporarily to a fall of pressure in the aorta; but if the loss 
of blood be not excessive, the pressure rises again, as the vessels adapt 
themselves to the changed conditions, and, as the result of stimulation of 
the vasomotor centre through local anaemia, show a greater degree of 
contraction. Under normal conditions the mass of blood is quickly in- 
creased through the absorption of fluids, and later by regeneration of the 
blood. Similarly, in anhydraemia — i.e., a diminution of the water of 
the blood — the arterial pressure is lowered and the blood-current 
slowed. After severe haemorrhages the arterial pressure is lowered for 
a greater length of time, the circulation is slowed, and the pulse, because 
of the lessened stimulation of the vagus-centre (Cohnheim), is frequent 
and small. 
In permanent diminution of the blood-mass — i.e., the condition 
known as chronic anaemia, which occurs under varying conditions — the 
vascular system is imperfectly filled, the blood-pressure lowered, and the 
blood-current slowed. Both heart and blood-vessels adapt themselves 
to the new conditions and become diminished in volume. In the case of 
marked deficiency of haemoglobin, degenerations of the heart-muscle, 
particularly fatty degeneration, frequently occur. 
Increase in the mass of the blood, through the injection of blood or 
salt-solution into the vessels, is followed in animals by temporary in- 
crease in pressure and in the velocity of the blood-current. Return to the 
normal is brought about, partly by dilatation of a sector of the vascular 
system, particularly in the abdomen, and partly through elimination of 
the surplus from the vessels. If the mass of blood comes to stand in 
abnormally high proportion to the body-weight, if there exists a per- 
manent plethora, the pressure in the aorta becomes permanently raised, 
the work of the heart is increased, and a corresponding hypertrophy of 
the heart develops. 
When the arterial blood-pressure is raised there occurs an increased giving- 
off of fluid from the blood, and thereby a concentration and diminution in the 
amount of the venous blood; in lowering of the blood-pressure, the amount of 
fluid given off is diminished and eventually an increased taking-up of fluid 
occurs. This change in the venous blood is, under normal conditions, compen- 
sated for in the lungs: in the first case, through taking-up of lymph from the 
lymphatics; in the second case, through giving-.off of lymph to the lymphatics 
(Hess: “ Beeinflussung des Fliissigkeitsaustausches zwischen Blut u. Geweben durch 
Schwankungen des Blutdruckes.” D. Arch. f. klin. Med., Bd. 79, 1903). INCREASED BLOOD PRESSURE. 
101 
§ 35. Increase of the general vascular resistance may occur in either 
the greater or the lesser circulation, and results in increased pressure 
behind the point of increased resistance, and diminished pressure be- 
yond it. 
In the systemic circulation the hindrance may lie either in the main 
vessel, the aorta, or in the arterial branches, whose degree of contraction 
maintains and governs the normal pressure in the aorta. Vascular con- 
traction involving a great number of arteries and their branches, and 
sufficiently well marked to increase the blood pressure, is generally a 
temporary phenomenon, passing off with relaxation of the arterial 
tension. Nevertheless, permanent increase in the aortic pressure with 
consequent hypertrophy of the left ventricle does occur; and this cannot 
be explained otherwise than as the result of the contraction of the lumen 
of the smaller arteries. Transitory arterial contraction and increase of 
pressure occur particularly through increase in the amount of carbonic 
acid in the blood. Permanent increase in aortic pressure is, on the other 
hand, a result of chronic disease of the kidney, in which the secreting 
parenchyma is destroyed. Inasmuch as the portion of the vascular system 
which is thus cut off is much too small to cause such an increase of 
pressure throughout the whole aortic system, and since the vessels leading 
to other organs might become correspondingly dilated, it must be as- 
sumed that in the case of contracted kidney some other hindrance to the 
circulation occurs in more extensive vascular areas. This hindrance 
would most naturally be sought in the apparatus which normally serves 
to keep the aortic pressure at its proper height, namely, in the smaller 
arteries of the body. Whether the condition is caused by nervous 
stimuli arising in the kidney, or by the action of retained urinary or other 
chemical substances on the vasomotor centres or directly on the vessel- 
walls, or whether the heart is excited by nervous stimuli to increased 
action, we are not at present able to say. 
Increase of resistance in the aorta may result from stenosis of this 
vessel, as occurs in rare cases at the isthmus, or from congenital narrow- 
ing of the whole aorta, from large aortic thrombi, or from extensive 
disease of the vessel-wall, in consequence of which the intima is rough 
and nodular, the entire vessel rigid, inelastic, and unyielding; or, finally, 
from dilatation of the vessel, whereby eddies are formed in the blood- 
stream. 
Lowering of resistance in the systemic circulation is possible 
through relaxation of the tone of a large part of the arteries, and this 
may happen when the vasomotor centre is paralyzed, or when the cervical 
cord is divided or partly destroyed. Since the blood, in this case, flows 
abnormally quickly from the arteries into the veins, the difference in blood- 
pressure between the arteries and veins is lessened, the current becomes 
slower, the heart receives too little blood during diastole, and, finally, the 
circulation may come to a standstill. 
Increase of resistance in the pulmonary circulation occurs most 
frequently as the result of disease of the lungs and pleura. Adhesions 
of the pleura, as well as spinal curvatures, which interfere with the ex- 
pansion of the lungs and their change of volume during inspiration, thus 
depriving the circulation of an efficient aid, may cause such increase in 
pulmonary resistance. Of great influence, moreover, are such affections 
of the lungs as emphysema, retraction and induration or destruction of 102 
DISTURBANCES OF THE CIRCULATION. 
lung tissue — all of which lead to the obliteration of pulmonary capil- 
laries; compression of the lung through pleural exudate; and, finally, 
compression of the pulmonary arteries by aortic aneurism or by tumors. 
If the hindrance is only slight, the blood, by collateral channels may 
make a new passage to the left heart without any increase of pressure; 
the rate of the current in the blood-vessels which are unobstructed alone 
being increased. Greater obstacles cause increase of pressure in the pul- 
monary artery and the right heart, and if the condition persists for some 
time the right ventricle through increased exertion may become hyper- 
trophic. This occurs, however, only when the heart-muscle is adequately 
nourished and when the mass of the blood is not diminished to cor- 
respond to the diminution of the area of the pulmonary vessels. If the 
right heart is not able to overcome the obstacles in the pulmonary circu- 
lation, the blood is dammed back on the right heart, and eventually into 
the systemic veins. 
Increase of the pressure in the right side of the thorax hinders the 
entrance of venous blood into the right heart, and causes the accumula- 
tion of blood in the systemic veins. Sudden increase of pressure may 
cause retrograde flow of blood into the neighboring veins. 
The observation that hypertrophy of the heart follows different diseases of the 
kidneys has been interpreted in various ways. Some writers seek the cause in an 
increase of the volume of the blood (Traube, Bamberger), others (Senator, Ewald) 
believe it to be due to the changed character of the blood, while others (Gull and 
Sutton) ascribe it to widespread change in the walls of the small arteries. Accord- 
ing to the investigations made up to the present time, there can be no doubt that the 
hypertrophy of the heart in diseases of the kidney is dependent on an increase of 
aortic pressure. This increase is best explained by increase of the resistance in the 
small arteries of the entire body, due to the contraction of the small arteries. This 
contraction must be brought about either through the direct action of urinary sub- 
stances contained in the blood or by some reflex stimulus from the kidneys, or 
finally by some influence exerted on the vasomotor centre. It is possible that the 
heart also may be excited to increased activity. 
II. Local Hyperaemia and Local Anaemia. 
§ 36. To the blood is assigned the function of supplying all the 
organs and tissues of the body with nourishment. The cells of which 
the various tissues are composed are able to maintain their existence 
without the advent of fresh nutritive material only for a short time; for 
this reason the majority of the tissues are supplied with blood-vessels, 
and those not possessing vessels of their own are placed in intimate con- 
nection with vascular structures. 
The demands of the different tissues for blood are not always the 
same, and there is consequently a corresponding increase or decrease in 
the amount of blood contained within an organ or tissue at any given 
moment. An organ rich in blood is designated hyperaemic; one poor 
in blood as anaemic. 
The regulation of the amount of blood which an organ receives under 
physiological conditions is brought about by a change in the resistance 
in the afferent arteries; this is effected entirely through variation in the 
calibre of the arteries. Since the total mass of blood in the body is not 
sufficient to fill all the vessels at the same time, an extra supply of blood 
to one organ is possible only by supplying a less amount to other parts. 
The change in the calibre of an artery is determined, aside from the 
blood-pressure, by the elasticity of its wall and the degree of contraction HYPERAEMIA. 
103 
of its muscle-fibres. These fibres are the regulating element; their 
activity is dependent partly on influences affecting them directly, and 
partly on nervous influences from the intramural plexuses and from the 
vasomotor centres in the medulla oblongata and the spinal cord, some of 
these stimulating, others inhibiting muscular action. 
When the departures from the average blood-supply of any part of 
the body overstep the physiological limits, or if such variations arise 
without physiological causes, or are unduly prolonged, the condition is 
spoken of as pathological hyperaemia and pathological anaemia. These 
conditions are brought about by the same regulating mechanism as that 
which governs the normal blood-supply. 
Hyperaemia of an organ is caused under pathological conditions 
either by increase in the arterial supply or through obstruction and 
damming-back of the venous out-flow; there are distinguished, accord- 
ingly, two forms, active or congestive (arterial) hyperaemia and passive 
or stagnation (venous) hypercemia. Active hyperaemia arises through 
increase of the afflux of blood (congestion), and may be idiopathic or 
collateral. The first of these plays the more important role. It depends 
on relaxation of the muscular tunics of the artery, which may be brought 
about either by paralysis of the vaso-constrictors (neuroparalytic con- 
gestion), or through stimulation of the vaso-dilators (neurotic conges- 
tion), or through direct weakening and paralysis of the muscles (as, for 
instance, by heat, bruising, action of atropine, brief interruptions of the 
blood-current), or, finally, through diminution of the external pressure 
exerted on the vessels. Collateral hypercemia is merely the result of 
diminished flow of blood to other parts. It occurs first in the immediate 
neighborhood of the parts whose blood-supply is lessened; later, the 
blood may be driven to such other and more distant organs as require it. 
Active hyperaemia is characterized by more or less redness and szvell- 
ing, which are striking in tissues rich in blood-vessels. The blood flows 
through the widened channels with increased velocity, and gives to the 
tissue the color of arterial blood. Superficial tissues which, because of 
their exposure, are slightly cooler than the deeper viscera, become, as a 
result of increased blood supply, warmer than those neighboring tissues 
which are less richly supplied. 
Passive Hyperaemia arises through retardation or obstruction of the 
flow of blood from the veins. General passive congestion of the systemic 
veins occurs in those cases in which, through weakness of the heart’s 
action, valvular insufficiency or stenosis, or obstructions to the pulmonary 
circulation, the emptying of the large veins into the right heart is hin- 
dered. In the pulmonary circulation stagnation of the blood-stream 
may be brought about by any cause hindering the outflow of blood from 
the lungs, particularly valvular lesions of the left heart, weakness of the 
left side of the .heart, and, more rarely, obstructions in the systemic 
arteries. Not infrequently stasis of the pulmonary circulation may reach 
such a degree that the blood is dammed back into the right heart, and 
into the veins of the systemic circulation (see §§ 34 and 35). 
Local passive congestion may depend directly on the fact that the 
progress of blood through the veins is not adequately supported by the 
activity of the muscles and the aspiration of blood from the veins dur- 
ing inspiratory enlargement of the thorax. The absence of the first 
factor is apparent in the branches of the inferior vena cava ; for example, 104 
DISTURBANCES OF THE CIRCULATION. 
in individuals who pass a large part of their time sitting or standing with- 
out active bodily exercise, so that the emptying of the deep-seated venous 
branches into the vena cava is dependent almost wholly on t]ie activity 
of the vein-walls, which by virtue of their elasticity work against the 
pressure of the column of blood resting on them. The absence of aspira- 
tion of venous blood may, on the other hand, make itself felt in dis- 
turbance of inspiration through inflammation or other disease of the 
lungs or pleura. 
A further cause of local passive hyperaemia consists in the narrowing 
or closing of individual veins, as in compression, ligation, formation of 
thrombi (§ 38), and invasion of the veins by new-growths. For ex- 
ample, the pregnant uterus may compress the pelvic veins, a thrombus 
may obstruct the cerebral sinuses or the femoral or portal veins, or a 
malignant tumor of the pelvis may grow into the pelvic veins. 
When through any of the above-mentioned processes, single veins 
become occluded, the effect is often negligible, inasmuch as the veins con- 
cerned may possess free communication with other veins, so that but 
slight obstruction is offered to the outflow of the blood. If, on the other 
hand, the occluded vein possesses no collateral communications, or small 
ones which are inadequate for the passage of blood — as is the case 
with the main divisions of the portal vein, the sinus of the dura mater, 
the femoral and renal veins — there results more or less marked passive 
congestion in the area drained by the vein in question. 
The effect of an obstacle to the outflow of blood shows itself first in 
that portion of the vein lying between the obstruction and the peri- 
phery, the blood-current becoming slowed or checked entirely, while at the 
same time there follows progressive dilatation of the veins through the 
continued afflux of blood from the capillaries. If through the effect of 
the elastic and contractile vein-walls the obstacle is overcome, the circula- 
tion is maintained, and the blood flows toward the heart through those 
channels which it still finds open. Not infrequently the small veins thus 
called on to perform increased labor become gradually dilated. When 
the obstacle cannot be overcome and communicating vessels capable of 
dilatation are not present, the circulation comes to a standstill, and 
thrombosis may be (§ 38) produced in the obstructed vessel and its tribu- 
taries. 
If congestion in a venous area extends to the capillaries, so that they 
become overfilled with blood, the affected tissue becomes blue-red or 
cyanotic, exhibiting at the same time a certain degree of szvelling. 
Both active and passive hyperaemia, observed during life, may, after 
death, show a different appearance, and not infrequently disappear 
entirely. This is especially the case in the active hypersemias of the 
skin, also in those of the mucous membranes. This is dependent on the 
fact that the tissues, put on the stretch by dilatation of the capillaries, 
contract on the latter, after the stoppage of the circulation, and by 
counter-pressure drive the blood from the capillaries into the veins. In_ 
this way a tissue which was red during life may become pale after death. 
On the other hand, tissues which during life were pale or at least showed 
no special redness, may after death take on a blue-red color. This takes 
place particularly on the sides and back of the trunk (in those parts 
not pressed on by the body-weight), on the neck, and the posterior 
aspects of the extremities of cadavers lying on their backs; and is to be HYPOSTASIS; ANEMIA 
105 
explained by the fact that after death the blood sinks to the most de- 
pendent parts of the body, and fills not only the veins, but finally the 
capillaries. This phenomenon is known as post-mortem hypostasis, 
and the areas of discoloration as “ death-spots ” or livores. They appear 
in a few hours after death, and are the more pronounced the greater 
the amount of blood contained in the skin and subcutaneous tissues at 
the time of death. 
In the internal organs post-mortem hypostasis is particularly notice- 
able in the pia mater, the dependent veins being usually more markedly 
distended with blood than those situated higher. In the lungs the set- 
tling of the blood causes engorgement not only of the veins, but also 
of the capillaries. 
If the circulation during life is imperfect, and mere results general 
passive congestion, the blood may collect in the dependent portions of 
the body, partly because it is not driven out of them, and partly because 
it sinks into these parts from those situated on a higher level. This 
phenomenon is also known as hypostasis, and occurs particularly in the 
lungs (hypostatic congestion). 
For the observation of the circulation and its disturbances during life the 
tongue or the web of the curarized frog spread on a glass plate may be used (Cohn- 
heirn, Virch. Arch., Bd. 40), by drawing it over a cork ring, which is cemented 
to a glass plate, and fastening it to the sides of the ring with pins. The pulsating 
arterial current and the continuous venous stream possess a clear zone of blood- 
plasma, in both.the normal and the quickened circulation. If, through ligation of 
the efferent veins, passive congestion is produced and the current slowed, the 
plasma-zone in the veins is lost, and both veins and capillaries become distended 
with red cells. After a time the tissue swells as the result of infiltration with trans- 
uded fluid. 
According to the investigations of von Landeerer (“ Die Gewebspannung,” Leip- 
zig, 1884), the wall of a capillary vessel supports only from one-third to one 
half of the blood-pressure. The remaining portion is borne by the tissues, which 
afford an elastic resistance, and thereby maintain the tension which is necessary 
to keep the blood in motion. In both active and passive hypersemia tissue-pressure 
and tissue-tension are increased; in anaemia they are diminished. 
§ 37. Local anaemia or ischaemia is the result of diminution in the 
afflux of blood. If the total mass of the blood is normal, the cause of 
the anaemia is purely local; if there is general poverty of blood, the local 
anaemia, in part at least, is secondary. 
Pathological diminution in the blood-supply to an organ is at times 
merely the result of an abnormal increase of the arterial resistance, due 
to contraction of the circular muscular coat. In other cases pathological 
obstructions — such as compression of the arteries, narrowing of the 
lumen through changes in the vessel-walls, deposits on the inner surfaces 
of the arteries, occlusion by emboli (see Fig. 1, p. 47), etc. — act as 
hindrances to the blood-stream. 
The immediate result of the narrowing of an artery is slowing of the 
blood-stream beyond the point of constriction. Complete occlusion of an 
artery brings the circulation beyond the obstruction to an immediate 
standstill. If back of the point of constriction or occlusion the artery is 
provided with communicating branches — the so-called arterial collaterals 
— the disturbance of the circulation may be compensated by increased 
afflux of blood through the collateral arteries; compensation is the more 
complete the larger and more distensible are the collaterals. If the nar- 
rowed or occluded artery possesses no collateral branches — if it is a so- 106 
DISTURBANCES OF THE CIRCULATION. 
called terminal artery — the slowing or cessation of the circulation be- 
yond the point of obstruction or occlusion cannot immediately be com- 
pensated for, and the affected area becomes partly or completely emptied 
of blood through contraction of the arteries and pressure of the tissues 
on the capillaries and veins. 
When the current and the pressure beyond a constricted point sink 
to a certain minimum, the driving force gradually becomes unable to 
propel the mass of blood. The red corpuscles stagnate in the veins and 
capillaries, so that the area supplied by the artery in jquestion becomes 
again filled with blood, which, however, is not in circulation, but at rest. 
The same thing occurs when, after complete occlusion of a terminal 
artery, the blood slowly and under low pressure enters the vessels of the 
affected area from small arteries incapable of adequate enlargement, or 
through anastomosing capillaries. Finally, accumulation of blood in the 
anaemic area may occur by reflux from the veins. This takes place when 
the intravascular pressure in the part has sunk to nothing in the arteries 
and capillaries, while in the veins a positive pressure exists. Passive 
congestion in the veins favors such reflux. 
A further cause of anaemia of one organ may be found in abnormal 
congestion of other organs, since in that case the total quantity of blood is 
not sufficient adequately to supply the remaining organs. Such an anaemia 
is designated collateral ancemia. 
All ancemic tissues are characterized by paleness. 
The significance of ischaemia lies especially in the fact that, persis- 
tence of imperfect blood-supply brings about tissue-degenerations (com- 
pare § 1). Total arrest of the blood-supply leads in a short time to death 
of the tissue involved. If the blood comes to flow anew into the degen- 
erating and dying tissues corresponding to the distribution of an ob- 
structed vessel and there stagnates, extravasation may take place, lead- 
ing to the formation of a hccmorrhagic infarct (compare § 44). 
The rapidity and completeness of the development of collateral circulation after 
the occlusion of an artery depend on the size, number and distensibility of those 
vessels which are in communication with the anaemic area. If these are numerous 
and distensible, the anaemic area is soon supplied with an approximately normal 
volume of blood. If this is not the case the disturbance of the circulation is 
more slowly compensated; and the stasis and increased pressure are found to 
extend farther back from the point of obstruction toward the heart, so that col- 
lateral hyperaemia occurs in vessels situated farther back toward the heart. In 
the further course of re-establishing the circulation the increase of volume and 
velocity remains confined to such vessels as communicate with the area of the 
obstructed artery, that is, confined to the capillary and arterial anastomoses, where 
the increase in volume and velocity becomes permanent. This leads to lasting 
dilatation of the vessels concerned, and at the same time to an increase in the 
vessel-walls, not only in thickness, but also in length, as is evident from their 
tortuosity. According to Nothnagel, increase in thickness of the walls of the 
anastomosing arteries may be demonstrated in rabbits about six days after the 
ligation of an artery; after the ligation of large vessels, the small arteries which 
carry on the collateral circulation become in the course of a few weeks capacious 
and thick-walled. 
ill. Coagulation, Thrombosis, and Stasis. 
§ 38. After death the blood in the heart and great vessels sooner or 
later coagulates with the formation of so-called post-mortem clots. If 
the clotting occurs at a time when the red blood-cells are evenly dis- 
tributed, the whole mass of blood becomes coagulated, forming soft, dark- COAGULATION AND THROMBOSIS. 
107 
red coagula which are known as cruor. If before clotting there occurs, 
through sinking of the red cells, separation of the blood into two layers—• 
a substratum rich in red corpuscles, and an upper layer consisting of 
plasma—then, if the latter coagulate, there will be formed gelatinous, 
Fig. 8.—A lardaceous clot from the cadaver. (Formalin, hematoxylin, and eosin.) x 500, 
light-yellow, elastic lumps and stringy masses having a smooth surface 
and not adherent to the vessel-wall, that are known as lardaceous or 
chicken-fat ” clots. These contain fibrin threads (Fig. 8) and 
scattered red and white blood-cells. Through the inclusion of red cells 
Fig. 9.—Coagulated blood in a fresh haemorrhagic infarct of the lung. (Muller’s fluid; 
hsematoxylin and eosin.) a, Alveolar septa without nuclei, containing capillaries filled with dark 
bluish-violet, homogeneous thrombus-masses; b, septa containing nuclei; c, vein filled with red 
thrombus; d, di, alveoli filled with firm blood clots; e, alveoli filled with serous fluid, fibrin, and 
leucocytes, x 90. 
in these formations, they may present in places a red or reddish-black 
color; if large numbers of leucocytes are present, they have a whitish color. 
When blood is drawn from an artery or vein into a foreign receptacle, 
coagulation will occur in a short time, as the result of adhesion to the 108 
DISTURBANCES OF THE CIRCULATION. 
sides of the receptacle. The blood becomes changed into a soft coherent 
mass. When freshly drawn blood is beaten with a solid body, the surface 
of the latter becomes covered in a short time with fibrin. If in the 
body large quantities of blood pass into the tissues—for example, into 
the pericardium or lungs—coagulation may likewise occur, and the ex- 
travasated blood acquires a firm consistence (Fig. 9). 
Under certain conditions there may be formed in the heart or blood- 
vessels during life, firm deposits, which are similar to cruor or to the 
fibrin formed by whipping the blood. These formations are known as 
thrombi, and the process which leads to their formation is thrombosis. 
According to their color thrombi may be distinguished as red, or white 
(yellow or grayish-white), and mixed. 
The pathogenesis of thrombosis centers in the chemistry of the co- 
agulation of the blood. The substances necessary for coagulation are 
fibrinogen, fibrin ferment 
(thrombin) and calcium salts. 
Fibrinogen and calcium salts 
are normally present in the 
blood. Thrombin, on the con- 
trary, is not present as such; 
otherwise coagulation would 
occur. It is supposed that it 
first appears in an inactive 
form—prothrombin. Moro- 
witz and Fuld independently 
put forward an explanation 
to account for the activation 
of prothrombin, namely, that 
thrombokinase (the zymo- 
plastic substance of Schmidt) 
in the presence of calcium 
salts transforms prothrombin 
into thrombin, as a result of 
which fibrinogen is coagulated. 
As to the origin of prothrombin and thrombokinase there is some un- 
certainty ; prothrombin, however, is probably provided by the blood plate- 
lets and is either secreted by them or results from their disintegration. 
Thrombokinase, on the other hand, is derived from the blood platelets, 
the leucocytes, the vessel walls or from the tissues generally, the testis 
being a convenient source from which to obtain it for experimental pur- 
poses (Mellanby). The problem of thrombokinase is further compli- 
cated by the presence of coagulins in the vessel walls and tissues, extracts 
of which, as has long been known, produce coagulation of fibrinogen 
(Welch). 
The immediate cause of ante-mortem intravascular coagulation is to 
be sought in increase in the fibrinogenic substance of the blood, together 
with diminution in the ability of the walls of the vascular apparatus to 
inhibit coagulation. Coagulation may be brought about by disturbances of 
the circulation, particularly retardation of the current and the formation 
of eddies which drive the blood plates against the vessel wall, and by 
changes in the vessel walls themselves. 
Fig. io.—Bundles and star-shaped clusters of fibrin 
threads within a biood-vessel. (Fibrin stain.) Prepa- 
ration taken from an inflamed tracheal mucous mem- 
brane. x soo. THROMBOSIS. 
109 
The formed elements which may enter into the composition of thrombi 
are blood platelets, fibrin, leucocytes and red corpuscles. The diversity in 
appearance and structure of thrombi is dependent on variations in the 
number, proportion and arrangement of their constituents. Histolog- 
ically, the intravascular clot is characterized by the formation of minute 
rods and threads which lie between the cellular elements as a delicate 
supporting meshwork or as stellate or fasicular groups arranged around 
centers. These rods and fibres are collectively known as fibrin and the 
centers around which the groupings occur are composed practically ex- 
clusively of blood platelets. The granular material found in thrombi, 
to which the older observers attached relatively little importance and 
which they interpreted as collections of finely divided fibrin or as 
detritus derived from white 
corpuscles, is now known to 
be an essential factor in the 
process of thrombosis and 
consists of blood platelets. 
Bizzozero, in 1882, de- 
scribed a new element of the 
blood in the form of small 
homogeneous structures 
which he designated blood 
plates. He regarded them as 
identical with the haemato- 
blasts previously described by 
Hayem. As a result of ex- 
perimental investigations, Biz- 
zozero concluded that these 
bodies played an important 
role in the coagulation of the 
blood. This view has been 
amply substantiated and is 
now universally accepted. At 
one time the blood platelets 
were regarded as disintegra- 
tion products of the red cells. 
This view has been abandoned. Cole, for example, has produced a 
specific agglutinating serum for blood platelets and his experiments 
militate against a genetic relationship between platelets and red blood 
corpuscles. According to Wright, the platelets are fragments of the 
cytoplasm of the bone marrow giant cells and occur only in those 
vertebrates in whose marrow giant cells are found. The number of 
platelets increases or diminishes in proportion to the number of giant 
cells in the marrow. Platelets are a constituent of normal blood, but 
occur in great abundance only in pathological conditions. Following 
Eberth and Schimmelbusch, many observers explain the beginning of 
thrombosis by the accumulation of pre-existing platelets round a foreign 
body or on the damaged inner wall of the heart or vessels associated 
with slowing or irregularities in the blood current. Contact with the 
altered surface sets up immediate viscus metamorphosis of the platelets, 
as a result of which they adhere to one another or to the foreign body 
or vascular wall. For example, if, in a vessel whose circulation is 
Fig. ii.—Section through a red thrombus formed 
in one of the veins of the thigh-muscles, after 
occlusion of the femoral vein. (Muller’s fluid; 
haematoxylin.) a, Fibrin-threads; b, leucocytes and 
granular masses, x 250. 110 
DISTURBANCES OF THE CIRCULATION. 
retarded, the intima is injured by compression or crushing or by chemical 
irritants, blood platelets may be seen adhering to the injured portion and 
in a short time the spot is covered. Variable numbers of leucocytes now 
become imbedded in the mass together with red cells which drop out of 
circulation and are entangled in the thrombus. 
There are five outstanding varieties of thrombi: (a) red, (b) white, 
mixed or laminated, (c) agglutinative or hyaline, (d) leucocytic, (e) 
fibrinous. 
(a) The red thrombus is formed in conditions attended by marked 
slowing of the circulation and is composed of red and white cells in the 
same relative proportions as they exist in normal blood, together with a 
network of fibrin (Fig. 11). In fresh clots in small vessels, it not 
Fig. 12/—Section from a mixed thrombus rich 
in cells. (Muller’s fluid, haematoxylin.) a, Red 
blood-cells; b, granular masses; c, reticular 
fibrin containing many leucocytes; d, threads of 
fibrin in parallel arrangement, x 200. 
Fig. 13.—Section from a white thrombus con- 
taining but few cells. (Muller’s fluid; haema- 
toxylin.) a, Granular masses; b, fibrogranular 
fibrin forming a net-like reticulum; c, fibrin- 
threads in parallel arrangement, x 200. 
infrequently is possible to demonstrate the presence of bundles and star- 
shaped clusters of fibrin, which radiate from centers composed of blood 
platelets. In such cases, however, it is not always possible to determine 
to what extent the coagulation is intra-vital or to what extent it is post- 
mortem. Such coagulation, however, is most frequently observed in in- 
flammed tissues, and the conclusion seems warranted that in these cir- 
cumstances it is a vital phenomenon. 
(b) White, mixed and laminated thrombi arise from the circulating 
blood in diseases of the vascular apparatus which are attended by gen- 
eral or local slowing or by irregularity of the blood stream, and are 
yellowish or of various shades of red or of alternating layers of red and 
white. Microscopic examination shows them to consist of masses of 
platelets and thread-like collections of fibrin together with variable pro- 
portions of leucocytes, red cells and blood platelets. In mixed thrombi, 
fibrin and red blood cells are combined, often in alternate strata, and 
among these elements are greater or less numbers of leucocytes and 
blood platelets. THROMBOSIS. 
111 
(c) Agglutinative or hyaline thrombi: Agglutinative thrombi occur 
in the smaller vessels—capillaries, arterioles and venules—and are char- 
acterized histologically by the appearance of closely packed and poorly 
defined red blood corpuscles which later become fused and transformed 
into a translucent hyaline substance. This variety of thrombosis has 
been observed in a number of conditions, among them, pneumonia, in 
the intestine in typhoid fever, and the stomach in carbolic acid poison- 
ing. They are particularly frequently encountered, however, in the 
smaller branches of the hepatic veins in eclampsia and are associated 
with haemorrhagic and necrotic foci in the parenchyma (haemorrhagic 
hepatitis). Agglutinative 
thrombi may be produced ex- 
perimentally by the injection 
of various micro-organisms, 
by ricin, ergot, freezing and 
haemagglutinative sera. 
(d) Leucocytic thrombi: 
In certain inflammatory pro- 
cesses, intravascular plugs oc- 
cur which are made up wholly 
or predominantly of poly- 
nuclear leucocytes (Welch). 
Small vessels are sometimes 
plugged by lymphocytes in 
chronic lymphatic leukemia, in 
the walls of the appendix in 
conditions attended by exces- 
sive hyperplasia of the lym- 
phoid elements normally resi- 
dent in the submucosa, etc. 
(e) In certain inflamma- 
tory lesions, notably croupous 
pneumonia, vessels of small 
size are sometimes encount- 
ered in which the lumen is 
more or less completely filled 
with fibrillated or whorl-like 
clumps of fibrin. An occa- 
sional leucocyte or small col- 
lections of platelets may sometimes be observed. This form of thrombosis 
is of negligible importance. 
Fig. 14.—Rapidly flowing blood-stream. a, Axial 
stream; b, marginal zone with isolated leucocytes, d. 
(After Eberth and Schimmelbusch.) 
Fig. 16. 
Fig. is.—Moderately slow blood-stream. a, Axial 
stream; b, peripheral zone with numerous leucocytes, d. 
(After Eberth and Schimmelbusch.) 
Fig. i6.—Markedly slow current, a, Axial stream; 
b, peripheral stream with blood-plates; c, collection of 
blood-plater; d, di, leucocytes. (After Eberth and 
Schimmelbusch.) 
The formation of thrombi may be studied under the microscope, both in cold- 
blooded and warm-blooded animals; and observations made in this manner, espe- 
cially by Bizzozero, Eberth, Schimmelbusch, and Lowit, have led to important 
results. 
When the blood flows with normal velocity through a vessel, there may be 
seen under the microscope a broad, homogeneous red stream in the axis of the vessel 
(Fig. 14, a), while at the sides there lies a clear plasma-zone (b) free from red 
cells. This may be observed in the arteries and veins, but best in the veins, while 
in the capillaries, which are just large enough to permit the passage of the red 
cells, this difference between the axial stream and plasma-zone is not apparent. 
In the axial stream the different constituents of the blood are not recognizable; 
in the plasma-zone there appear, from time to time, white corpuscles (Fig. 14 d), 
which roll slowly along the vessel-wall. 112 
DISTURBANCES OF THE CIRCULATION. 
If the blood-stream becomes retarded to the degree that the red cells of the 
axial stream are indistinctly recognizable (Fig. 15, a), the white corpuscles which 
loll slowdy in the plasma-zone, at times adhering to the vessel-wall, become con- 
stantly increased (Fig. 15, d), so that they finally lie in great numbers in this 
zone. 
If the current is still further retarded so that the red cells become plainly 
recognizable (Fig. 16, a), there appear in the peripheral plasma-zone, in addition 
to the colorless corpuscles (d), blood-plates (b), which increase in number with 
the retardation of the current, while the leucocytes again become diminished. 
When arrest of the blood-current occurs, there follows a distinct separation of the 
corpuscular elements in the lumen of the vessel. 
If, in the vessel in which the circulation is retarded, the intima is injured at a 
certain point by compression or crushing, or by means of chemical agents, as 
corrosive sublimate, nitrate of silver, or sodium chloride, and if the lesion of the 
wall does not lead to complete stoppage of the circulation, blood-plates may be 
seen adhering to the injured portion; and in a short time the injured spot is covered 
with many layers (Fig. 16, c). Often leucocytes (di) become embedded in this 
mass, and their number is the greater the more numerous they are in the plasma- 
zone. Under certain conditions they may partly cover the blood-plates. In case 
of great irregularity of the circulation or more severe changes in the vessel-wall, 
red cells may become adherent to the vessel-wall or to the colorless deposit already 
formed. Not infrequently portions of the thrombus-mass are torn loose and a 
new deposit of blood-plates occurs. The vessel may finally be closed as the result 
of continued deposit of the blood-elements. 
When at any point blood-plates in large numbers have become adherent to the 
vessel-wall, they become after a time adherent to one another and finally fused into 
a compact mass. Eberth designates the sticking together of the blood-plates con- 
glutination, their fusion as viscous metamorphosis. 
If we compare the observations made on warm-blooded animals by Bizzozero, 
Eberth, and Schimmelbusch, and more recently by Lowit and Gutschy, with the his- 
tological findings in thrombi occurring in the human subject, we are warranted in 
the conclusion that the formation of thrombi in the circulating blood of man 
occurs in the same way as that observed in the lower animals. Thrombosis is, 
therefore, directly dependent on two causes: disturbances of the circulation, par- 
ticularly retardation of the current and the formation of eddies which drive the 
blood-plates against the vessel-wall; and local changes in the vessel-walls. It 
is also probable that thrombosis is favored by pathological changes in the blood. 
From the variety of conditions under which thrombosis in man occurs, we must 
assume that at one time one cause, at another time another, plays the chief part in 
the formation of the thrombus, or that all three may take an equal part. 
According to Arthus and Pages, the blood flowing from the veins becomes inca- 
pable of coagulating spontaneously if sodium oxalate, sodium fluoride, or soaps are 
added to it in such quantities that the mixture contains 0-07-0.1 per cent of the 
oxalate, or about 0.2 per cent of the fluoride, or 0.5 per cent of soap. These act 
by precipitating the calcium salts. If to blood, kept fluid by treatment with 
oxalic acid, one-tenth of its volume of a one-per-cent solution of calcium chloride 
is added, coagulation occurs in six to eight minutes, and the calcium salts pass into 
the combination of the fibrin-molecule. The fibrin-ferment can act on the fibrin- 
ogen only in the presence of calcium salts. Under the influence of the fibrin-fer- 
ment, and the presence of calcium salts, the fibrinogen undergoes a chemical change 
which results in the formation of a calcium-compound, fibrin. Hammarsten, who 
holds that the presence of calcium is not necessary for the change of fibrinogen into 
fibrin, attempts to explain the observation of Arthus and Pages, on the assumption 
that the calcium salts are necessary factors for the conversion of prothrombin into 
thrombin. 
If blood be allowed to flow beneath a layer of oil, into a vessel coated with a 
film of vaseline, it will not coagulate (Freund); and from this it may be assumed 
that the cause of coagulation is to be found in the adhesion of the blood to a 
foreign body, 
A. Schmidt, in his work on the blood, published in 1892, in which he collects 
the results of many years of study on the coagulation of the blood, regards the 
fibrin-ferment or thrombin as a cell-derivative, which arises from an inactive ante- 
cedent substance, prothrombin, under the influence of certain zymoplastic substances 
which are also cell-derivatives. He likewise regards the fibrinogenic substance, or 
metaglobulin, as a product of disintegration of cellular protoplasm. VARIETIES OF THROMBI. 
113 
§ 39. According to the cause of the injury to the vessel-wall there 
may be distinguished: traumatic, infectious, and thermic thrombi, as well 
as those produced by degenerative changes in the wall, foreign bodies, 
and tumor proliferation. Thrombi occurring in individuals with poor 
circulation are designated marasmic or cachectic. 
Thrombi also may be classed according to their relation to the vessel- 
lumen. Thus thrombi attached to the wall of the heart (Fig. 17, a) or 
blood-vessel are known as parietal thrombi, those situated on the valves 
of the heart or veins (Fig. 18, d) are termed valvular thrombi. In both 
cases the thrombi may consist only of delicate, membranous, translucent 
or hyaline deposits; but are often thick and firm and project into the 
lumen of the heart or vessels. Their surface often shows ribbed eleva- 
tions which are paler than the other portions. A thrombus completely 
closing the lumen of the vessel is called an obturating thrombus (Fig. 
18, a, b). The coagula first formed are designated primary or autoch- 
Fig. 17.—Polypoid heart thrombi firmly attached between the trabeculse of the left ventricle. 
a, Thrombus with smooth surface; b, thrombus with open cavity of degeneration. (Natural 
size.) 
thonous, those subsequently deposited on these as induced thrombi. 
Through growth by accretion a parietal thrombus may become changed 
to an obturating one. In this way it not infrequently happens that on 
an originally white or mixed thrombus a red one (Fig. 18, c) is formed; 
the thrombosis at the beginning occurring in circulating blood, while 
later, after closing of the vessel, the blood comes to a standstill and clots 
en masse. The reverse may occur—that is, on a thrombus originally 
red there may be deposited white or mixed coagula—when a red throm- 
bus obturating a vessel becomes smaller by contraction, and thus opens 
up a channel for the passage of blood. 
Thrombi may occur in any part of the vascular system. In the heart 
they are formed chiefly in the auricular appendages and in the intertra- 
becular spaces, or on any diseased spot (Fig. 17, a) in the heart-wall. 
They begin usually in the recesses between the trabeculae, but through 
continual accretions form large coagula which project above the surface 
in the form of polypoid masses (Fig. 17). They are sometimes more 
or less spherical in shape, with a broad base; at other times club-shaped; 
their surface is ofted ribbed. In rare cases large spherical or knobby 
thrombi may become loosened; and, if they cannot pass the ostium, lie 114 
DISTURBANCES OF THE CIRCULATION. 
free in the corresponding chamber of the heart. Such free globular 
thrombi are sometimes seen in (the auricles in stenosis and insufficiency 
of the auriculo-ventricular orifices. After detachment they may in- 
crease in size through new deposits of fibrin. Masses of coagula which 
are deposited on inflamed valves are known as valvular polypi. Parietal 
and valvular polypi may reach such 
proportions as to fill a large part of 
the heart-chambers. 
In the arterial trunks thrombi 
may occur in a variety of places, par- 
ticularly behind constrictions and in 
dilatations. Occasionally in cachectic 
individuals with a degenerate intima, 
parietal, white, or mixed thrombi, 
adherent to the surface, are formed 
in the aorta. 
In the veins thrombi are occa- 
sionally formed in the pockets of ihe 
valves (Fig. 18, d), from which they 
may protrude and develop into ob- 
turating thrombi. Often a thrombus 
may grow from a smaller vein (a), 
where it was primary, into the lumen 
of a larger vein (&). Thus, a 
thrombus having its origin in a small 
vein of the lower extremity may grow 
into the inferior vena cava and even 
reach the heart. Of especial import- 
ance, because of the resulting local 
disturbances, are the obturating 
thrombi of the femoral veins, the 
renal veins, the sinus of the dura 
mater, the venae cavae, and the portal 
veins. 
Thrombosis in the small vessels 
is most frequently the result of dis- 
ease of the surrounding tissues, par- 
ticularly infectious, toxic, and necro- 
tic processes. The thrombi are, for 
the greater part, hyaline; in their 
composition the red blood-corpuscles 
have the chief share, fusing into a homogeneous mass. Nevertheless, it 
may be demonstrated occasionally, by means of proper technique 
(Weigert’s staining method), that they also contain fibrin. Thrombi of 
smaller vessels occur also after burns of the skin (Klebs, Welti, Silber- 
mann) and often in cases of poisoning—for example, with corrosive 
sublimate (Kaufmann)—and are found especially in the smaller vessels 
of the lung. They frequently occur in haemorrhagic infarcts (Fig. 9, a). 
Thrombi originating in the capillaries may involve the efferent veins, 
partly for the reason that through obturation of numerous capillaries 
the blood flows more slowly into the veins, partly for the reason that dis- 
integrating red cells and blood-plates pass into the veins in large num- 
bers. 
Fig. of femoral and 
saphenous veins, a, b, Obturating mixed 
and laminated thrombus; c, red throm- 
bus showing peripheral attachment; d, 
thrombus protruding from a valve. 
(Reduced one-fourth.) SEQUELAE OF THROMBOSIS. 
115 
The first deposits in the formation of a parietal thrombus consist of 
delicate, translucent, or whitish layers. The fully formed thrombus is 
a rather firm, dry mass, adherent to the inner surface of the vessel 
or heart, and in color and structure varying according to the conditions 
mentioned above. Thrombi, originally soft and moist, undergo in time a 
process of contraction, and become firmer and more dry. By means of 
contraction vessels closed by obturating thrombi 
may become partially opened for the passage of 
blood. 
In the event of marked contraction, the fibrin, 
blood-plates, and red cells become changed into 
a firm mass, which may remain in this condition 
for a long time, and finally undergo calcification. 
This may occur in both valvular heart-thrombi 
and thrombi located in the vessels. The chalky 
concretions formed in the veins are known as 
phleboliths; those occurring in the arteries as 
arterioliths. 
Contraction and calcification are relatively 
favorable sequelae of thrombosis. Much less 
favorable are the more frequent processes of de- 
generation occurring in thrombi, which are 
known as simple and as puriform softening. In 
simple softening the central portion of the 
thrombus becomes changed into a grayish-red, or 
gray, or grayish-white grumous mass, consisting 
of disintegrated and shrunken red corpuscles, 
pigment-granules, and colorless, granular debris. 
If the softening extends to the superficial layers, 
and if there is sufficient strength of blood-current 
in the neighborhood%of the thrombus, the pro- 
ducts of disintegration may be swept into the 
circulation. If larger pieces become loosened 
and transported by the blood-stream emboli are 
produced (see Fig. 1, page 47). 
In puriform softening the thrombus breaks 
down into a yellow, or grayish-yellow, or reddish- 
yellow, grumous, creamy, and at times foul- 
smelling mass, consisting of pus-corpuscles and 
a large amount of finely-granular substance, 
composed of fatty and albuminous detritus and micrococci or other 
bacteria. 
The process of softening of a thrombus, associated with purulent in- 
filtration of the vessel-wall, is designated purulent thrombophlebitis or 
thrombo-arteritis accordingly as it involves a vein or an artery. The 
inflammation of the vessel-wall may take its start either in the softening 
thrombus or in the tissues adjacent to the vessel. In the latter case 
softening of the thrombus is coincident with the inflammation of the 
vessel-wall or follows it. These processes occur most frequently in the 
neighborhood of purulent foci. 
The most favorable sequel of thrombosis is organization of the 
thrombus—that is, substitution of the thrombus by vascularized 
Fig. 19. — Remains of a 
thrombus of the right femoral 
vein occurring three years 
before death, a, Obliterated 
portion of the vein (the 
right common iliac artery 
was also obliterated); b, c, d, 
connective-tissue cords in the 
lumina of the vein and its 
branches; e, fresh thrombus. 
(Natural size.) 116 
DISTURBANCES OF THE CIRCULATION. 
connective tissue derived from the proliferating cells of the vessel-wall. 
The thrombus itself takes no part in the organization; it is a dead mass 
which excites proliferation of the surrounding tissues (Fig. 20, b, c, d). 
Fig. 20.—Obliteration of a pulmonary artery by connective tissue after embolic plugging of 
its lumen. (Muller’s fluid, hasmatoxylin, and eosin.) a, Artery wall; b, connective tissue filling 
the vessel-lumen; c, d, newly formed blood-vessels, x 45. 
The cicatricial tissue formed in the place of the thrombus contracts 
in the course of time. Cicatrices formed after ligation may thus be- 
come very small. Such a cicatrix in the continuity of a vessel may appear 
simply as a thickening of the vessel- 
wall, or there remain only threads and 
trabeculae (Fig. 19, b, c, d), which 
cross 'the lumen of the thrombosed 
vessel, so that the blood-stream can 
once more pass the affected spot. Not 
infrequently the connective-tissue 
strands crossing the vessel cause 
marked narrowing of the lumen; or 
the vessel may become obliterated 
(Fig. 19, a), and converted for a 
greater or less distance into a fibrous 
cord. 
Pieces broken from a thrombus 
and carried into an artery and lodged 
—that is, emboli—induce new de- 
posits of fibrin on their surface. 
Later they undergo the same changes 
as thrombi, and may soften, contract 
(Fig. 21, a), or become calcified. If 
the emboli are non-infective they are 
apt to be replaced by vascular con- 
nective tissue (Fig. 20, b, c). 
In many cases the new-formation of connective tissue leads to ob- 
literation of the artery (Fig. 20). In other cases in the place of the 
embolus there is developed only a ridge of connective tissue or a nodular 
Fig. 21.—Remains of embolic plugs in 
a branch of the pulmonary artery, a, 
Contracted embolus traversed by connec- 
tive-tissue threads; b, cords of connective- 
tissue crossing the orifices of branch 
vessels. (Natural size.) SEQUELzE of thrombosis. 
117 
or flat thickening of the irutima. In still other cases the lumen of the 
vessel is traversed by strands of connective tissue (Fig. 21, b), which 
either run separately or form a fine- or coarse-meshed network. 
Fig. 22.—Embolism of an intestinal artery, with suppurative arteritis, embolic aneurism, and 
periarterial, metastatic abscess. (Alcohol, fuchsin.) a, b, c, d, e, Layers of the intestinal wall; 
f, artery wall; g, embolus, surrounded by pus-corpuscles, lying in the dilated artery which is partly 
destroyed by suppuration; h, parietal thrombus; i, periarterial purulent infiltration of the sub- 
mucosa; k, veins gorged with blood. X 27. 
If pyogenic organisms are present, as is the case when the emboli 
arise from a thrombus lying in a suppurating focus, a purulent process 
is produced (Fig. 22, i) at the site of lodgment (Fig. 22, g). 
Literature. 
(Blood plates, Coagulation of the Blood, and Thrombosis.) 
Arthus et Pages: Nouvelle theorie chimique de la coagulation du sang. Arch, 
de phys., ii., 1890. 
Bizzozero: Blutplattchen u. Blutgerinnung. Obi. f .d. med. Wiss., 1882, 1883; 
Virch. Arch., 90 Bd.; Arch, per le Sc. med., 1883; Arch. ital. de Biol., i., 
ii., iii., iv. and xvi.; Festchr. f. Virchow. Internat. Beitr., i., 1891. 
Eberth u. Schimmelbusch: Die Thrombose nach Versuchen u. Leichenbefun- 
den, Stuttg., 1888; Dyskrasie u. Thrombose. Fortschr. d. Med., vi., 1888. 
Eisen: Blood-plates. Journ. of Morph., xv., 1899. 
Flexner: Agglutination Thrombi. Univ. of Penns. Med. Bull., 1902. 
Gutchy: Blutgerinnung und Thrombose. Beitr. v. Ziegler, xxxiv., 1903. 
Halliburton: The Coagulation of the Blood. British Med. Journ., 1893. 
Hammarsten: Lehrb. d. phys. Chemie, Wiesbaden, 1899. 
Hayem: Du sang et de ses alterations anatomiques, Paris, 1889. 
Lowit: Blutgerinnung. Sitzber. d. K. Akad. d. Wiss. in Wien, 89, 90 Bd., 1884; 
Blutplattchen u. Blutgerinnung. Fortschr. d. Med., iii., 1885; Die Beo- 
bachtung der Circulation am Warmbluter. Arch. f. exp. Path., xxiii., 1887; 
Blutplattchen u. Thrombose. Ib., xxiv., 1888; Studien zur Physiologie u. 
Pathologie des Blutes, Jena, 1892. 118 
DISTURBANCES OF THE CIRCULATION. 
Morawitz: Blutgerinnung. D. Arch. f. klin. Med., 79 Bd., 1904; Vorstufen v. 
Fibrinfermente. Fol. haem., i., 1904. 
Osier: Trans. Ass. Am. Phy., 1887. 
Pearce: Experimental Production of Liver-Necroses by the Injection of 
Hemagglutinative Sera. Jour, of Med. Research, 1906. 
Schmidt, A.: Die Lehre v. d. fermentativen Gerinnungsercheinungen, Dorpat, 
1877; Zur Blutlehre, Leipzig, 1892; Weitere Beitrage z. Blutlehre, Wies- 
baden, 1895. 
Welch: Thrombosis and Embolism, Allbutt & Rolleston’s System of Medicine, 
1899. (Lit.) 
Wright, A. E.: Contr. to the Study of the Coagulation of the Blood. Jourr. of 
Path., i., 1893. 
Fig. 23.—Congestive stasis in the vessels of the corium and papillae of the plantar surfaces of 
the toes from a man dying of valvular disease, heart failure, and arteriosclerosis. (Muller’s fluid, 
alum carmine.) Toes presented a deep violet color, and beginning gangrene, x 20. 
§ 40. Stasis or stagnation is characterized by retardation of the cir- 
culation without coagulation of the blood. The red blood-cells are so 
closely pressed together that the small vessels are filled or distended, and 
the outlines of the individual cells cannot be distinguished (Fig. 23), 
The condition is one of marked passive congestion. When the blood 
entering a certain area finds its avenues of escape impeded, the circu- 
lation in the small veins and capillaries, and even in the smallest affer- 
ent arterial branches, comes to a state of almost complete arrest. Since 
from the arteries there come with every pulse-wave fresh masses of 
blood to the congested area, the capillaries and veins become distended STASIS; CEDEMA. 
119 
and the pressure within these rises to the height of that at the point of 
divergence of the nearest permeable artery. In this way the red blood- 
cells become so closely packed that their contours are no longer dis- 
tinguishable, and the contents of the vessel form a homogeneous, scarlet- 
red column (Fig. 23). The red blood-cells, however, are not fused; 
as soon as the impediment to the outflow is removed and the circulation is 
restored, the corpuscles become once more separated from one another. 
Stasis may be caused by many influences which affect the vessel-wall 
and the blood itself. Thus, heat and cold, acids and alkalies, concentrated 
solutions of sugar and salt, chloroform, alcohol, etc., cause stasis. These 
act by abstracting water from the blood, and by producing changes in the 
composition of the corpuscles, and vessel-walls; as a result, the red cells 
become less mobile and the vessel-walls offer increased frictional resist- 
ance to the blood-stream, and at the same time permit the fluid portions 
of the blood to pass through more readily. 
IV. (Edema. 
§ 41. The fluid which permeates the tissues is essentially a tran- 
sudate from the blood, though under certain conditions fluids contained 
in cells and fibres may also pass into the intervening spaces. The passage 
of fluid from the vessels is in part a process of filtration and in part a 
Fig. 24.—Stasis-oedema of the papillary bodies of the skin of the leg from a case of mitral 
stenosis. (K. Ziegler, 1. c.). a, Lymphocytes; b, connective tissue fibrillae with cells; c, red blood- 
cells; d, blood-vessel, x 300. 
secretion, accomplished by means of a specific function of the capillary 
walls. The fluid secreted by the capillaries mingles with the products of 
metabolism in the tissues, and is taken up by the lymph-vessels, and 
through the thoracic duct is returned to the blood. 120 
DISTURBANCES OF THE CIRCULATION. 
Increase in the transudation of the fluids of the blood causes more 
marked saturation of the tissues, which may be compensated for by 
absorption through the lymph-vessels. This compensation has, however, 
its limits; with increased transudation from the blood-vessels there is 
produced more or less permanent over-saturation of the tissues. 
The condition produced by collection of fluids in the tissues is known 
as dropsy, oedema, or hydrops. According to its extent there may be dis- 
tinguished general and localized hydrops. (Edema extending over the 
superficial portions of the body is known as anasarca. 
The transudate from the blood which constitutes oedema or hydrops 
is poorer in albumin than the plasma. The fluid collects at first in the 
tissue-spaces, pushing apart the tissue-elements (Fig. 24, b), but may soak 
into the tissue-elements 
themselves and cause swell- 
ing of cells and fibres, and, 
under certain conditions, 
the formation of so-called 
vacuoles (Fig. 25), due to 
the collection of droplets in 
the cells. 
This may be frequently 
demonstrated in the epithe- 
lium of the body-surfaces 
and of glands, but at times 
becomes evident in other 
tissue elements—for ex- 
ample, in connective-tissue 
cells and muscle-fibres 
(Figs. 25, 26). Moreover, 
it often happens in oede- 
matous tissues that cells be- 
come loosened from their 
basement-membrane, par- 
ticularly in the lungs and 
serous membranes and are mixed with the fluid. In oedema of the 
skin, the epidermis (Fig. 27) may be separated and lifted from the 
papillary bodies, while the fibrillse of the latter are pushed apart. 
Tissues which are the seat of oedema are swollen. The degree of 
swelling depends on the structure of the affected tissue. The skin and 
subcutaneous tissue are able to take into their lymph-spaces large quan- 
tities of fluid, so that an extremity may become enormously swollen. In 
this condition it is pale, doughy in consistence, and pits on pressure. On 
incision an abundance of clear fluid escapes. 
The lung behaves in a similar way. Owing to limited space it cannot 
become greatly distended, but it contains vast numbers of alveoli filled 
with air which, in the advent of oedema, is displaced by fluid, and this 
on pressure escapes from the cut surface, mingled with air-bubbles. 
(Edema of the kidney, which may become marked, is caused by re- 
tention in the dilated tubules of the water secreted by the glomeruli. In 
the connective tissue between the tubules infiltration of fluid may also 
occur. 
Fig. 25.—Hydropic connective-tissue cells from the 
subcutaneous tissue of a case of chronic oedema due to 
stasis. (K. Ziegler, 1. c.) x 400. CEDEMA, 
121 
The amount of blood contained in cedematous tissues is variable, and 
their color varies accordingly. 
Body-cavities which are the seat of dropsical effusion contain at one 
time a large, at another time only a small amount of clear, usually light- 
yellow, rarely colorless, alkaline fluid, which at times contains a few 
fibrin flakes (see the chapter on 
Inflammation). Organs are 
compressed by the effusion; 
cavities are dilated. 
A collection of transuded 
fluid in the abdominal cavity is 
known as ascites. 
The albumin-content of tran- 
sudates is not the same in all 
the cavities and tissues, but 
differs in pronounced degree. According to Reuss, the albumin-content 
of transudations of the pleura is 22.5 pro mille; that of the pericardium, 
18.3; of the peritoneum, 11.1; of the subcutaneous connective-tissue, 5.8; 
of the membranes of the brain and spinal cord, 1.4. These facts may be 
taken as proof of the different constitution of the vessel-walls in the 
various tissues of the body. 
§ 42. According to their etiology we may distinguish five varieties 
of oedema: oedema due to arterial congestion; oedema from stagnation of 
blood; oedema caused by hindrance to the outflow of the lymph; oedema 
Fig. 26.— Longitudinal section of cedematous 
muscle-fibres from the calf muscles in a case of 
chronic oedema of the legs. (Flemming’s solu- 
tion, safranin.) x 45. 
Fig. 27.—Inflammatory oedema of the papillary bodies, with elevation of the epidermis from the 
papillary bodies by an inflammatory exudate, from a case of phlegmon of the thigh. (K. Ziegler, 
1. c.) a, Corium; b, exudate consisting of fluid, fibrin and leucocytes, x 40. 
caused by disturbance of the capillary secretion due to changes in the 
capillary walls; and oedema ex vacuo. The fourth is designated inflam- 
matory, hydraemic or cachectic, or neuropathic oedema, according to the 
clinical features. 
CEdema due to arterial congestion occurs acutely in localized areas, 
in the skin and subcutaneous tissue, larynx, bronchi (asthma), nose, 
periosteum, and muscles (angio-neurotic oedema). In individuals show- 122 
DISTURBANCES OF THE CIRCULATION. 
ing the tendency in marked degree, bullae may be formed in the skin. In 
angio-neurotic oedema toxic influences assume an important part. It 
not uncommonly happens, for example, that the ingestion of straw- 
berries, oysters, etc., is succeeded by oedema of the eye-lids of such an 
extent as to produce closure; if the soft tissues of the larynx are involved 
symptoms of suffocation may arise and death may occur from occlusion 
of the glottis. Urticaria is a variety of angio-neurotic oedema. It is 
probable that the changes in question are of the nature of anaphylactic 
phenomena. 
(Edema due to stagnation of blood arises when, as a result of 
impediment to the outflow of blood, the pressure in the capillaries rises 
and the fluid of the blood seeks a lateral outlet, so that an increased 
amount escapes. The amount of escaped fluid is larger the greater the 
discrepancy between inflow and outflow; it is therefore increased through 
coincident increase of the inflow. The escaping fluid is always poor in 
albumin, but with increased pressure in the veins the albumin-content is 
increased (Senator). 
The immediate result of increased transudation from the blood- 
vessels is increase in the lymph-flow, and this may be sufficient to carry 
off the fluid. If it does not suffice, the fluid collects in the tissue-spaces 
and oedema results. According to Landerer, this is favored by the fact 
that the elasticity of the tissues becomes diminished as the result of the 
long-continued increase of pressure to which they are subjected. 
Obstruction to the outflow of lymph, as experiments have shown, 
is not ordinarily followed by oedema. The lymph-vessels possess such 
extensive anastomoses that obstruction to the outflow does not readily 
occur. Even when all the lymph-channels of an extremity are obstructed, 
if the amount of lymph formed is normal no oedema results, inasmuch 
as the blood-vessels are able to take up the lymph. Only occlusion of the 
thoracic duct is likely to lead to stagnation of lymph and the production 
of oedema, particularly ascites, but even in this case collateral channels 
may be opened in sufficient numbers to carry off the lymph. 
Although lymphatic obstruction is not ordinarily sufficient in itself to 
produce oedema, it does increase oedema caused by concomitant transu- 
dation from the blood-vessels. 
Pathological changes in the walls of the capillaries and veins of 
such nature as to cause increase in the vascular secretion, and thus to 
give rise to oedema, may occur as the result of long-continued conges- 
tion and imperfect renewal of blood. Such changes occur, however, more 
frequently as the result of prolonged ischaemia, lack of oxygen, action of 
high or low temperatures, the development of tumors (especially in the 
serous membranes), infection, and intoxication. It is also probable that 
irritation or paralysis of the vasomotor nerves may lead to increase of 
vascular secretion. Just what changes the vessels suffer under these con- 
ditions we are not able to state, but it may be assumed that alteration of 
the endothelial cells and of the cement-substance renders the vessels more 
permeable. The oedemas so produced may be classed according to their 
cause as toxic, infectious, thermal, traumatic, ischaemic, neuropathic, 
etc.; and such a classification has much to commend it. Hitherto the 
forms of oedema under consideration, with the exception of the neuro- 
pathic, have been arranged in two groups—namely, inflammatory and 
cachectic. CEDEMA. 
123 
Inflammatory oedema is to be referred to alteration of the vessel- 
wall, and occurs as an independent affection, in the form of circumscribed 
or diffuse swelling or as hydropic effusions, and as a coincident pheno- 
menon in the neighborhood of inflammatory processes. In the latter case 
it is designated collateral oedema. Inflammatory is distinguished from 
stagnation-oedema by the fact that the transuded fluid is richer in albu- 
min and in the number of white blood-corpuscles, and in the fact that 
larger masses of coagula (Fig. 27, b) occur in it (see chapter on In- 
flammation). Its cause is to be sought in infectious and toxic, some- 
times in thermal and traumatic influences, at other times in temporary 
ischaemia. 
As to hydraemic or cachectic oedema, it was formerly believed that 
hydraemia—'that is, diminution of the solid elements of the blood—as 
well as hydraemic plethora—that is, retention of water in the blood— 
could cause increased transudation from the vessels. It was supposed 
that the vessel-walls behaved as dead animal membranes, and allowed 
fluid poor in albumin to filter more easily than one rich in albumin. The 
vessel-wall is not, however, a lifeless membrane, but a living organ. 
Hydrsemia experimentally produced does not, according to Cohnheim, 
give rise to oedema. Even when hydraemic plethora is produced by filling 
of the blood-vessels with watered blood, and is followed by increased 
transudation, leading to oedema, the oedema so produced occurs only 
when the proportion of water becomes very high, and does not develop 
in the same regions where the so-called hydraemic oedema in man appears. 
We must therefore assume that the oedema of cachectic individuals, as 
well as that occurring in individuals suffering from impairment of renal 
function, depends on alteration of the vessel-wall, caused either by the 
hydraemic character of the blood or by a poison or poisons in the blood. 
Probably other lesions through which the elasticity of the tissues is 
diminished are also concerned. Hydrcemia favors the occurrence of 
oedema, but is not the sole cause and certainly does not determine its 
localization. 
Cachectic oedema is allied to stagnation-oedema and to inflammatory 
oedema, in that at one time the circulatory disturbance is a prominent 
feature, at another time the vascular alteration. 
CEdema ex vacuo occurs chiefly in the brain and spinal cord, and 
arises when a portion of the brain or cord is lost and not replaced by 
other tissue. In atrophy of the brain or cord the subarachnoid spaces 
become enlarged, occasionally the ventricles. The fluid has the same 
albumin content as the normal cerebrospinal fluid. Local defects become 
filled by dilatation of the nearest subarachnoid spaces or of the ad- 
jacent portions of the ventricles, or through collection of fluid at the site 
of the defect itself. 
V. Haemorrhage and the Formation of Infarcts. 
§ 43. By haemorrhage is understood the escape of all the constituents 
of the blood from the vessels (extravasation) into the tissues or on a 
free surface. It may be arterial, venous, or capillary, or from the heart. 
The blood which has escaped is termed an extravasate. For special 
forms of haemorrhage a variety of terms is used. If the haemorrhagic 
foci are small, and form more or less sharply outlined, punctate, red or 124 
DISTURBANCES OF THE CIRCULATION. 
dark-red spots, they are called petechice; if larger and not sharply out- 
lined, they are known as ecchymoses, or suggillations. If the tissue is 
firmly infiltrated with escaped blood, but not torn or destroyed, the con- 
dition is spoken of as a hcemorrhagic infarct. If the extravasated blood 
forms a large mass, it is known as a hccmatoma. 
The blood which escapes from the vessels into the tissues collects in 
the tissue spaces (Fig. 28). Large haemorrhages may completely conceal 
the structure of the tissue (Fig. 29, d). Delicate tissues, as those of the 
brain or spinal cord, may be destroyed by large haemorrhages. 
If the haemorrhage occurs on the free surface of an organ, the blood 
either escapes externally or is poured into a neighboring cavity. 
Haemorrhage from the nose is called epistaxis; vomiting of blood 
hccmatemesis ; bleeding from the lungs, haemoptysis; from the uterus, 
Fig. 28.—Haemorrhage in the skin near the knee; from a man eighty-one years of age. (Formalin, 
haematoxylin, and eosin.) x 80. 
metrorrhagia and menorrhagia (during the menses) ; hasmorrhage from 
the urinary organs, hcematuria; from the sweat-glands, hcematidrosis. 
A collection of blood in the uterine cavity is designated hecmatometra, 
in the pleural cavity hccmothorax, in the tunic of the testicle hcematocele, 
in the pericardium hcemopericardium, in the peritoneum hemoperitoneum, 
etc. 
Haemorrhages of the skin not caused by trauma are termed purpuric 
(Fig. 28). Collections of blood and fluid beneath the epidermis in place 
of the dissolved deeper epithelial layers are known as haemorrhagic 
blebs. 
Recent extravasations show the color of either arterial or venous 
blood. Later the extravasate shows alterations characterized particularly 
by color-changes. Suggillations of the skin become brown, then blue, 
and green, and finally yellow. In time the extravasate is absorbed (see 
Chapter V.), and during absorption tissue-proliferation often occurs. 
Large collections of blood may become organized into connective tissue 
or be encapsulated (see Chapter VII.). HAEMORRHAGE. 
125 
Haemorrhage may occur from rupture of the heart or vessel-wall 
—that is, per rhexin or per diabrosin. This is the only form of 
cardiac and arterial haemorrhage. From the capillaries and veins haemor- 
rhage may also occur per diapedesin—that is, the red cells escape through 
the vessel-wall without the occurrence of a tear. Often such haemor- 
rhages are small and of slight extent; in other cases the process con- 
tinues for a longer time, and infiltration of the tissues reaches a 
significant degree. Haemorrhages by diapedesis are not always small, 
haemorrhages by rhexis not always large. Rupture of a capillary or 
Fig. 29.—Traumatic cerebral haemorrhage. (Formalin, hematoxylin, and eosin.) a, Normal 
brain substances; b, blood-vessel; c, perivascular collection of blood; d, larger area of haemorrhage 
with destruction of the brain substance, x 100. 
small vein does not give rise to a large haemorrhage; on the other hand, 
haemorrhage through diapedesis can reach an important size. 
The causes of interruption of continuity of the heart and vessel- 
walls are traumatic injuries, increase of intravascular pressure, and 
diseased conditions of the heart and vessel-wall. Increase of pressure 
in the capillaries and smallest veins can lead to rupture without the aid 
of vascular changes, particularly in marked passive congestion. The 
heart, normal arteries, and normal veins of large size cannot be ruptured 
through increase of pressure alone, but abnormally thin-walled or 
diseased areas in the heart, arteries, or veins may be so ruptured. 
Newly formed vessels are easily torn. 
Diapedesis may be caused by increase of pressure in the capillaries 
and veins, as well as by increased permeability of the vessel-wall. If 
the outflow of the venous blood in a given area be obstructed, diapedesis 
of red cells from the capillaries and veins takes place as a result of in- 
creased pressure in the vessels. Diapedesis as a result of changes in the 
vessel-wall occurs particularly after mechanical, chemical, and thermal 126 
DISTURBANCES OF THE CIRCULATION. 
injuries. Further, abnormal permeability of the vessel-walls is observed 
when for a long period the vessels have not been traversed by the blood- 
stream, and their nutrition has suffered in consequence. 
When an individual shows a special tendency to haemorrhage, the 
condition is designated haemorrhagic diathesis. Two forms may be 
distinguished—congenital and acquired. 
Congenital haemorrhagic diathesis or haemophilia, depends most 
probably on abnormal constitution of the vessel-walls. The composition 
of the blood may also be pathological, so that a haemorrhage once started 
is not arrested, as usual, by coagulation of the blood. 
Acquired haemorrhagic diathesis occurs in those diseases known 
as scurvy, morbus maculosus Werlhofii, purpura simplex, purpura 
(peliosis) rhuematica, purpura haemorrhagica, haemophilia, and melaena 
neonatorum (gastric and intestinal haemorrhages) ; in many infections— 
septicaemia, endocarditis, typhus fever, cholera, smallpox, plague, yellow 
fever; in intoxications, e. g., phosphorus poisoning, after snake-bites, 
etc.; and, finally, in pernicious anaemia and leukaemia. 
Hcumorrhagcs per rliexin cease when the extravascular pressure comes 
to equal the pressure in the bleeding vessel, or when narrowing of the 
vessel and coagulation and thrombosis close the rent. Heemorrhage by 
diapedesis ends with cessation of blood-supply to the bleeding vessel, or 
when the intravascular pressure is lowered and the vessel-wall restored 
to its normal state. 
The process of diapedesis may be observed in the frog’s mesentery or web. 
If the efferent veins are ligated, the capillaries and veins are seen to be engorged 
with blood. After a certain time the red blood cells begin to pass from the capil- 
laries and veins (see Cohnheim, “Allgem. Path.,” i, and Virch Arch., 41 Bd.). 
Arnold (Virch. Arch., 58, 62 u. 64 Bd.) believed that, at the place of exit of the 
corpuscular elements, spaces between the endothelial cells must exist, and these 
he designated stomata; later he found that the supposed openings consist of heap- 
ing-up of the cement-substance between the endothelial cells. Under pathological 
conditions the cement-substance gives way and allows the red blood-cells to pass 
through. 
§ 44. The sudden closure of an artery by thrombosis, embolism, 
ligation, or other means, leads, as has already been stated (§ 39), to 
stoppage of the circulation beyond the point of obstruction, after the 
vessel has more or less completely emptied itself by contraction of its 
walls. At the same time there is an increase of pressure in the vessel 
from the point of obstruction back to the point of divergence of the 
nearest branch. If the branches of the artery beyond the point of 
obstruction have free communication with some unobstructed artery, the 
latter by becoming dilated may be able to supply a sufficient amount of 
blood to the affected area to restore the circulation. 
If the obstructed artery has no collateral connections through which 
it may draw its blood-supply, the portion of tissue deprived of blood 
remains anaemic and dies, giving rise to an anaemic infarct. Paren- 
chymatous organs—for example, the spleen and kidneys—present in in- 
farcted areas a cloudy, opaque, yellowish-white, often clay-colored 
appearance. (See § 48.) 
When the obstructed vessel possesses no collateral anastomoses, as 
in a terminal artery, but if, on the other hand, there is a scanty influx 
of blood from neighboring capillaries or veins, a haemorrhagic infarct HAEMORRHAGE. 
12 7 
may be formed. The capillaries of the area rendered anaemic by the 
obstruction become gradually filled with blood from the capillaries of 
the adjacent vascular area, and from the veins by retrograde flow. The 
blood flowing in from adjacent capillaries is under low pressure, which 
is not sufficient to drive the blood through the obstructed area into the 
veins. When conditions of pressure become such that a retrograde cur- 
rent sets in from the veins to the capillaries, restoration of the circulation 
becomes impossible. 
The imperfect circulation in the obstructed area, which, through 
coagulation of the blood in the veins and capillaries, is finally brought 
to a standstill, leads sooner or later to degeneration and necrosis of the 
vessel-wall, and to increased permeability. As a result, if the afflux of 
blood be continued, there occur in the stagnated area diapedesis of red 
Fig. 30.—Haemorrhagic infarct of the lung. (Haematoxylin and eosin.) Alveoli filled with 
blood; scattered pale nuclei in the alveolar septa and in the blood of the alveolar spaces, belonging 
partly to connective-tissue cells and partly to leucocytes, x 40. 
cells and infiltration of the tissue with extravasated blood, through which 
the obstructed area acquires a dark-red color and firmer consistence; a 
hcemorrhagic infarct is thus formed (Fig. 30). 
Embolic hcemorrhagic infarcts occur in the lungs (Fig. 30), but are 
formed only when there exists passive congestion; if the pulmonary cir- 
culation is normal the disturbances produced by embolism are quickly 
compensated. In the systemic circulation embolic haemorrhages are con- 
fined almost entirely to the distribution of the superior mesenteric 
artery, whose branches, though not terminal, possess but few anastomoses. 
Ancemic infarcts occur especially in the spleen and kidneys. Around the 
periphery of the anaemic area there is always more or less haemorrhage, 
so that the pale infarct is surrounded by a hcemorrhagic border or at 
least by hcemorrhagic spots. In obstruction of the cerebral arteries or 
those of the extremities, or the central artery of the retina, punctate 
haemorrhages may occur. In the infarcted area the tissues are wholly 
or for the greater part dead, and the specific elements of the organ in 128 
DISTURBANCES OF THE CIRCULATION. 
particular (Fig. 32, c, d) die quickly. After a time inflammation arises 
in the neighborhood of anaemic and haemorrhagic infarcts, with the forma- 
tion of a cellular (Fig. 32, /) or a cellular and fibrinous exudate; this 
is followed by proliferation of fixed cells, and the dead area is gradually 
replaced by connective tissue (see Part II. of Chapter VII.). 
Literature. 
(Hccmorrhagic Infarction.) 
Cohnheim: Untersuch. fib. d. embol. Processe, Berlin, 1872; Allgem. Pathol., 
Berlin, 1882. 
Welch: Haemorrhagic Infarction. Trans. Assn. Amer. Phys., 1887. 
VI. Lymphorrhagia. 
§ 45. Lymphorrhagia occurs when the continuity of a lymph-vessel 
is interrupted and lymph is poured into the neighboring tissue. Since 
the pressure in the lymph-vessels is low—that is, not greater than in the 
surrounding tissues—outflow of lymph can occur only when the injured 
vessel lies on the surface, or when a natural cavity is at hand into which 
the lymph can flow, or when, through the cause producing the rupture, 
an open space is formed in the tissues. For example, escape of lymph 
together with blood may take place from wounds, but the outflow is 
stopped by slight counterpressure. If, after the wounding of a lymphatic, 
the opening persists, there is formed a lymph-fistula, through which 
considerable quantities may be lost. Important and often dangerous is 
rupture of the thoracic duct, which sometimes occurs as the result of 
traumatism, and occasionally as a result of obstruction to the lymph-flow 
at some point in the lumen of the duct (after inflammation or by the 
invasion of tumors). The lymph is poured into the thoracic or abdominal 
cavity, giving rise respectively, to chylous hydrothorax or chylous ascites; 
in rare cases to chylopericardium. 
It sometimes happens that the urine, as it comes from the bladder, has the 
appearance of a milk-white, or yellowish, or, through the admixture of blood, a red- 
dish emulsion; and contains albumin and finely-divided fat-droplets. This is known 
as chyluria. It occurs as an endemic disease in certain tropical regions (Brazil, 
India, the Antilles, Zanzibar, Egypt) where it is caused by a parasite, the Filaria 
Bancrofti, which inhabits the lymph-vessels of the abdominal cavity and there 
produces its embryos (Filaria sanguinis) ; these, during the repose of the patient 
in a horizontal position, swarm in great numbers in the blood, and are also found 
in the chylous urine. The connection between chyluria and the invasion of the 
lymph-vessels has not been satisfactorily demonstrated by anatomical investiga- 
tions ; ibut it is probable that the chyle-like fluid does not come from the blood 
through the kidneys; but, as a result of obstruction in the lvmph-circulation, chyle 
escapes from ruptured lymphatics of the bladder and mingles with the urine 
(Scheube, Grimm). In corroboration of this view is the fact that, at autopsy, the 
abdominal lymphatics exhibit marked dilatation (Havelburg), while the kidneys are 
but little changed; and further, according to an observation made by Havelburg, 
the urine obtained from the ureter showed no admixture of chyle, though chyluria 
was present at the same time. 
The anatomical cause of the non-parasitic chyluria is still unknown. 
(Chylous Effusions in the Body-cavities; Chyluria.) 
Busey: Amer. Jour, of Med. Sciences, 1889. 
Edwards: Chylous and Adipose Ascites. Ref. Handb. of Med. Sciences, 1901. 
Lothrop and Pratt: Amer. Jour, of Med. Sciences, 1900. 
Literature. CHAPTER V. 
Retrograde Disturbances of Nutrition and Infiltrations of 
tissues. 
§ 46. Retrograde disturbances of nutrition are characterized in a 
general way by degeneration of the affected tissue and by diminution in 
size and disappearance of the individual tissue elements, the functional 
capacity being at the same time lozvered. 
Tissue infiltrations are characterized by the deposit of pathological 
substances which have been formed in the body or introduced from with- 
out. The functional capacity of the part affected is diminished. In 
some cases, infiltration is merely a result of degeneration; in others it 
may itself constitute the chief feature in a degenerative process. 
Retrograde disturbances of nutrition may effect the body in its fully 
developed state or during its development and growth; in either case 
it may lead to abnormal smallness of a part or tissue. In the fully de- 
veloped body, diminution in size of an organ or tissue due to disappear- 
ance of individual tissue elements or to reduction in their size, is desig- 
nated atrophy. If, in the period of development, an organ or part totally 
fail of development or is represented by rudimentary structures, the con- 
dition is known as agenesia or aplasia. If the development of a part pro- 
ceed to a certain extent but still does not attain the normal, the condition 
is known as hypoplasia. 
The causes of tissue degenerations and associated atrophy are to 
be found in those injuries to which the tissues are exposed during life; 
but atrophy may also depend on intrinsic conditions. The latter is 
exemplified by tissues which, in old age, reach their physiological limita- 
tions and become incapable of nourishing themselves. In certain tissues 
similar regressive changes occur earlier in life; for example, in the ovary 
and thymus. 
As extrinsic harmful influences which may lead to degenerations 
should be considered all those agencies mentioned in Chapter I. Dis- 
turbances of circulation, lack of oxygen and food supply, and intoxica- 
tions play a very important role. In the majority of cases degenerations 
are localized, so that we may speak of degenerations of special tissues 
or of special organs. Not infrequently the disturbances of nutrition 
are more general, so that the entire organism suffers. Thus the picture 
of a general disease may be produced by a degenerative or atrophic con- 
dition of the blood — that is, diminution in the number of red blood- 
cells (oligocythsemia), at times also deficiency of hsemoglobin (chloro- 
sis), so that a permanent condition of insufficient blood-supply or a 
general anaemia is produced, the nutrition of the body being corre- 
spondingly impaired. 
As the result of diminished ingestion of food, or of disturbed me- 
tabolism, and of increased waste of the proteids and fats of the body, 
there may result a condition of general emaciation and weakness, often 130 
THE RETROGRADE CHANGES. 
associated with anaemia, a wasting of the entire body, which is designated 
cachexia or marasmus. If under such circumstances it appears likely 
that certain substances are formed in the body, which, when taken up 
into the blood and tissue juices, cause contamination or alteration of 
these, the condition may be spoken of as a dyscrasia. 
II. Death. 
§ 47. All life comes sooner or later to an end — to death. When this 
occurs at an advanced age, without preceding symptoms of disease, it 
nqay be regarded as the normal termination. When death occurs pre- 
maturely — that is, at an age earlier than the average — and when pre- 
ceded by symptoms of disease, it must be regarded as pathological. It 
is obviously impossible to draw any sharp line of separation between 
physiological and pathological death. 
An individual is dead when all his functions have ceased. Death is 
inevitable at that instant when one or more of the functions indispensable 
to life has ceased, though it is not necessary that at that moment all 
should have ceased. Indeed, it often happens, that after life is irretriev- 
ably lost, many organs are still capable of function, and it is only after 
a certain time that all the organs die. The life of the body passes by 
progressive cessation of the functions of its different organs into the state 
of death. 
Cessation of the functions of the heart, lungs, and nervous system 
results in immediate death of the entire organism. Cessation of the 
functions of the intestines, liver, or kidneys leads to death after a certain 
length of time, often measured by days. Destruction of the sexual 
glands does not endanger the life of the individual, and likewise man may 
spare one or more of his organs of special sense. 
The occurrence of death is usually determined by the last respiration 
and by stoppage of the heart. With cessation of respiration it is im- 
possible for any organ to remain alive after a certain short period. Stop- 
page of the heart likewise makes further nourishment of the tissues 
impossible, in consequence of which the central nervous system is unable 
to continue. 
After death the body may present a variety of appearances. The aspect of the 
visible portions is largely dependent on the distribution of the blood at the time 
of death. An abundant supply of blood in the skin gives it a blue-red color, anaemia 
gives it a pale color. Further, preceding disease may alter the external appear- 
ance of the body in different ways. 
Within a certain time after death various changes occur in the tissues of the 
body, which may be regarded as the absolute signs of death. In the first place the 
temperature of the body falls, sometimes rapidly, at other times slowly, until it 
reaches the temperature of the surrounding air. It must be borne in mind, how- 
ever, that the temperature at times does not begin to sink immediately after death, 
but first rises somewhat. The rate of cooling of the body depends partly on the 
character of the body itself, and partly on the nature of its surroundings. The 
time required may vary from one to twenty-four hours. 
The coldness of the dead body is termed algor mortis. 
At the time of death the skin for the greater part becomes pale; but after six 
to twelve hours, sometimes earlier, bluish-red spots appear on the skin over the 
dependent parts of the body. These are known as death-spots or livores mortis 
(post-mortem hypostasis), and are due to the accumulation of blood in the veins 
and capillaries. They are not found in those parts subjected to the weight of the 
body. Their number and size depend on the amount of blood in the skin at the 
time of death. Parts which have been cyanotic during life may retain this appear- DEATH; NECROSIS. 
131 
ance after death, especially the head, fingers, and toes. The color of post-mortem 
hypostasis is usually blue-red; the intensity of the color varies; in cases of poison- 
ing with carbon monoxide it is a bright red. 
The weight of the body causes flattening of those muscular parts upon which 
it rests. 
Sooner or later there occurs stiffening and contraction of the muscles, due to 
coagulation of the contractile substance (Brueke, Kiihne). This is known as 
cadaveric stiffening or rigor mortis. It usually comes on about four to twelve 
hours after death, but may occur almost immediately or as late as twelve to twenty- 
four hours. It begins usually in the muscles of the jaw, throat, and neck, and 
extends from them to the trunk and extremities. After twenty-four to forty- 
eight hours it usually vanishes, but under certain conditions may persist for several 
days. 
Rigor mortis affects also the smooth muscle fibres; contraction of these in the 
skin gives rise to the so-called goose-flesh of the cadaver. 
Decomposition of the cadaver begins with the disappearance of rigor mortis. 
Its occurrence is shown by the odor of putrefaction, by changes of color in the 
skin and mucous membranes, and changes in the consistence of the tissues. The 
commencement and progress of putrefaction depend partly on the nutrition and 
the nature of the disease preceding death, partly on the surroundings, especially 
the temperature. Not infrequently putrefaction may occur in dead areas even 
before death of the body as a whole. When putrefactive bacteria are present in 
the body, decomposition may begin immediately after death. 
An early sign of decomposition is greenish discoloration of the skin, appear- 
ing first over the abdomen. With the progress of putrefaction the unpleasant 
odor and discoloration increase; gases are formed in the intestine, later in the 
blood and tissues, which become soft and friable. 
Shortly after death the cornea becomes lustreless, and the eyeball loses 
its elasticity and shrinks, due to changes in the humors. If the lids are not closed, 
the uncovered portions of the eyeball show the results of drying. Whenever the 
skin has lost its epidermis the exposed tissues undergo desiccation. 
If the phenomena of life be reduced to a minimum, there may result a condi- 
tion of apparent death which may be mistaken for real death. Though post- 
mortem hypostasis, rigor mortis, and putrefaction are unmistakable evidences of 
death, these changes may not take place until some time after death, so that an 
interval is left during which it may be doubtful whether death has actually oc- 
curred. To ascertain the true condition it must be determined by appropriate exam- 
ination whether the heart still beats, whether respiration still takes place, whether 
the blood still circulates, and whether the nerves and muscles retain their irri- 
tability. 
Conditions which simulate death occur under a variety of circumstances, for 
example, in cholera, in catalepsy, hysteria, after excessive bodily exertion, violent 
concussion of the central nervous system, sever haemorrhage, suspension of respir- 
ation through hanging, strangulation, or drowning, in certain cases of poisoning, 
after lightning-stroke, prolonged exposure to cold, etc. The duration of this 
condition is usually short, but may occasionally be extended. 
III. Necrosis. 
§ 48. Local death, or death of individual cells or groups of cells, is 
known as necrosis. As a result of necrosis the functions of the affected 
tissue are forever lost. 
Necrosis of a cell-group or of an entire organ is only rarely attended 
by immediately recognizable changes of structure. The slight histological 
changes which cells undergo during the process of death do not always 
permit us to determine the cessation of life; nor does the macroscopic 
appearance of visible portions of the body always inform us when a part 
has become necrotic. 
Necrosis is evident on anatomical investigation only when certain 
changes in structure have occurred, either coincidently with death or 
subsequently. Necrosis is shown by immediate histological changes only 
in a limited number of instances; in all other cases necrosis is followed 132 
THE RETROGRADE CHANGES. 
by sucn changes after a longer or shorter interval. According to the 
nature of the tissue-changes it is possible to distinguish different varie- 
ties of necrosis. 
Histologically, necrosis of a cell is shown first by disintegration and 
disappearance of the nucleus, the chromatin breaking up to form small 
clumps and granules which pass into the cytoplasm and are dissolved 
(karyorrhexis). At other times the nucleus shows signs of shrinking, 
and takes the stain more deeply than under normal conditions (pyknosis). 
In other cases the nucleus retains its form but loses its staining power, 
and then dissolves and disappears (Fig. 31, c, d), so that in well-fixed and 
well-stained preparations no trace whatever can be found (karyolysis). 
Thus, in an anaemic infarct of the spleen or kidney the nuclei of the 
spleen and kidney cells are lost 
soon after the death of the tissue 
(Fig. 32, c, d, f, g). At the 
same time the affected area be- 
comes pale, cloudy, yellowish- 
white, or cream-colored; so that 
the presence of necrosis may be 
recognized by the naked eye. 
The protoplasm of dying 
cells sooner or later undergoes 
changes which, according to the 
mode of death, may begin before 
the cells die, or take place only 
after the cells are dead. The 
kind of change is dependent on 
three factors: the nature of the 
cells themselves, the character 
of the destructive influence, and 
the amount and character of 
the fluids surrounding and in- 
filtrating the cells. Amoeboid 
cells usually assume a globular 
form after death. Cell-bodies, rich in protoplasm, often become, 
before or after death, markedly granular, less frequently homo- 
geneous and lumpy (Fig. 31, c, and Fig. 32, e). Through the 
taking-up of fluid the protoplasm or even the nucleus may become 
swollen and show drops of fluid (vacuoles) ; and this may lead to 
breaks in the continuity of the protoplasm (plasmoschisis). Not in- 
frequently as a result of plasmochisis portions of the cell may be ex- 
truded or cut off. The end of all these changes is disintegration of proto- 
plasm and nucleus into granular masses, the process often being accom- 
panied by the formation of fat. 
The injurious influences which give rise to necrosis may be divided 
into five groups. The first two include those which destroy the tissue 
directly — mechanical and chemical forces. A third group comprises 
those of thermal character. Elevation of the temperature of a tissue 
to 54°—68° C. for any length of time leads to its death. Higher 
temperatures act more quickly. Refrigeration to low temperatures 
likewise can be borne but a short time. A fourth group is caused by 
infection. A fifth group is caused by cessation of nourishment and 
Fig. 31.—Necrosis of the epithelium of the 
urinary tubules in icterus gravis. (Muller’s fluid, 
gentian violet.) a, Normal convoluted tubule; b, 
ascending portion of the loop; c, convoluted tubule 
with necrotic epithelium; d, convoluted tubule with 
only a part of its epithelium necrotic; e, normal 
stroma with blood-vessels, x 300. NECROSIS. 
133 
oxygen to the tissues, and is known as ischaemic necrosis or local 
asphyxia (Fig. 32). 
All those factors which affect the circulation in any part and lead to 
stoppage of the blood-supply — such as thrombosis, embolism, ligation, 
pressure, etc., may lead to necrosis of tissue. Not only permanent ces- 
sation of circulation, but also temporary stoppage lasting beyond a cer- 
tain time, leads to death of the affected tissue. Whether haemorrhage 
occurs in such cases is immaterial, and influences only the appearance 
Fig. 32.—From the edge of an anaemic infarct of the kidney. (Muller’s fluid, haematoxylin, and 
eosin.) a, Normal kidney tissue; 01, normal kidney-tubules with stroma infiltrated with leucocytes; 
b, normal glomerulus; c, necrotic tissue without nuclei, showing granular coagula in the tubules; 
d, necrotic swollen glomerulus with few nuclei; e, tubules without nuclei in a stroma still con- 
taining nuclei; f, necrotic tissue with cellular, g, with haemorrhagic infiltration, x 50. 
of the part. Hcemorrhagic infarction has, therefore, the same significance 
as ancemic necrosis associated with hcemorrhage. 
When death follows quickly on the action of an injurious agent, 
it is spoken of as direct necrosis. When it occurs slowly and is pre- 
ceded by tissue-degenerations it is designated indirect necrosis or 
necrobiosis. 
Mechanical, chemical, thermal, and infectious agents may act 
coincidently, or separately, one after the other. When the tissue is 
damaged by any one of the group, the blood often suffers changes 
which lead to stasis and coagulation in the capillaries, as well as in 
the veins and arteries, and in this way the circulation is arrested. 
Whether injury will cause necrosis of tissue depends, not only on 
its nature and severity, but also on the condition of the tissue at the 
time of injury. A tissue whose vitality has been lowered as the re- 
sult of long-continued disturbances of circulation, changes in the 
composition of the blood, etc., dies more easily than the normal. In 
typhoid fever relatively slight pressure on the trochanters, elbows, 
sacrum, heels, etc., may suffice to bring about necrosis of the skin and 134 
THE RETROGRADE CHANGES. 
subcutaneous tissues. Such forms of necrosis are known as marasmic 
necrosis or marasmic gangrene, and as decubitus or decubital necrosis. 
The course of necrosis is dependent on the character of the affected 
tissue, its location, the manner of its death, and the cause of the 
necrosis. Further, the amount of lymph and blood in the tissue, the 
opportunity afforded for the access of air and putrefactive organisms, 
together with preceding tissue changes are of significance in deter- 
mining the character of the necrosis. 
As the result of necrosis of certain tissues, there always develops 
inflammation of greater or less intensity in the surrounding parts. (Fig. 
32, /). This reactive inflammation is most marked when the necrotic 
area becomes gangrenous. The necrotic area becomes isolated or se- 
questrated ; this process is spoken of as a sequestrating or limiting in- 
flammation, and the dead area thus shut off is called a sequestrum. A 
more detailed description of these inflammatory processes will be found 
in Chapter VII. 
Five chief sequelae of necrosis may be distinguished: 1. The dead 
tissue may be removed by absorption, or cast off, and its place taken by 
normal tissue {regeneration). 2. The dead tissue is similarly removed, but 
instead of normal tissue being restored, the defect is filled wholly or in 
part by connective tissue, so-called cicatricial tissue. 3. The necrotic 
tissue is cast off or liquefied, the defect is not filled in and an ulcer remains. 
Should this heal without regeneration of the lost tissue there remains a 
scar. 4. The necrotic tissue is partly absorbed, but a portion remains as 
a sequestrated mass which not infrequently becomes calcified and sur- 
rounded by a connective-tissue capside. 5. The fifth sequel of necrosis 
is cyst-formation. The necrotic area becomes encapsulated by connective 
tissue, the dead tissue becomes liquefied, and the space filled with fluid. 
This sequel of necrosis occurs most frequently in the brain. 
By many writers there is recognized besides these forms of necrosis a special 
variety designated neuropathic necrosis, that is, necrosis resulting from a lesion 
of the central or peripheral nervous system. By some the cause of such necrosis 
is referred to a lesion of the trophic nerves, while others refer it to disturbances 
of circulation, pressure, and mechanical injury of anaesthetic and paralyzed por- 
tions of the body. According to observations made on men, as well as in experi- 
ments on animals, injuries and disturbances of circulation play the most important 
role in the production of this form of necrosis, and can never be wholly excluded. 
The time required to kill tissue by shutting off the circulation varies with 
different tissues. Ganglion-cells, kidney epithelium, and liver-cells die quickly, 
while surface epithelium and connective tissue may live for hours. Epidermis under 
certain conditions may remain alive for a number of days, and still retain its power 
of proliferation (see Transplantation). 
§ 49. According to the condition of the tissue, four chief forms 
of necrosis may be distinguished: coagulation-necrosis, caseation, lique- 
faction-necrosis, and gangrene. 
Coagulation-necrosis is characterized by coagulation, either extra- 
cellular, in the fluids about the cells; or intracellular, leading to changes 
in the cells. 
Coagulation-necrosis with extracellular coagulation is exemplified by 
both intravascular (Figs. 10, 13) and extravascular coagulation of the 
blood, inasmuch as this phenomenon constitutes death of the blood; and 
in fact destruction of cells does occur. Further, there may be considered 
as belonging to this class the various forms of coagulation which occur NECROSIS. 
135 
in inflammations, on the surface and in the interior of the tissues (see 
Chapter \ II.) and which are characterized by the formation, in some 
cases, of stringy fibrin, in other cases by granular or hyaline masses of 
coagula. 
Intracellular coagulation occurs when dead cells are infiltrated with 
coagulable lymph. The cells lose their nuclei and present either a granu- 
lar (Fig. 31, c, d, and Fig. 32, c, d, e) or hyaline appearance. They remain 
in this condition for a time and then break down into granules and are 
dissolved. 
This phenomenon is most frequently observed in anaemic, toxic, and 
thermal necroses, for example, in anaemic infarcts of the kidney (Fig. 
32) and of the spleen, also in many inflammations which are associated 
with infiltration of the tissues, due to exudation from the blood- 
vessels. In the necrosis of striped muscle, which is of frequent 
occurrence in typhoid fever and other infections, the contractile sub- 
stance acquires a waxy appearance and breaks up into hyaline lumps. 
The necrotic tissue of anaemic infarcts is yellowish-white, or cream- 
colored. Muscles containing many dead fibres in a state of hyaline coagu- 
lation are pale red, and of dull lustre, resembling fish-flesh. Inflamed 
tissues undergoing coagulation necrosis are cloudy, opaque, and grayish- 
white ; but the color may undergo marked changes through admixture of 
blood or imbibition of bile, as in the intestine, for example. 
The structure of a tissue which is the seat of coagulation-necrosis, 
may still be recognized if only the more delicate parts have been de- 
stroyed. When all parts have been changed, the tissue may be con- 
verted into a structureless, hyaline, or granular mass, containing no nuclei 
or few. This change takes place often in the necrosis of inflamed tis- 
sues which are infiltrated with exudate. There frequently may be demon- 
strated in these necrotic areas intercellular stringy fibrin; occasionally 
in anaemic infarcts, but more often in inflammatory necroses. 
Caseation is a form of coagulation-necrosis, and is characterized by a 
cheesy appearance. The dead tissue resembles yellowish-white, hard 
cheese, or raw potato, or is white, soft, dry or moist, resembling thick 
cream. 
Typical caseation occurs most frequently in tubercles and represents 
the end of the retrogressive changes in this condition. It also occurs in 
syphilitic granulomata and in cellular tumors; inflammatory exudates 
may also become changed into cheesy masses. 
The process of caseation takes place gradually, and is to be re- 
garded as a form of necrobiosis. The cells are changed successively into 
non-nucleated, homogenous or lumpy masses, which disintegrate and 
break up into granules. At the same time there often appears between 
the cells a delicate, thread-like or hyaline substance, sometimes forming 
a framework around the cells or at other times more lumpy or granular 
—'the so-called “fibrinoid substance!’ Typical fibrin (Fig. 33, a) stain- 
ing deep blue with Weigert’s fibrin stain is often present. It may be 
assumed that both represent coagulation-products of fluid which has 
escaped from the blood-vessels. 
Through progressive cleavage and disintegration of the dead cells, 
and of the fibrinoid substance and fibrin, the tissue is ultimately reduced 
to a finely granular mass, in which no traces of the original structure can 
be perceived. 136 
THE RETROGRADE CHANGES. 
The cheesy metamorphosis of fibrino-cellular exudate, which is found 
especially in the lungs in the neighborhood of tubercles, is similarly 
brought about by disappearance of the nuclei, and the disintegration of 
cells and fibrin into a non-nucleated granular mass. 
The granules of the soft cheesy masses in tuberculous and non-tuber- 
culous foci are chiefly albumin particles, more rarely fat-droplets. The 
fate of such masses may be liquefaction and pultaceous softening, absorp- 
tion, desiccation or calcification. 
Colliquation or liquefaction-necrosis is characterized by the fact that 
the necrotic parts become dissolved in the fluids of the tissues. The 
dissolution may be accomplished by swelling and liquefaction, or by 
Fig. 33.—Fibrin-containing tubercle from the lung. (Alcohol, haematoxylin, fibrin stain.) 
a, Fibrin; b, giant-cell; c, cellular portion of the tubercle, x 300. 
breaking up of the tissue-elements, or by a combination of these processes. 
Thus, in burns of the second degree the cells of the epidermis, which 
have been killed by the heat, become dissolved in the fluid exuding from 
the papillae (Fig. 34, d, /). In the case of anaemic infarcts of the brain 
the necrotic brain-substance undergoes softening, and becomes con- 
verted into a milky, pultaceous mass and the products of destruction dis- 
integrate into smaller particles, which, either free or enclosed in cells, 
become absorbed or dissolved. In suppurative processes necrotic tissue 
is dissolved in fluids exuded from the blood-vessels. Necrosed areas 
in the mucosa of the stomach become dissolved through the digestive 
action of the gastric juices. 
Coagulation and liquefaction may follow or precede each other. For 
example, the products of coagulation may again become dissolved. In 
gangrenous blebs produced by solution of epithelial cells coagulation 
may occur, the products of which are later dissolved. Necrotic foci 
arising in the course of granulomata or other inflammations, often be- 
come liquefied. GANGRENE. 
137 
In both coagulation and liquefaction of tissues the process depends on 
the action of ferments, which are derived from living protoplasm or 
are contained in the dead tissue. The liquefaction of tissue by ferments 
is designated autolysis. The action of autolytic ferments also takes 
place in portions of tissue that have been kept outside the body in fluids 
that inhibit the growth of bacteria, and such liquefaction is attended by 
the formation of various products of decomposition. 
The changes described above as occurring in dead or dying tissues are not the 
only ones which take place during tissue-destruction. They are the chief types 
which occur in the course of relatively rapid necrosis. Many of the tissue-de- 
generations described in the following paragraphs lead, not infrequency, to death 
of tissue, and consequently must be regarded as belonging to the processes classed 
as necrobiosis. Granular, fatty, mucous, and hydropic degeneration often end in 
destruction of cells; and the same result may be reached in hyaline and amyloid 
transformation of connective-tissue, in that not only the ground-substance is per- 
manently altered, but the cells also die. 
Fig. 34.—Blister of cat’s paw, caused by hot sealing-wax. (Alcohol, carmine.) a, Horny 
layer of the epidermis; b, rete Malpighi!; c, normal papilla; d, swollen epithelial cells whose nuclei 
are in part visible, and in part have disappeared; e, epithelial cells lying between the papillae, the 
upper ones swollen and elongated, the lower ones preserved; f, total liquefaction of the epithelium; 
g, swollen cells of the interpapillary cell-masses, which have lost their nuclei; h, a similar cell-mass 
which has been completely destroyed, and raised from the basement-membrane, by the coagulated 
subepithelial exudate k; i, flattened papillary body infiltrated with cells, x 150. 
§ 50. Under gangrene may be classed those forms of necrosis in 
which tissue, partly through exposure to the air, partly through the 
agency of bacteria, suffers changes similar in appearance to those occur- 
ring in burned tissues. If necrotic tissue through exposure to air loses 
water by evaporation and becomes dry, the condition is designated dry 
gangrene (gangrcena sicca) or mummification. When the dead part 
remains moist, the terms moist gangrene (gangrcena humida) or 
sphacelus may be applied. If through the agency of bacteria there oc- 
curs foul-smelling putrefaction, the condition is known as putrid gang- 
rene (gangrcena fcctida). Development of gas-bubbles as a result of 
putrefactive changes leads to emphysematous gangrene (gangrcena 
emphysematosa). 138 
THE RETROGRADE CHANGES. 
Moist gangrene and putrid gangrene are in general identical, since 
bacteria develop only in moist tissues. Nevertheless dry gangrene is 
not infrequently putrid, since bacteria may develop in the tissue before 
drying takes place. Dry gangrene may also develop from moist gangrene, 
or through the absorption of water become changed into the latter. 
When gangrenous tissue contains a large amount of blood, it appears 
black, dark brown, or greenish-black in color, and is called black gan- 
grene. If, on the other hand, the dead tissues are anaemic, the condi- 
tion is sometimes spoken of as white gangrene, although the expression 
is often inappropriate, since there is more or less discoloration of the 
dead part. 
In gangrene of superficial parts of the body, there may be distin- 
guished, according to the temperature of the part, cold and warm gan- 
grene, the latter designation being used when the area is kept warm by the 
blood flowing through neighboring tissues. 
Gangrene may be caused by external injuries, heat, cold, corrosives, 
crushing, pressure, infection, etc., as well as by disturbances of circu- 
Fig. 35.—Dry gangrene of the toes, due to calcification, narrowing, and obliteration of their 
arteries. 
lation, characterized by interference with the arterial inflow or the 
venous exit, or both. 
Gangrene due to disturbance or arrest of the circulation occurs not 
infrequently in old people (senile gangrene), involving the extremities, 
particularly the toes, feet, and legs. It is usually of the dry variety, 
and is dependent partly on general disturbances of the circulation and 
partly on disease of the arteries of the extremities (arterial sclerosis, 
thrombosis, embolism) (Fig. 35). The dying parts appear bluish-black 
as a result of venous stasis. 
Gangrene from cold aflfects chiefly the tips of the extremities — nose, 
and ears — and is characterized by changes similar to those described 
above. 
Gangrene from heat is confined to the area directly afifected by the 
heat. 
Pressure-gangrene or decubitus {bedsore) occurs in marasmic indi- 
viduals, most frequently over the sacrum and heels, both of which are 
exposed to pressure when the individual lies on his back. The bedsore 
begins with the formation of bluish-red spots, within whose area the 
tissue dies, and through the agency of bacteria undergoes decomposi- 
tion and finally disintegrates. The gangrenous area may be of large 
extent, especially over the sacrum; the bone may be laid bare through 
destruction of the overlying soft parts. HYPOPLASIA; AGENESIA; ATROPHY. 
139 
Toxic gangrene occurs in ergot poisoning as a result of the con- 
traction of the small vessels and formation of thrombi. The tips of the 
extremities are usually affected. The prolonged application of dilute 
solutions of carbolic acid to wounds of the extremities not infrequently 
produces local death of tissues. 
Infectious gangrene occurs in the skin and subcutaneous tissue, and 
may be associated with gas-formation particularly in infections produced 
by or associated with the bacillus aerogenes capsulatus and related micro- 
organisms. Infections associated with putrid gangrene may occur in the 
internal organs, chiefly the lungs and intestines. 
So-called neuropathic gangrene occurs when a tissue affected with 
either sensory or motor paralysis is wounded or subjected to continued 
pressure. It is dependent partly on circulatory disturbances and partly on 
infection. Gangrene resulting from withdrawal of the influence of 
trophic nerves has not yet been demonstarted. Symmetrical gangrene 
which affects corresponding parts of the extremities and has been re- 
garded by many as a neuropathic disease, is probably dependent on 
changes in the blood-vessels; likewise, the perforating ulcer of the foot 
(mal perforant du pied), which begins as a callosity following me- 
chanical influences, and is characterized by an accompanying gangrene 
which rapidly penetrates into the deeper tissues, is dependent on the 
closure of an artery of the foot. 
In moist gangrene the tissues break down with varying rapidity, the 
fasciae resisting the longest. If the gangrene comes to a standstill, the 
dead tissue becomes sequestrated through a zone of demarcation — that 
is, becomes separated from the living tissue and under favorable condi- 
tions may be thrown off. In the case of necrotic portions of bonq a long 
time is required for sequestration. Extension of gangrene leads sooner 
or later to death, especially if toxic substances or bacteria are taken into 
the blood or lymph. 
There is a variety of gangrene which occurs frequently, although not exclu- 
sively, among Polish and Russian Jews, most commonly in young adults, and 
between the ages of 25 and 35 — hence the designations “ die Hebraische krankheit,” 
presenile or juvenile gangrene. Buerger, from a study of the pathological changes 
in the vessels of this disease has designated the condition thrombo-angeitis 
obliterans. The patients complain of indefinite pains in the feet, in the calf of the 
leg or in the toes, and of a sense of numbness or coldness whenever the weather 
is unfavorable. One or both feet may be markedly blanched, cold to the touch, and 
pulsation in the dorsalis pedis or posterior tibial artery may be wanting. After 
the lapse of months — sometimes years—a blister, bleb, or ulcer develops near the 
tip of one of the toes, usually the big toe, frequently under the nail, and when this 
condition ensues, local pain becomes intense. Dry gangrene of the involved toe now 
occurs and, indeed, the entire foot may share in the process of death. The exciting 
cause of the changes in the vessels is totally unknown. (Buerger, American 
Journal Medical Sciences, 1908.) 
IV. Hypoplasia, Agenesia, and Atrophy. 
§ 51. Hypoplasia may affect the body as a whole or single organs or 
parts of organs, either during intra-uterine or post-embryonal develop- 
ment. 
When the entire skeleton or the greater part of it is under-developed, 
and especially if the bones do not attain their normal length, the affected 
individual is abnormally low in stature, and is called a dwarf (Figs. 
36 and 37). The individual parts may be well proportioned (Fig. 36), or 140 
THE RETROGRADE CHANGES. 
asymmetrically developed (Fig. 37). For example, the trunk may be 
of normal size, while the extremities are short (Fig. 37) ; or both the 
trunk and the extremities may be abnormally small, while the head is of 
normal size, and consequently appears relatively large for the body. When 
the vice of development affects individual parts of the skeleton, or is 
Fig. 36.—Skeleton of a female cretin, thirty-one years of age, 118 cm. in height, with klino- 
cephalic skull. The cartilage sutures of the diaphyses of the long bones and pelvic bones still 
show; as does also the frontal suture. The individual parts of the skeleton are, on the whole, in 
the proper proportion, the upper extremities alone being relatively short. 
Fig 36. 
Fig. 37- 
Fig. 37.—Skeleton of a female dwarf of fifty-eight years of age, 117 cm. in height, with very 
short extremities, and long trunk. The cartilage sutures are still present; the articular ends of the 
bones are thick. 
more marked in certain parts than elsewhere, stunting results. For 
example, defective development of the cranium gives rise to microcephalus 
and micrencephalus; defective development of the humerus results in 
shortening of the arm; and through hypoplasia of the lateral masses of 
the sacrum the transverse diameter of the pelvis becomes diminished. 
The central nervous system and the genito-urinary tract in particular 
suffer stunting of development, although the intestines, heart, lungs, liver, ATROPHY. 
141 
etc., do not escape similar disturbances of growth. For example, the 
entire brain, or one of the hemispheres, may fail of development. The 
intestine may be represented by a thin canal or by a solid cord. The 
uterus not infrequently remains in an undeveloped state, and occasionally 
the entire generative apparatus may remain undeveloped throughout adult 
life. Marked hypoplasia of the kidney is not rare. 
The tissue composing hypoplastic organs or parts of organs, though 
of less bulk than normal, may present no other abnormalities of struc- 
ture. In certain cases hypoplasia may be associated with agenesia of 
individual parts. Thus, in hypoplasia of the ovary the development of 
Fig. 38.—(Bellevue Hospital.) Excessive atrophy of muscle tissues. 
ova and the ripening of follicles may fail; in hypoplasia of the brain there 
may occur defective development of the ganglion-cells and nerve-fibres, 
at times portions of the brain may consist of membranous masses in 
which no ganglion-cells are present. In hypoplasia of the lung there may 
be complete failure of development of the alveoli, so that the lung consists 
entirely of bronchi embedded in connective tissue. 
§ 52. Atrophy is diminution in the size of an organ due either to re- 
duction in size or disappearance of its individual elements. It may occur 
at any period of life, and is a common result of many pathological pro- 
cesses. Within certain limits it may be regarded as a physiological phe- 
nomenon, in that in old age there constantly occurs a retrograde change 
in all the organs, associated with diminution in size. Certain organs 142 
THE RETROGRADE CHANGES. 
undergo atrophy with partial or total loss of functional power be- 
fore old age, for example, the thymus, which atrophies even before the 
end of the period of growth; and the ovary, a part of whose ova are 
discharged during the period of sexual activity, the remainder being de- 
stroyed. The lymphoid tissues suffer atrophy at a comparatively early 
age, the bones and muscles at a later date. 
Atrophy of an organ is characterized chiefly by diminution in size. 
In atrophic conditions of the muscles the affected portions of the body 
become smaller, and in marked cases the extremities appear as if con- 
sisting of skin and bones. When atrophy of an organ is uniform, its 
normal shape is preserved; but if the atrophy progresses more rapidly 
in certain parts than in others, the surface may show local depressions 
and cicatricial contractions, so that, for example, the liver or kidney, may 
present a knobbed or granular appearance. When tissues which are 
undergoing atrophy are prevented from contracting, as in the case of 
the bones and lungs, the external form is preserved. In bone, the medul- 
lary spaces and Haversian canals become enlarged, and a condition re- 
Fig. 39.—Section of an atrophic muscle, from a case of progressive muscular atrophy, 
(Muller’s fluid, Bismarck brown.) a, Normal muscle-fibres; b. atrophic muscle-fibres; c, peri- 
mysium internum, the nuclei of which, at Ci, seem to be increased in number, x 200. 
suits which is known as ex centric atrophy or osteoporosis. In the lungs 
the alveoli become confluent into large air-spaces as the result of disap- 
pearance of the intervening walls. 
In atrophy of glands and muscles there frequently occurs a change 
of color, though this is of secondary importance. Either the normal 
pigment of the organ is brought out more distinctly by atrophy, or asso- 
ciated with the atrophy there is a deposit of pigment (brown or pigment 
atrophy), or the change of color may be dependent on the blood-content 
of the atrophic tissue. 
The diminution in size of atrophic organs is the result of diminution 
in size and disappearance of the histological elements composing them. 
In the majority of organs, particularly glands, muscles, and bones, the 
cells which perform the special function of the affected organ, are 
affected in atrophy to a greater degree than the connective-tissue frame- 
work. Indeed, it may be observed that the connective-tissue elements 
are preserved, or even increased in number, while the more highly special- 
ized elements have disappeared. Thus, in atrophic muscle the contractile 
substance within the sarcolemma may disappear to a great extent with- 
out the occurrence of any atrophy of the connective tissue between the 
muscle-bundles. The nuclei of the connective tissue may even be in- 
creased in number. ATROPHY. 
143 
In atrophy of the kidney the epithelial cells of the tubules (Fig-. 40, a) 
become smaller and may vanish so that the tubules collapse. Likewise, 
the epithelium of the glomeruli is lost and the capillaries are obliterated. 
The same thing occurs in simple atrophy of the liver, in that many of 
the cells of a lobule may disappear without any perceptible decrease of the 
supporting reticulum. Likewise the ganglion cells of the brain and 
spinal cord may atrophy without the neuroglia being diminished. Not 
infrequently the latter may become increased. 
In atrophy of bones the true bone-tissue becomes diminished. In 
atrophy of the bone-marrow the total mass of marrow-cells is diminished. 
The supporting cells may take up an increased amount of fat; but, on 
the other hand, the fat in the cells of the marrow may vanish, so that 
spaces filled with fluid are formed between the supporting cells. 
Atrophy may take place 
without any apparent change 
of structure in the tissue- 
elements (Fig. 39), the con- 
dition being reached through 
loss of volume of the indi- 
vidual parts. Both the cell- 
body and nucleus become 
smaller; the latter change 
may be observed particularly 
in the liver in starvation. 
This form is known as simple 
atrophy, and is to be distin- 
guished from the degenera- 
tive atrophies, in which the 
tissue-elements shozv changes 
in structure. Thus a cell 
may become granular, and 
undergo fragmentation, or 
may swell and liquefy, or 
there may be formed in the 
cell drops of fat or mucus; 
all of these changes signifying degenerative conditions of the protoplasm. 
Degenerative changes can occur at the same time in the nuclei, as shown 
by fragmentation, distorted shape, clumping of chromatin or its diffusion 
into the protoplasm, swelling and liquefaction of the nucleus. These 
processes lead ultimately to disappearance of the nucleus and destruction 
of the cell. 
According to their genesis the several forms of atrophy may be 
classed as active or passive. In the former the cell is no longer able to 
make use of the food brought to it; in the latter the food is either not 
supplied in sufficient quantity or proper form, or substances are brought 
to the cells which impair their function. Active atrophy is part of the 
involution of old age, but occurs under pathological conditions, especi- 
ally in nerves, glands, and muscles whose function is in abeyance. 
The clinician prefers another classification of atrophy; namely, senile 
atrophy, atrophy due to impaired nutrition, pressure atrophy, atrophy of 
disuse, and neuropathic atrophy. 
Senile atrophy is partly active, and partly passive, in that it is not 
simply the result of the diminishing vital energy of the cell, but also 
Fig. 40.—Senile atrophy of the kidney. (Alcohol, 
alum-carmine.) a, Normal urinary tubules; b, normal 
glomerulus; c, stroma with blood-vessels; d, atrophic 
and obliterated glomerulus; e, small artery, with thick- 
ened intima; f, atrophic and collapsed urinary tubules. 
X 200. 144 
THE RETROGRADE CHANGES. 
depends on narrowing and obliteration of the vessels conveying nourish- 
ment to the cells. It may occur in all the organs, but is often more 
marked in one than in another, notably in the bones, kidneys, liver, 
brain, and heart, all of which may undergo marked loss of volume. 
Atrophy due to impaired nutrition may result from insufficient 
supply of food to the body as a whole, or from extensive loss of fluids. 
In these cases the whole body is affected, though the fat, blood, muscles, 
and the abdominal organs suffer to a greater extent than the remaining 
tissues. Local atrophies may result from local disturbances of circula- 
tion, and are frequent sequelae of diseases of the arteries in which the 
vessel lumen is narrowed. Further, they are of frequent occurrence in 
or after inflammatory processes; in these cases the condition is not of 
the nature of simple atrophy, but of degenerative changes leading to the 
death of cells and tissues. 
Pressure-atrophy occurs when a tissue is subjected for a length of 
time to moderate pressure. It depends partly on direct injury to the 
tissues and partly on disturbance of the circulation. The most typical 
examples are atrophy of the liver caused by the pressure of the edge 
of the ribs on the organ due to tight-lacing (“corset-liver”), and the 
disappearance of bone following the pressure of an aneurism, tumor, or 
accumulation of fluid. 
Atrophy of disuse occurs in the muscles, glands, bones, ski, 1, and 
other tissues. In muscles and glands the atrophy is active, the nutritive 
processes diminishing as the result of lessened functional activity. In the 
other tissues the atrophy is largely dependent on the lowering of nutri- 
tion of the disused parts, though a change in the power of assimilation 
of the cells cannot be excluded. When the inactivity occurs during the 
period of development the condition is to be regarded as hypoplasia, 
though no sharp line can be drawn between hypoplasia and atrophy, since 
in the former there may also be disappearance of structures which had 
undergone a certain degree of development. 
Neuropathic atrophy is a result of diseased conditions of the nervous 
system. 
For example, after destruction of the anterior horns or the motor 
roots of the spinal cord, there follows atrophy of the corresponding 
nerves and muscles. After injury of peripheral nerves the skin often 
becomes atrophic. According to many authors, disease of the nerve- 
trunks of one side of the face is followed by unilateral neuropathic facial 
atrophy, but by others (Mobius) the neuropathic nature of this condition 
is contested. Unilateral affections of the brain in foetal life or during 
childhood may lead to atrophy of the opposite side of the body (con- 
genital and infantile hemiatrophy). 
V. Cloudy Swelling and Hydropic Degeneration. 
The term cloudy swelling or parenchymatous or granular degenera- 
tion is applied to that form of cell-degeneration which is characterized 
histologically by swelling and enlargement of the cells due to the for- 
mation in the protoplasm of free granules, which according to their 
microchemical properties (solubility in acetic acid, insolubility in alka- 
lies and ether) are to be regarded as albuminous bodies. The epithelial 
cells of the kidney and liver (Fig. 41), and the heart-muscle frequently 
show this degeneration, acquiring a cloudy appearance, as if covered with CLOUDY SWELLING. 
145 
dust, while at the same time their normal structure and form are lost. 
Thus, in cloudy swelling of the kidney-epithelium the rod-like markings 
of the protoplasm are lost (Fig. 42, a), as are the cell-processes projecting 
into the lumen of the tubules. The cells (b. c. d) are 
swollen, plump and granular. This change is to be 
regarded as a disorganisation of protoplasm following 
absorption of fluid, and leads to partial separation of 
the solid and liquid constituents of the protoplasm. 
At the same time the nucleus swells and undergoes 
disorganisation. 
Recovery is possible at a certain stage of the 
process, and the cells may be restored to normal. In 
other cases the cell-body is destroyed, breaking into 
granular fragments. Fatty degeneration often suc- 
ceeds cloudy swelling. 
Cloudy swelling may occur in the cells of any of the parenchymatous 
organs, as the liver, kidneys, or heart, during the course of infectious dis- 
eases, particularly scarlet fever, typhoid, smallpox, erysipelas, diphtheria, 
septicsemia, etc. The affected organs present a cloudy, often gray appear- 
ance ; in marked cases the organ may appear cooked, the blood-content is 
slight, the consistence doughy, and the details of structure are lost. 
Fig. 41.—Cloudy swell- 
ing of liver-cells (scrap- 
ing from the cut sur- 
face of the liver of a 
man dying of septi- 
caemia, examined in 
normal salt solution.) 
X 35°. 
Fig. 42.—Cloudy swelling of kidney epithelium. (Chromic acid, ammonia, glycerin.) 
a, Normal epithelium; b, beginning cloudy swelling; c, advanced stage of cloudy swelling; 
d, desquamated degenerated epithelium, x 600. 
It is not improbable that autolytic processes (see paragraph 49) play a 
role in parenchymatous degeneration (Landsteiner). Orgler regards it as auto- 
lysis accompanied by increase of the water-content. The granules which be- 
come visible and show double refraction he regards as protagon, which, during 
autolysis, is either preserved because of its slight solubility or during the course 
of the process is precipitated in the form of granules. 146 
THE RETROGRADE CHANGES. 
According to the investigations of Symmers (Jour. Exp. Med., 1907), the 
process of autolysis results in morphological changes, not only in certain fixed 
tissue cells, but in those of the blood. The changes are characterized mainly 
by solution of the hyaloplasm with exposure of the spongioplastic network and 
retention of the cell membrane, giving the cell a finely reticulated appearance. 
The effects of autolysis are particularly noticeable in the liver, where it some- 
times occurs focally, at other times over a wide distribution. Extensive auto- 
lytic degeneration of the liver not infrequently is to be observed in the toxaemias 
of pregnancy and in patients dead of uraemia. 
§ 54. Hydropic degeneration is that form frequently observed in 
cells of different kinds, whereby they become swollen through the im- 
bibition of -fluid — it is an intracellular oedema. When epithelial cells 
undergo this change the contents 
appear clear, the granules of the 
protoplasm are pressed apart by the 
fluid, often crowded into a ring at 
the periphery; the cells thus resem- 
ble plant-cells. Globules of clear 
Fig. 43.—Hydropic degeneration of muscle- 
fibres from the calf muscle in chronic oedema 
of the leg. (Flemming’s solution, safranin.) 
X 45. 
Fig. 44.—Transverse section of a muscle- 
bundle showing hydropic degeneration of its 
fibres. (Muller’s fluid, hasmatoxylin.) a, 
Muscle-fibre with small drops of fluid; b, 
muscle-fibre with large drops, x 66. 
fluid may often be formed in the cells. The nucleus swells and 
becomes changed to a bladder-like structure containing clear fluid. 
In muscles showing hydropic degeneration clear droplets of fluid 
appear between the fibrillse, pushing the latter apart (Figs. 43 and 44, 
a, b). Through the abundant formation of such drops the muscle fibres 
may acquire in places a foamy appearance (Fig. 43). At first, the muscle 
fibres between these drops remain preserved, but finally undergo frag- 
mentation and liquefaction. 
Hydropic <legeneration of cells may be the result of oedema (Figs. 
43 and 44) ; it occurs in inflammatory foci (Fig. 34) and in tumor- 
cells. In inflammation the degenerative character of the process is 
more marked than in simple oedema; and complete liquefaction of the 
cells may result. In oedema the cells, in spite of their hydropic condition, 
may remain alive for a long time. 
VI. Fat Deposit and Fatty Degeneration. 
§ 55. Fat, in a form that can be demonstrated microscopically, is 
widely distributed through the human and animal organism. It ap- 
pears most prominently in the subcutaneous and subserous tissues and 
bone-marrow; in these regions adipose tissue develops at a certain time 
during embryonal life or in childhood. Less prominent, and in part 
visible only on microscopic examination, is the fat present in various 
glands, in ganglion-cells, leucocytes, surface epithelium, duct epithe- 
lium, endothelium, etc. FATTY CHANGES. 
147 
The fat of adipose tissue occurs in the connective-tissue cells in 
which it is deposited in the form of droplets that often become con- 
fluent, so that the fully developed fat-cell appears as a spherule sur- 
rounded by a cell-membrane and containing a nucleus. In prepara- 
tions mounted in Canada balsam the fat-drop is represented by a clear 
vacuole (Fig. 46, c) the fat itself having been dissolved by the ether 
used in the process of preparation. Sudan III. and Scharlachroth stain 
fat a yellowish-red (Fig. 45), while treatment with osmic acid, which 
Fig. 45.—Adipose tissue from the panniculus of the heart. (Formalin, hasmatoxylin, and Sudan 
III.) a, Fat tissue; b, muscle; c, muscle infiltrated with fat tissue, x 40. 
is reduced by the fat, causes the fat-drops to become blackened 
Fig. 48, c). 
The fat contained in the special adipose tissues of the body is 
stored fat which the organism, in case of necessity, may use for its 
preservation, and it may be designated fat for consumption or tempo- 
rary fat. Its abundance may be regarded as an indication of the 
condition of nutrition; when this is good the adipose tissues are well 
developed, in starvation and marasmus they may vanish entirely. 
There occurs atrophy of fat-tissue, in which the fat-cells contain only 
small droplets or no fat at all, in the latter case reverting to the type 
of ordinary connective-tissue cells. The atrophic fat-lobules often take 
on a pale yellow color through the formation of pigment in the cells 
(yellow atrophy of adipose-tissue). Through the collection of fluid be- 
tween the atrophic fat-cells the fat-tissue (most frequently in the cardiac 
panniculus) becomes translucent, resembling myxomatous tissue (serous 
atrophy of adipose tissue). 
Hyperplasia of adipose tissue leads to the condition known as 
obesity, adipositas, or lipomatosis. It is dependent primarily on ex- 
cessive food-supply; but there are frequent exceptions to this rule, since 148 
THE RETROGRADE CHANGES. 
in many people an increased formation of panniculus does not take place, 
no matter how rich the food-supply. Again, an abundant deposit of fat 
occurs in some individuals when the food-supply does not exceed the 
Fig. 46.—Lipomatosis of the calf muscles, associated with atrophy. (Muller’s fluid, carmine.) 
a, Transverse section of normal fibre; 01, of atrophic fibre; 02, transverse section of sarcolemma 
tube containing disintegrated contractile substance; b, connective tissue; c, fat-tissue, x 60. 
normal. In such cases the cause of the lipomatosis must be sought in 
inability on the part of the organism to destroy the fat brought to or 
arising in it. 
Fig. 47.—Spinal muscular atrophy with lipomatosis, in ascending atrophy of the anterior 
horns of the spinal cord. (Muller’s fluid, Bismarck brown.) Section from the calf muscle. 
a, Transverse section of atrophic muscle-fibres; b, perimysium; c, fat-tissue; d, artery; e, vein. 
X 60. 
In general lipomatosis the deposit of fat takes place first in the normal 
fat-depots, and later in places that normally contain no fat, for ex- 
ample, in the connective tissue of the muscles, in the myocardium, and LIPOMATOSIS. 
149 
beneath the endocardium. Local lipomatosis may occur in various 
regions of the body, for example, in an arm, the front of the neck, nape, 
etc., and leads to deformities of the affected regions resembling elephan- 
tiasis. When occurring in circumscribed masses or nodules the con- 
Fig. 48.—Skin with sweat glands, from the sole of the foot. (Osmic acid.) a, Thick gland 
coils with fine fat droplets; b, slender gland coils without fat droplets; c, fat drops lying about 
the gland coils, x 390. 
dition is classed with the fatty tumors known as lipomata (see Lipoma). 
Local lipomatosis occurs as a disease of muscles, particularly those of 
the calves of the legs (pseudo-hypertrophic muscular paralysis) (Fig. 
46, c) through the development of adipose tissue in the perimysium 
Fig. 49.—Fatty liver from a case of pulmonary tuberculosis. (Flemming’s solution, safranin.) 
a, Central portion of the liver-lobule; b, peripheral zone containing fat; c, periportal connective 
tissue, x 30. 
internum. At the same time they become weaker, since many of the 
muscle-fibres (Fig. 46, a, a1} a2) disappear. Finally, in other cases 
adipose tissue may develop secondarily in places where other tissue has 
disappeared, for example, in muscles (Fig. 47, c) that have become 150 
THE RETROGRADE CHANGES. 
atrophic as the result of disease of the anterior horn of the spinal cord 
or in lymph-nodes that in old age have lost the greater part of their 
lymphocytes. 
The fat of the glandular organs occurs ordinarily in small, even 
minute droplets, but in the case of great abundance of fat larger 
droplets may be formed. The sebaceous, Meibomian, and lachrymal 
glands, and adrenals are normally rich in fat. It occurs to a lesser 
extent in the testicles and ovaries; still less in the salivary glands, 
thyroid and sweat glands (Fig. 48, a). The kidneys have the least 
fat-content of any of 
the glands. During the 
period of functional ac- 
tivity (testicles and ovar- 
ies) and in advanced 
age the fat-content is, 
in general, somewhat 
increased. The fat-con- 
tent of glands is but 
slightly dependent on 
the general nutrition, so 
that it does not dis- 
appear during starvation 
(Traina). This glandu- 
lar fat may be desig- 
nated permanent or 
intrinsic fat. 
The liver holds a 
special position among 
the glands so far as fat is 
concerned. As do other glands it contains a certain number of fine fat- 
droplets which do not disappear during starvation. In addition there 
also occurs a temporary storage of fat which, beginning in the periphery 
of the lobule, extends toward the centre (Fig. 49, b) ; and, finally, the 
liver may become completely changed into cells containing fat, and the 
parenchyma acquires a straw-color. 
Fatty infiltration of the liver may result from excessive food-supply, 
but is more frequently observed in marasmic individuals, particularly 
in consumptives whose panniculus is atrophic. Inability on the part of 
the liver to destroy or to give off again the fat brought to it from the 
intestine or from the fat-depots appears to be the cause of this phe- 
nomenon. 
Muscle-fibres, surface epithelium, the epithelium of different gland- 
ducts, connective-tissue cells, vascidar endothelium, leucocytes, etc., 
show a variable content of fat; but without changes that can be regarded 
as degenerative in nature. In individual cases it is evident that the fat- 
content is dependent on an abundant supply from the intestine or of 
transportation from the fat-depots, especially in those cases in which 
the leucocytes or the vascular endothelium (particularly that in the liver) 
are rich in fat. In other cases there are functional states during which 
a rich supply of fat appears (muscles). 
Fig. so.—Fat-granule cells in an anaemic area of softening 
in the brain. (Marchi’s fluid.) a, Fat-granule cells; b, blood- 
vessels. x 280. 
All animal fats are mixtures of olein, palmitin and stearin, that is, com- 
binations of oleic acid (CwHsiCh), stearic acid (CisHseOs) and palmitic acid FATTY DEGENERATION. 
151 
(C16H32O2) with the trivalent alcohol glycerin (C3H5[OH]3) to form neutral 
esters, the so-called triglycerides. Whether taken in as free fatty acids, as 
neutral fats, or as soaps, the process of absorption is always the same; they 
appear constantly in the form of neutral fats in the channels through which 
absorption takes place. 
In close relationship to the body-fats stand the lecithins (combinations of each 
single molecule of glycerin-phosphoric acid with two molecules of fatty acid and the 
complex of an ammonium base, cholin), the protagons, and the cholesterins, sub- 
stances which occur in small amount in various tissues, but abundantly in the myelin 
of the brain and peripheral nerves. Cholesterin occurs also in the bile. 
The fat contained in the human organism is derived primarily from the 
food-fat taken up in the intestine. In the early weeks of life, when the intestine 
of the nursing infant is still abnormally permeable, the finest fat-droplets are 
taken up as such and carried through the lymph-stream into the blood. In later 
life the taking up of unchanged fat through the intestinal epithelium probably 
occurs to a slight degree or not at all, that is, the fat is, for the greater part, split 
up in the intestinal canal, and through the combination of the fatty acids with 
the alkali present in the intestine there are formed soaps soluble in water, which 
are absorbed by the epithelium. Even in the intestinal epithelium these soaps 
are changed into spherules of neutral fat (just as absorbed peptone is again 
changed into albuminate). The glycerin necessary for this change is absorbed 
directly from the intestine, where it is present in a free state arising from the 
splitting of the neutral fats. 
In the entrance of the fat into the cells of the fat-depots the fat-molecule 
is again split up and then reconstructed in the cells. 
According to Arnold, the entrance of fat into the cells is associated in many 
cases with a certain activity of the plasmosomes, and is therefore connected with 
the cell-granules, which he regards as the morphological products of the function 
of the plasmosomes. In intracellular fat-formation, designated by him as granular 
fat-synthesis, which occurs in leucocytes and lymphocytes, also in endothelial, 
connective-tissue, cartilage, epithelial and gland cells, soap is taken into the cells in 
soluble form and undergoes granular change into fait. The fat-droplets appear at 
the site of the antecedent granules. 
In this manner there arise in part the so-called fat-granule cells, leucocytes 
and lymphocytes closely packed with fat-droplets, that occur in areas of necrosis 
and inflammation, particularly in the central nervous system (Fig. 50, a). 
According to Arnold the uniform size of the fat-droplets speaks in favor of such 
an origin. Such granule-cells may also be formed through phagocytosis; that is, 
the amoeboid cells may take up through their protoplasmic movements fat-droplets 
lying free in the tissues (in softening of the brain and spinal cord they arise through 
disintegration of the medullary sheaths). In the event of such occurrence, chemical 
and morphological changes in the material taken up are not excluded. 
The carbohydrates form a second source of fat-formation in the organism, 
but the chemical processes attending the formation of fat from carbohydrates have 
not been determined. It is probable that the amount of fat so formed is rela- 
tively much less than the fat taken in as such from the food. It is still a ques- 
tion as to whether fat can be formed in the body from albumin. Since many 
facts speak for the transformation in the animal body of certain groups of the 
albumin-molecule into glycogen or grape-sugar, the theoretical possibility of 
the formation of fat from albumin cannot be denied {Kraus). 
Of the fats and lecithins present in the organism, those containing oleic 
acid alone reduce osmium tetraoxide to a black osmium hydroxide, so that treat- 
ment with osmic acid or Flemming’s solution does not show the presence of 
palmitin and stearin. On the other hand, Sudan III and Scharlach-roth (pon- 
ceau) stain all the fats. 
§ 56. Fatty degeneration or fat-metamorphosis is that condition of 
the cells in zvhich fat-droplets appear in the protoplasm in such manner 
as to indicate a change in the chemico-physical cell-structure. In a part 
of the cases this change may be inferred from the appearance of the 
cells, in that fragmentation, disintegration (Fig. 51, e, /), and separation 
of the cells from their substratum may be demonstrated. 
The views of Virchow were formerly accepted, that in lipomatosis 
there occurred a deposit of fat from the blood and tissue-juices; while 152 
THE RETROGRADE CHANGES. 
fatty degeneration represented the formation of fat from the albumin 
of degenerating cells. Recent investigations make the latter view doubt- 
ful. Although the possibility of formation of fat from albumin cannot 
be denied, it has not yet been proved that this is the case in the so-called 
fatty degeneration of cells. 
In many cases what we call fatty degeneration is the expression of 
a molecular physical rearrangement of the cells, a fat-metamorphosis, in 
which the fat contained in the 
cells in a form that cannot be 
recognized microscopically is 
separated out in the form of 
visible droplets. Therefore, 
an increase in the actual fat- 
content of the cell does not 
occur in fatty degeneration. 
Renal cells that on micro- 
scopical examination show no 
fat may, nevertheless, contain 
twenty per cent of fat. 
Should degeneration occur, so 
that the fat becomes visible in 
the form of droplets, the total fat-content is not increased (Rosenfeld, 
Kraus). A process similar to that taking place in the body occurs during 
the autolysis of tissue preserved aseptically in the incubator, fat-droplets 
Fig. 51.—Fat-containing liver- 
;ells. a and b, Fat-infiltration; 
d, e, f, fatty degeneration, 
x 400. 
Fig. 52.—Fatty- 
degeneration of 
the heart-muscle, 
x 350. 
Fig. 53.—AnEemic and fatty necrosis of the myocardium 85 hours after the closure of a 
coronary artery. (Flemming’s solution, safranin.) a, Necrotic; b, fatty muscle fibres; c, con- 
nective tissue with leucocytes containing fat. x 300. 
becoming visible in such tissues (Hansen, Wentscher, Kraus, Muller, and 
others). When fat as such is not present in the cells it may arise through 
chemical decomposition of lecithin, cerebrin, and protagons (myelin) 
contained in the cells. 
A second source of fat appearing in fatty degeneration is the fat 
brought to the affected cells by the blood and tissue-juices, arising either 
from the fat contained in the food or transported from the fat-depots 
in other tissues. For example, in phosphorus-poisoning transportation 
of fat from the panniculus to the liver takes place. It is probable that FATTY DEGENERATION. 
153 
the same thing occurs in other intoxications (arsenic, alcohol, chloro- 
form, oleum pulegii). In such cases increase in the fat-content of the 
affected organ must occur, 
but this is not always the re- 
sult of synthesis of fat, that 
is, the formation of higher 
fatty acids and glycerin and 
their combination, but is a 
taking-up of fat that, either as 
such or as soaps, has been 
given over to the blood. 
In the condition which we 
call fatty degeneration, the 
fat appears usually in the 
form of fine droplets (Figs. 
52, 53, b, 54, b, and 55, b), 
but these may become con- 
fluent to form larger drops 
(Fig. 56), particularly during 
the disintegration of the cell 
(Fig. 51, /). The conditions 
under which the fat of fatty 
degeneration appears make it 
probable that the cells which 
are the seat of fatty metamorphosis are still living, but have been injured 
by external influences. In anaemic infarcts of the spleen, kidneys, and 
heart, the fatty cells (Fig. 
53, b) are found in the 
zone of transition between 
the necrotic (a) and the 
living tissue; that is, where 
the circulation of the blood 
and lymph is weak, but has 
not ceased. The appear- 
ance of fatty cells in glands 
(Fig. 51, c, d, e, /), in the 
endothelium of the blood- 
vessels, or the cells of the 
heart-muscle (Fig. 54, b) 
occurs in intoxications and 
infections as the result of 
cell-injury through toxic 
action. Chronic fatty de- 
generation of the heart- 
muscle (Fig. 55, b) is seen 
in valvular lesions, pul- 
monary emphysema, gen- 
eral anaemia; in the renal 
epithelium of consump- 
tives it occurs partly as the 
result of diminished supply 
of oxygen, and partly from the action of toxic substances. Experimental 
investigations have shown that long-continued elevation of the body 
Fig. 54.—Fatty degeneration, vacuolization, and dis- 
organization of the heart-muscle in a patient dying 
from pneumonia and nephritis. (Flemming’s, safranin.) 
a, Transverse section of normal muscle-cell; b, muscle- 
cell in a state of fatty degeneration; muscle-cells with 
vacuoles; d, disorganized cell, x 400. 
Fig. 55.—Marked fatty degeneration (chronic) of the 
heart-muscle. (Flemming’s solution, safranin.) a, Nor- 
mal muscle; b, muscle which has undergone fatty de- 
generation. x 8o. 154 
THE RETROGRADE CHANGES. 
temperature leads to fatty degeneration of different tissues (heart, 
kidneys, and liver). 
A mild grade of fatty degeneration cannot be seen with the naked 
eye. The more severe forms give an opaque yellowish color to colorless 
tissues, as, for example, the intima of blood-vesselsiand the heart-valves, 
which frequently show patches of fatty metamorphosis. The cortex of 
a kidney in a state of fatty degeneration becomes grayish or yellowish. 
In the heart-muscle the yellowish discoloration of fatty degeneration, 
particularly when the change is localized in small foci (Fig. 55, b), 
Fig. 56.—Fatty degeneration of the renal epithelium, from a case of chronic pulmonary 
tuberculosis. (Formalin, hematoxylin, Sudan III.) x 300. 
stands out prominently (“tiger-heart”). The change is best seen im- 
mediately beneath the endocardium covering the papillary muscles of the 
left ventricle. 
It is not always possible to decide whether the fat present corresponds to 
a physiological or pathological condition. We can no longer accept the view 
that fine droplets of fat in the cells signify a pathological condition, since most 
glands and other tissues, for example, muscle-fibres, contain fat-droplets under 
normal conditions. 
In fat transportation the fat may appear in the blood in the form of large 
or small droplets (lipsemia). This is most marked in traumatic lesions of adi- 
pose tissue leading to fat-embolism. Large fat-drops that remain in the ves- 
sels disappear slowly. Proliferation of the vessel-wall may occur at the site of 
the embolism, not only after the direct introduction of fat into the blood-vessels, 
but also after feeding with fat, as in the administration of cod-liver oil (Wuttig). 
If fasiting dogs are fed with mutton-tallow, there is a deposit of mutton-tallow 
in the fat depots. If they are then poisoned with phosphorus, oleum pulegii, or 
phloridzin, their livers, which show fatty degeneration as the result of the poison- 
ing, are found to contain mutton-fat in addition to the animal’s own fat (Rosen- 
feld). According to Leick and Winchler, the mutton-fat under these conditions is 
also found in the heart-muscle. In dogs fed with iodopin and afterward poisoned 
with phosphorus, the iodized fat passes into the liver. In animals devoid of adipose 
tissue no fatty degeneration occurs in the liver after poisoning with phosphorus or 
phloridzin (Rosenfeld, Fibiger). . 
In the case of aseptic autolysis of the liver outside the body Waldvogel has made 
chemical and histological investigations which seem (to show that fat and fat-like FATS; CHOLESTERIN. 
155 
products of disintegration may arise in loco; and there occurs an increase in those 
bodies which, related to albumin, have a fat-like (jecorin, lecithin, protagon) or 
fatty character (fat-acids, neutral fat). In phosphorus-poisoning (Waldvogel and 
Tintemann) protagon and jecorin appear as disintegration-products of albumin (the 
lecithin present is for the greater part transformed into substances which after 
acetone precipitation make up the residue of the substances soluble in ether). 
Similar disintegration of the albumin-molecule occurs in autolysis. 
According to Dietrich, fat does not occur in the process of autolysis. 
In certain degenerating cells doubly refractive droplets similar to fat 
are found, but they stain only slightly with osmic acid (adrenals, corpus 
luteum, etc.). They are regarded by various authors (Albrecht, Kaiser- 
ling, Orgler, etc.) as myelin, similar in character to the myelin of nerve- 
fibres. It is also probable that protagon appears in this form. Such 
droplets may be found in the autolysis of cellular tissues. 
The kidneys may contain less fat than normal and yet show much 
fat both to the naked eye and on microscopical examination, as the 
Fig. 57.—a, Cholesterin plates; b, free cluster of margarin needles; c, needles enclosed within 
fat-cells; d, grass-like bunch of margarin needles, x 300. 
result of liberation of the fixed fat in fatty degeneration. The invisible 
fat is set free and becomes visible. The condition of fatty degenera- 
tion may be defined, therefore, as an infiltration of fat from outside into 
cells degenerating under the influence of poisons or other injurious 
agents {liver, heart-muscle, pancreas) or as a setting free of the invisible 
intracellular fat through autolysis {kidneys, spleen, muscle). 
§ 57. The fats in the human body consist almost entirely of a 
mixture of the glycerin-esters of oleic, palmitic, and stearic acids which 
are designated olein, palmitin, and stearin. The first is fluid at ordinary 
temperatures, the second melts at 46°, the third at 53° C. Since the 
body-fats contain varying proportions of olein, palmitin, and stearin, 
they vary in consistence and melting point. If after death the tissues of 
the body are cooled below the melting-point of the contained fat, the 
stearin and palmitin separate and form stellate or feathery needles 
(Fig. 57, b, c, d), which are commonly called margarin needles, and 
are found sometimes in fat-cells, at other times free. 
Cholesterin occurs in the form of delicate rhombic plates (Fig. 57, 
a), the edges and corners of which are often notched. These crystals 
may be found wherever there are masses of detritus containing fat, aris- 156 
THE RETROGRADE CHANGES. 
ing from degenerating cells or extravasations of blood, as in collections 
of fluid in the tunica vaginalis testis, in dilated sebaceous glands, or in 
softened areas in the wall of diseased vessels (aorta, iliacs, etc.). 
When the substance in which the cholesterin plates are formed is fluid, 
they may be visible to the naked eye as glistening scales. 
Cholesterin (C27H440) is a constituent of bile, and is furnished by 
the mucous membrane of the gall-bladder and bile-ducts, and held in 
solution by the bile salts and soaps. It is also found in the medulla of 
nerve-fibres, and in small amounts in the blood, where it is held in 
solution by fats and soaps. According to Burchard traces of cholesterin 
are found in all the organs. 
Cholesterin is insoluble in water, dilute acids, caustic alkalies, and 
cold alcohol; it is soluble in boiling alcohol, ether, choloroform, and 
benzol. 
When treated with a mixture of five parts of concentrated sulphuric 
acid and one part of water the edges of cholesterin crystals take on a 
carmine-red color, which gradually passes into violet. Sulphuric acid 
and water in the proportions of three to one give a violet color to the 
edges of the crystals. Concentrated sulphuric acid containing a trace 
of iodine colors the crystals violet, blue, green, and red. 
The origin of cholesterin is not known. It is probable that it is an 
intermediate product in the decomposition of albumin, since it is found 
in those pathological conditions in which albuminous substances are in 
process of disintegration. 
Literature. 
(Cholesterin.) 
Rosenbloom: Arch. Int. Med., 1913, 12, 395. 
VII. The Deposit of Glycogen. 
§ 58. Glycogen (C6H10Or,)n is a carbohydrate which is readily con- 
vertible into sugar; and in the body is formed chiefly from the carbohy- 
drates of the food. 
In the tissues of the body, glycogen is found as a hyaline substance, 
most often in the cells, but occasionally in the tissue-spaces. It usually 
occurs in the form of spherules or lumps of different sizes. In the cells 
these spherules are most frequently found in the neighborhood of the 
nucleus. 
Glycogen is soluble in water, but the solubility of that found in dif- 
ferent tissues varies (Langhans) ; that found in the liver, kidneys, mus- 
cles, and pus-corpusles is more easily soluble than that of cartilage- 
cells and surface epithelium. Fixation of the tissue in alcohol renders 
the glycogen less soluble in water. After death the glycogen of the liver 
is quickly converted into sugar through the action of a diastatic ferment. 
Glycogen becomes brownish-red when treated with iodine. By the 
method of Best, glycogen is stained red with carmine (Fig. 58, b, c). 
Glycogen is present in almost all the tissues of the embryo, in the 
foetal membranes at an early period of development; and in the adult 
body in the liver-cells, muscles, heart, cartilage, in the epithelium of 
various organs, in the leucocytes, and in the blood-serum (Gabritschew- GLYCOGEN. 
157 
ski). During starvation the glycogen of the liver is diminished, and in 
other pathological conditions may disappear. 
Glycogen appears in increased amount, particularly in diabetes, in 
the blood and kidneys. The epithelium of the renal tubules contains 
numbers of small drops (Fig. 58, b), and large drops (c). Since this 
deposit leads to destruction of cells, the condition may be designated 
glycogen degeneration. 
Glycogen also occurs in inflammatory foci (Gierke), usually in the 
polynuclear leucocytes, but also in the so-called epithelioid cells, fibro- 
Fig. 58.—Glycogen degeneration of the renal epithelium in a case of diabetes. (Compare 
Gierke, 1. c.) a, Normal tubules; b, epithelium with early stage of glycogen deposit; c, advanced 
glycogen deposit with epithelial destruction, x 300. 
blasts, and the giant-cells developing from these, and in the tissue border- 
ing on the inflammatory area. Glycogen is also found in many tumors, 
carcinomata and sarcomata. 
It is difficult to determine the significance of the glycogen appearing in 
pathological conditions. Since glycogen is abundant in embryonal tissues and 
in quickly growing tumors, Brault is of the opinion that its appearance is a sign of 
increased proliferative cell activity; but the presence of glycogen in large amounts 
in pus-cells does not agree with this theory. Moreover, in tumors it is not found 
in the regions of most active cell proliferation. According to Gierke, glycogen 
appears by preference in those tissues deprived of circulation. A certain parallel 
exists between the occurrence of fatty degeneration and glycogen deposit. Both 
changes are found, for example, in inflammatory foci and at the edge of necrotic 
areas. In both cases degenerating cells are present that are able to take up both fat 
and glycogen, but can no longer change them. 
According to Wolff, the leucocytes in normal blood contain glycogen, but this 
glycogen is easily soluble, and therefore difficult to demonstrate. In many inflam- 
matory exudates the glycogen of the leucocytes becomes less soluble and can be 
more easily demonstrated. 
The iodophile hyaline substance contained in the tissues is not a pure glycogen, 
but is most probably a combination of glycogen with an albumin-like substance. 158 
THE RETROGRADE CHANGES. 
To avoid the solution in water of glycogen in fresh preparations, a syrupy solution 
of iodine in gum (Ehrlich) or iodine-glycerin (Barfurth) may be used. Sections 
of tissues hardened in alcohol are treated (Langhans) with a dilute tincture of 
iodine (1 part tincture iodine to 4 parts absolute alcohol), and cleared in oleum 
origani in which the reaction is preserved for a long time. The reaction is also 
preserved in hard Canada balsam. For the staining of glycogen with carmine, Best 
gives the following method: the sections are first stained with haimatoxylin and 
then for three-fourths to one hour in a mixture of two parts of a solution of car- 
mine (carmine 1.0 grm., ammonium chlorate 2.0 grms., lithium carbonate 0.5 grm., 
a,q. dest. 50 grms., brought to a boiling-point, after which there is added 20 c.c. of 
liq. ammon. caust.), 3 parts of liq. am. caust. and 6 parts of methyl alcohol. They 
are decolorized for a few minutes in a mixture of 2 parts methyl alcohol, 4 parts 
absolute alcohol, and 5 parts water, and mounted in Canada balsam. 
Literature. 
{Glycogen.) 
Barfurth: Histochem. Untersuch. iiber das Glykogen. Arch. f. mikr. Anat., 25 
Bd., 1885. 
Best: Ueber Glykogen, inspes. bei Entziindung. Beitr. v. Ziegler, xxxiii., 1903. 
Brault: Glycogenese dans les tumeurs. Arch, des sc. med., 1896; La production 
du glycogene dans les tissus qui avoisinent. Arch. gen. de med., 1899; 
Le pronostic des tumeurs. L’ceuvre med.-chir., 1899. 
Ehrlich: Glykogen im diabetischen u. im norm. Organismus. Zeit. f. klin. Med., 
vi., 1883. 
Fichera: Verteilung der Glykogen bei Glykosurie. Beitr. v. Ziegler, xxxvi., 
1904 (Lit.); 
Gabritschewski: Glykogenreaction im Blute. Arch. f. exp. Path., 28 Bd., 1891. 
Gierke: Glykogen in d. Morphologie d. Zellstoffwechsels. B. v. Ziegler, xxxvii., 
1905. 
Langhans: Glykogen in pathol. Neubildungen u. Eihauten. Virch. Arch., 120 
Bd., 1890. 
Pfliiger: Glykogen. Pfliigers Arch., 96 Bd., 1903 (Lit.). 
Reich: Glykogen Reaktion des Blutes. Beitr. v. Bruns, 42 Bd., 1904 (Lit.). 
Wolff: Zur Los. d. Glykogen.problems. Z. f. klin. Med., 51 Bd., 1904. 
VIII. Mucous Degeneration. 
§ 59. Mucous degeneration has its physiological prototype in the 
production of mucus by the mucous membranes and mucous glands, and 
in the formation of mucus in the connective tissue of the umbilical cord, 
tendons, bursse, and synovial membranes. In the umbilical cord the 
mucus occurs as a jelly-like matrix; in the joints, bursas, and tendon- 
sheaths it forms a clear, stringy fluid. 
In the epithelium of the mucous membranes the mucus appears first 
in the goblet-cells (Fig. 59, a), forming a clear substance which stains 
with haematoxylin. In mucous glands, during the process of mucus 
formation, the epithelial cells swell, their central portions become clear, 
and the granules of the protoplasm are reduced to small groups or 
strands. The so-called mucous corpuscles of the salivary secretion, 
which are characterized by glassy, transparent contents and vibrating 
protoplasmic granules, are round cells which have undergone mucous 
degeneration. 
The mucus formed from the protoplasm of the cells may be discharged, 
and the cells remain intact, or they may be destroyed. 
Mucus is produced in the same way under pathological conditions as 
under normal (Fig. 59, a). In catarrh of the mucous membranes there 
is increased formation of mucus by the cells of the superficial epithelium 
as well as those of the glands. In mucous membranes covered with MUCOID DEGENERATION. 
159 
cylindrical cells the number of goblet-cells is increased, and in the secre- 
tion there are found cells which have undergone complete mucous degen- 
eration — that is, they have been converted into glassy masses enclosing 
few granules. Other cells contain mucus 
in the form of drops of varying size. 
The epithelium of diseased tissues may 
also undergo mucous degeneration, in a 
manner similar to that occuri ing in normal 
tissues. Thus the epithelial lining of cysts 
of the ovary and of intestinal tumors may 
often contain numerous goblet-cells (Fig. 
60, a), and cells which have undergone total 
mucous degeneration (b). In the so-called 
gelatinous or mucoid carcinoma (colloid 
carcinoma) a large part of the epithelial 
cells suffers mucous metamorphosis. 
Of the connective tissues, which may 
suffer mucous degeneration and acquire a 
gelatinous, transparent appearance, may be 
mentioned fibrous connective tissue, carti- 
lage, bone, adipose tissue, bone-marrow. 
In these tissues it is chiefly the ground- 
substance (Fig. 61, b) which undergoes 
mucous change and is converted into a 
homogeneous, structureless mass. The cells 
themselves may remain unchanged, or may 
become fatty, or even undergo mucous de- 
generation. In the last event the entire 
tissue ultimately forms a hyaline mass, in 
which only scattered fibres of connective 
tissue, or single cells or groups of cells are 
left to suggest the original tissue. 
The stringy, or gelatinous material, which results from mucous de- 
generation, does not represent a single chemical substance; in it there 
Fig. 59. — Formation of mucus 
within the epithelial cells of an 
adenomatous pclyp of the small in- 
testine. (Alcohol, hsematoxylin.) 
a, Epithelium with dark-stained 
(hsematoxylin) drops of mucus 
within the cells; b, free mucus; c, 
leucocytes in the epithelium, x 300. 
Fig. 60.—Epithelial cells which have undergone mucous degeneration, from a cystadenoma of 
the ovary, a, Cells showing slight change; b, cells showing marked degree of mucous change, 
x 400. 
Fig. 61.—Mucous degeneration of the connective tissue of the aortic valves (osmic acid, 
glycerin), a, Fibrous tissue; b, myxomatous tissue. X 350. 
Fig. 60. 
Fig. 61. 
may be found different varieties of mucins as well as of pseudomucins. 
The mucins (submaxillary, intestinal, and tendon mucin) are 
nitrogenous substances resembling albumin. They dissolve or swell in 
water forming a mucoid fluid, from which they may be precipitated in 160 
THE RETROGRADE CHANGES. 
a stringy form by means of alcohol or acetic acid; but differ from the 
true albumins in the fact that the precipitate is not redissolved in an 
excess of the acid. The precipitated mucins are soluble in neutral salt- 
solutions, caustic alkalies, and alkaline carbonates; and are gradually 
converted into alkali-albuminates in case of solution by the last named. 
All mucins contain nitrogen and sulphur; their content in carbon, 
oxygen, nitrogen, and sulphur varies in the different forms. 
Pseudomucin also dissolves in water, forming a gelatinous fluid, 
from which it may be precipitated in stringy masses by alcohol. The 
precipitate redissolves in water. Solutions of pseudomucin are not pre- 
cipitated by acetic acid. 
Pseudomucin is found particularly in ovarian cystomata, and is the 
cause of the gelatinous character of the cyst-contents. It is produced 
by the epithelium of these tumors (Fig. 60) ; and in its formation the 
same changes take place in the cells, as in the formation of mucin from 
epithelium. In all probability the mucous substance present in gelat- 
inous carcinomata is a body closely related to pseudomucin or metalbu- 
min — that is, there are different varieties of pseudomucin (Pfan- 
nenstiel), of which the two mentioned are examples. 
IX. Formation of Epithelial Colloid and Epithelial Hyaline 
Concretions. 
§ 60. The epithelial formation of colloid is a process closely related 
to the epithelial production of mucus; it consists partly in secretion of 
colloid by gland-cells, and partly in conversion of cells into colloid. 
Fig. 62. 
Fig. 63. 
Fig. 62.—Colloid in enlarged thyroid gland. (Alcohol, haematoxylin.) a, Follicle filled with 
cells; b, follicle showing lumen; c, masses of colloid; d, capillary; e, connective-tissue septum with 
artery, x 60. 
Fig. 63.—Secretion of colloid in the thyroid. (After Bozzi.) a, Colloid; b, secreting cells 
with granules. 
Physiologically, colloid is found in the thyroid (Fig. 63), where it 
appears in the form of hyaline, rather firm, colorless, or faintly broivn- 
ish, jelly-like masses, which fill the vesicles, but from these may extend 
into the lymph-vessels of the thyroid. Pathological collections of colloid 
occur both in residual thyroid tissue and in newly-formed glandular- 
tissue of pathological nature. The accumulation causes a more or less 
marked distention of the vesicles, and leads to enlargement of the gland, 
known as colloid goitre. HYALIN. 
161 
The secretion of colloid is characterized by the formation of homo- 
geneous granules and spherules in that portion of the epithelial cells 
next to the lumen of the vesicle (Fig. 63). Some of the cells may be 
completely filled with these granules. In excessive and atypical forma- 
tion desquamated cells may 
become converted into hy- 
aline colloid. 
The colloid of the thy- 
roid is found on micro- 
scopical examination to be 
homogeneous; and because 
of its physical properties it 
may be designated epi- 
thelial hyalin. As a rule 
it incloses no cellular ele- 
ments, although degenerat- 
ing cells may be found in 
it. Alcohol and acetic acid 
cause no clouding, or pre- 
cipitation in the form of 
threads, as happens in the case of mucin when so treated. By Van 
Gieson’s method colloid is stained orange-red, while the connective tissue 
takes a fuchsin-red. It must be noted that the contents of the thyroid 
follicles, which are designated colloid, are not always of the same char- 
acter. At one time the substance is firm, at another soft or even fluid, 
or at least is readily soluble in water. In preparations fixed in alcohol 
granulation or cleav- 
age may be caused 
by contraction; 
moreover, the stain- 
ing reactions are not 
always the same. 
The chemical 
nature of the thy- 
roid colloid is not 
fully known, and it 
is probable that the 
contents of the folli- 
cles are of variable 
composition. It is 
most probably an 
albuminoid body 
which is combined 
with iodothyrin, the 
active principle of 
the thyroid gland. 
Epithelial hyalin 
is also found in the 
glandular elements of the hypophysis cerebri, in the tubules of diseased 
kidneys (Fig. 64), in the prostate (Fig. 66, d), in cysts of the paro- 
varium (Fig. 65, d), in the glands of the stomach, and more rarely in 
other glands. In the last-named organs the hyalin occurs in the form of 
a uniformly homogeneous mass completely filling the gland-lumen, or as 
Fig. 64.—Dilated urinary tubules filled with colloid. 
(Muller’s fluid, hsematoxylin, and eosin.) x 250. 
Fig. 6s.—Colloid concretions in the cystic dilated tubules of 
the parovarium. (Formalin, Van Gienon’s stain.) _ a, b, Gland- 
tubules of the parovarium; c, cysts containing colloid concretions 
(d). x 8o. 162 
THE RETROGRADE CHANGES. 
hyaline, in part laminated concretions (Fig. 65, d, and 66, d) of more or 
less firm consistence. 
It must not be assumed that the last-named formations are identical 
in their chemical composition with thyroid colloid. The only thing 
which they possess in common is this: they both represent transformed 
protoplasm of gland-cells — a substance which is hyaline, possesses a 
certain firmness, and does not react to chemical reagents in the same 
manner as does mucin. These concretions may also undergo changes 
which necessitate, on their part, a different behavior toward micro- 
chemical reactions. This is particularly true of the prostatic concre- 
Fig. 66.—Section from a hypertrophic prostate with concretions. (Muller’s fluid, haematoxylin, 
and eosin.) a, Stroma; b, glands; c, dilated glands; d, concretions, x 45. 
tions, which not infrequently show, when treated with iodine, a reaction 
that has been taken as evidence that they are composed of amyloid ma- 
terial (see § 63). It may be proved, both in the case of prostatic con- 
cretions and of renal colloid, that they represent cell-material which has 
become changed into hyaline substance. In the case of renal colloid, 
however, it is only under special conditions that the participation in its 
formation of albumin derived from the glomeruli may be excluded. 
Colloid is a collective term which is applied to a variety of formations that pos- 
sess certain physical attributes in common. There is great difference of opinion 
among authors as to the application of the term. Under colloid degeneration, 
for example, von Recklinghausen places mucous, amyloid, and hyaline degenerations; 
including under the last-named epithelial colloid-formation, hyaline degeneration 
of connective tissue, as well as hyaline coagulation-necroses and hyaline thrombi. 
Marcliand gives the term a more limited application, but includes under colloid 
certain forms of epithelial mucin-formation (particularly in tumors), and also 
hyaline formations in connective tissue. Inasmuch as colloid is not a chemical 
entity, and as its staining-reactions do not differentiate it from other hyaline sub- 
stances, Ziegler thought it expedient to apply the term only to those hyaline 
products of epithelium which do not possess the characteristics of mucin. He, 
therefore, also classified as colloid those epithelial concretions which on account 
of their reaction with iodine (brown or blue color when treated with dilute iodine 
solutions) have hitherto been regarded as amyloid bodies If objection is made 
to the classification of these formations as colloid, they may be placed under the CORNIFICATION. 
163 
heading of epithelial hyalin. (Ziegler’s application of the term colloid has been 
respected in the present revision.) 
Hyaline spherules have been described by Russell and others, particularly in 
cancer cells, and, at one time, were regarded in certain quarters, as etiologically 
related to cancer. It is now generally believed that these so-called “ fuchsin bodies ” 
represent phagocytised and hyalinised red blood cells. They occur in a wide variety 
of conditions and are noticably frequent in the mucosa of the stomach in pernicious 
anemia. 
In certain infections, notably typhoid fever and influenza, the lower end of the 
rectus muscles not infrequently shows changes characterized by hyalinization, the 
areas appearing smooth, opaque and grayish pink in color. On microscopic ex- 
amination, it is found that the muscle fibres are swollen, opaque and glassy (Zen- 
ker’s degeneration.) In the recently prevailing pandemic of influenza, this variety 
of degeneration was encountered in the rectus muscles in a considerable proportion 
of all cases examined at autopsy. Rupture of the hyalinized muscle fibres occa- 
sionally occurred with the production of extensive haemorrhage into the sheath and 
mechanical disintegration of the remaining muscle fibres. In still other cases, 
hyaline degeneration and haemorrhage were followed by secondary infection and 
abscess formation. 
Literature. 
{Colloid.) 
Pratt: Goitre. Ref. Handb. of Med. Sc., 1902. 
Russel: Characteristic Organism of Cancer. Brit. Med. Journ., ii., 1890. 
X. The Pathological Cornification of Epithelium. 
§ 61. Cornification of surface epithelium is a physiological process, 
characterized by the fact that the cells in the outer strata of the prickle 
layer of the stratum germinativum undergo horny change. This corni- 
fication takes place first at the periphery of the cells and in the bridge- 
like processes binding the cells together, at the same time the inner por- 
tions of the cell and the nucleus shrink, so that the cells become changed 
into scales. This horny substance or keratin is a modified albuminoid 
body of homogeneous composition, and is capable of resisting digestion by 
the gastric or pancreatic juices. 
As accompaniments of cornification there appear in the cells of the 
prickle layer hyaline granules and spherules resembling colloid, which 
stain intensely with nuclear stains and are known as keratohyalin. In 
those areas of the skin possessing a thick horny layer, there is formed 
a stratum of keratohyalin-containing cells; this is known as the stratum 
grannlosum. In those places where the horny layer is thin, the stratum 
granulosum is imperfectly developed and exhibits breaks of continuity. 
Pathological cornification may occur as a wide-spread or localized 
increase of the horny layer, resulting in hypertrophy of the epidermis 
(see Chapter VI., § 76), or hyperkeratosis. This phenomenon may be 
primary — that is, due to causes inherent in the skin (ichthyosis, lichen 
pilaris)—or acquired as the result of external influences, mechanical 
lesions (callosities, corns), infections and inflammations. Further, there 
may occur disturbances in the process of cornification of the skin, so 
that certain pathological manifestations recognizable by the naked eye 
make their appearance, such as desquamation of the skin. Such changes 
are included under the term parakeratoses. They occur especially as 
sequelae or concomitant phenomena of infections of the epidermis, and 
of inflammations of the corium and papillary body, sometimes without 
any recognizable cause; and in these cases either the process of cornifica- 
tion or of the formation of keratohyalin, or both, is disturbed. 164 
THE RETROGRADE CHANGES. 
Finally, pathological cornification often occurs in regions where nor- 
mally it either does not occur at all or but to a slight extent. In the skin 
the cornification may extend to the ducts of the sebaceous glands and to 
the hair-follicles (ichthyosis) or to the sweat-glands (porokeratosis). 
Further, pathological cornification occurs not infrequently in the mucous 
membrane of the mouth, giving rise to white thickenings of the epithe- 
lium or to hair-like formations (hairy tongue). Horny change may be 
observed also in the mucous membrane of the middle ear, in the mastoid 
cells, in the descending urinary passages, and in these places it may lead 
to the formation of shining white scales (formation of cholesteatomata). 
Cornification of cancer cells is very frequently seen, particularly in 
cancers of the skin, in which the horny scales are found usually in the 
form of round masses resembling onions or pearls. Similar horny prod- 
ucts are also found in cholesteatomata of the pia and brain. 
The pathological formation of horny substance in the mucous mem- 
branes or in tumors takes place either simply through cornification of the 
cell-membranes with contraction of the cell, or it may be combined with 
the formation of keratohyalin as in the case of typical cornification. 
The formation of keratohyalin and the cornification of epithelial cells 
often are irregularly distributed, particularly in cancers. 
XI. Amyloid Degeneration and the Amyloid Concretions. 
§ 62. Amyloid degeneration is characterized primarily by the de- 
posit of an albuminoid substance (amyloid) in the connective tissues 
of blood vessels, so that the involved organ increases in bulk and ac- 
quires a glassy, homogeneous appearance. The degeneration may occur 
in almost all the organs of the body; but is especially frequent in the 
spleen, liver, kidneys, intestine, stomach, adrenals, pancreas, and lymph 
nodes. It is rarely observed in adipose tissue, thyroid gland, aorta, 
heart, muscles, ovaries, uterus, and urinary passages. 
Extensive deposits of amyloid may be recognized by the naked eye, 
as the affected parts present a translucent appearance resembling bacon 
(lardaceous degeneration). 
In the spleen the deposit of amyloid occurs first in the walls of the 
blood vessels of the lymphoid follicles, and the follicles finally are con- 
verted into homogeneous, translucent bodies (Fig. 67, b) resembling 
grains of boiled sago — this form of amyloid spleen is known as sago 
spleen. When the amyloid change occurs throughout the spleen-pulp 
it may be recognized on the cut surface as more or less distinct spots or 
streaks. Ultimately the greater part of the substance of the spleen may 
be replaced by amyloid material. The spleen is thus enlarged, its con- 
sistence becomes hard, and the organ may finally be transformed into 
a bacon-like substance (lardaceous spleen). 
The liver, in well-marked amyloid degeneration, is increased in size 
and consistence. On section, the liver-tissue is found to be replaced to 
a greater or less extent by translucent, lardaceous masses, between which 
the remaining liver cells appear brownish or yellowish from abundance 
of contained fat. 
The kidney, in cases of extensive amyloid change, is likewise enlarged 
and hardened, and on section shows hyaline, lardaceous spots and streaks 
of firm consistence. More often the kidney is normal in size or only 
.slightly enlarged, but increased in consistence, while in the cortex the AMYLOID. 
165 
presence of amyloid material is revealed by minute waxy, translucent 
spots corresponding to infiltrated glomeruli. In order to bring these 
out it may be necessary to treat the tissue with iodine. In still other 
instances the amyloid is apparent only on microscopic examination. 
In intestine and lymph nodes the degeneration usually cannot be 
recognized without the aid of the microscope and chemical reagents; 
and the same is true in regard to the other organs which are more 
rarely affected, such as adipose tissue, heart-muscle, the great blood- 
vessels, the thyroid gland, etc. 
The substance which is deposited in amyloid degeneration forms 
Fig. 67.—Amyloid degeneration of the splenic follicles and neighboring tissue. (Muller’s 
fluid, hxmatoxylin, and eosin.) a, Transverse section of splenic artery; b, amyloid areas; c, pulp; 
d, trabeculae, x 30. 
shining, homogeneous masses, which exhibit a characteristic reaction 
with iodine as well as with various aniline dyes. Iodine dissolved in 
water, or better in a solution of potassium iodide, and poured over the 
affected tissue, stains the amyloid substance dark brownish-red (mahog- 
any brown). In thin sections, under the microscope, the amyloid appears 
bright brown-red (Fig. 68, b) while the remaining tissue is a straw- 
yellow color. 
In marked amyloid degeneration, when the tissues are of wooden 
hardness, the iodine reaction sometimes gives a blue or green color. Prep- 
arations which have been changed to mahogany brown through the 
action of iodine become still deeper brown when treated with dilute sul- 
phuric acid or with a solution of zinc chloride, or they may become 
bright red, violet, blue, or green. This reaction is, however, imperfect 
in the majority of cases. 
Methyl violet stains amyloid ruby red (Fig. 69, a, b), while the nor- 
mal tissue takes a blue or dark blue-violet. 
Because of the peculiar reaction with iodine, Virchow was led to-re- 
gard the amyloid substance as a non-nitrogenous body related to cellu- 166 
THE RETROGRADE CHANGES. 
lose or starch, inasmuch as cellulose when treated with iodine and con- 
centrated sulphuric acid becomes bright blue, and starch similarly 
treated gives an ultramarine color. Virchow accordingly gave the name 
amyloid to the newly discovered substance. Several years later Fried- 
reich and Kekule showed that amyloid is a nitrogenous body of albu- 
minous nature. According to the investigations of Ivrawkow amyloid 
is a firm combination of chondroitin-sulphuric acid with albumin. 
The reactions of amyloid enable us to detect its presence in the tis- 
sues when it is present in such small amounts as to be otherwise invisible. 
In the microscopic examination of fresh preparations care should be 
Fig. 68.—Section from an amyloid liver, treated with iodine solution, x 35. 
taken to wash out the blood from the tissue, since the color resulting 
from the combination of blood and iodine may be deceptive. 
Amyloid is resistant to acids and alkalies. Alcohol and chromic acid 
do not affect it; it is also resistant to putrefactive changes. 
Amyloid is deposited in the ground-substance of the connective tis- 
sue of blood-vessels, especially in the walls of the small vessels. Living 
cells are not affected. In the connective tissue the amyloid substance 
appears first between the fibrillse. 
Amyloid degeneration as a rule is associated with diseases which are 
of hopeless chronicity and are characterized by the long-continued drain 
of albuminous elements from the blood and, in many instances, by the 
destruction of bone and cartilage. The condition is by no means as 
common now as formerly, since improved methods of treatment have 
tended to modify those diseases with which amyloid is most frequently 
associated. In 5,900 autopsies performed at Bellevue Hospital, amyloid 
degeneration occurred in 27 cases (0.5 per cent.) ; in 17 cases it was 
associated with ulcerative tuberculosis of the lungs, and in 10 of these AMYLOID. 
167 
there were tuberculous ulcers of the intestine; in 6 cases amyloid was 
associated with ulcerative syphilides; in 2 cases with chronic suppurative 
pyelonephrosis; in one case with ulcerative carcinoma of the stomach; 
in another with chronic pyogenic osteomyelitis. The order of frequency 
with which the organs were involved was as follows: Spleen 23 times; 
liver 18; kidney 17; adrenals 7; gut, lymph nodes and heart once each. 
In the acini of the liver the amyloid is found along the capillaries. 
The endothelium (Fig. 70, c) is covered on its outer side by a thick layer 
of a homogeneous, glassy substance, which may be broken up through 
numerous clefts into lumpy masses (c) of amyloid material. The liver- 
Fig. 69.—Amyloid degeneration ot the splenic follicles and pulp. (Alcohol, methyl violet, 
hydrochloric acid.) a, Follicle showing marked degeneration; b, pulp showing beginning degenera- 
tion. x 300. 
cells between the amyloid masses are either intact (a) or compressed (b), 
and atrophic, or may have disappeared. They often contain fat. The 
afferent blood-vessels of the liver, particularly the media of the arteries, 
may also show amyloid deposits. 
In the kidneys (Fig. 71) the amyloid is found particularly in the 
vessel-walls. The capillaries of the glomeruli (&) may be thickened and 
homogeneous; likewise the arteries (i), the veins, and the capillaries (k) 
of other parts of the renal parenchyma may show amyloid deposits. In 
the intestinal mucosa the deposit is also found in the walls of the blood- 
vessels. 
In fat-tissue, which is occasionally extensively involved, the amyloid 
substance is found in the vessel-walls, and in the connective tissue, and 
the membranous sheath of the fat-cells may be converted into a hyaline 
mass. In the spleen the connective-tissue trabeoulse (Fig. 69, a, b) and 
vessel-walls are especially likely to be affected, and may suffer marked 
thickening. In striped muscle the perimysium internum and the sarco- 
lemma are involved. In glandular organs possessing a tunica propria, for 
example, the mucous glands and kidneys, this membrane may become 
greatly thickened. 
The effects of amyloid degeneration on the functions of the affected 
organ are indicated by the degenerative and atrophic alterations in the 168 
THE RETROGRADE CHANGES. 
cells of the parenchyma. The connective tissue itself is permanently 
changed; the insoluble amyloid is never removed from it. 
The deposit of amyloid substance in the blood-vessels leads to 
marked thickening of their walls, and to narrowing or even obliteration 
of their lumina (Fig. 71, b), and in this way to permanent disturbance 
of circulation. The amyloid masses may compress neighboring epithelial 
structures (Fig. 70) and cause them to atrophy. Often there is asso- 
ciated fatty degeneration of the epithelium (Fig. 71, e, /), particularly in 
the kidneys; this change is not to be referred wholly to the disturbances 
of circulation caused by the amyloid deposit. It is more likely that the 
Fig. 70.—Amyloid degeneration of the liver. (Alcohol, Van Gieson’s.) a, Liver-cells, in part 
containing fat; b, compressed liver-cells; c, amyloid, x 240. 
fatty degeneration, at least in part, is a pathological process running 
parallel with the amyloid disease, and caused by the same conditions pro- 
ducing the latter. Consequently, in some cases the amyloid change may 
be slight, while the fatty degeneration is marked. 
In the spleen and lymph nodes the lymphoid cells lying in the meshes 
of the thickened reticulum disappear as the result of atrophy. In muscles 
the contractile substance diminishes in proportion to the increase of the 
amyloid deposit in the intervening connective tissue. 
Amyloid deposit is usually a sequel of cachexia due to chronic ulcer- 
ative tuberculosis of different organs, chronic suppuration (for example, 
of the bones), syphilis or chronic dysentery. In the cachexia of carci- 
noma it is but rarely observed. In rare cases the degeneration occurs 
without being associated with any of the above-mentioned diseases. 
According to investigations by Czerny, Krawkow, Lubarsch, David- 
sohn, Maximow, Nowak, Petrone, and Schepilewsky amyloid may be 
produced experimentally in the spleen, liver, kidneys, and intestines of 
various animals, rabbits, chickens, doves, mice, and dogs, through the 
production of suppurations lasting several weeks. Amyloid may de- 
velop also in horses that are inoculated with diphtheria bacilli. Suppura- 
tive processes caused by staphylococci and oil of turpentine appear in AMYLOID. 
169 
particular to favor the formation of amyloid. In a number of cases amy- 
loid was also successfully produced through injections of decomposed 
bouillon, dead cultures of staphylococci, rennet-ferment, and pancreatin 
(Schepilewsky), when the inflammation produced by these agencies ran 
a somewhat chronic course. Krawkow observed the beginning of amy- 
loid formation after three days, Nowak after eight days. 
The origin of the amyloid substance has not been definitely deter- 
mined. The results of experimental investigation vary greatly, the de- 
generation often being absent in chronic suppuration (particularly in 
dogs). It is probable that the blood brings to the tissues some substance 
Fig. 71.—Section of an amyloid kidney. (Muller’s fluid, osmic acid, methyl violet.) a, Nor- 
mal vascular loops; b, amyloid vascular loops; c, fatty glomerular epithelium; ci, fatty capsular 
epithelium; d, fat-drops lying against the outer surface of the capillary walls; e, fatty epithelium 
in situ; f, desquamated and fatty epithelium; g, hyaline coagula (cast); h, t-ansverse section of a 
cast composed of fat-drops; i, amyloid artery; k, amyloid capillary; l, cellular infiltration of the 
connective tissue; m, round cells within the tubules, x 300. 
which is changed into amyloid at the site of deposit. It has been many 
times shown that as the antecedent of amyloid there is found a hyaline 
substance in the tissues, which does not give the amyloid reactions. 
Similar observations have occasionally been made in man. The material 
from which amyloid arises is formed, perhaps, by disintegrating pus- 
cells or tissue-cells at the seat of the primary disease and thence enters 
the blood-stream. 
According to Krawkow, there are found normally in the wall of the horse’s 
aorta, in the ligamentum nuchse of cattle, in the stroma of the spleen of calves, 
and in the mucous membrane of the stomach, combinations of chondroitin-sulphuric 
acid which are closely related to amyloid. According to Neuberg, amyloid proper 
is a basic albumin in the process of metamorphosis combined with chondroitin- 
sulphuric acid. From this last-named combination the basic albumin body may be 
easily differentiated chemically. 170 
THE RETROGRADE CHANGES. 
Literature. 
{Amyloid.) 
Davidsohn: Exper. Erzeugung von Amyloid. Virch. Arch., ISO Bd., 1897; 
Erkennung zweier Stadien der Amyloidentartung. Ibid., 155 Bd., 1899. 
Edens: Histopathologie lok. u. allg. Amyloiddegeneration. B. v. Ziegler, xxxv., 
1904. 
Krawkow: Exper. Erzeug. v. Amyloid. Cbl. f. allg. Path., 1895; Arch, de 
med. exp., 1896; Chemie der Amyloidsubstanz. Arch. f. exp. Path., 40 Bd., 
1897. 
Wells: Chemical Pathology, 1920. 
§ 63. The form of amyloid degeneration just considered is a disease, 
which usually appears as an affection of several organs, or, if confined 
to a single organ, as a change extending throughout the whole organ. 
There is, however, a form of 
amyloid disease appearing as a 
local infiltration of the tissues or 
in the form of free concretions. 
The local amyloid infiltrations 
occur in cellular granulations and 
in tissues showing chronic inflam- 
matory processes; and in scars. 
They are also found occasionally in 
tumors in which other retrograde 
changes have begun. In certain 
cases only small deposits are found 
in the affected tissues, usually in 
the vessel-walls. In other cases 
larger nodules may be formed, and 
may acquire a wooden hardness. 
Here also the amyloid substance 
is deposited in the ground-substance 
of the tissue; but it has been 
claimed by some authors (Rahl- 
mann) that the cells of the tissue 
may acquire a hyaline appearance and give the amyloid reactions. 
Such local infiltrations of amyloid have been found in the inflamed 
conjunctiva, in syphilitic scars of the liver, tongue, and larynx, in in- 
flamed lymph nodes, in the urinary bladder, ulcers of the leg, and in 
tumors of the larynx and stomach. Tumor-like nodules of amyloid also 
occur in the conjuctiva, tongue, larynx, lymph nodes, and trachea under 
conditions in which it is impossible to establish any relationship between 
them and inflammatory processes, and where besides the hyaline masses 
there is but little normal connective tissue present. According to Burow, 
Manasse, von Schrotter, Zahn, and others, such nodules may arise also 
from connective-tissue tumors. 
Free concretions or corpora amylacea occur most frequently in the 
tissues of the central nervous system, especially in the substance of the 
spinal cord, and in the ependyma of the ventricle. They are found also 
in the prostate. In the nervous system they appear as small (Fig. 72, r), 
dull-shining, mostly homogeneous bodies, more rarely consisting of a 
Fig. 72.—Corpora amylacea. a, Laminated 
prostatic concretions. x 200. b. Corpus 
amylaceum from an old hsemorrhagic infarct 
of the lung, with haematoidin crystals in its 
nucleus. x 200. c, Corpora amylacea from 
the spinal cord, x 400. HYALINE DEGENERATION. 
171 
nucleus and an outer shell (Redlich) ; in the prostate they form larger 
(Fig. 72, a) bodies which usually show distinct stratification. Corpora- 
amylacea have also been found in carcinomata (Wagner, Langhans), and 
have been repeatedly observed in the lung, where they occur in inflam- 
matory areas, haemorrhagic extravasations (b), and in emphysema. 
Corpora amylacea cannot be regarded as of the same nature as the 
progressive amyloidosis of connective tissue. Some of them, it is true, 
give characteristic amyloid reactions, and the corpora amylacea of the 
nervous system, in particular, become blue or brownish-violet when 
treated with iodine and sulphuric acid. But, in the case of these bodies, 
we have to do with formations which are dependent on local conditions 
for their origin; and are derived in part from epithelium, and in part 
from connective-tissue cells. They are, therefore, to be regarded as 
modified epithelial (§ 60), or connective-tissue hyalin (§ 65). The pros- 
tatic concretions are formed through the fusion of degenerating epi- 
thelial cells (epithelial colloid, § 60) ; similar bodies found in the lungs 
and in tumors are likewise composed of disintegrated cells, though in part 
of albumin derived from the blood. The corpora amylacea of the ner- 
vous system probably arise from fragments of swollen axis-cylinders to 
which, perhaps, remains of the medullary sheath still cling. 
Literature. 
(Local Formation of Amyloid and Amyloid Concretions.) 
Manasse: Tumorformiges Amyloid des Larynx. Virch. Arch., 159 Bd., 1900. 
Posner: Ueber Prostataconcretionen. Zeitsch. f. klin. Med., 16 Bd., 1889. 
Redlich: Die Amyloidkorperchen des Nervensystems. Jahrb. f. Psych., x., 
\m. 
Tschistowitsch: Amyloidtumoren d. Retroperitonealdriisen. V. A., 176 Bd., 
1904. 
XII. Hyaline Degeneration of Connective Tissue and the Hyaline 
Products of Connective-tissue cells. 
§ 64. Under the head of hyaline degeneration of connective tissue 
may be grouped those changes in which the fibrous ground-substance 
acquires a hyaline character without giving the specific reactions of amy- 
loid (Fig. 73). The change may involve connective tissue, altered by 
chronic inflammation, as well as the newly formed connective tissue of 
inflammatory lesions and the stroma of tumors. Hyaline degenera- 
tion is found most often in the connective tissue of the thyroid (Fig. 
73, b) ; the valvular endocardium; intima of the arteries; the entire wall 
of the smaller vessels, particularly of the brain and spinal cord; the 
lymph nodes (Fig. 75, a, b) ; glomeruli of the kidney ; the connective tissue 
and blood-vessels of tumors of the dura mater (psammoma), parotid, 
and submaxillary glands (angiosarcoma) ; the connective tissue of scars; 
the peripheral portions of tuberculous nodules; the connective tissue of 
chronically inflamed tendon-sheaths and bursae (Fig. 74, b). 
Hyaline degeneration of connective tissue possesses no specific stain- 
ing reactions, as does amyloid. Staining with Van Gieson’s acid fuch- 
sin and picric acid gives to hyalin in the great majority of cases an in- 
tense fuchsin red; but this reaction is sometimes wanting. It is prob- 
able that the transformation of connective tissue known as hyaline repre- 
sents a variety of degenerative conditions. 172 
THE RETROGRADE CHANGES. 
In many cases (hyalinisation of the heart-valves or of the intima of 
arteries) the tissue appears on microscopic examination to be thick, 
homogeneous and poorly 
nucleated, and the condi- 
tion has been designated 
sclerosis. The gradual 
disappearance of the 
nuclei, the subsequent cal- 
cification or softening even 
to the point of complete 
disintegration (for ex- 
ample in sclerotic areas of 
the intima), the sequestra- 
tion of the altered tissue 
from the normal (for ex- 
ample, in the degenerated 
portions of the walls of 
bursse), all point to the fact 
that the process is de- 
generative in character. 
In other cases the ap- 
pearance of the hyaline tis- 
sue resembles closely that 
of amyloid degeneration, 
and there is associated with 
the hyaline change a pronounced increase of bulk, particularly in the 
small vessels of the central nervous system, of the spleen, renal glomeruli 
and lymph nodes, more 
rarely in the connective 
tissue itself. There oc- 
cur moreover, though 
rarely, certain forms of 
hyaline degeneration in- 
volving the heart (Fig. 
76, b, c), serous mem- 
branes, intestinal wall, 
etc., with the formation 
of glassy masses, which 
in part give the amyloid 
reaction, and in part do 
not. In proliferations 
of the conjunctiva there 
frequently has been ob- 
served hyaline degeneration of the reticular ground-substance with 
nodular thickenings; this material gives the amyloid reaction only 
in part. It may therefore be assumed that there is a form of hya- 
line degeneration of connective tissue which is closely related to amyloid, 
and may become changed into the latter; and that it arises through the 
deposit of a hyaline insoluble albuminous body probably derived from 
the blood. 
Fig. 73.—Hyaline degeneration of the connective tissue 
FT100?101’ Van Gieson’s.) a, Follicles 
containing colloid; b, hyaline connective tissue; c. blood- 
vessel, x 300. 
Fig. 74.—Hyaline degeneration of the connective tissue of 
the wall of a tuberculous bursa. (Muller’s fluid, haematoxylin, 
and eosin.) a, Fibrous connective tissue; b, hyaline con- 
nective tissue. X 40. 
The preparation shown in Fig. 76, was taken from the heart of a woman of 
fifty-five years of age, the greater part of the heart-wal1 presenting hyaline HYALINE DEGENERATION. 
173 
degeneration. In both endo- and pericardium there were numerous hyaline nodules 
and flattened masses. The muscle tissue was in part degenerated, as shown in the 
figure. Associated with this condition there was extensive degeneration of the 
blood-vessels, particularly of the intestines, tongue, lungs, heart and urinary blad- 
Fig. 75. 
Fig. 76. 
Fig. 75.—Hyaline degeneration of the blood-vessels of an atrophic axillary lymph-node. 
(Alcohol, carmine.) a, Hyaline vessel with open lumen; b, obliterated vessel, x 200. 
Fig. 76.—Hyaline degeneration of the connective tissue of the myocardium. (Alcohol, 
haematoxylin, carmine.) a, Normal connective tissue; b, hyaline connective tissue; c, hyaline 
masses; d, transverse section of normal muscle-cells, of atrophic (e). x 250. 
der. The peritoneum wras also thickly covered with hyaline nodules. The fact 
that the small areas and the periphery of the larger ones gave no iodine-reaction, 
while the central portions of the larger areas did so, appears to point conclusively 
to a close relationship between hyaline degeneration and amyloid. A similar case 
has been described by Steinhaus. 
§ 65. Hyaline products arise from certain spherical masses of con- 
nective-tissue cells arranged in concentric layers, which, in a manner 
similar to the cornification of epithelial cells, become changed into a 
hyaline substance containing no nuclei. 
These formations occur most frequently in 
the meninges, the choroid plexus, and the 
pineal gland, and in the new-growths arising 
in these regions. Through subsequent 
calcification they lead to the formation of 
laminated concretions (see § 66, Fig. 84). 
Another kind of hyalin possibly owes 
its origin to secretory activity of connective- 
tissue cells. This may be designated secretory connective-tissue hyalin, 
but it must be noted that the cells themselves may be converted into 
hyaline products. The variety of hyalin is perhaps oftenest observed 
as red-staining spherules lying free in the tubules of chronically inflamed 
kidneys. The fuchsinophile bodies of Russell were formerly included in 
the same category, but are now regarded as phagocytised red corpuscles 
which have undergone hyaline transformation. 
Fig. 77.—Calcification of the 
media of the aorta, x 350. 
Von Recklinghausen gives to the term hyalin a more comprehensive meaning 
than Ziegler. He includes under hyaline degeneration pathological changes which 
Ziegler placed under other heads. He defines hyalin as an albuminous body which 
stains intensely with eosin, carmine, picrocarmine, and acid fuchsin; is homogeneous 
and strongly refractive; is but slightly changed by acids; and in its. resistance to 
alcohol, water, ammonia, and acids resembles amyloid, but does not give the iodine 
reaction. As hyalin he includes epithelial colloid and the hyaline products of con- 
nective tissue cells, as well as hyaline degeneration of the ground substance of the 174 
THE RETROGRADE CHANGES. 
connective tissue, also hyaline thrombi, and the hyaline coagula of inflammatory 
exudates, and hyaline tissue-necroses. According to Von Recklinghausen all of 
these formations result from the fusion of the elements of neighboring cells. From 
their external appearance, all may be designated hyalin; but the following varieties 
must be reeognized: epithelial hyalin (colloid, keratohyalin), connective-tissue hyalin 
(hyaline degeneration of the ground-substance of connective-tissue, hyaline pro- 
ducts of cells, and cells which have become hyaline), blood-hyalin (hyaline thrombi), 
exudative hyalin (hyaline coagula of exudates on mucous membranes, serous sur- 
faces, inflamed connective tissue, in the urinary tubules, tubercles, etc.), and 
hyaline tissue-necroses. In the case of connective-tissue hyalin a distinction must 
be made between the hyalin formed as a secretion in the cells (closely related to 
epithelial colloid, in its mode of origin), and hyaline degeneration of the ground- 
substance of connective tissue. 
XIII. Petrifaction of Tissues and the Formation of Concretions 
and Calculi. 
§ 66. It is of rather frequent occurrence for firm crystalline or amor- 
phous masses to be deposited in various parts of the body; and when the 
deposits are of such extent as to cause hardening of the affected tissue, 
the resulting condition is known as petrifaction, or when the deposit con- 
sists of lime-salts (particularly carbonates and phosphates) as calcifica- 
tion.. 
The deposit may occur, in the first place, in a tissue which forms an 
integral element of an organ, and which bears its normal relation to the 
surrounding tissues. In other cases it takes place in portions of tissue 
which have been loosened from their surroundings; or in insoluble sub- 
Fig. 78.—Calcification of the media of the femoral artery. (Silver preparation.) a, Intima; 
b, media; c, adventitia, x 40. 
stances which have become changed into a firm state; or, finally, in 
foreign bodies which have entered the body from without, and form the 
centres of a process of incrustation. 
In the first case there arise petrifactions of the tissues; in the sec- 
ond, free concretions and calculi. It is to be noted, however, that un- 
der certain conditions free concretions may become firmly attached to 
the tissues of the organ in which they lie, by means of tissue-prolifera- 
tions extending into or surrounding them. On the other hand, a calci- TISSUE PETRIFACTION. 
175 
fled portion of tissue may in the course of time gradually become loosened 
from its surroundings and ultimately form a free concretion. 
Deposit of lime salts occurs in the form of fine colorless gran- 
ules (Fig. 77) which when treated with silver (von Kossa) take on a 
black color (formation of silver phosphate) (see Figs. 78, b, 80, and 81, 
B, b). When closely crowded they become confluent, and give rise to 
chalky foci (Fig. 78, b) that are usually not sharply circumscribed; they 
Fig. 79.—Calcified vessels in the cerebellum. (Alcohol, haematoxylin.) x ioo. 
may form also circumscribed spherical concretions (Fig. 79). In the 
blood-vessels calcification may begin either in the connective tissue, 
muscle-fibres, or in the elastic tissue. 
I he cause of petrifaction is to be found in local tissue-changes, in 
that the deposit of lime-salts occurs in places where the tissue has al- 
ready died or is in process of degeneration. For example, lime salts 
may be deposited in pulmonary infarcts (Fig. 80), in thrombi, in ne- 
Fig. 8o.—Calcification of a necrotic lung in the periphery of a haemorrhagic infarct six 
weeks old. (Formalin, silver treatment.) x ioo. 
erotic foci arising during the course of inflammations, in dead cells, 
particularly renal epithelium (Fig. 82, d, e), and liver-cells (von Kossa) 
that have been killed as the result of intoxications (mercuric chloride, 
lead, aloin, bismuth, copper salts, iodine, and iodoform). A frequent 
antecedent to the deposit of lime-salts is hyaline degeneration of con- 
nective tissue, often associated with a deposit of fat. This occurs in the 
thickened intima of the blood-vessels and heart-valves, in the media of 
the medium-sized arteries, particularly in the extremities, in inflamma- 
tory new-formations of connective tissue (for example, in the serous 176 
THE RETROGRADE CHANGES. 
membranes), in the connective tissue of the kidney pyramids of old 
people (Fig. 81, A, B), and in degenerated thyroid glands. In dying adi- 
Fig. 8i.—Hyaline degeneration and calcification of the connective tissue of the kidney papillae. 
A, Stained with ha:matoxylin and eosin. B, Treated with silver nitrate, a, Collecting tubules; 
b, blood-vessel; c, connective tissue showing hyaline degeneration and calcification, x 300. 
A 
p> 
pose tissue (fat necrosis in the neighborhood of the pancreas) chalky 
soap may be formed. 
The hyaline character of the degenerated connective tissue shows well 
both in staining with Van Gieson’s and with simple hsematoxylin. With 
the latter stain the calcified connective tissue becomes a diffuse dark 
blue color (Fig. 81, A, c). The same 
staining reaction occurs in calcified 
necrotic cells (Fig. 82, d, e). This 
reaction holds good only for the de- 
posit of carbonates and phosphates, 
but not for the oxalates of lime. 
In rare cases there may occur a 
deposit of lime-salts in organs which 
show but slight changes — for ex- 
ample, in the lungs. Since in such 
cases there is destruction of bone— 
osteomalacia, caries, tumors, etc.— 
this deposit is regarded as metastatic 
in nature, due to the over-loading 
of the blood with lime salts. Even 
under these circumstances the im- 
mediate cause of the calcification is 
local, and is dependent on retro- 
gressive changes; the increased ab- 
sorption of bony structures is but a 
favoring factor. According to in- 
vestigations of Kockel and Kischensky 
the elastic lamellae of the small and 
medium-sized vessels in particular be- 
come calcified, but the elastic fibres 
and capillaries of the pulmonary 
interalveolar septa are also involved. 
Fig. 82.—Calcification of the epithelium 
of the kidney-tubules following sublimate 
poisoning. (Alcohol, haematoxylin.) Patient 
died seven days after the poisoning, a, 
Normal tubules; b, tubule with desquamated 
epithelium; c, tubule with de~quamated 
and necrotic epithelium possessing no 
nuclei; d, e, tubule with degenerated and 
calcified epithelium, x 300. CALCIFICATION. 
177 
The calcification may afifect either small or large areas, and in the 
latter case causes hardening and white coloration of the tissues. Oc- 
casionally it appears in the form of sharply circumscribed spherical, or 
nodular (Figs. 83 and 84, a, b, c), or long spicule- (Fig. 84, d), or 
cactus-like formations, and there arise in consequence concretions in 
the tissue that occasionally may be recognized with the naked eye. 
Under physiological conditions such concretions are found in the form 
Fig. 83. 
Fig. 84. 
Fig. 83.—Calcareous concretions, a, Concretions from an inflamed omentum; b, calcareous 
masses from a tuberculous lymph-gland which had undergone caseation, x 200. 
Fig. 84.—Section from a psammoma of the dura mater, with concretions. (Alcohol, picric 
acid, haematoxylin, eosin.) a, Hyaline nucleated rpherule with enclosed calcareous granule; 
b, calcareous concretion with hyaline non-nucleated capsule, embedded in fibrous connective 
tissue; c, calcareous concretion surrounded by hyaline connective tissue; d, calcareous spicule in 
connective tissue; e, calcareous spicule containing three separate concretions, embedded in the 
connective tissue. X 175. 
of laminated chalky spherules in the pineal gland and choroid plexus, 
forming the so-called brain-sand (acervulus cerebri). As pathological 
formations they occur in different regions, in tumors of the meninges 
known as psammomata, in caseous masses or in indurated connective 
tissue (Fig. 83, a). The origin of these formations may best be studied in 
the psammomata and is to be referred to transformation of tissue cells 
(Fig. 84, a, b, c), or of fibrous connective tissue (d) into a hyaline mass 
that at first may contain nuclei (a), and later loses them (b, e), and 
takes up lime-salts. Spherical concretions arise chiefly from hyaline 
masses formed from cells (a, b, c) ; spicules (d) arise through the 
calcification of hyaline connective tissue, but spherical concretions (e) 
may also arise in hyaline connective tissue. 
Formation of bone or ossification may follow the calcification of a 
tissue, either as the result of new tissue-formation, or of metaplastic 
development of osseous tissue. This has been observed in the media of 
calcified blood-vessels of the extremities and in the aorta, but may occur 
also in calcified lymph-nodes, in the neighborhood of calcified necrotic 
areas in the lungs, and in thickened serous membranes, etc. One of the 
most striking examples of the latter form of involvement is complete 
calcification and ossification of the tunica vaginalis testis. 
According to the investigations of Gierke, calcifying tissues (foetal bones, the 
enamel of the dentine, sand bodies of the choroid plexus, placental calcifications, 178 
THE RETROGRADE CHANGES. 
calcified ganglion-cells) contain more or less iron, and there occur also iron-con- 
taining cell-necroses (epithelial casts in sublimate poisoning) which stain like 
calcified tissue, but are not calcified. In other cases (fully developed bone in ex- 
trauterine life, calcified thrombi and calcified vessels) iron is not present. 
Klotz {Jour, of Exper. Med., 1905, 1906) suggests that the formation of cal- 
cium soaps is the first step in the formation of pathological masses of calcification, 
these soaps later undergoing transformation into the less soluble phosphate and 
carbonate. 
Wells (Jour, of Exper. Med., 1905) found but minute traces of calcium soaps 
in calcifying matter. It is therefore, probable that calcium-soap formation may be 
an important step in the process of pathological calcification, but is not an essential 
one. The especial affinity of calcium for cartilage, hyaline connective tissue, etc., 
cannot at present be explained. 
Literature. 
(Calcification of Tissues, and Formation of Concretions in the Tissues.) 
Buerger & Oppenheimer: Bone Formation in Sclerotic Arteries. Jour. Exp. 
Med., 1908. 
Ernst: Ueber Psammome. Beitr. v. Ziegler, xi., 1892. 
Kaufmann: Die Sublimatintoxication, Berlin, 1888; Virch. Arch., 117 Bd., 1889. 
Kischensky: Kalkablagerungen in Lunge und Magen. C. f. a. P., xii., 1901. 
v. Kossa: Kiinstlich erzeugbare Verkalkungen. Beitr. v. Ziegler, xxix., 1901. 
Mallory: Calcareous Concretions in the Brain. Journ. of Path., ii., 1894. 
Virchow: Kalkmetastasen. Virch. Arch., 8 u. 9 Bd. 
For an excellent resume of Calcification and Ossification, see Gideon Wells, 
Arch, of Int. Medicine, 1911. 
§ 67. The more common petrifactions consist of deposits of phos- 
phate of lime, sometimes of carbonate; with these magnesium salts may 
be mixed. Under special conditions there occur deposits of uric-acid 
salts; particularly in the disease known as gout, which is a disturbance 
of general nutrition characterized by the deposit of uric acid in the 
tissues. 
Gout is usually inherited, rarely acquired; it occurs frequently in 
certain regions, for example, in England and in North Germany; and is 
rare in other countries, as South Germany. Of the cause of the disease 
we have no positive knowledge. It is characterized by the deposit of 
uric-acid salts, chiefly sodium urate, with which small quantities of 
carbonate and phosphate of lime are sometimes associated. The deposit 
of these salts usually takes place during acute paroxysms characterized 
by pain and inflammation, but departures from a typical course 
may occur. The deposits are found in the kidneys, skin, subcutaneous 
tissue, tendon sheaths, tendons, ligaments, bursae, and articular cartilages, 
but may finally involve almost all the organs. The metatarsophalangeal 
joint of the great toe is the favorite site of deposit, and often the first 
part affected. The deposits consist of clusters of slender needles 
(Fig. 85), in whose neighborhood the tissues are degenerate or 
necrotic; from this it may be assumed that the urates entering the tissues 
in solution give rise to necrotic changes in the latter. 
The areas of necrosis and incrustation are at first of small size, but 
occasion inflammation and tissue-proliferation in their neighborhood. GOUT, 
179 
With the occurrence of other paroxysms the deposits become larger, so 
that nodules (the so-called tophi) are formed. These consist of white, 
plaster-like masses, and may 
form marked thickenings in the 
joints and tendons (Fig. 86). 
In the joints the articular 
cartilages appear as if sprinkled 
with plaster-of-Paris, but later 
the white masses may permeate 
the entire articular cartilage. In 
the kidneys necrosis and inflam- 
mation may lead to contraction 
and induration of the organ. 
The deposit affects chiefly the 
medullary pyramids, but is also found in the cortex. 
According to Garrod and Ebstein the acute paroxysms in gout depend 
on excessive accumulation of 
uric acid, either as the result 
of deficient excretion by the 
kidneys (Garrod) or of local 
changes (Ebstein). Accord- 
ing to Pfeiffer the gouty pre- 
disposition is due to the fact 
that the uric acid in the body- 
fluids is produced in a form 
which is soluble with diffi- 
culty, and is deposited in the 
tissues in such quantity as to 
cause localized necrosis. The 
symptoms of the gouty 
paroxysm are supposed to 
depend on increased alkalinity 
of the body-fluids and as a re- 
sult there follows partial 
solution of the deposited uric 
acid, in the course of which 
pain and inflammation are 
produced. On the other 
hand, von Noorden regards 
the formation and deposit of 
uric acid as a secondary 
process, due to the local ac- 
tion of a special ferment, and 
quite independent of the 
amount and condition of the 
uric acid in other parts of the 
body. 
§ 68. Free concretions 
are formed in various ducts 
and cavities which are lined 
Fig. 85.—Deposits of needle-shaped crystals of 
sodium urate in the articular cartilage. (After 
Lancereaux.) x 180. 
Fig. 86.—Gouty nodes of the hand. (After 
Lancereaux.) 180 
THE RETROGRADE CHANGES. 
by epithelium, as in the intestines or in the ducts of glands pouring their 
secretions into the intestine, in the gall-bladder, urinary passages, and 
respiratory tract. The concretions formed in the blood-vessels and 
serous cavities might also be included in this group, although they are for 
the greater part united to the surrounding tissues. 
All free concretions possess an organic base or nucleus. Thus 
enteroliths which form in the in- 
testines have a nucleus of in- 
spissated faeces, or foreign bodies 
which have been swallowed, such 
as hairs (bezoar stones or 
cegagropilce), or indigestible por- 
tions of vegetable food, etc., in 
and about which phosphates (am- 
monium-magnesium and calcium 
phosphate), and carbonates are 
deposited. In the mouth in- 
crustations of the teeth, known 
as dental calculi or tartar, 
are formed by the deposit of 
lime-salts in masses of mucus, cell-detritus, and bacteria. In the same 
way there are formed in the ducts of the salivary glands and pancreas 
oval or spherical faceted, or irregularly nodular concretions, through the 
calcareous impregnation of substances derived from the epithelium of 
the gland. 
Bronchial calculi are formed by the calcification of thickened secretion ; 
the stones found in veins and 
arteries (phleboliths and 
arterioliths) from the calci- 
fication of thrombi; prostatic 
calculi through the calcifica- 
tion of the so-called amyloid 
concretions; nazrel stones 
through the incrustation 
of desquamated epithelium, 
hairs, and other substances 
which enter the navel-de- 
pression. 
The biliary calculi or 
gall-stones found in the bile 
passages and gall-bladder 
are small granules, or larger 
spherical, oval, or faceted 
stones (Fig. 87), which on fracture appear to consist purely of crystalline 
masses. By proper methods it may be shown that these stones also 
possess a nitrogenous ground-substance. 
According to their composition gall-stones may be classed as choles~ 
terin, cholesterin-pigment, bilirubin, biliverdin-calcium, and calcium 
carbonate stones. The first two varieties are the most common; they 
Fig. 87.—Faceted stones from the gall-bladder. 
Natural size. 
Fig. 88.—Section through a small cholesterin stone after 
removal of the cholesterin. x 13. CALCULI. 
181 
present a rayed, crystalline, often laminated fracture; and vary in color 
and mottling according to the amount of bile-pigment present. When 
no pigment is present they may be colorless and translucent. 
If the cholesterin be dissolved out of a stone, it will be found that 
Fig. 89.— (Bellevue Hospital.) Stones in left kidney; secondary distention and tortuosity 
of both ureters; gangrenous cystitis. 
the form of the stone is preserved, and a delicate yellowish mass 
remains. This, when cut into sections, is found to consist of a 
homogeneous substance (Fig. 88) with concentric stratification and 
radiating clefts or spaces which were formerly occupied by the crystal- 182 
THE RETROGRADE CHANGES. 
line masses. A similar ground-substance may be demonstrated in other 
calculi after solution of their calcium salts. 
The majority of all gall-stones are the result of the incrustation of 
an organic substratum, derived from the mucous membrane of the biliary 
passages and the gall-bladder, following injury produced by infections, 
most commonly the typhoid and colon bacilli. Thus gall-stones may be 
brought about experimentally by injecting typhoid bacilli into the blood 
stream after mechanical injury of the mucosa of the gall-bladder, and 
living bacilli may be demonstrated in gall-stones long after the sub- 
sidence of typhoid fever. Inflammation of the bile-passages (angiocho- 
litis) leads to desquamation and destruction of the epithelium, and in 
the products derived from these changes bilirubin and cholesterin are 
deposited. When once a 
concretion is formed it in- 
creases in size through new 
products of cell-disintegra- 
tion which become en- 
crusted with cholesterin, 
pigment, and calcium. Ac- 
cording to Naunyn the 
original nucleus of the con- 
cretion undergoes a change, 
in that it separates into 
fluid, and into firm, gran- 
ular masses of pigment, 
calcium, and crystals of 
•cholesterin which are de- 
posited on the outer crust, 
so that the stone contains 
a cavity filled with fluid. 
In the course of time this 
fluid may be replaced by 
cholesterin, as may the pig- 
ment and calcium in the re- 
maining portions of the 
stone. In addition calcium carbonate may be deposited. 
The cholesterin masses from which the concretions are formed are 
derived from the disintegration of epithelial cells; likewise, the lime- 
salts combining with bilirubin are furnished by the mucous membrane. 
The urinary calculi, gravel, and stones are also composed of an 
organic ground-substance in which various constituents of the urine be- 
come deposited. According to location we may distinguish calculi of the 
kidney and those of the descending urinary passages. In the kidneys the 
deposits may form small granules lying in the tissue itself, or free in 
the lumen of the urinary tubules in products derived from the disintegra- 
tion of epithelial cells. This is true of the calcifications which, as men- 
tioned above, occur in necrosed renal epithelium after poisoning with 
■corrosive sublimate, bismuth, aloin, copper-salts, iodine, phosphorus, 
potassium chromate, and oxalic acid, and also applies to some of the 
gouty deposits. The so-called uric-acid infarct of the new-horn, a con- 
dition characterized by the appearance of yellowish-red stripes in the 
medullary pyramids, also belongs in this category. The condition is not 
infrequently seen in children dying during the first few weeks after birth. 
Fig. 90.—Uric-acid infarct of the new-born. (Alcohol, 
haematoxylin. Drawn from a preparation that had been 
washed in water.) Transverse section through the 
pyramid of the kidney. a, 1 ransverse section of un- 
changed collecting tubule from the papilla; b, dilated col- 
lecting tubule filled with uric-acid concretions; c, remains 
0f concretions after washing with water, x 200. CALCULI. 
183 
The epithelium of the tubules is usually well preserved, but in places 
desquamation and disintegration of cells may be found. The lumina of 
Fig. 91.—Coral-shaped stone from the bladder composed of calcium oxalate and phosphate. 
Natural size. 
Fig. 92.—Transverse section of two stones from the bladder, closely fitted together, and consisting 
of sodium urate and ammonium-magnesium phosphate. Natural size. 
Fig. 91. 
Fig. 92, 
the tubules are filled with small, colorless or yellow 
granules of urates or uric acid, which at times show 
fine radiating lines (Fig. 90, b). On solution of 
these granules a delicate stroma remains (c). If 
from t'he presence of the infarct further changes in 
the epithelium are produced, leading to the forma- 
tion of albuminous material in the tubules, single 
granules may develop through accretion into large 
stones, but this is rare. 
In the pelvis of the kidney, in the ureters, 
urinary bladder, urethra, and under the prepuce, 
concretions may be formed, as sand, gravel, or 
stones. The last-named are oval or spherical, and 
smooth, or rough and nodular, not infrequently re- 
sembling a mulberry or mass of coral (Figs. 91 
and 92). When several stones lie close together, 
their surfaces may become faceted (Fig. 87). 
Those found in the kidney may form casts of its 
pelvis and of the calyces. 
When examined in section, urinary calculi are 
sometimes homogeneous, at other times stratified 
(Fig. 92) or show radiating lines. Not infrequently 
there may be seen a nucleus and several zones of 
different appearance. The crystalline masses lie 
partly in the spaces of the stroma, and partly in the 
latter itself; it may be assumed that the stroma is a 
product of the mucosa of the urinary passages, and 
that its formation follows catarrhal inflammations 
or necroses of epithelium leading to the collection of 
mucus or cell-detritus in the tubules. 
What substances are deposited in the products 
of the mucous membrane depends on existing con- 
ditions. If the excretion of uric-acid salts by caus- 
ing tissue-necrosis has produced conditions favoring 
Fig. 93.—Incrusted lead- 
pencil, 12 cm. long, taken 
from the male urinary 
bladder. Reduced i/io. 184 
THE RETROGRADE CHANGES. 
the development of concretions, the deposits in the organic ground-sub- 
stance consist chiefly of urates. Decomposition of urine with the forma- 
tion of ammonium-magnesium phosphate leads to calculi consisting chiefly 
of this substance. Cystin calculi may be formed when cystin is excreted 
by the kidneys, as the result of inability on the part of the tissues to de- 
compose it. Once a stone is formed, the irritation which it causes, as well 
as decomposition of the retained urine, favors growth by accretion. Like- 
wise, foreign bodies (Fig. 93), which have entered the bladder from 
without, may lead to the formation of calculi. 
Intestinal calculi are more common in horses and cattle than in man; undi- 
gested vegetable material and hairs which have been licked off and swallowed 
form the starting-point of such concretions. The true stones, which occur espe- 
cially in horses, are rather hard masses consisting chiefly of magnesium phosphate; 
the false stones consist of hairs and vegetable fibres which are more or less en- 
crusted. Occasionally balls are found which consist almost wholly of hair (cegagro- 
pili or besoar stones). In ruminating animals they are found in the rumen or 
reticulum; in hogs, in the small intestine. 
According to Schuberg, the enteroliths of herbivorous animals consist chiefly 
of carbonates; those of carnivorous, of phosphates. The composition of those 
found in man varies according to the food ingested. 
Urinary calculi are classified according to their composition as follows: 
1. Calculi composed chiefly of uric acid or urates. 
Pure uric-acid calculi are usually small, yellow, reddish, or brownish in color, 
and hard. 
Stones consisting of urates are rarely pure. They are usually covered on the 
surface with a coating of calcium oxalate and ammonium-magnesium phosphate. 
2. Calculi composed chiefly of phosphates and carbonates. 
To this class belong stones composed of calcium phosphate, ammonium-mag- 
nesium phosphate, and calcium carbonate. The last two varieties are rare. All 
these calculi are white or grayish-white. The triple phosphate stones are soft and 
friable, the others hard. 
3. Stones composed of calcium oxalate. 
These are hard and rough, and of a brown color. 
4. Cystin calculi. 
These are soft, waxy, and of brownish-yellow color. 
5. Xanihin calculi. 
These are cinnebar-red in color, smooth, and have an earthy fracture. 
Ebstein and Nicolaier succeeded in producing urinary calculi by feeding ani- 
mals with oxamide, an ammonium derivative of oxalic acid. The greenish-yellow 
concretions thus produced in dogs and rabbits consist essentially of oxamide; on 
section they present a concentric laminated structure showing radiating striations. 
They possess an albuminous stroma derived from the necrosis and desquamation of 
epithelium caused by the action of the oxamide during excretion. 
Literature. 
{Free Concretions.) 
Cushing: (Gall-stones Lit.). Bull. Johns Hopkins Hosp., 1898. 
Ebstein u. Nicolaier: Kiinstl. Darstellung von harnsauren Salzen in der Form v. 
Spharolithen. Virch. Arch., 123 Bd.; Exper. Erzeugung von Harnsteinen, 
Wiesbaden, 1891. 
Lewis and Simon: Cystinuria with Diaminuria. Amer. Journ. of Med. Sc., 1902. 
Schuberg: Bau u. chem. Zusammensetzung v. Kothsteinen. Virch. Arch., 90 
Bd., 1882. 
Shattock: Calculi of Calcium Oxalate from a Cyst of the Pancreas. Journ. of 
Path., iv., 1896. 
Smith: Concretions and Calculi. Ref. Hand'b. of Med. Sc., 1901. PATHOLOGICAL PIGMENT. 
185 
XIV. The Pathological Formation of Pigment. 
§ 69. Both connective and epithelial tissues in various parts of the 
body normally contain autochthonous pigment, which lies in the cells, 
and consists of yellow, brown, or black granules, or gives a diffuse yellow 
or brown color to the cells. The autochthonous pigments are melanin, 
lipochrome and haemofuscin. 
Melanin is found in the lower cells of the rete Malpighii, in the color- 
ing matter of the hair, and in the choroid coat of the eye and retina. 
In the pigment-cells of the skin the granules are chiefly yellow and 
brown; in the retina they are black. 
The autochthonous pigments may be increased under various 
physiological and pathological conditions. 
For example, during pregnancy the pig- 
ment of the skin is more or less increased 
(chloasma uterinum), particularly in 
brunettes. In Addison’s disease, which 
is dependent on pathological conditions 
of the adrenals (see § 26), there occurs 
decided pigmentation of the skin as a 
result of increase of the normal pigment. 
Not infrequently spots of a bronze color 
appear in the mucous membranes of the 
mouth and elsewhere. 
Intense grades of pathological pig- 
mentation are met with in freckles, 
lentigines, pigmented moles (Fig. 94) 
and warts, and in melanotic tumors (see 
Chapter VIII.) The pigment is 
melanin, and the amount may be so great 
as to give the tissues a pure black color. 
The pigment lies for the greater part 
in the cells (chromatopliores), more 
rarely in the intercellular substance. It 
is composed of yellow, brown, or black 
granules; not infrequently individual 
cells may be diffusely pigmented. In 
Addison’s disease the granules are found 
partly in epithelial cells, especially in 
those lying directly on the connective 
tissue (Fig. 95, A, a, b, and B, a), and 
partly in branched chromatophores 
(A, c, cly d), whose pigmented processes 
extend up between the epithelial cells 
(B, *)• . 
In pigmented spots in the skin and in melanotic sarcomata the pig- 
ment is contained in specially differentiated connective-tissue cells of 
large size, and in cells of apparently normal size for the given tissue, 
often in connective-tissue cells in the neighborhood of vessels and in the 
vessel-walls. 
The pigments described are products of specific cell-activity; and we 
must suppose that many cells form pigment from the material brought 
to them. Tn the majority of cases the pigment appears to be formed in 
Fig. 94.—Large hairy pigmented mole 
over the back and buttocks, with scat- 
tered spots of pigmentation over trunk 
and shoulders. (After Rohring.) 186 
THE RETROGRADE CHANGES. 
the places where it is found; yet different investigations make it probable 
that the pigment may at times be transported. The pigment of the 
epidermis and of the hairs, at least in part, is not formed in the epithelial 
cells themselves, but in branched connective-tissue cells, or chromato- 
phores. (Fig. 95, A, c, d, and B, c) which lie just beneath the rete, and 
send processes between the epithelial cells, through which the pigment is 
transferred to the latter. 
The fact that the pigment is often found about the blood-vessels 
would seem to indicate that the material from which it is formed is 
derived from the blood, and 
this view was once accepted 
by many. Against it is the 
fact that neither in the blood 
nor in the neighborhood of the 
blood-vessels are there evi- 
dences of the disintegration cf 
red cells, and the theory of 
hsematogenous derivation now 
finds little if any favor. 
The attempt has been 
made to solve the problem by 
chemical investigations; and 
the results obtained favor the 
theory that the pigment is a 
product of cell-activity, and is 
formed from albuminous 
bodies. The different forms 
of melanin, in which group 
the pigments of the skin and 
choroid are placed, are, ac- 
cording to the investigations 
of von Nencki, Sieber, Abel, 
Davids, and Schmiedeberg, 
nitrogenous bodies rich in 
sulphur, but vary greatly in composition. According to Schmiedeberg 
the differences in the several melanins depend on their mode of origin, 
inasmuch as these pigments represent the final product of a long scries 
of metamorphoses of albumin. The albuminous bodies do not furnish 
the material for the building up of the final product (Schmiedeberg), 
but it is derived from sulphur-containing bodies formed by the cleavage 
of albumins, and from which certain carbon-containing groups have 
already been split off, so that there arise combinations which in propor- 
tion to their carbon-content are rich in sulphur; from these the melanins 
are formed. 
Iron may be present in small amounts in melanotic pigment, but is 
usually absent and is not necessary to the production of melanin. 
In the case of abundant formation, melanin may be excreted in the 
urine. 
Lipochrome is the term applied to the coloring-matter of adipose 
tissue, corpora lutea, ganglion-cells (Rosin), of the greenish tumors 
known as chloromata (Krukenberg), and of the muscle cells of the 
heart in brown atrophy. It is greatly increased in the subcutaneous 
fatty tissues in pernicious anemia, giving a lemon-yellow color to the 
skin. Of the origin and nature of this pigment nothing definite is known. 
Fig. 95.—A, and B, Pigmented cells of the skin 
from a case of Addison’s disease with caseous tuber- 
culosis of both adrenals. (Alcohol, carmine.) a, 
Pigmented epithelium cells from the deepest layer, 
in a section cut at right angles to the surface. 
A, b, Pigmented epithelial cells from a section made 
parallel to the surface. B, b, Epithelial cells con- 
taining no pigment; c, c 1, nucleated pigmented con- 
nective-tissue cells, the processes of which, in B, 
push between the epithelial cells; d, pigmented cell- 
processes. x 350. AUTOCHTHONOUS PIGMENTS. 
187 
Haemofuscin (von Recklinghausen, Goebel) is the iron-free, yel- 
lowish granular pigment found in smooth muscle of stomach and in- 
testine. According to von Recklinghausen, this pigment is derived from 
the blood, but it has not been established that it is a haemoglobin-deriva- 
tive. The sulphur-content (Rosen feld) makes it not unlikely that the 
haemofuscin granules belong to the melanin group. It is a striking fact 
that when treated with “ fat-stains ” the haemofuscin-granules are found 
to be fat-containing just as lipochrome stains as fat (Lubarsch). 
According to von Kolliker, “the pigment of the hair and epidermis is derived 
from pigmented connective-tissue cells which lie just beneath the deepest layers of 
the epithelium of the hair-bulbs and of the rete, and send processes between the 
delicate cells of these layers. These processes divide into long fine ramifications 
which lie in the intercellular spaces and may even penetrate into the cells them- 
selves, and in this way transfer their pigment to the latter.” The. pigment of the 
ganglion cells and of the cells of the retina arises, on the other hand, in the ecto- 
dermal cells themselves. Riehl and Ehrmann agree with von Kolliker. Karg ob- 
served that, following the transplantation of white skin on the surface of a leg- 
ulcer in a negro, the grafted portions became black in from twelve to fourteen 
weeks; and he concludes that, in the pigmentation of the epidermis, pigmented con- 
nective-tissue cells penetrate between the epithelial cells and convey pigment to the 
latter. Microscopic examination showed the presence of pigmented processes be- 
tween the epithelial cells at a time -when the latter had not yet became pigmented. 
Von Wild has shown that in melanosarcomata of the skin, pigmented connective- 
tissue cells may penetrate between the epithelial cells. Similar connective-tissue 
cells are found in the pigmented portions of the skin or mucous membranes in 
Addison’s disease, usually, however, in certain areas only and not everywhere. 
According to von Fiirth, neither sulphur nor iron is necessary to the formation 
of melanin. The melanin-molecule contains, however, active atom-groups which 
enable it to combine with certain complexes rich in sulphur and iron. The investi- 
gations of Bertrand, Biedermann, Schneider, von Fiirth, Gessard, and others make 
it probable (von Fiirth) that the formation of melanotic pigment depends on the 
action of an oxidative ferment (tyrosinase), upon tyrosin or other hydroxylized 
substances of an aromatic nature. In the abundant formation of melanin in tumors, 
melanin or melanogen may be excreted in the urine, so that this at the time of dis- 
charge is black or gradually becomes black when exposed to the air and light. 
According to Spiegler, the results of chemical investigation exclude the deri- 
vation of melanin from haematin. He also demonstrated the existence of a white 
chromogen which is the cause of white wool in sheep and of gray hairs. 
In domesticated animals there occurs a peculiar melanosis of the inter- 
nal organs, occasionally associated with melanosis of the subcutaneous tissue. 
The affected organs (heart, lungs, intestines, etc.) present in varying numbers 
grayish or black spots, looking like ink-spots, which are produced by the deposit 
of pigment in connective-tissue cells which otherwise appear normal. 
Under the title of ochronosis, Virchow described a condition characterized 
by the deposition of brownish, blackish, or bluish black iron-free pigment, particu- 
larly in the cartilaginous structures of the body, but also in tendons, joint capsules, 
periosteum, and certain internal organs. The pigment stands in close relationship 
to melanin. Clinically, the pigmentation is most frequently noted in the cartilages 
of the external ear and of the nose, and in the sclerae and skin. Pathologically, the 
costal cartilages, the intervertebral discs, the articular surfaces of the large joints 
and the rings of the trachea are almost constantly pigmented. The epiglottis and 
laryngeal cartilages are usually less often and less deeply colored. The ligaments 
and tendons are involved in a considerable percentage of cases. Of the internal 
organs, the intirna of the heart or the aorta is the most frequently pigmented. In 
cartilage, the deposition of the pigment takes place in the matrix, the capsule and 
cells being spared or only slightly affected, unless the cells themselves have been 
injured, and then pigment is apt to be deposited in large quantities. In a consider- 
able proportion of cases, ochronosis is attended by destructive lesions in the larger 
joints, sometimes giving rise to symptoms comparable to those of arthritis defor- 
mans. In many instances ochronosis has been shown to follow the long continued 
application of dilute solutions of carbolic acid to chronic, leg ulcers and the like 
(Poulsen: Ziegler’s Beitr., 1910). The urine is characterized by the presence of 188 
THE RETROGRADE CHANGES. 
homogentisic acid (alkapton) which is a substance derived chemically from the 
destruction of proteins, particularly tyrosin and phenylalanine. Whether the long 
continued use of carbolic acid so influences protein metabolism as to cause the 
formation of homogentisic acid in the tissues and its liberation through the urine, 
has not been determined. Gross and Allard (Arch. f. exp. Path. u. Pharm., 1908) 
were unable to extract homogentisic acid from cartilage, but by placing pieces of 
fresh cartilage in dilute solutions for a period of from three to six weeks, they 
found the characteristic color changes of ochronosis. 
Literature. 
{Autochthonous Pigments.) 
Abel: Bemerk. iiber thier. Melanine u. das Hamosiderin. Virch. Arch., 120 Bd., 
1890. 
von Fiirth: Phys. u. chem. Unters. iib. melanot. Pigment. C. f. a. P., xv., 1904 
(Lit.). 
Goebel: Pigmentablagerung in der Darmmuskulatur. Virch. Arch., 136 Bd., 
1894. 
Krukenberg: Grundziige der vergl. Physiol, der Farbstoffe u. d. Farben, Heidel- 
berg, 1887. 
v. Nencki u. Sieber: Weitere Beitr. z. Kenntniss d. thier. Melanins. Ib., xxiv., 
1888. 
v. Recklinghausen: Hamochromatose. Tagebl. d. Naturforschervers., Heidel- 
berg, 1889. For a complete review of the subject see Sprunt, Arch, of Int. 
Med., 1911. 
Rosenfeld: Das Pigment der Hamochromatose des Darms. Arch. f. exp. Path., 
48 Bd., 1900. 
Rosin: Bau der Ganglienzellen. Deutsdh. med. Woch., 1896. 
Schmiedeberg: Ueber die Elementarformeln einiger Eiweisskorper und liber 
die Zusammensetzung u. d. Natur d. Melanine. Arch. f. exp. Path., 39 Bd., 
1897. 
Spiegler: Ueber das Haarpigment. Beitr. z. chem. Phys., iv., 1903. 
§ 70. Haematogenous pigments are those whose origin from the 
coloring-matter of the blood may be demonstrated beyond doubt. Such 
pigmentations are known as haemochromatoses. 
Rxtravasates of blood soon undergo changes which are visible to 
the naked eye. Extrava- 
sates in the skin become 
brown, then blue, green, 
and finally yellow. Small 
haemorrhages into the tis- 
sues, as in the peritoneum, 
pleura, and lungs, may 
show for a long time as 
reddish-brown spots; in de- 
composing cadavers their 
color may be slate or black. 
Large haemorrhages, as in 
the brain or lungs, assume 
after a time a rust-brown 
color, which later changes 
to ochre-yellow, yellow, 
yellowish-brown, or brown. All these variations of color correspond to 
changes in the haemoglobin and in the iron which it contains. 
Whenever haemorrhage occurs in the tissues or into a cavity, a 
portion of the plasma and of the red cells may be taken up unchanged 
through the lymph-vessels. Another portion of the corpuscles loses its 
Fig. 96.—A, Cells containing amorphous blood-pigment; a, 
those with few large fragments of red blood-cells; b, c, 
those containing great numbers of small disintegration- 
products of red blood-cells; B, rhombic plates and needles 
of hiematoidin. x 500. HHEMATOGENOUS PIGMENTS. 
189 
haemoglobin, the pale stroma of the cells remaining. The escaped hemo- 
globin diffuses through the tissues, and from it are formed the different 
products which give rise to the changes of color in the neighborhood of 
the extravasate. A part of the absorbed haemoglobin may be excreted 
as urobilin (urobilinuria) ; another part may be precipitated in the 
tissues in the form of granules or crystals. The latter are yellowish-red 
or ruby-red rhombic plates and needles of hematoidin (Fig. 96, B) ; 
and represent a frequent residuum of haemorrhages. A portion of the 
diffused haemoglobin may also be taken up by cells, the latter acquiring 
a diffuse yellowish pigmentation, or showing the presence of yellow and 
brown granules. 
A third portion of the blood-corpuscles disintegrates at the site of 
the extravasation, and forms yellozv and brown granules and lumps. 
The pigment which arises directly from the disintegration of red cor- 
Fig. 97.—Cells containing hasmosiderin and haematoidin from an old haemorrhagic focus in 
the brain. (Alcohol, Berlin-blue reaction.) a, Cells containing hsemosiderin; b, cells containing 
haematoidin; c, fat-granule cells which have become clear; d, newly formed connective tissue. 
X 300. 
puscles, as well as the crystals and granules precipitated from dissolved 
haemoglobin, are often taken up by cells, partly leucocytes and partly cells 
derived from proliferating tissue (Figs 96, A, and 97, a, b). 
At the beginning of the disintegration of red corpuscles the coloring- 
matter present is haemoglobin, but the yellow and rusty masses and 
granules which are found both in the cells and lying free, and which 
eventually become changed into darker pigment, are no longer haemo- 
globin itself, but derivatives of haemoglobin. According to their com- 
position these may be divided into two groups, one iron-free, the other 
containing iron. The former is known as hematoidin, the latter as 
hemosiderin. 
Haematoidin (identical with bilirubin) is a ruby-red (Fig. 96, B) or 
reddish-yellow (Fig. 97, b) pigment occurring in crystalline form, or as 
granules, which may be amorphous, hut often show a somewhat angular 
shape (Fig. 97, b), suggesting imperfect crystals. Haematoidin is soluble 
in chloroform, carbon disulphide, and ether; insoluble in water and 
alcohol. It appears to be formed when haemoglobin is but slightly 
exposed to the action of living cells, as in the centre of large extrava- 
sates and in haemorrhages into the body-cavities, for example, into 
the pelvis of the kidneys or the subdural space. It may be produced 
artificially by the introduction beneath the skin or into the peritoneal 190 
THE RETROGRADE CHANGES. 
cavity of capsules containing blood, so that the blood in the capsules 
is exposed to the action of tissue-fluids but not of cells. 
The granules and crystals of hsematoidin are found in the tissues 
free (Fig. 96, B), or enclosed in cells (Fig. 97, b). In the latter case 
they are taken up after they have been precipitated; occasionally it may 
happen that hasmatoidin in solution is taken up by fixed connective-tissue 
cells, for example, cartilage or fat-cells, and then precipitated in solid 
form. 
Haemosiderin, the derivative of the red blood-cells which contains 
iron in demonstrable quantity microscopically, is found in the tissues as 
yellow, orange, and brown granules and lumps which become darker in 
the course of time. They are for the greater part contained in cells, 
and in part are formed within the cells. 
When treated with potassium ferrocyanide and dilute hydrochloric 
acid haemosiderin be- 
comes deep-blue 
through the formation 
of Berlin blue (ferric 
oxide salt of hydro- 
ferrocyanic acid) (Fig. 
97, a). When treated 
with ammonium sul- 
phide there is formed 
a black sulphide of 
iron. 
Hemosiderin appears 
to be formed particu- 
larly when the blood in 
an extravasate or in a 
thrombus is subjected 
to the action of living 
cells; consequently it is seen more frequently in small extravasates and at 
the periphery of large ones. The formation of hemosiderin may take place 
either in the cells or free in the tissue. The pigment enclosed in cells 
(sideroferous cells) may have been formed from disintegrated red cor- 
puscles, or from dissolved haemoglobin which has been absorbed by the 
cells. In favor of the latter mode of formation is the diffuse yellow color 
seen in both wandering and fixed cells, which becomes blue when the 
Berlin-blue reaction is applied. Further, when haemoglobin is excreted 
through the kidneys, iron-containing pigment-granules form in the renal 
epithelium; and moreover fixed cells, as cartilage-cells, which could 
hardly be supposed to act as phagocytes and take up fragments of red 
cells, often contain granules of haemosiderin, even when lying outside 
the immediate neighborhood of the extravasate. 
The free pigment and pigmented cells cause distinct pigmentation of 
the extravasate and its neighborhood. The pigmented cells pass into 
the lymph-vessels and metastasis of pigment takes place, as a result of 
which pigment is found in the lymph-vessels and in the lymph-nodes, 
(Fig. 98). Later it may be taken up by the fixed tissue-cells. In time 
the haemosiderin is destroyed and disappears. The view that haemosiderin 
is changed into melanin, is not supported by facts. The brownish-black 
granules in the lungs, which have been explained as due to such a change, 
Fig. 98.—Accumulation of pigment-containing cells in the 
lymph-nodes after resorption of an extravasate of blood. 
(Muller’s fluid, carmine.) a, Cortical node; b, lymph-sinus; 
c, cells containing pigment-granules. X 100. HEMATOGENOUS PIGMENTS. 
191 
consist of one or several minute particles of carbon surrounded by a coat- 
ing of haemosiderin. 
If haemosiderin is brought into contact with hydrogen sulphide it be- 
comes black; and as the result of such reaction there may be produced 
in the cadaver black and green spots or a more diffuse discoloration, 
known as pseudomelanosis. It is observed most often in the in- 
testine, peritoneum, and in suppurating wounds, since in these regions 
hydrogen sulphide is more likely to be formed by putrefaction. 
Ziegler uses the term hsemochromatosis in its strict sense, namely, to indicate 
a condition in which the associated pigments are derived from haemoglobin. The 
term hemochromatosis, however, is widely, if somewhat loosely, employed to 
designate a condition which many regard as a distinct morbid entity and which 
is characterized by the deposition not only of an iron-containing pigment, but of 
one which is free from iron. Neither pigment is traceable to haemoglobin. More- 
over, the condition is attended by increase in the pigmentation of those tissues 
which normally contain pigment. Haemochromatosis is probably best interpreted 
as a metabolic process implicating different tissues, and characterized by the 
deposition in them of pigments formed as a result of disturbances in the chromo- 
genic structures of the proteid molecule. According to this view, the iron-con- 
taining pigment in haemochromatosis, haemosiderin, is derived from iron-containing 
proteids native to the pigmented tissues; certainly there is no dissemination of 
pigment by metastasis. The non-iron-containing pigment in haemochromatosis is 
haemofucsin. In the majority of all cases of haemochromatosis, the skin presents 
a diffuse bronze discoloration and diabetes is present (diabete bronze of the 
French). The cause of the diabetes is unknown. While in most cases the pan- 
creas is pigmented, the islands of Langerhans are unchanged, so that the diabetes 
cannot be ascribed to anatomical changes in these structures. In most cases of 
haemochromatosis the liver is cirrhotic. Haemochromatosis is not common. It occurs 
oftenest in males. Of sixty-three cases collected by Sprunt (Arch. Int. Med., 1911) 
only one was in a female. In Bellevue Hospital, eight cases were observed among 
6,000 autopsies. Two of these were associated with cirrhosis and primary carci- 
noma of the liver, and still another with myelomatosis. Haemochromatosis as an 
attendant phenomenon in cirrhosis of the liver with primary carcinoma is exceed- 
ingly rare, but has also been observed by Runte (Inaug. 'Disser. Wurzburg, 1901) 
and by Loehlcin (Ziegler’s Beitr., 1907) and Wintcrnits (Virch. Archiv., 1913). 
In haemochromatosis the organs most frequently involved are the liver, pancreas, 
spleen, lymph nodes and heart muscle. In this connection it is interesting to recall 
that Krets, in twenty-six cases of atrophic cirrhosis of the liver, was able to 
demonstrate iron-containing pigment in fourteen, the remaining organs being free 
from pigment. At Bellevue Hospital we have been able to confirm this observation 
in a number of instances. 
§ 71. When large numbers o£ red blood-cells break down in the 
circulating blood, dissolved haemoglobin or methaemoglobin may pass 
into the plasma, and fragments of red cells may be carried in the circu- 
lation. Such destruction of red cells occurs to a marked degree in poison- 
ing with arsenic, toluylendiamin, potassium chlorate, and morels; to a 
lesser degree in other conditions, such as infections, malaria, in pernicious 
anaemia, and in overheating of the body. The passage of haemoglobin or 
methaemoglobin into the blood-plasma leads to the condition of liccmo- 
globinccmia; the plasma is colored red. When the amount of dissolved 
haemoglobin in the blood is large, a portion may be excreted through the 
kidneys, giving rise to hemoglobinuria or methemoglobinuria, in which 
conditions the urine may present a bloody appearance, or vary from clear 
brownish-red to dark reddish-black. This occurs particularly in the 
first-named poisons, but occasionally after the action of other injurious 
influences, for example, exposure to cold (periodical hsemoglobinuria). 
When formed products arise from the disintegration of red cells, 
such as corpuscular fragments after extensive burns, they collect in the 192 
THE RETROGRADE CHANGES. 
capillaries of the liver, spleen, lymph-nodes, and bone-marrow, and to 
a less extent in other organs; and are sooner or later taken up by phago- 
cytic cells. 
As the result of increased supply of haemoglobin to the liver the 
functional activity of this organ 
is increased, so that the amount 
of pigment in the bile may be 
greater than normal; under cer- 
tain conditions oxyhsemoglobin 
may appear in the bile (Stern). 
When the blood-destruction is 
great, the liver may not be able 
to dispose of all the pigment 
brought to it; and in conse- 
quence derivatives of haemo- 
globin are deposited in the 
liver and other organs, or ex- 
creted by the kidneys. In the 
former event there may arise 
more or less extensive haemo- 
chromatosis of different 
organs, the cells of which 
show an ochre-yellow or brown color. The derivatives of haemoglobin 
deposited in this way are partly iron free pigments and partly hemosiderin. 
Fig. 99.—Infiltration of the cells of the liver-rods 
with yellow haemosiderin granules, from a case of 
pernicious anaemia. (Osmic acid.) a, Haemosiderin; 
b, cells in a state of fatty degeneration, x 250. 
Fig. ioo.—Haemochromatosis of the liver. (Alcohol, carmine.) a, Acini; b, peritoneum; 
c, branches of the portal vein; d, infiltrated periportal connective tissue; e, pigment lying within 
the liver-acini; f, central veins, x 20. 
The deposits of iron-containing pigment in the liver appear in the 
form of yellow granules and lumps, which are enclosed in leucocytes HEMATOGENOUS PIGMENTS. 
193 
lying in the capillaries. The deposits are found also in the form of 
granules in the endothelial cells of the capillaries (to which the stellate 
cells of Kupffer belong), and in the liver-cells (Fig. 99, a). In many 
diseases, for example, pernicious anaemia, the cells contain so much iron 
pigment that the liver takes on a characteristic yellowish-brown color. 
The iron-pigment which is carried to the spleen is deposited chiefly 
in the free cells of the pulp; but granules are also found in the fixed 
cells. In the lymph-nodes the iron granules are found in the free cells 
Fig. ioi.—Haemosiderin deposit in the bone-marrow (mixed fatty and lymphoid marrow) in 
icterus. (Alcohol, carmine, Berlin-blue reaction.) x 300. 
of the lymph-channels. In the bone-marrow retained hsemosiderin (Fig. 
101) is found in cells lying in the capillaries, and partly in the endo- 
thelium and marrow-cells; the number of iron-containing cells may be 
marked. 
In the kidneys the hsemosiderin granules are most abundant in the 
epithelium of the convoluted tubules (Fig. 102, a), but are also found in 
the lumina of the tubules (b), in the epithelium of Bowman’s capsule 
(f), and in the endothelium.of the capillaries. In marked deposits the 
kidney may show signs of pigmentation to the naked eye. 
The hsemosiderin found in different tissues is brought to them in 
the form of small lumps or granules contained in leucocytes. On the 
other hand, another part is precipitated in the cells from substances 
brought to them in solution. Since the cells (liver-cells, kidney epi- 
thelium, endothelium of the blood-vessels, and the cells of the lymph- 
nodes, bone-marrow, and spleen) not infrequently show a diffuse blue 
color after the iron-test has been applied, the iron must be diffused 
through the cell-protoplasm, and converted later into granular form. It 
is also possible that the diffuse coloration may arise from solution of iron 
in the cells. According to the observations of different investigators, 
it appears that besides the colored deposits of pigment, colorless granules 
or an iron-albuminate may be present in the cells. This theory is sup- 
ported by the fact that more pigment granules are visible after the iron 
reaction has been applied, than could be seen before. 194 
THE RETROGRADE CHANGES 
The deposit of iron-free pigments, hcomatoidin or bilirubin is not of 
frequent occurrence in hsemochromatosis, but occasionally yellow gran- 
ules which do not give the iron reaction are found in the organs named 
above; and it may, therefore, be assumed that the pigment in part may 
be constantly free from iron. 
By certain writers the mottled pigmentation of the skin which develops in 
chronic arsenic poisoning, and which is due to the deposit of small yellowish-brown 
granules in the corium and epidermis is classed with the hsemochromatoses and is 
referred to the degenerative influence of arsenic on the bone-marrow and blood. 
Fig. 102.—Hematogenous deposits of iron in the kidney in pernicious malaria (contracted 
in Bagamayo). (Alcohol, carmine, Berlin-blue reaction.) a, Convoluted tubules, whose 
epithelial cells contain iron granules and are stained diffusely blue; b, iron-granules in the lumen 
of the tubules; c, straight tubules; d, glomerulus; e, epithelium of the capsule, containing iron- 
granules. X 150. 
It should be noted, however, that the pigment does not give the iron reaction, and, 
moreover, that pigment in epithelium that is derived from haemoglobin is not per- 
manent; and that no increased destruction of red blood-cells occurs in habitues of 
arsenic (Muir). 
In malaria two pigments are formed as a result of the destruction of red cells 
by the parasite. One of these is formed by the malarial plasmodium itself, is 
contained in the parasite, is black, and gives no iron reaction. Its nature is not 
known. 
The second pigment is haemosiderin, which passes into the blood-plasma as the 
result of the destruction of red blood-cells, and is deposited in the liver, spleen, 
and bone-marrow. In marked destruction of blood there may occur siderosis of 
the kidneys (Fig. 102), and excretion of iron in the urine. 
Froin, Nonne and others have described a condition attended by yellowish dis- 
coloration of the spinal fluid (xanthochromia) in which the protein content is 
increased to such an extent that, when the fluid is removed, it coagulates sponta- 
neously. The condition may be encountered in compression of the spinal cord 
and its meninges from any cause which leads to the formation of a cul-de-sac 
distal to the site of compression. In these circumstances, Hanes (Amer. Jour. 
Med. Sc., 1916) is of the opinion that the yellowish color of the fluid is due to 
transudation of blood serum owing to interference with the circulation at the 
site of compression. Pleocytosis may or may not be present, depending on whether 
the meninges are inflamed. Xanthochromia of the spinal fluid is to be sharply dis- 
tinguished from staining by haemoglobin derivatives (erythrochromia), which may 
occur in a number of conditions attended by haemorrhage into the cerebro-spinal 
fluid. ICTERUS. 
195 
Literature. 
{dlcemochromatosis; Iron Absorption; Deposit and Excretion.) 
Biondi: Ablagerung von Hamosiderin bei Hamatolyse. Beitr. v. Ziegler, xviii., 
1893 (Lit.). 
Dutton: Iron in the Liver and Spleen in Malaria. Jour, of Path., v., 1898. 
Futcher: Hsemochromatosis with Diabetes Mellitus. Am. J. of the Med. Sc., 
19°7. 
Hunter: Action of Toluylendiamin. Journ. of Path., iii., 1895. 
Muir: Arsenical Poisoning. J. of Path., vii., 1901. 
Opie: Hsemochromatosis. Journ. of Exp. Med., iv., 1899. For an admirable 
review of this subject see Sprunt, Arch, of Int. Med., 1911. 
§ 72. Icterus or jaundice is a pathological discoloration of tissues 
due to bile-pigment. It is a symptom which occurs in numerous dis- 
eases of the liver, and is often encountered as a fugitive process in the 
first few days of life (icterus neonatorum). 
The pigment which characterizes icterus is apparent during life in 
the skin, conjunctiva, and urine; in the cadaver the internal organs — 
serous membranes, lungs, kidneys, liver, subcutaneous and intermuscular 
tissues, blood-plasma, clots in vessels, etc.— may show icteric coloration. 
In recent cases the icteric color is yellow; in long-standing cases the skin 
takes on an olive-green or dirty grayish-green color, while similar color- 
ations occur in the internal organs, particularly in the liver, and often in 
the kidneys. 
Icterus results from the entrance of bile-pigment (bilirubin) into 
the blood and fluids of the body. The urine excreted contains elements of 
bile, particularly the pigments. As the result of disease in the biliary 
passages or liver the outflow of bile is hindered, and the bile is then 
taken into the lymphatics and blood-vessels of the liver. Such damming 
back of bile may be caused by narrowing or closure of the large bile-ducts 
through scar-tissue, through gall-stones wedged in the lumen, or tumors 
developing in the bile ducts or compressing them; or through inflam- 
matory processes or tumors of the liver which compress or obliterate the 
smaller ducts, and in this way hinder the outflow of bile. 
In the case of stasis of bile in the liver-lobules the intercellular bile- 
capillaries become dilated and filled with bile-thrombi (Fig. 103, a, b). The 
dilatation also affects the blind side branches extending toward thq 
capillaries, and these may be broken through, so that the bile eventually 
gains entrance into the lymph-channels and blood. Further, the bile- 
pigment is heaped up in the liver-cells themselves (c), and the endo- 
thelium of the blood-capillaries (d, d1} e) is stained. 
When bile-pigment obtains entrance to the blood, the tissues of the 
body become gradually permeated and acquire an icteric color. If phago- 
cytes containing granules of bilirubin are present in the circulating blood, 
they may accumulate here and there, particularly in the spleen and bone- 
marrow. After a time the bile-pigment held in solution in the tissue- 
lymph may become precipitated as solid particles, chiefly in granular 
form, but sometimes as crystals in the fixed and wandering cells of the 
connective tissue, in the liver-cells, and in the renal epithelium. The 
crystals are in the form of rhombic plates and needles, similar to those 
of haematoidin (Fig. 96). In severe cases of icterus many of the tissue- 
cells contain pigment, and, as a result of metastasis of cells containing 
pigment, accumulations of the latter in the lymph-nodes may occur. 196 
THE RETROGRADE CHANGES. 
In kidneys in which bile-pigment is being excreted deposits of bilirubin 
occur, particularly in the epithelium of the urinary tubules (Fig. 104, 
a, d), which in consequence may become desquamated. If, as the result 
of damage to the secreting cells through the excretion of bile-pigment, 
there are formed, as usually is the case, hyaline casts — that is, hyaline 
coagula in the albumin-containing urine in the tubules — these likewise 
become colored (Fig. 104, b, c). 
Associated with the bilirubin in icterus there is sometimes a deposit 
Fig. 103.—Obstructive icterus of the liver, due to compression of the ductus choledochus 
by a cancer of the gall-bladder. (Sublimate, alum-carmine.) a. Intra-acinous bile-capillaries, 
moderately dilated and filled with bile; b, widely dilated intra-acinous bile-capillary, containing 
large mass of pigment; c, bile-pigment in the liver-cells d, d\, endothelium stained with bile- 
pigment; e, desquamated endothelium stained with bile-pigment; f, pigment mass surrounded by 
cells; g, rupture of the pigment contained in a bile-capillary into a blood-capillary, with bile- 
stained cells in the neighborhood, x 365. 
of hcemosiaerin which may become so abundant in the bone-marrow 
(Fig. 101), spleen, and lymph-nodes, and occasionally in the liver, that 
discoloration of the organs named is dependent in part on iron-pigment. 
When increased destruction of red blood-cells takes place in the 
blood-vessels, hsematoidin or bilirubin, in addition to hsemosiderin, is 
formed in different parts of the body (see § 71) ; but the formation of 
bilirubin outside of the liver is slight and is not sufficient to cause ex- 
tensive icteric coloration of the tissue, so that, according to one view, 
pure hcematogenous jaundice does not occur. The liver is the great 
elaborator of bilirubin, and in cases of increased destruction of blood- 
cells the liver-function is increased and there is increased production and 
excretion of bile-pigment. Icterus due to increased destruction of blood- 
cells can occur only when there are present in the liver such changes 
as cause passage of bile into the blood. 
The question as to whether there is a haematogenous as well as a hepatogenous 
variety of jaundice has long been an object of discussion, and remains unsettled at 
the present time, in spite of numerous experimental investigations directed toward ICTERUS. 
197 
its solution. Since, as a matter of fact, bilirubin may be formed in different kinds 
of tissue from extravasated blood, the occurrence of haematogenous icterus would 
a priori appear probable. Experimental investigations as to the results of the 
destruction of red cells in the circulating blood, particularly through the action of 
arsenic, toluylendiamin, and potassium chlorate, have shown that the derivatives of 
blood-pigment which are formed in the tissues and there retained for a long time 
are essentially iron-containing pigments (hsemosiderin), while the production of 
bilirubin is practically confined to the liver, which for the time being secretes an 
increased amount of richly pigmented bile. 
According to the investigations of Minkowski and Naunyn, the urine of geese 
and ducks after removal of the liver contains no bile-pigment — a fact which would 
Fig. 104.—Icterus of the kidney in obstructive jaundice. (Sublimate, carmine.) a, Tubular 
epithelium containing yellowish-brown granules; b, large casts stained yellowish-green; c, cast 
containing pigmented cells; d, desquamented epithelium containing bile-pigment granules, x 200. 
indicate that the transformation of blood-pigment into bile-pigment is ordinarily- 
confined to the liver. The inhalation of arseniuretted hydrogen for a few minutes 
is sufficient to produce in geese an intense polycholia and hsematuria, the urine 
containing haemoglobin in solution, disintegrating red cells and biliverdin. If the 
liver from such a goose be removed, the biliverdin quickly disappears from the 
urine, and no trace of bile-pigment can be demonstrated in the blood. It is there- 
fore evident that in arsenic poisoning the formation of bile-pigment is confined to 
the liver, in which organ leucocytes enclosing iron-containing fragments of broken- 
down red cells are found to be present. 
In so far as it is possible to judge from experimental investigations which have 
been made up to the present time, pure haematogenous jaundice does not appear to 
be improbable. The mere fact of the occurrence of jaundice after intoxications, 
inhalation of ether and chloroform, transfusion of blood, snake-bite, septicaemia, 
typhoid fever, yellow fever, paroxysmal haemoglobinuria, etc., cannot be taken as 
proof of the existence of haematogenous jaundice. There is, indeed, in these con- 
ditions increased destruction of red blood-cells; but jaundice, if it occurs, may be 
due to the fact that a portion of bile-pigment, which is produced in excess, has 
found its way into the blood. According, however, to Whipple and Hooper, the in- 
travenous injection of haemoglobin into dogs with the liver excluded is followed 
by the excretion of bile pigment in the urine and jaundice of the fat tissues. 
(Jour, of Exp. Med., 1913.) Moreover, there are well-defined varieties of haemolytic 
icterus in which the destruction of red cells takes place in the spleen and in which 
removal of the spleen is almost invariably followed by disappearance of the jaundice. 
According to von Kupffer and Pfeiffer, the bile-capillaries terminate in intra- 
cellular secretory vacuoles; from these, according to Nauwerck, Stroebe, and 
Browicz, delicate intracellular secretory canaliculi are given off, forming a network 
around the nucleus. Schafer describes small canaliculi within the liver-cell cora- 198 
THE RETROGRADE CHANGES. 
municating with the blood-capillaries. Arnold opposes the view that any preformed 
system of canals exists in the liver cells. 
In the icetrus occurring so frequently in the new-born (Schmorl) there occurs 
both a diffuse and a scattered yellowish coloration of the brain limited to the 
neighborhood of the nuclei, while in later life the brain, even after long-continued 
icterus, remains free from pigment. With the nuclear icterus there are also found 
ganglion-cells stained with bile. 
Literature. 
(Icterus.) 
Abramow u. Samoilowicz: Pathogenese d. Ikterus. Virch. Arch., 176 Bd., 1904. 
Auld: Haematogenous Jaundice. Brit. Med. Journ., i., 1896. 
Harley: Pathology of Obstructive Jaundice. Brit. Med. Journ., 1892; Leber u. 
Galle wahrend dauernden Verschlusses von Gallen- und Brustgang. Du 
Bois-Reymond’s Arch., 1893. 
Minkowski u. Naunyn: Pathologie d. Leber u. d. Ikterus. Arch. f. exp. Path., 
xxi., 1886. 
§ 73. Pigmentation of the tissues through materials introduced 
from without occurs when substances possessing a color of their own 
gain entrance and are able to remain for some time without suffering 
changes. The number of such substances is large, and the manner of 
Fig. 105.—Deposit of cinnabar in tattooed skin. (Alcohol, alum-carmine.) a, Epithelium; 
b, corium; c, cinnabar, x 80. 
entrance varied. The most common avenues of entrance are the lungs, 
wounds, and intestinal tract. The most familiar pigmentation through 
wounds is tattooing of the skin, which is frequently practiced by indi- 
viduals civilized as well as uncivilized. 
The method of tattooing colored figures, etc., consists in the intro- 
duction of insoluble granular pigments, such as carbon, india-ink, cin- 
nabar, sepia, burnt sienna, ultramarine, chromate of lead, etc., into slight 
wounds of the skin. The pigments are rubbed into the wounds, whence 
they penetrate and infiltrate the tissue in their immediate neighbor- 
hood. A portion of the pigment remains in the corium (Fig. 105, c) ; 
another portion is carried to the lymph nodes, which become pigmented. 
The lungs and their lymph nodes may become intensely pigmented 
through the inhalation of colored dust, such as coal-dust, soot, iron-dust, 
etc. Through the inhalation of coal-dust the lungs may become black. EXTRINSIC PIGMENTS. 
199 
Y\ hen coal-dust is taken into the lungs in the respired air a portion 
of the pigment is carried to the peribronchial lymph nodes, which may 
become black. When the deposit is abundant the lymph nodes may 
undergo softening and give off pigment into the lymph-stream. If the 
nodes are situated in the neighborhood of a vein, the pigment-deposit 
and the softening may involve the vein-wall, so that particles of coal- 
dust may pass into the blood-stream, and be carried to other organs, 
the spleen, liver, and bone-marrow (see § 21). 
From the intestine only soluble substances are absorbed, and perma- 
nent pigmentation can therefore occur only when these are precipitated 
in the tissue as solid particles which 
retain a distinguishing color. The 
most frequent of such pigmenta- 
tions is that known as argyria, 
which is due to the long-continued 
use of silver preparations, whether 
taken by mouth or applied to 
mucous membranes, e.g., the nose, 
or to chronic ulcerative lesions of 
ihe skin. In argyria the skin may 
show only a slight bluish tinge, but 
in more pronounced cases the sil- 
very discoloration lends a ghastly 
appearance. The internal organs 
may present more or less pigmenta- 
tion. The silver is deposited in the 
ground-substance of the tissue in 
the form of fine granules, more 
especially in the glomeruli, and the 
connective tissue of the medullary 
pyramids (Fig. 106, b), the intima 
of the great vessels, adventitia of 
the smaller ones, in the neighbor- 
hood of mucous glands, the papilke 
of the skin, connective tissue of the 
intestinal villi, and in the choroid 
plexus of the lateral ventricles. 
Deposits may also occur in the ser- 
ous membranes, but the epithelial 
tissues, the brain, and the cerebral 
vessels escape. Extensive deposits of silver in the medullary portion of 
the kidneys may lead to the formation of hyaline connective tissue and 
to calcification. 
Iron taken into the body in excessive amounts, may be deposited in 
the bone-marrow, spleen, and lymph-nodes; but the pigmentation thus 
produced is rarely visible to the naked eye. In lead-poisoning there 
may be seen a grayish-black discoloration of the gums, due to the deposit 
of sulphide of lead in the connective tissue produced through the action 
of hydrogen sulphide on lead which is present in solution in the mucous 
membrane. 
Fig. 106.—Deposits of silver in the pyra- 
midal portion of a rabbit’s kidney, after 
seven months’ administration of silver salts 
(experiment by von Kahlden.) (Alcohol, 
hematoxylin.) a, Epithelium of the collect- 
ing tubes; b, connective tissue with brown 
silver granules, x 500. 
A variety of exogenous pigmentation has recently been described tinder the 
title of carotinsemia, and is characterized by the presence in the blood and urine 200 
THE RETROGRADE CHANGES. 
of pigments derived from diet rich in carotin — carrots, spinach, the yolk of eggs, 
oranges, etc. The condition is evidenced by a peculiar orange-yellow tint of the 
skin which simulates jaundice, but is easily differentiated from the latter by lack 
of discoloration of the conjunctivse. (Palmer and Eckles, Journ. Biol. Chem., 1914; 
Palmer, Ibd., 1916; Hess and Myers, Carotinaemia, Journ. Amer. Med. Assn., 1919.) 
XV. The Pathological Absence of Pigment. 
§ 74. Absence of pigment occurs as a congenital condition, and is 
termed albinism or leucopathia congenita. In such cases the absence of 
pigment may extend over the entire body (albinismus universalis, albi- 
nos) ; in other cases it is restricted to certain portions of the skin (albi- 
nismus partialis). In those parts of the skin which are destitute of pig- 
ment the hairs likewise contain no pigment, and appear white or yellowish- 
white (poliosis or leucotrichia congenita universalis, et circumscripta). 
In universal albinism the pigment of the retina, choroid, and iris may 
be wanting, so that the choroid, from the 
blood which it contains, appears red, and 
the iris, according to the angle of obser- 
vation and the degree of illumination, 
appears bluish-white or red. On micro- 
scopic examination no pigmented cells 
are to be found. 
A second form of albinism is known 
as vitiligo or leucopathia acquisita. 
This occurs later in life, either as a 
sequel to certain diseases (scarlet fever, 
typhus, recurrent fever), or as a symp- 
tom of an epidemic disease of unknown 
etiology (vitiligo endemica), or finally 
without any recognizable cause. The 
formation of white spots, in which the 
hairs are also white (leucotrichia ac- 
quisita circumscripta), takes place usu- 
ally symmetrically, and may extend over 
the greater part of the body (Fig. 107). 
The white areas are surrounded by a 
border of deeply pigmented skin; this 
suggests that with disappearance of pig- 
ment at one point the pigment is trans- 
ferred to adjacent parts. The loss of 
color in the hairs (as in old age) begins 
in the root, no more pigment being trans- 
ferred from the hair-papilla to the bulb. 
Finally the pigment-cells of the papilla 
disappear altogether. 
A third form of loss of pigment is 
associated with traumatic or infectious 
inflammations of the skin, particularly in 
syphilis and leprosy; this condition is 
known as leucoderma. 
In scars of the skin which remain white, the newly formed tissue 
replacing the defect does not possess the power of producing pigment. 
Not infrequently such a scar may be surrounded by a pigmented border. 
Fig. 107.—Vitiligo endemica (after a 
SihS)ph received from Pr0feSS°r FORMATION OF CYSTS. 
201 
In mild forms of inflammation, in which the tissue of the skin suffers no 
loss (syphilis), the disappearance of color may immediately follow the 
inflammation, or not until later, in which case there may occasionally 
occur a preceding stage of increased pigmentation. According to Ehr- 
mann the lack of pigment in such cases is to be explained either by the 
fact that no chromatophores are present in the corium to furnish pigment 
to the epithelium, or the changed epithelium is not able to take up the 
pigment from the latter when present. The pigment which still remains 
in the cutis may then be absorbed. 
According to Miinch, vitiligo is of common occurrence in Turkestan, and is 
considered by the natives (Sarts) to be contagious, so that they isolate the affected 
individuals and confine them with lepers in enclosed courts. It is probable that in 
the literature vitiligo endemica has been many times confused with lepra maculosa, 
and has been described under the designation “white leprosy of the Jews.” 
XVI. The Formation of Cysts. 
§ 75. A cyst is a circumscribed cavity which is shut off from the sur- 
rounding tissues by a connective-tissue membrane or by tissue of a more 
complex structure, and possessing contents differing in nature from the 
capsule. Cysts may occur in any tissue. When composed of but a sin- 
gle chamber, the cyst is called a simple 
cyst; when divided into a number of 
compartments, it is known as a mul- 
tilocular cyst. 
The most common form is the so- 
called retention-cyst, which arises from 
the accumulation of secretions in pre- 
existing spaces which are lined with 
epithelium or endothelium. 
In glands provided with ducts, re- 
tention-cysts are formed as the result of 
obstruction of the duct, provided secret- 
ing epithelium exists behind the point of 
obstruction. Such cysts are of frequent 
occurrence in the sebaceous glands, hair 
follicles, uterine glands, mucous glands 
of the intestinal tract, tubules of the 
epididymis (Fig. 108, c), urinary 
tubules; less frequent in the biliary 
passages, in the breast, pancreas, in the 
glands of the mouth, etc. Larger open 
canals, such as the ureters, vermiform 
appendix, and Fallopian tubes, may also undergo cystic dilatation as the 
result of the collection of secretions. Obstruction of a duct may be due 
to accumulation of secretion, to the formation of adhesions, cicatricial 
obliteration, compression, or constriction of its lumen. 
Closed glandular cavities and tubes, such as the follicles of the 
thyroid and the glandular tubes of the parovarium, may become cystic 
when their walls produce an abnormal amount of secretion. Likewise, 
the remains of foetal passages and clefts, for example, remains of the 
branchial clefts, urachus, Muller’s ducts, etc., may become cystic. 
Fig. 108.—Section of the testicle and 
epididymis, with multiple cysts in the 
head of the epididymis. a, Testis; 
b, epididymis; c, nmltilocular cysts. 
Slightly reduced. 202 
THE RETROGRADE CHANGES. 
Small cysts such as those developing in mucous glands, vary in size 
from a millet seed to that of a pea. Larger cysts, such as occur in the 
liver and ovaries, may attain the size of a fist and even larger. 
The contents of cysts depend on the nature of the tissue in which 
they are formed. Thus cysts of sebaceous glands and hair-follicles con- 
tain a pultaceous, white, or grayish-white, more rarely brown, mass, 
which consists of squamous cells in various stages of disintegration, fat- 
globules and cholesterin. The cysts occurring in mucous glands contain 
a fluid which is either clear, or white and cloudy, as the result of the 
presence of cellular elements. Haemorrhage into a cyst gives a red or 
brown color to the contents. When great numbers of cells are present in 
cyst-contents, the whole may become converted into a semi-solid fatty 
mass, and eventually undergo calcification. Cysts of the thyroid and 
kidneys contain colloid masses, or a clear though occasionally cloudy 
fluid. 
Retention-cysts lined with endothelium may develop from lymph- 
vessels, lymph-spaces, bursae, and tendon-sheaths. Here also the content 
of the cyst is dependent on its place and mode of origin. 
As retention-cysts tend to increase in size the stretching of the cyst- 
wall would ultimately lead to a defect in the continuity of the wall if no 
new formation of tissue took place. Cyst formation is not purely a de- 
generative process; new formation of tissue takes place in the epithelial 
or endothelial lining of the cyst, and the connective-tissue elements of 
the wall also increase, so that in spite of the stretching, the wall becomes 
no thinner, and may even increase in thickness. Moreover, cyst forma- 
tion is often associated with pathological overgrowth of glandular 
tissue, and in this way constitutes a secondary change in hyperplastic 
or tumor growths. It is, therefore, sometimes impossible to draw a 
sharp line between the simple cystic dilatations of preexisting gland- 
canals and gland-spaces, and those tumors, the cystomata, which are 
characterized by cyst formation (see Cystoma). 
A second form of cyst is the degeneration-cyst, which arises through 
partial disintegration and liquefaction of tissue. Cysts formed in this 
manner occur in the brain, hypertrophic thyroids, and in tumors. They 
may contain a clear or cloudy, or at times haemorrhagic exudate. 
A third form of cyst results from the formation of a connective- 
tissue capsule around foreign bodies, which have found entrance to the 
tissues, for example, about a bullet; or about necrotic areas, or 
haemorrhagic extravasates. 
A fourth variety of cyst is formed by parasites which pass through 
a cystic stage in the course of their development in the body, and are 
likewise surrounded by a connective-tissue capsule. CHAPTER VI. 
Hypertrophy and Regeneration. Results of Tissue-Trans- 
plantation. Metaplasia. 
I. General Considerations. 
§ 76. In a broad sense, hypertrophy is increase in the size of a tissue 
or organ, due either to increase in the size or in the number of the in- 
dividual elements, in such a way that the structure of the hypertrophic 
tissue is like that of the normal, or at least does not differ essentially 
from it. 
In a limited sense hypertrophy is increase in size due to enlargement 
of the individual elements 
alone; enlargement due to in- 
crease in the number of the 
individual elements being des- 
ignated hyperplasia. 
If the enlargement affects 
the entire body, for example, 
if a newly born child weighs 
5-8 kgm., or if an individual 
should reach the height of 
180-200 cm., the condition is 
called giant growth. When 
the enlargement affects in- 
dividual parts of the body, for 
example, the entire head or 
one-half of it, or one ex- 
tremity, or the vulva, it is 
called partial giant growth. 
Hypertrophic growths of the 
skin and subcutaneous tissues, 
leading to disfigurement sug- 
gesting the appearance of the 
pachydermata, are known as 
elephantiasis(Figs. 109, 110). 
In giant growth all the 
elements are uniformly en- 
larged. In elephantiasis the 
connective tissue of the skin 
and subcutaneous structures is especially likely to become increased; 
nevertheless the structure of these growths may vary greatly. In one 
case all the connective-tissue elements may be uniformly increased, in 
another case only individual elements; for example, the connective tissue 
of the nerves, blood- or lymph-vessels. It is therefore possible to dis- 
tinguish different forms of elephantiasis according to the structure of the 
hypertrophic part; elephantiasis neuromatosa, angiomatosa, lymphan- 
aiectatica, lipomatosa, fibrosa, etc. 
Fig. 109.—Elephantiasis femorum neuromatosa. 204 
THE PROGRESSIVE CHANGES. 
Hypertrophy of the horny layer of the epidermis attended by the 
formation of plates, scales, or even spines, is designated ichthyosis be- 
cause of a fancied resemblance to the external covering of the fish. The 
condition is usually inherited and its cause is unknown (ichthyosis con- 
genita) Fig. Ill, c. 
In other cases during the first years of life, localized thickenings 
of the horny layer develop, consisting of small scales or plates, or larger 
ones, giving the skin a rough and checkered appearance.- The corium and 
the papillae are usually not involved in the ichthyosis; but occasionally the 
papillary bodies may be hyper- 
trophic, thus increasing the rough 
and nodular appearance of the sur- 
face (ichthyosis hystrix). When 
the excessive cornification is 
sharply limited to areas of small 
size, there are formed circum- 
scribed warts with rough epithelial 
covering, known as ichthyotic 
warts. In rare cases there may be 
developed a more extensive horny 
layer over the hypertrophic papillae, 
whose scales are arranged at right 
angles to the surface of the skin; 
these occasionally attain such size 
that they are called cutaneous 
horns (Figs. 112, 113). 
The excessive and coarse de- 
velopment of hair over those parts 
of the body where only downy hair, 
or no hair at all, should be found 
is known as hypertrichosis. Ab- 
normal hairiness may cover a large 
or small area, and depends either 
on persistence and abnormal de- 
velopment of the lanugo (hyper- 
trichosis lanuginosa fcEtalis) (Fig. 
114), or on pathological develop- 
ment of the secondary hairs. Ex- 
cessive growth of the nails leads to 
the condition known as hyper- 
onychia, which is often followed 
by the claw-like deformity desig- 
nated onychogryphosis. It is to be noted, however, that pathological over- 
growths of the nails are usually acquired. 
Next to the enlargements associated with general or partial giantism 
the bones most frequently undergo hypertrophy corresponding to ele- 
phantiasis of the skin. The head is usually affected, the bones of which 
may undergo enlargement (Fig. 115), leading to a deformity in which 
the head comes to resemble that of a lion, hence the name leontiasis 
ossea. Further, there often develop on the skull or other bones circum- 
scribed bony growths known as exostoses. 
It cannot always be stated to what extent hypertrophy of the tissue 
is to be attributed to congenital predisposiion, inasmuch as many extrinsic 
Fig. iio.—Elephantiasis cruris lymphan- 
giectatica. CONGENITAL HYPERTROPHIES. 
205 
influences are able to produce proliferations of tissue similar to those 
due to intrinsic causes. For example, cutaneous horns and elephantiasis- 
like thickenings of the skin may develop as the result of inflammation. 
Fig. in.—Ichthyosis congenita. Section through the skin of the trunk of the body (alcohol, 
picrocarmine.) a, Corium, with glands; b, papillary body, with rete Malpighii; c, hypertrophic 
horny layer of the epidermis; d, dilated hair-follicles, lined with horny epithelium; e, hairs, 
x 40. 
In general, the early appearance of a hypertrophic growth and the 
absence of any obvious etiological factor, speak for the congenital nature 
of the condition. The fact that later influences may apparently cause the 
growth does not preclude the existence of a congenital predisposition. 
Thus the excessive bony 
growths of the head 
above mentioned may fol- 
low trauma or acute in- 
flammations. External in- 
fluences may therefore be 
the exciting but not the 
primary cause of the 
change. 
Not infrequently the 
tendency to excessive 
growth may show itself in 
premature development 
of certain organs, the structure remaining normal. The sexual organs 
are most frequently affected. Girls, even in the first years of life, may 
show development of breasts and external genitals and growth of hair 
corresponding to that of the sexually ripe woman; and menstruation may 
be established at this early period. 
Fig. 1X2.—Cornu cuta- 
neum, from back of hand. 
(Natural size.) 
Fig. i 13.—Cornu cuta- 
neum,. from arm. (Nat- 
ural size.) 
The size of the body as well as of its separate parts and organs shows con- 
siderable variation within physiological limits, according to the race, family, and 
individual. The variation in the relation of the size of single parts and organs to 
that of the entire body is less marked. 206 
THE PROGRESSIVE CHANGES. 
The average height of the body in well-built individuals is, according to 
Vierordt (“Daten u. Tabellen fur Med.,” Jena, 1893), as follows: Men 172 cm., 
women 160 cm.; of the new-born, males 47.4 cm., females 46.75 cm. The average 
body-weight in Europe is for men about 65 kgm., that of women about 55 kgm., 
that of the new-born about 3,250 gm. 
The average weight of the internal organs is as follows, the figures in paren- 
theses being for the new-born: Brain 
1,397 (385) gm., heart 304 (24) gm., 
lungs 1,172 ( 58) gm., liver 1,612 (118) 
gm., spleen 201 (11.1) gm., right kidney 
131, left kidney 150 gm., both kidneys 
299 (23.6) gm., testicles 48 (0.8) gm., 
muscles 29,880 ( 625) gm., skeleton 
Fig. i 14.—Head of a hairy individual, a 
woman. (After Hebra.) 
Fig. iis.—Leontiasis ossea, occurring in a 
boy affected with general giant-growth. (Ob- 
served by Buhl.) 
11,560 (445) gm. Expressed in percentages of body-weight the figures for 
adults and new-born are (the latter in parentheses) : Heart 0.52 (0.89), 
kidneys 0.48 (0.88), lungs 2.01 (2.16), stomach and intestines 2.34 (2.53), 
spleen 0.346 (0.41), liver 2.77 (4.30), brain 2.37 (14.34), adrenals 0.014 (0.31), 
thymus 0.0086 ( 0.54), skeleton 15.35 (16.17), muscles 43.09 (23.4). 
Literature. 
(Tissue-Hypertrophy of Congenital Origin,') 
Amheim: Congen halbseitige Hypertrophie. Virch. Arch., 154 Bd., 1898 (Lit.). 
Behrend: Hypertrichosis. Eulenburg’s Realencyklop., 1896 (Lit.). 
Esoff: Ichthyosis. Virch. Arch., 69 Bd., 1877. 
Nonne: Elephantiasis congenita hereditaria. Virch. Arch., 125 Bd., 1891. 
§ 77. Hypertrophies due to external causes arise in response to 
increase in the activity of the tissue, to diminished use, defective retro- 
grade change, or to prolonged or frequently repeated mechanical, chem- 
ical, and infectious irritations. Removal of pressure may sometimes be 
followed by localized hypertrophy. 
Hypertrophy from overwork is most frequently observed in muscles 
and glands, but may also occur in other tissues. If the heart is called 
on to do an extra amount of work as the result of diseased conditions of 
the valves, aorta or kidneys, and if such conditions exist for some ACQUIRED HYPERTROPHY. 
207 
time, that part of the heart-muscle on which the extra work falls suffers 
more or less pronounced hypertrophy, so that as a result the mass of the 
heart may reach several times that of the normal. 
In similar manner the unstriped muscle of the bladder, ureters, uterus, 
intestine, and blood-vessels may become hypertrophic from persistent 
increase in activity. 
As the result of increase of strain from whatever cause bones may 
become thickened, and the 
trabeculae of the medullary por- 
tion increase in size. 
Of the glands the kidneys, 
and liver in particular are able 
to change their size according 
to functional demands, and 
may present marked hyper- 
trophy. Should one kidney be 
destroyed, the other may be- 
come so enlarged that it reaches 
approximately the same weight 
that the two together originally 
possessed. Likewise the liver 
after destruction of a part of 
its parenchyma may make good 
its loss by hypertrophy of the 
remainder. Since in this way 
compensation for the defect 
and restoration of function are 
brought about, such increase is 
designated compensatory 
hypertrophy. The same term 
may be applied to muscle- 
hypertrophy, if through it 
functional disturbances are 
compensated. Compensatory 
hypertrophy is said to occur in 
similar circumstances in adre- 
nal tissue. In other glands, 
such as the salivary glands, 
ovaries, testicles, and mammae, 
compensatory hypertrophy 
either does not occur at 
all, or takes place only dur- 
ing the period of development. The loss of an Ovary or testis 
in adult life can hardly result in increased activity and hyper- 
trophy of the remaining organ. Extirpation of the larger part of the 
thyroid gland is not followed by pronounced hypertrophy of the remain- 
ing portion; on the other hand, the hypophysis undergoes enlargement 
which must be regarded as compensatory. In the lungs, increase in the 
activity of one portion after the loss of another results usually in over- 
distention which eventually may lead to atrophy. On the other hand, 
if during embryonic life defective development of one lung takes place, 
the other lung may undergo compensatory growth, which in case of total 
agenesia of one lung may reach a pronounced degree. For the other 
Fig. 116.—(Bellevue Hospital.) Showing the 
peculiar hypertrophy and malformation of the 
lower extremities in Paget’s disease, so-called 
osteitis deformans. 208 
THE PROGRESSIVE CHANGES. 
organs the general principle may be applied that compensatory hyper- 
trophy more nearly approaches perfection the younger the individual. 
In the brain compensatory growth of one part after the loss of another 
is possible only during the early stages of development. 
Hypertrophy from lessened use occurs in tissues which are nor- 
mally subject to attrition from constant use. For example, diminished 
desquamation of the horny layer of the epidermis leads to pathological 
thickening. If, as the result of the destruction of an opposing tooth 
or an oblique position, the incisor teeth in rodents are not worn down 
by use, they may grow into long, curved tusks. Hypertrophy due to de- 
fective retrograde change occurs in organs which after a definite 
period of physiological growth undergo diminution in size. For ex- 
ample, the uterus after pregnancy may remain abnormally large as the 
result of failure of involution. The thymus gland, which should begin 
to atrophy after the tenth year of life, may persist for a much longer 
period. In bones lessening of pressure may be followed by hypertrophy. 
In idiots whose brains are deficient in size there is often hyperostosis 
of the inner surface of the base of the skull (Chiari), and unilateral 
hyperostosis of the skull is sometimes associated with corresponding 
hypoplasia of the brain. 
Frequently repeated or protracted mechanical, thermal, chemical, 
or infectious irritations give rise to proliferative processes leading to 
hypertrophies, which because of their etiology and course must be re- 
garded as chronic inflammations; such formations are placed under 
the head of inflammatory hypertrophy. They are characterized often 
by the fact that in the enlargement of the organ, not all of its parts are 
equally involved; certain elements, usually the connective tissue, occa- 
sionally the epithelium, undergo hypertrophy to such a degree that the 
structure of the organ (skin, gland, etc.) is no longer typical. 
If the skin is frequently subjected to irritation and pressure, for 
example, the toes through an ill-fitting boot, there may arise thickening 
of the horny layer of the epidermis, known as callus or corn (clavus). 
Prolonged irritation of the skin in the neighborhood of the genital open- 
ings, caused by gonorrhoeal discharges, may be followed by elongation 
and branching of the papillae with thickening of the epithelium, leading 
to the formation of warty, cauliflower-like growths known as venereal 
warts or condylomata acuminata. Chronic inflammations of the corium 
and subcutaneous tissue, due to infection or to animal parasites (Filaria 
Bancroft!), not infrequently give rise to fibrous hypertrophies known as 
elephantiasis. Such hypertrophies may attain extraordinary proportions. 
In similar manner there may occur in the bones, as the result of chronic 
infectious processes (syphilis, for example), extensive hypertrophies 
characterized by increased formation of bone-substance. 
In the majority of cases those tissue-hypertrophies which appear 
during life as acquired formations, the causa efficiens may be recognized 
with more or less certainty but there are also cases in which, at the pres- 
ent time, this is either impossible or possible to a limited extent. For 
example, there are enlargements of the spleen, and of lymphadenoid tis- 
sues in various localities which are of the nature of hypertrophies, whose 
causes we are unable to recognize. Imperfect, also, is our knowledge of 
(the etiology of the enlargements of the extremities, resembling partial 
giant-growth, which have been described as ostcoarthropathie hypertro- 
phiante (Marie). REGENERATION. 
209 
In Germany the designation acromegaly is applied to all forms of enlargement 
of the ends of the extremities that lead to paw-shaped deformity of the hands and 
gigantesque appearance of the feet, while Marie attempts to draw a line between 
acromegaly and osteoarthropathie hypertrophiante. He holds that in acromegaly 
the hands and feet are not deformed, but are symmetrically enlarged, the thicken- 
ing and broadening diminishing toward the tips of the extremities, so that the 
terminal phalanges of the fingers and toes are but slightly thickened, while, on the 
other hand, in osteoarthropathie hypertrophiante the terminal phalanges are enlarged 
to resemble drumsticks, and the articular ends of the bones are irregularly thick- 
ened. In the first affection the lower jaw is lengthened, in the latter it is thickened. 
Marie believes that osteoarthropathie hypertrophiante is a sequel of inflammatory 
affections of the lungs and pleurae, and designates the condition osteoarthropathie 
Fig. i i 7.—The skin-portion of a laparotomy wound sixteen days old (Muller’s fluid, Van 
Gieson’s). a. Epithelium; b, corium; c, subcutaneous adipose tissue; d, scar in corium; e, new 
epithelium; f, scar in adipose tissue. X 38. 
hypertrophiante pneumique, and holds that the connection between these processes 
is to be found in the taking up into the body-fluids of poisonous products from the 
inflammatory foci in the lungs, so that the affection of the bones is to be regarded 
as an infectious toxic hypertrophic inflammation. 
The association of acromegaly with tumors of the hypophysis of different kinds 
has been definitely determined, but the character of the tumors in some cases would 
indicate increase of function, in other cases diminution or loss. 
The cause of the nodular hypertrophy of the thyroid gland, occurring so fre- 
quently in many regions, is unknown. 
§ 78. Regeneration is that process through which tissues which have 
been destroyed are restored. It is the result of new-formation of cells, 
which arise' through the division of preexisting cells. 
Regeneration presupposes that the injured tissue is capable of pro- 
liferation, and is a phenomenon which in all cases is dependent on 
extrinsic causes. In the fully developed organism, each tissue can pro- 210 
THE PROGRESSIVE CHANGES. 
duce only new tissue of its own or a closely related kind. The specifi- 
city of tissues is so decided that epithelial cells can never give rise to 
connective tissue, and connective tissue can never produce epithelium. 
Ectodermal cells cannot produce intestinal epithelium; kidney epithelium 
can produce only cells having the character of kidney epithelium, but 
never liver-cells or those of mucous glands, or connective tissue. Muscle- 
tissue can arise only from muscle-cells. Nerves and neuroglia can never 
arise from connective tissue. Only cells which are closely related can 
arise from the same parent-tissue. Thus the periosteum can produce 
Fig. ii8.—Healing ulcer of the small intestine, with formation of new gland-tubes in the 
proliferating submucosa. (Muller’s fluid, hxmatoxylin). a, Mucosa; b, submucosa; c, d, muscu- 
laris; e, serosa; f, remains of the floor of the ulcer not yet covered over with epithelium; g, over- 
hanging edge of the ulcer; h, portion of floor of ulcer covered with epithelium; i, newly formed 
glands in the submucosa; k, deep crypt lined with epithelium, x 18. 
ordinary connective tissue, cartilage, or bone — that is, tissues which are 
modifications of the same connective-tissue. 
In tissue defects in which only single cells are lost (for example, 
in the loss of single connective-tissue cells), or in more extensive de- 
struction of cells without interruption in the continuity of the connective 
tissue of the blood-vessels (as the loss of localized areas of surface epi- 
thelium, or a group of gland cells or of pulmonary epithelium), com- 
plete regeneration, restitutio ad integrum, may take place, and the tissue 
be restored to a condition corresponding to that existing before the in- 
jury. After injuries in which the continuity of the mesodermal support- 
ing tissue is broken, with or without associated injury to tissues of ento- 
and ectodermal origin, regeneration is incomplete; at the point of in- 
jury tissue is formed which departs more or less from the normal in both 
structure and function. In general this is newly formed connective tissue, 
designated scar (Fig. 117, d) or cicatricial tissue. Defects of the skele- 
ton are replaced by scar-tissue which arises from the periosteum and 
endosteum, and by virtue of the peculiar properties of these tissues new 
bone develops in the scar, the structure coming eventually to resemble that 
of normal bone. 
In many instances cicatricial tissue consists purely of vascularized con- 
nective tissue (Fig. 117, d). Scars bordering on ectodermal or entoder- 
mal tissue may become covered by epithelium (Fig. 117, e). Occasionally REGENERATION. 
211 
the structure of cicatricial tissue may be modified, in that specific tissue- 
formations grow i)ito it secondarily or are preserved in it as remains of 
preexisting structures. The first process occurs most frequently in scars 
of the mucous membrane of the in- 
testine (Fig. 118), and of glands 
in the neighborhood of their ex- 
cretory ducts. In defects of 
mucous membranes which are re- 
placed by scars formed through 
proliferation of connective tissue 
(Fig. 118, b, /), the surface is first 
covered with epithelium (g, h, k), 
later epithelial ingrowths develop 
which bear the character of tubular 
glands (i). Gland-ducts (bile- 
ducts, ducts of the salivary glands) 
may grow into developing scar- 
tissue, and form new tubes or solid 
cords of cells. Such new-forma- 
tion of ducts may occur not only 
in the neighborhood of traumatic 
injuries, but also in the course of 
inflammations of the glands in 
question. 
On the other hand, regeneration 
of gland-tissue proper in the neigh- 
borhood of scars is wanting in the 
majority of instances, (liver, kid- 
neys, testicles, ovaries, thyroid, 
mammary glands). Only in the 
salivary glands does the develop- 
ment of new ducts lead to the 
formation of gland-lobules. 
In muscle-scars (Fig. 119) it 
is said that new muscle-fibres (d) 
grow from the ends of the old ones 
(a), so that the scar becomes 
gradually replaced by muscle. 
The remains of specific tissue- 
elements in the area of cicatrization 
may be observed in both muscles 
and glands, especially at the per- 
iphery of traumatic injuries and 
anaemic necroses (Fig. 120), and 
in inflammatory foci. The gland- 
ular remnants in the scar usually 
present an atrophic appearance, 
(Fig. 120, b), but islands of normal 
tissue (d) may also be enclosed, 
and it is possible that these may 
even undergo compensatory growth. 
In inflammatory processes in 
Fig. ng.—Scar of muscle and tendon, thirty, 
two days old (Flemming’s solution, Van 
Gieson’s). a, Old muscle; b, tendon; c, scar; 
d, newly formed muscle-fibres, x too. 212 
THE PROGRESSIVE CHANGES. 
glandular organs characterized by destruction of perenchyma, and by 
the regeneration and overgrowth of connective tissue, there are often 
seen atrophic remains of gland-tissue, and between these, islands of un- 
injured gland-tissue that have undergone hypertrophy. 
The mass of the scar is rarely equal to the mass of the tissue lost; 
there persists after the loss of considerable tissue a more or less marked 
defect. In circumscribed areas of skin, mucous membranes, glands, 
brain, etc., such a defect gives rise to cicatricial depression. Numerous 
Fig. 120.—Peripheral zone of an embolic scar (Muller’s fluid, hsematoxylin and eosin). 
a, Scar showing obliterated glomeruli, but no tubules; b, indurated tissue with atrophic tubules, 
the glomeruli being preserved; c, normal cortical tissue; d, island of normal tubules in the 
scar, x 30. 
cicatricial depressions in an organ may occasion atrophy characterized 
by irregular configuration of the surface. 
The loss of tissue en masse, for example, a toe, is in man never 
replaced. Such defects are closed by scar-tissue which on superficial 
parts of the body becomes covered with epithelium. 
In man and other mammals, the regenerative capacity of tissues is rela- 
tively slight. This depends on the fact that human and other mammalian cells 
are so highly differentiated that they are unable to revert to such a low embryonal 
state as to produce different forms of tissue. In spite of this limitation the regen- 
erative powers are sufficient to restore continuity and to preserve the external 
covering of the body. If as the result of local loss of tissue, the life of the organ- 
ism be endangered through inability of the tissues to restore the lost part, there 
exists in certain organs (liver, kidneys) the power of compensating for such loss 
through hypertrophy of remaining normal tissue. 
In the lower animals the power of regeneration is greater than in mammals; 
and further is greater in the earlier stages of ontogenesis, so that, in many animals 
(tritons, ascidians, echinoderms, teleosts), the first two or even the first four 
segmentation cells still possess the power of forming an entire embryo.. Insects 
possess during the larval state marked power of regeneration, which later is lost. 
In protozoa each animal may quickly supplement itself through division. In 
the fresh-water polypi fragments of the body may develop into the entire animal. 
The angle-worm is able to replace either tail or head end when these are cut off. 
The wood-louse can replace its feet and antennae, the snail its tentacles and anterior 
extremity, crabs and crayfish their claws and legs. Salamanders are able to restore 
legs, eyes, and tails, and lizards and slow-worms their tails, when these are broken REGENERATION. 
213 
off. In frogs, snakes, and fishes, on the other hand, the power of regeneration 
diminishes as the scale of animal life is ascended, yet this does not happen equally 
in the case of all animals, and animals closely related to each other may show dif- 
ferent capacities for regeneration. Further, in the same animal the regenerative 
power is not the same in all organs; for example, in tritons the regenerative 
capacity of the internal organs is slight. Moreover, the power to form a new 
portion of the body, as a tail or extremity, for example, does not prove that all 
the tissues of the portion of the body in question possess an especial capacity for 
proliferation. In crayfish and crabs regeneration of the claws and legs takes place only 
from certain places; in injuries occurring at other points, the new extremity is 
thrown off only at that place where a new-formation is possible. In tritons, 
fractures of the bones heal slowly, although they are able to reproduce their 
extremities. 
§ 79. The cause of cell-proliferation underlying hyperplastic and re- 
generative changes in tissue varies according to the conditions under 
which proliferation occurs. 
The “stimulus” may consist in the removal of hindrances to 
growth, since experience teaches that the majority of the cells of the 
body possess the power to divide, even those cells in which the process 
of division has apparently been in abeyance for long periods of time. 
There may also be present a formative stimulus, which increases both 
the reproductive capacity and the tendency to reproduction. Such a 
stimulus may act independently — that is, without the removal of influ- 
ences inhibiting growth — this is assumed in cases in which after the 
loss of a portion of an organ the remaining portion (liver, kidney) 
undergoes compensatory hypertrophy, although, even in these circum- 
stances, it is difficult to exclude changes in the equilibrium of cells 
brought about mechanically or otherwise, and affecting the relationship 
of cells to one another or the elements of individual cells. 
The stimuli which are able to excite growth and cell division are 
known in part only. They appear to be identical with the stimuli which 
excite or increase functional and nutritive activity. In muscles, hyper- 
trophy is brought about by increased contraction following nervous excita- 
tion. Liver and kidney tissue undergo hypertrophy when, as a result of 
loss of a large area, the remaining portions are obliged to do an increased 
amount of work. 
Whether other formative stimuli exist cannot be stated with certainty. 
Increased supply of blood and nutrition, believed by many to act as a 
formative stimulus, is not in itself sufficient to excite regeneration of 
cells; it gives rise merely to increased deposit of fat. Increase of the 
temperature of tissues may hasten the process of cell division and thus 
promote tissue proliferation; but it is doubtful if it can directly excite 
proliferation in resting tissues. The action of heat followed by prolifera- 
tion (for example, in the skin) produces local changes of a degenerative 
nature, so that the occurrence of proliferation may be explained as due 
to the removal of influences that otherwise inhibit growth. 
There are chemically active substances that are capable of exciting 
proliferation. Thus, slight irritation of the skin produced by iodine is 
capable of causing proliferation without preceding detectable degenerative 
changes, although it is probable that degenerative changes in these circum- 
stances do occur, but are of such nature as readily to be overlooked. In 
addition, such substances as Sudan III, scarlet-red, ether, indol, etc., 
when injected in the tissues, provoke a remarkable growth of epithelium 
and other tissues that, in certain instances, may resemble a neoplasm. 
It has been suggested that the effect of such substances is due to solution 214 
THE PROGRESSIVE CHANGES. 
of the lipoid membrane which is supposed to envelop each cell, thus 
exposing the nucleus to influences from which it otherwise is protected. 
Finally, it must be noted that even the hypertrophied muscles and 
glands, following increased activity, cannot be regarded as the direct 
result of nervous or chemical stimuli, but we must assume that, with 
the increased labor, there is excessive consumption of cell elements 
which excites regenerative processes, the latter leading not only to restora- 
tion of the elements that are lost, but also to enlargement of the cell 
mass, together with the formation of new cells. 
§ 80. The division of the nucleus and cell-body, on which the 
formation of new tissue depends, may occur through direct segmenta- 
Fig. 121. 
Fig. 122. 
Fig. 123- 
Fig. 12i.—Enlarged nucleus. Increase in the chromatin framework. 
Fig. 122.—Thick, open skein, with segmentation of the threads into chromosomes; the 
nucleolus and nuclear membrane have disappeared. 
Fig. 123.—Grouping of the completed chromosomes into a star-or wreath-form. 
tion, that is, through transverse constriction of the elongated nucleus 
and protoplasm without increase or characteristic grouping or move- 
ment of the chromatin elements of the nucleus. It appears, however, 
that direct division of the nucleus leads to the production of cells 
which are able to form new tissue only when it is connected with 
that form of cell-division known as karyokinesis or karyomitosis or 
indirect segmentation, which is characterized by increase of the nuclein 
or chromatin, and a definite cycle of changes of form and movements on 
the part of the latter. 
Karyomitosis follows a typical course in the normal growth of tissue, 
but deviations are frequently seen in pathological formations. 
A resting nucleus consists of the nuclear membrane, and the nuclear 
contents. The latter are composed of a colorless nuclear fluid and the 
nuclear substance. To the nuclear substance belong the nucleolus and 
scattered granules and threads which form a framework staining with 
nuclear stains. 
When the nucleus undergoes division, there occurs, first, increase of 
the chromatin, and the chromatin framezvork becomes more distinct 
(Fig. 121). The nuclear substance then forms a close skein, which, with 
disappearance of the nuclear membrane and the nucleolus, becomes 
changed into an open skein with thick threads (Fig. 122), whose indi- 
vidual components divide themselves into nuclear segments or chro- 
mosomes (in man these number eighteen) (Figs. 122, 123). 
These segments then group themselves in the equatorial plane of the 
nucleus with their angles directed toward the centre, forming, when KARYOKINESIS. 
215 
viewed from the polar aspect, a wreath-like (Fig. 123), and later a star- 
like figure, lying in the equatorial plane, that has been designated the 
mother-star (Figs. 124, 125), or equatorial plate. 
Sooner or later two poles become visible in the so-called polar field 
that is, two extremely small spherules, which are known as the polar or 
central corpuscles or centrosomes. At first these lie close together, but 
later separate and act as centres about which the nuclear elements group 
Fig. 124. 
Fig. 125. 
Pig. 126. 
Fig. 127. 
Fig. 128. 
Fig. 129. 
Fig. 124.—Completely developed mother-star; polar view. 
Fig. 125.—Mother-star; equatorial view. 
Fig. 126.—Stage of metakinesis. Single loops visible, their angles pointed toward the pole; 
delicate spindle-figure within the nucleus. 
Fig. 127.—Daughter-star; side view (nucleus barrel-shaped); spindle-figure in the nucleus 
and the radial arrangement of protoplasm are visible. 
Fig. 128.—Daughter-stars separated; the upper one presenting polar aspect, the lower one a 
side view. 
Fig. 129.—Daughter-skein with fine threads (above), and with lattice-work (below). Com- 
pleted division of the protoplasm. 
themselves. Between these there is formed the nuclear spindle (Figs. 
126, 127) which consists of fine threads which do not stain with nuclear 
stains, and converge in the polar corpuscles. In the neighborhood of the 
polar corpuscles themselves the granules of the protoplasm present a 
radial arrangement, giving rise to figures (Fig. 127) which are known 
as ray-figures, stars, or attraction-spheres. In the succeeding stage of 
division of the nucleus, a movement takes place among the chromosomes 
leading to the formation of loops, whose angles are directed toward the 
pole. Later the loops divide in halves which, following the direction of 
the spindle-fibres, move toward the poles and form two stars (Figs. 126- 216 
THE PROGRESSIVE CHANGES. 
128) which are known as daughter stars. From the star-figures the 
daughter-star passes successively through the thick-skein and then the 
fine-skein stage (Fig. 129, upper part) which finally changes into the 
nuclear framework (Fig. 129, lower part). During the later stages of 
the process a new nuclear membrane is formed. 
In the stages of the segmented skein, or later as may be seen in the 
large nucleated cells of cold-blooded animals, there occurs longitudinal 
Fig. 130. 
Fig. 131. 
Fig. 130.—Mother-star, with chromosomes split longitudinally. (After Rabl.) 
Fig. 13i.—Metakinesis. The halves of the chromosomes are separating from each other and 
turning toward the poles. (After Rabl.) 
splitting of the chromosomes (Fig. 130). In the change of position of 
the chromosomes known as metakinesis the halves of the split threads 
separate from each other (Fig. 131) so that each daughter-star receives 
half of the substance of each chromosome. 
Division of the cell-protoplasm usually takes place at the time 
the daughter-star changes into the ordinary nuclear condition, and con- 
sists in constriction and separation of the protoplasm (Fig. 129). It 
is probable that a complicated interrelation- 
ship exists between the nucleus and cell- 
protoplasm; but the nucleus is to be re- 
garded as the more highly organized sub- 
stance, as the centre of cellular potentiality. 
The nuclei are also the bearers of heredity, 
while the protoplasm governs the relations 
of the cell with the outer world. 
Variations from the typical karyokin- 
esis may consist in the occurrence of 
pluripolar division in place of the bipolar, 
so that two to six or more nuclear 
spindles and a correspondingly increased 
number of equatorial plates (Fig. 132, a) 
may be formed. Further, in place of the 
simple mother-star there may be formed a complicated figure out of the 
chromatin loops, from which several daughter-stars may be evolved. 
Not infrequently there occur asymmetrical divisions of the nucleus (Fig. 
132, b, c), particularly in tumors, but also in regenerative or inflammatory 
new-formations of tissue. 
There are also divisions of the nucleus which are characterized by 
abnormal size, abnormal richness in chromatin, and manifold variations 
Fig. 132.—a, Pluripolar division- 
figure; br c, asymmetrical division- 
figures. ATYPICAL CELL DIVISION. 
217 
of form. As types of such division are the large oval or bean-shaped 
(Fig. 133), knobbed or convoluted, lobulated and branched (Fig. 134), 
wreath-shaped, linked, basket-shaped (Fig. 135) nuclei, and other forms. 
Finally, there are occasionally found in the cells more or less extensive, 
indistinctly-outlined heaps of granular and lumpy chromatin (Fig. 136). 
Fig. 133. 
Fig. 134. 
Fig. 135, 
Fig. 136 
Fig. 133.—Cell with oval, slightly knobbed giant-nucleus, rich in chromatin. 
Fig. 134.—Cell with lobulated giant-nucleus. 
Fig. 135.—Cell with basket-shaped giant-nucleus. 
Fig. 136.—Cell with large masses of chromatin. All these cells from a sarcoma of bone. 
(Stroebe, Beitriige von Ziegler, VII.) 
Such nuclear forms are found in the cells of the bone-marrow, 
and in tumors which arise from the bone-marrow or periosteum, 
but have been observed elsewhere, particularly in certain sarcomata. 
Certain of these forms are due to contraction, and have nothing to do 
with cell-division. In other cases these changes of size and form pre- 
cede division of the 
nucleus through con- 
striction, sometimes 
with, sometimes with- 
out increase of the 
chromatin. Arnold 
has designated divi- 
sion by constriction 
with increase of the 
chromatin as indirect 
fragmentation, that 
without such increase 
as direct fragmenta- 
tion. Indirect frag- 
ment a tion differs 
from mitosis or in- 
direct segmentation in 
the lack of orderly 
arrangement of the 
chromatin in threads, 
and in the irregularity with which the separation of portions of chromatin 
results in new nuclei. 
Variations in the cell-protoplasm occur, either as total failure of the 
protoplasm to divide after division of the nucleus has taken place, or 
as delayed division. These phenomena are observed in both mitotic and 
amitotic division of the nucleus, and lead to the formation of multinuclear 
giant-cells (Fig. 137). 
Fig. 137.—Proliferating adipose tissue from the subcutaneous 
panniculus, twenty-six days after cauterization with trichloracetic 
acid (formalin, haematoxylin). a, Multinuclear fat-cells; b, pro- 
iferating connective tissue, x 300. 218 
THE PROGRESSIVE CHANGES. 
Cells of the bone-marrow and of tumors arising from the bones show 
this phenomenon with special frequency. Proliferating fat-cells like- 
wise form multinuclear giant-cells (Fig. 137, a). Besides this form of 
multinuclear giant-cell there also occur those formed by the confluence 
of cells, which are known as syncytial giant-cells. (Compare the 
sections on Inflammation and Tuberculosis). 
Literature. 
(Cells and Cell-division.) 
For a complete exposition, see Wilson: “The Cell in Development and 
Inheritance,” New York, 1897. 
II. The Processes of Hyperplasia and Regeneration in Various 
Tissues. 
§ 81. The morphological changes in the regeneration and hyper- 
plasia of epithelium are relatively simple. The karvomitoses (Fig. 
138, a-d) show for the greater part a typical course. The division of 
the protoplasm takes place either in the later stages of nuclear division 
or follows shortly thereafter. Giant-cells may arise through failure of 
the protoplasm to divide. 
Epithelium arises only from epithelium. It is to be noted, however, 
that under certain conditions regenerating epithelium may change its 
character. This may occur, 
for example, in cicatriza- 
tion of ulcers in the trachea. 
Defects in the ciliated col- 
umnar epithelium are re- 
paired by low columnar or 
flat cells which later be- 
come changed into high 
columnar cells. 
Small losses of super- 
ficial epithelium are re- 
placed through regenera- 
tive growth of neighboring 
cells (Fig. 139, d, diy d2), 
The epithelium bordering 
on the defect pushes over 
the denuded surface and 
begins to proliferate. The 
division of the nucleus and cell-protoplasm takes place not only on the 
edge of the defect, but at some distance from it. In the intestine 
the loss of superficial epithelium is made good by proliferation of the 
epithelial cells in the crypts of Lieberkuhn. Likewise glandular epithe- 
lium may be restored after loss, provided the basement membrane 
on which it rests is not changed. After destruction of liver-tissue the 
epithelium of the bile-ducts (Fig. 138) proliferate, and the cell-division 
may extend to a relatively great distance from the site of injury. Ex- 
perimental wounds of the liver heal through the formation of connective 
tissue, into which offshoots of the bile-ducts penetrate, while local re- 
production of liver-tissue does not take place. Likewise, in the kidneys, 
Fig. 138.—Regenerative proliferation of the epithelium 
of bile-ducts, in the neighborhood of a wound of the liver 
five days old (Flemming’s solution, safranin). a, Enlarged 
nucleus of epithelial cell, with increase of chromatin; b, 
epithelial cell with mother-skein; c. epithelial cell with 
mother-star; d, epithelial cell with daughter-skein; f, con- 
nective-tissue cell with daughter-star, x 400. REGENERATION OF EPITHELIUM. 
219 
testicles, thyroid, and ovary the production of glandular tissue in the 
connective-tissue scar is slight or wanting, and does not lead to the 
formation of functionating tissue. In the salivary and mucous glands, 
Fig. 139.—Healing of blister caused by a burn (alcohol, alum-carmine). Section through the 
skin of a cat’s paw, forty-eight hours after the production of a blister, a, Horny layer; b, rete 
Malpighii; c, corium; d, newly formed epithelium; d\, dz, newly formed epithelium already 
differentiated into different layers; e, old, degenerated epithelium; /, pus-cells; g, exudate; 
h, sweat-glands, x 25. 
on the other hand, branching of the gland-ducts is followed by the forma- 
tion of new alveoli. 
When portions of the mucosa and submucosa of the intestine are lost 
as a result of ulcerative processes, there occurs during healing glandular 
proliferation, which, according to the nature of the defect, forms partly 
typical, partly atypical (Fig, 118, i) glands that grow into the submucosa. 
Fig. 140.—Development of blood-vessels by formation of offshoots; from preparations taken 
from inflammatory granulations, a, b, c, d, Different forms of offshoots, some solid (b, c), others 
becoming hollow (a, b, d), some simple (a, d), some branching (b, c), some without nuclei 
(a, d) ; some with nuclei (b, c) ; d, offshoot to which fibroblasts have applied themselves. 220 
THE PROGRESSIVE CHANGES. 
The new formation takes its start from the old glands, whose epithelium 
pushes over the edge and base of the ulcer (Fig. 118, g, h) and lines any 
depressions which may be present (k). In similar manner ulcerative 
defects of the gastric mucosa are made good; and even extensive ulcers 
may become covered with gland-containing mucosa, although the glands 
seldom attain mature development. 
The epithelial portions of the uterine mucosa which are lost, as a 
physiological process, during menstruation and parturition, are restored 
in a manner similar to the healing of pathological defects of the endo- 
metrium. The new-formation of epithelium takes its origin from the 
glandular remains. 
Compensatory hypertrophy of a kidney or liver is brought about 
through the enlargement of existing renal tubules, 
or liver-columns respectively. After wounds or 
other injuries of the liver and kidney it is highly 
doubtful if regeneration of functionating par- 
enchyma ever occurs. 
§ 82. If tissue is to be reproduced in considera- 
ble amount, the presence of blood-vessels is essen- 
tial, since it is only through these that sufficient 
nutrition can be brought to the growing tissue. 
The development of new blood-vessels takes 
place through the formation of offshoots from pre- 
existing vessels (Fig. 140). In the vessel-wall 
there occurs proliferation of the endothelium (Fig. 
141), in which division of the nucleus occurs by 
karyomitosis. 
As the first step in the formation of a new 
vessel, there is seen on the outer side of some 
capillary loop a tent-like elevation which terminates 
in a fine protoplasmic thread standing out from the 
vessel (Fig. 140, a), and gradually becoming 
longer and longer. There is thus formed at the 
beginning an arch of granular protoplasm, which 
ends in a protoplasmic thread (a), and after a time 
comes to contain nuclei. This thread may penetrate 
into another vessel, or unite with some other arch 
which it meets, or may finally return to the same vessel from which it 
started. 
Further, from the solid arch itself new secondary arches may spring 
(Fig. 140, b, c), or at its end there may be formed a club-shaped swell- 
ing (O- 
The originally solid arch becomes hollow after a certain time (b, a) 
through liquefaction of its central part, and the space thus formed im- 
mediately or soon comes to communicate with the lumen of the blood- 
vessel (a), or else there is developed an extension of the vessel-lumen 
into the arch. The blood of the mother-vessel finds its way at once into 
the daughter-vessel and widens it. As the hollowing-out process ad- 
vances and extends to the point of entrance of the protoplasmic arch into 
another vessel, there is finally formed a new capillary loop permeable for 
blood. 
Fig. 141.—Two vessels 
of the papillary body, 
whose endothelial cells are 
in process of proliferation 
(six days after painting 
the back of the foot with 
tincture of iodine) (Flem- 
ming’s solution, safranin, 
and picric acid), a, Nu- 
cleus with chromatin 
framework; b, b 1., skein- 
forms; c, mother-star; d, 
connective-tissue cell with 
nuclear division-figure; e, 
lymphocytes. X 350. REGENERATION OF BLOOD-VESSELS. 
221 
Immediately after the opening of a way for the blood the capillary 
tube possesses a homogenous wall. After a certain length of time the 
protoplasm groups itself about the nuclei, which have in the mean time 
divided and multiplied in the wall, so that ultimately the capillary 
comes to be made up of flattened endothelial cells. As Arnold has 
shown, the boundaries of the individual endothelial cells may be made 
visible through the injection of a solution of silver into the vessel. At 
this time the wall for the greater part appears thickened, partly from 
proliferation of the cells of the vessel-wall, but also from the fact that 
formative cells from the neighborhood heap themselves on the surface of 
the young vessel (Fig. 140, d), adapt themselves to the wall, and so 
strengthen it. 
At the time of the formation of the offshoots, the endothelial cells of 
the capillaries are swollen, and often reach such a size that the cross- 
section of a capillary looks not unlike a gland-tube lined with epithelium 
(Fig. 142, d). At the same time 
mitotic figures appear in the 
endothelium (Fig. 141, a-c), and 
later division of the nucleus and 
cell-protoplasm takes place. 
In what relation this pro- 
liferation stands to the forma- 
tion of the offshoots is not 
clearly understood; but doubt- 
less the latter spring from pro- 
liferating cells and represent 
cell-processes. The proliferation 
of endothelium, on the other 
hand, does not always lead to 
new vessels, but may result only 
in thickening of the vessel-wall 
and finally in obliteration of the 
lumen. 
In the transformation of 
newly formed capillaries into arteries and veins the increase of tissue is 
the result of continued proliferation of the cells of the vessel-wall. Ihe 
muscle-fibres first appearing in the outer wall of the capillary tube are 
finely-branched cells whose nuclei lie parallel to the long axis of the 
capillary and whose processes surround the endothelial tube. After 
about fourteen days elastic fibres may appear in new-formed vessels 
(arteries). 
Fig. 142.—Proliferating periosteum, four days 
after fracture of a bone (Flemming’s solution, 
haematoxylin). a, Osteoblasts with large nuclei; 
b, osteoblast with division-figure; c, two _ cells 
shortly after division, showing thread-skein in 
nucleus; d, blood-vessel with proliferating en- 
dothelium; e, endothelial cell with nuclear division- 
figure; f, large lymphocytes; g, small lymphocytes. 
x 350. 
It is difficult to decide whether the new-formation of blood-vessels is intra- 
cellular through the hollowing out of the solid buds of a single cell or whether 
it is intercellular through the formation of a space between two cells. The off- 
shoots from the sides of the vessel-wall or from the end of the vessel give the 
impression of solid cell processes, but the possible participation of the protoplasm 
of two cells in the formation of such processes cannot be excluded. 
The new-formation of lymph-vessels in new connective tissue is intercellular. 222 
THE PROGRESSIVE CHANGES. 
Literature. 
(New-formation of Blood-vessels.) 
Arnold: Die Entwicklung d. Blutcapillaren. Virch. Arch., 53 Bd., 1871; 54 Bd., 
1872. 
Flemming: Theilung von Pigmentzellen u. Capillarwandzellen. Arch. f. mikr. 
Anat., 35 Bd., 1890. 
Mayer: Muskularisierung der Kapillaren. Anat. Anz., xxi., 1902. 
Maximow: Entziindl. Neubild. v. Bindegewebe. B. v. Ziegler, Supp. v., 1902. 
§ 83. The connective-tissue structures are almost all capable of 
both hyperplastic and regenerative proliferation. This is especially true 
of formed connective tissue, and periosteum and endosteum; while 
cartilage possesses but slight regenerative capacity, and fully developed 
Fig. 143.—Isolated cells from a granulating wound (picrocarmine). a, Lymphocyte; 
ai polynuclear leucocytes; b, different forms of mononuclear fibroblasts; c, formative cell with 
two nuclei; c 1, multinuclear formative cells; d, fibroblasts in stage of connective-tissue formation; 
e, fully developed connective tissue, x 500. 
bone none at all. Usually proliferating fibrous connective tissue gives 
rise to fibrous tissue, both in independent formations of connective tissue 
and in the supporting tissue of the glands, lungs, lymph-nodes, etc. The 
periosteum, bone-marrow, perichondrium and cartilage produce in addi- 
tion to fibrous connective tissue and marrow-tissue also cartilage and 
bone. 
Hyperplastic and regenerative proliferations of connective tissues 
are ushered in by cell-division in the course of which karyomitoses 
occur. 
After injuries of the tissue these proliferations begin soon, for ex- 
ample, in wounds of the skin, or in fractures of bones; in the latter case 
even as early as the second day single cells of the periosteum become en- 
larged and show division-figures. Besides mitoses, direct division of 
nuclei takes place. REGENERATION OF CONNECTIVE TISSUE. 
223 
\\ hen only a few cells are destroyed newly formed cells replace them 
without the occurrence of marked structural changes in the tissues. If, 
on the other hand, a considerable amount of new tissue is produced in a 
short time, the proliferating cells form embryonic tissue consisting 
of cells, blood-vessels, and fibrillated ground-substance (Fig. 142). The 
extent of such formation naturally varies and is dependent partly on the 
capacity of the tissue for proliferation, and 
partly on the lesion leading to the prolifera- 
tion. 
Proliferating cells are always larger than 
the cells of fully developed, resting connec- 
tive tissue. They contain one, sometimes 
two large, bladder-like nuclei with nucleoli, 
(Figs. 142, 143), though multinuclear cells 
(Fig. 143, rx), so-called giant-cells, also occur. 
In association with proliferating cells there 
are often cells that have escaped from the 
blood vessels, but which take no part in the 
formation of the new tissue. 
All those cells which are the antecedents 
of future tissue are designated formative cells; those giving rise to 
fibrous connective tissue are called fibroblasts (Figs. 143, b, c, d, e; 144, 
a), those forming cartilage and bone are known as chondroblasts (Fig. 
146, a, c) and osteoblasts (Fig. 142, a, b, c) respectively. 
The shape of formative cells varies greatly (Fig. 143, b, c, d, e), and 
is dependent, partly on spontaneous changes of form and partly on the 
,, _ . , 
nective tissue from fibroblasts 
pihcyafinemiground- 
<:)'bfifiroblast'witiTjacen t*'fibres! 
x 400. 
Fig. 14s.—Scar of the skin, two years old, showing newly formed elastic fibres (alcohol, 
orcein), a, Corium with normal elastic fibres; b, scar with newly formed elastic fibres, x 500. 
influence of environment, which under certain conditions compels the 
cells to take definite forms. The cells producing connective tissue usually 
present the greatest variety of form. 
When connective tissue is developed from cellular embryonic 
tissue, fine fibrillce (Fig. 143, d, e) appear in certain parts of the cell- 
protoplasm, or there is formed a homogeneous intercellular substance 
(Fig. 144, b) in which fibrillse later appear. The formative cells at the 
same time diminish in size, and lie, for the most part, in small clefts 
(Fig. 143, e) in the ground-substance. 224 
THE PROGRESSIVE CHANGES. 
Elastic fibres appear in newly formed connective tissue at a late 
stage, about three weeks at the earliest, and at the beginning form fine 
Fig. 146.—Periosteal formation of cartilage in a fracture five days old (Flemming’s solution, 
haematoxylin, glycerin). o, Cellular embryonic tissue; b, cartilare; c, proliferating periosteal 
chondroblasts; d, cartilage-cells; di, da, nuclear division- figures in cartilage-cells; e, ground- 
substance of embryonic tissue; f, ground-substance of the cartilage; g, capsule of cartilage-cells; 
h, proliferating endothelium of a blood-vessel, x 320. 
fibrillse, which (Fig. 145, b) represent processes of older fibrils (a) and 
in part arise independently. They are a differentiation product of the 
ground-substance and have no relation to the cells. 
Fig. 147.—Endosteal formation of bone from masses of osteoblasts (Muller’s fluid, picric 
acid, haematoxylin, Carmine). Preparation from the inner callus of a fourteen-day old fracture 
of the fibula of a man twenty-five years of age. a, Fat-cells of the endosteum; b, endosteum con- 
taining no fat; c, scattered osteoblasts; d, groups of osteoblasts; e, first step in the formation of 
the ground-substance of bone; f, developing trabeculae of bone; g, layer of osteoblasts lying upon 
the newly formed trabeculae of bone; h, blood-vessel. X 150. 
They develop most abundantly in newly formed connective tissue in 
the blood-vessels and in the skin, but also in other regions, for example, 
in connective-tissue proliferations of glands, serous membranes, etc. REGENERATION OF BONE AND CARTILAGE. 
225 
In the development of hyaline cartilage there appears between the 
cells a hyaline basement-substance (Fig. 146, /), while the chondroblasts 
(c) assume a more rounded form (d). In time the ground-substance in- 
creases, the chondroblasts grow smaller and lie in rounded cavities whose 
walls are denser than the rest of the ground-substance and later form the 
part of the basement-substance called the cartilage-capsule (g). 
In the development of bone from cellular embryonic tissue there 
appears between the formative cells a dense homogeneous or fibrillated 
Fig. 148.—Formation of osteoid trabeculae from the proliferating periosteum. Preparation 
from a fourteen-day old fracture (Muller’s fluid, picric acid, hematoxylin, carmine), a, Fibres 
belonging to the outer periosteum; b, embryonic tissue; c, osteoid tissue; d, cartilage; e, bone- 
marrow. x 75. 
basement-substance (Figs. 147, e, f; 148, c), osteoid tissue, which becomes 
impregnated with lime-salts and transformed into bone. When the 
ground-substance between the osteoblasts is of a loose fibrillar nature 
(Fig. 147, d) the transition into osteoid tissue is brought about through 
thickening of the ground-substance (e, /). The osteoblasts lie in spaces 
of irregular outline (Figs. 148, c; 149, b), and are known as bone-cor- 
pascles. In extensive development of cellular embryonic tissue the 
change into bone is limited to certain parts of the tissue, and trabeculae 
(Fig. 148, c) are formed, which do not 
undergo full development into bone 
and are not calcified, so-called osteoid 
trabeculae. The embryonic tissue (b) 
lying between becomes changed into 
marrow-tissue, the cells being united to 
each other through processes, while be- 
tween them there appears a fluid base- 
ment-substance, in which round-cells later 
are embedded. If bone-tissue is to be 
deposited around old bony trabeculae, the 
osteoblasts (Fig. 149, c) arrange them- 
selves on the surface of the latter, and 
later produce bone (b) which appears as a lamella. 
Fibrillated connective tissue, bone, and cartilage are closely related 
and one may be transformed into the other (see § 88). 
Mucous tissue arises from embryonic tissue through the forma- 
tion of a mucin-containing, homogeneous, gelatinous basement-substance 
between the cells, which become united through processes to form a net- 
work. 
Fig. 149. — Formation of bone, 
through deposits made by osteoblasts 
upon the surface of old bone (Mul- 
ler’s fluid, picric acid, haematoxylin, 
carmine). a, Old bone; b, newly 
formed bone; c, osteoblasts, x 260. 226 
THE PROGRESSIVE CHANGES. 
Lymphadenoid tissue can develop from embryonic tissue through 
the formation of a supporting reticulum in which lymphocytes gather. 
In injured lymph-nodes, the cells of the reticulum proliferate and form 
fibrous tissue; development of this connective tissue into lymphadenoid 
tissue either does not take place at all or but to a very slight degree. 
Spleen-tissue is not formed anew after injury; the wound heals 
through cicatrisation, nor does compensatory hypertrophy take place after 
the removal of large portions of the organ. 
Fat-tissue arises through the taking up of fat into fibroblasts, the 
cells becoming changed through the confluence of the infiltrated fat- 
droplets. 
The basement-substance of the tissues described above is a pro- 
duct of the protoplasm of the formative cells. Whether portions of 
the cell-protoplasm are changed directly into intercellular substance, or 
whether they secrete the latter, or separate it from the intercellular fluid, 
is a difficult question to answer; it is probable that only the first two 
methods of formation occur. 
Fibrillar connective tissue can develop from any connective tissue possessing 
the power of proliferation, but there must first be formed an intermediate stage of 
embryonic tissue. 
Bone arises from the periosteum, perichondrium, and endosteum, but may 
also develop from other connective-tissue substances, for example, from the inter*, 
muscular connective tissue and the connective tissue of blood-vessels. 
Cartilage arises from proliferating perichondrium, periosteum, endosteum, and 
from cartilage itself; but may also be developed from other connective tissues, for 
example, the connective tissue of the testicle and parotid. 
New lymphadenoid tissue may, under pathological conditions, arise either from 
lymphadenoid tissue or fat-tissue {Bayer) or from fibrillated connective tissue. 
It is formed from the latter most frequently in the connective tissue of the mucosa 
and submucosa of the intestinal tract, as well as in the glandular organs; rarely in 
the intermuscular connective tissue. New hsemolymph-nodes are formed in adipose 
tissue after splenectomy (IVarthin). 
Mucous tissue may develop from any proliferating connective-tissue substance, 
but rarely appears in large masses, and is usually a transitory form passing over 
either into fat or connective tissue. 
Fat-tissue develops particularly in those regions normally containing fat, but 
occurs also at times in other places, for example, in the reticular connective tissue 
of atrophic lymph-nodes, in the perimysium internum of atrophic muscles, etc. 
The close relationship of the connective-tissue substances to each other enables 
the different forms to pass from one to another without the need of an intermediate 
stage of embryonic tissue produced by proliferation. Further details in regard to 
this point are contained in § 88. 
§ 84. The regeneration of red blood-cells or erythrocytes occurs 
through mitotic division of nucleated young forms known as erythro- 
blasts (Bizzozero, Neumann, Flemming). In the adult this new- 
formation is restricted to the bone-marrow, and this is true also of other 
mammals, birds, reptiles, and tailless amphibians, while in the tailed 
amphibians and in fishes the spleen also shares in the process. In em- 
bryonic life the formation of the red blood-cell takes place throughout 
the vascular system, but later becomes restricted to the spleen, liver, and 
bone-marrow, and finally to the bone-marrow alone. 
The entrance of the red blood-cell into the circulation takes place 
after loss of its nucleus. 
In increased new-formation of red cells following loss of blood, as 
well as in chronic anaemias, nucleated red cells may appear in the circu- 
lating blood. The fatty marrow may again take on the character of REGENERATION OF BLOOD AND MUSCLE. 
227 
splenoid marrow, this change being accomplished by congestion of the 
blood-vessels with increase in the red cells of the marrow, while the fat 
in the recticulum disappears. 
The new-formation of colorless cells of blood and lymph, the 
leucocytes, occurs in the lymph-nodes and in the lymphoid deposits 
in the mucous membranes and spleen; and in the bone-marrow. The 
mononuclear cells, known as lymphocytes, develop almost exclusively 
in lymphoid foci, in the germinal centres of which mitoses may not in- 
frequently be found. (Fig. 150). The poly- 
nuclear leucocytes and eosinophile cells, on 
the other hand, are formed in the bone- 
marrow. Whether the large cells with clear 
nuclei known as mononuclear leucocytes, and 
the transition-forms with horseshoe-shaped 
nuclei, are formed in the bone-marrow is 
doubtful. They are often regarded as 
lymphocytes. 
A pathological increase of the colorless 
cells (leucocytosis) may take place through 
increased emigration of cells from the forma- 
tive tissues without actual increase in cell- 
production. Long-continued persistence of 
such an efflux, however, presupposes in- 
creased production. 
Transitory increase in the white cells is 
designated leucocytosis, while a permanent 
one is called leukccmia. The former is 
characterized by increase in the neutrophile 
polynuclear leucocytes, rarely by increase in the lymphocytes. Two forms 
of leukzemia are distinguished: lymphatic leukccmia, in which the 
lymphocytes are increased, and myeloid leukccmia, characterized by the 
appearance in the blood of myelocytes, mononuclear cells arising in the 
bone-marrow and provided with neutrophilic or eosinophilic granules. 
§ 85. The regeneration of transversely striated muscle takes its 
start from portions of old muscle-fibres; and although, after injury to a 
muscle, the intermuscular connective tissue may be excited to prolifera- 
tion, there is formed only connective tissue, or probably the sarcolemma 
of new fibres, but never new contractile substance. 
The first signs of formative activity in muscle-fibres after injury ap- 
pear in the nuclei, which become elongated and divide into a varying 
number of fragments. Mitotic division occurs early and seems to be 
the only way in which multiplication takes place. 
The behavior of the contractile substance of the muscle differs ac- 
cording to the nature and extent of the injury. In traumatic, toxic, and 
anaemic injuries it suffers fragmentation, so that the muscle-cells lie 
between the detritus of the muscle-fibres. Crushing and tearing bring 
about separation of the contractile substance. The ends of the muscle- 
fibres, in such case, may be conical, oblique, transverse, or irregular, but 
not infrequently become split into pointed filaments (Fig. 151, a). 
Mitotic division takes place, not only in nuclei that rest on living 
fibres (a), but also in the muscle-cells between the separated fibres (b) ; 
and in both places leads to the production of large cells, which form 
multinuclear masses at the ends of the muscle-fibres (e, f) as well as in 
Fig. 150. — Section from the 
germinal centre of mesenteric 
gland (after Flemming), a, Large; 
b, small lymphocytes; c, karyomi- 
toses; d, direct nuclear division or 
nuclear fragmentation; e, cells 
containing near the nucleus “ tin- 
gible bodies ” and small yellow 
pigment granules, whose signifi- 
cance is unknown, x 400. 228 
THE PROGRESSIVE CHANGES. 
the body of the fibres (c). Into these the transversely striated muscle- 
substance passes without a sharp line of demarcation. There occurs, there- 
fore, with the multiplication of nuclei an increase of the sarcoplasm of 
the muscle-fibres. 
The muscle-cells not connected with living contractile substance be- 
come changed into cells with large nuclei (b). Through continued divi- 
sion of the nucleus these cells become transformed into multinuclear 
protoplasmic masses (d) ; a scar in muscle tissue from eight to thirty 
Fig. 151.—Portions of muscle-fibres showing regenerative proliferation, from muscle-wounds 
of different ages (Flemming’s, safranin). o, Pointed ends of the split stump of a muscle-fibre, 
with nuclear division-figures, three days after laceration of the muscle; b, proliferated muscle- 
nuclei transformed into cells rich in protoplasm, one of which is in process of mitotic division; 
c, piece of a muscle-fibre eight days after tying the muscle; d, giant-cells, enclosing necrotic 
pieces of muscle, from a muscle scar twenty-six days old; e, f, muscle-fibres ending in proto- 
plasmic masses (muscle-buds), e, from a muscle scar ten days old; f, from one twenty-one days 
old; g, dividing muscle-fibres from a muscle-scar forty-three days old. x 315. 
days old, contains giant-cells which often enclose the remains of old mus- 
cle-fibres (d) in large numbers. 
New muscle develops for the greater part from the richly nucleated 
sarcoplasm, which appears in and at the ends of the fibres, and through 
increase of size causes increase in the thickness and length of the mus- 
cles. With the transformation of the sarcoplasm into fibrillse there 
gradually appears longitudinal and later transverse striation, a sign that 
the structure has completed its development in the way characteristic 
of muscle. 
The greater number of proliferating muscle-cells which have no con- 
nection with living fibres die; but it is to be noted that they persist for a 
long time, so that not infrequently there may be seen in muscle-scars 
from eight to forty days old protoplasmic masses rich in nuclei. These 
may form long, connected bands, or rows of separate pieces of proto- 
plasm. There can be no doubt that certain of these cells become trans- 
formed into transversely striated muscle-substance; this takes place by 
the formation of new and independent muscle-fibres or by union with old 
muscle-fibres or muscle-buds. The formation of disconnected muscle 
occurs particularly when the contractile substance is destroyed while the 
sarcolemma remains intact (as in Zenker’s degeneration in typhoid 
fever). On the other hand, the formation of buds is observed especially 
at the ends of fibres which have been divided. REGENERATION. 
229 
The buds springing from the ends or sides of muscle-fibres may cause 
simple elongation of the fibre, frequently deviating from its original 
direction (/). Often there are fibres which have split into two or three 
parts (g), and thus pass into the muscle-scar. As far as we know, this 
splitting of the fibre occurs early (a), before the proliferating muscle- 
nuclei have formed much sarcoplasm, so that proliferation appears first 
in the split portions. As a result of such splitting a muscle-scar may 
contain a greater number of muscle-fibres than were originally present in 
the affected area. 
Hypertrophy of transversely striated muscle takes place through en- 
largement of the individual fibres; the thin muscle-fibres in particular 
becoming increased in thickness. The nuclei do not increase in number. 
On the other hand, nuclear increase does take place in growth in the length 
of the muscle; and is the result, most probably, of amitotic division 
(Morpurgo). 
Regeneration of heart-muscle has not been positively demon- 
strated. After injuries of the heart, division figures appear in the mus- 
cle-cells, but after a few days these can no longer be demonstrated, and 
the wound heals through the formation of ordinary scar-tissue. Focal 
degenerations of the myocardium likewise heal by connective-tissue cica- 
trization. 
New-formation of smooth muscle-fibres occurs after traumatic or 
toxic and ischaemic degeneration. It occurs also in muscle tumors and is 
initiated by mitotic division of the nuclei, followed by division of the 
cells. According to the results of experimental work and of observa- 
tions on the muscle tissues of man, the reproduction of fibres after in- 
juries and focal degenerations is slight, ceasing after a short period. 
Thus, defects in the muscularis of the stomach and intestines or of the 
bladder are, for the most part, closed by connective tissue. 
Hypertrophy of smooth muscle-fibre is a phenomenon of frequent 
occurrence. In the pregnant uterus the muscle-cells may reach five to 
ten times the ordinary size. Of other organs the bladder most fre- 
quently shows marked hypertrophy of smooth muscle. 
§ 86. Regeneration of the nerve-elements of the central nervous 
system through the reproduction of ganglion-cells most probably 
does not occur in man and mammals in post-embryonal life. According 
to the investigations of Stroebe, on the other hand, divided nerve-fibrils 
(in mammals) may grow lengthwise to a certain extent through sprouting 
of the axis-cylinder; this is particularly true of the fibres of the pyramidal 
tracts and the posterior roots, both of which after being divided grow 
into the scar-tissue at the site of the wound, the former in a downward 
direction, the latter upward. Complete restoration of nervous tissue does 
not take place, and a defect in the spinal cord due to trauma is replaced 
partly by connective-tissue, in part by neuroglia. According to Borst, 
new axis-cylinders may be formed within the new neuroglia in the neigh- 
borhood of cerebral lesions, and medullary nerve-fibrils may be produced 
by the outgrowth of old fibres. 
Regenerative and hypertrophic proliferations of neuroglia are phe- 
nomena which occur frequently in diseased conditions of the central 
nervous system, and follow degenerative changes of the nervous ele- 
ments, or destruction of the neuroglia, or they may appear without such 
antecedents, in the latter case arising during the period of development. 230 
THE PROGRESSIVE CHANGES. 
The new-formation is brought about by mitotic division of the nuclei 
and bodies of the glia- or of the ependyma-cells. 
The newly formed 
glia-cells produce a 
profusion of delicate 
fibrillar processes 
(Fig. 152, a), and, as 
in the normal tissues 
of the central nerv- 
ous system, there 
may be distinguished 
among these two 
varieties of cells 
which are known as 
astrocytes (Deiter’s 
cells), the so-called 
“mossy cells” 
(Kurzstrahler) and 
“spider-cells” (Lang- 
strahler) with long, 
stiff, less-freely 
branching processes 
(a). The processes 
of these cells form sometimes a loose, sometimes a dense felt-work of 
fine fibrillae (a, b) in which the cells, which have but little protoplasm, are 
embedded. After full development of the 
tissue separation of the processes from the 
cell-bodies may take place. The thickening 
of the tissue caused by the proliferation be- 
longs to the process known as sclerosis. 
Regenerative new-formation of the 
nerve-fibres of the peripheral nervous 
system is of frequent occurrence and takes 
place in all those cases in which the con- 
tinuity of a nerve-fibre is entirely or partially 
interrupted. For its accomplishment, how- 
ever, it is necessary that the ganglion-cells 
whose processes form the nerve-fibres in 
question be preserved. 
When a nerve has been severed, the axis- 
cylinders and medullary sheaths, in the distal 
portion, undergo degeneration, the latter 
breaking up into drop-like detritus, which 
later is dissolved. During the disintegration 
of nerve-fibres the nuclei beneath the sheath 
of Schwann undergo mitotic division and 
form cells rich in protoplasm, which may 
take up the products of destruction of the 
nerve-fibres. 
Of the proximal portion of the nerve the 
peripheral extremity alone degenerates, as 
far as the next Ranvier’s node, or the one beyond. 
Fig. 152.—Sclerotic tissue from the posterior columns of a 
case of multiple sclerosis (Muller’s fluid, Mallory’s method). 
a. Glia-cells with numerous processes, seen in longitudinal sec- 
tion; b, sclerotic tissue with transversely cut glia fibres, x 500. 
Fig. 153. — Old and newly 
formed nerve-fibres from an ampu- 
tation-stump, in longitudinal sec- 
tion (Muller’s fluid, Weigert’s 
stain). a, b, Old nerve-fibres, 
from which several young nerve- 
fibres have grown; c, neurilemma 
with young nerve-fibres, x 180. REGENERATION. 
231 
The regeneration of nerves begins a few days after the operation, 
in the proximal portion, about 0.4-2 cm. above the cut end. 
The first change consists in swelling 
of individual axis-cylinders in the peri- 
pheral parts of the nerve-bundle of the 
proximal end, which is followed by 
splitting-off of two to five or more new 
axis-cylinders. The axis-cylinders aris- 
ing in this way from the old ones grew 
in a longitudinal direction (Fig. 153, a,b) 
and form, within the sheath of Schwann, 
whole bundles (Figs. 153, c; 154, e) of 
newly formed nerve-fibres, which fill the 
old nerve-tubes, and indeed stretch 
them; sometimes remains of old fibres 
are visible in the same sheath (Fig. 
154, /). Single fibres may even break 
through the old 
sheath of 
Schwann, and 
then extend 
further in the 
e n d o neurium, 
or penetrate the 
perineurium in- 
to the epineur- 
ium. 
In this way there are formed on the 
lower end of the proximal portion of the 
nerve a large number of new nerve-fibres, 
which in the beginning consist only of the 
newly formed axis-cylinders, but immedi- 
ately surround themselves with a medullary 
sheath, which by reason of its irregular de- 
velopment gives to the nerve-fibres a vari- 
cose appearance (Fig. 153, c). Later the 
fibres acquire a neurilemma-sheath — that 
is, a connective-tissue covering which is 
probably formed from the nerve-corpuscles 
concerned in the proliferation. 
When a nerve is entirely severed and 
there is no possibility of union with the 
distal portion — as, for example, occurs in 
all amputations — there is formed in the 
region of the cut end an embryonic tissue, 
springing from the connective tissue of 
the nerves, which later becomes changed 
into connective tissue. In the beginning 
free from nerves, this connective tissue be- 
comes penetrated by young nerves grow- 
ing out from the fibres of the nerve-stump, 
Fig. 154.—Cross-section of a nerve- 
bundle of the median nerve just 
above a wound dividing the nerve, 
made four months previously (Mul- 
ler’s fluid, carmine), o, Perineurium; 
b, endoneurium; c, cross-section of a 
vessel; d, old unchanged nerve-fibre; 
e, bundle of newly formed nerve- 
fibres; f, newly formed nerves, with 
remains of old fibres inside the same 
sheath, x 200. 
Fig. 155.—Amputation-neuroma of 
the sciatic nerve, in longitudinal sec- 
tion _ (amputation of nerve nine years 
previously) (Muller’s fluid), a, Nerve; 
b, neuroma: x 3. 232 
THE PROGRESSIVE CHANGES. 
which, arranged in small bundles, or scattered, grow into the connective 
tissue in every direction (Fig. 155). Not infrequently the growth of 
nerves is so extensive that nodular or clubbed swellings (Fig. 155, b) 
arise on the ends of the nerves. Such a swelling is known as an amputa- 
tion-neuroma. 
When a nerve after division is again united, or if the division is only 
partial, the nerve-fibres growing out from the proximal end, after pene- 
trating the connective tissue formed in the wound, may in part, or all, 
find their way into the peripheral portion of the nerve where, in the 
mean time, the nerve-fibres have been destroyed. In this way the distal 
end may again become neurotizcd — that is, supplied by new nerves. 
According to investigations of Forssmann, the direction of the newly 
growing fibres is governed by chemotactic influences arising from the 
disintegration-products of the old nerve-fibres. 
According to the investigations of Vanlair the growth of a regenerat- 
ing nerve is about 0.2—1 mm. daily, according to the character of the 
tissue. A portion of the new nerve-fibres may penetrate into the old, 
empty sheath of Schwann; others extend into the epineurium and peri- 
neurium, and in this situation grow toward the periphery to the end-organ. 
Single fibres may pass by the end of the nerves, and grow toward the 
periphery, either along the old nerves or by an independent route. Many 
fibres, which leave the old route, are finally lost in the tissues. In the 
lower portion of the intermediate substance (Vanlair) the nerve-strands 
begin to collect into bundles again, and with the formation of a peri- 
neurium about the latter, the regenerated nerve takes on more and more 
the structure of a normal nerve. 
The above-described process of regeneration requires for its accom- 
plishment weeks or even months, and sometimes is not complete after 
several months. 
The question of the regeneration of the central nervous system is still under 
discussion. It is generally accepted that in the cold-blooded animals, reptiles, 
and tailed amphibia, regenerative new-formation of portions of the central 
nervous system can take place. In warm-blooded animals, particularly in the 
mammals, the majority of experimental investigations have failed to demonstrate 
regenerative new-formation of ganglion-cells. Tedeschi, Vitsou and others, claim 
to have observed, after injuries of various kinds, both new-formation of 
neuroglia and of ganglion-cells and nerve-fibres; but the investigations carried out 
in my laboratory by T schist owitsch seem to me to contradict these assertions. The 
results obtained by Grunert in experimental work with pigeons agree with the con- 
clusions arrived at by Tschist owitsch. 
Monti and Fieschi could demonstrate no evidences of regeneration in the 
ganglion-cells of the sympathetic after injuries. Torelli found only degenerative 
changes in the ganglion-cells of the intervertebral ganglion after injury. 
The new-formation of peripheral nerve-fibres has been made the subject of 
experimental research, and different observers have come to different con- 
clusions (see Stroebe, l. c.). The above-described mode of new-formation I regard 
as firmly established, in so far as its essentials are concerned, on the ground of 
personal investigations. I have been unable to confirm the views of Neumann, 
Dobbcrt, Daszkiewicz, Cattani, Wier Mitchell, Gluck, Beneke, von Bungner, Wieting, 
and others, who hold that the new fibres in the distal portion of the severed nerve 
rise autochthonously from the nuclei of the sheath of Schwann, or from the old 
axis-cylinder, or from a protoplasmic mass formed by chemical transformation of 
the medullary sheath and axis-cylinders (Nemnann-Dobbert). The view held by 
Bethe, that the nerve-fibres arise without participation of the ganglion-cells in the 
fused ectodermic cells whose remains later represent the cells of Schwann, appears 
to me to have been shown by von Kolliker to be incorrect. Likewise, the attempt 
made by Neumann and Wieting (Marchand) to bring into accord the established REGENERATION. 
233 
fact of the outgrowth of the axis-cylinders of the proximal portion into the 
scar uniting the severed ends, with the theory of the origin of new nerve-fibres 
from the nuclei of the sheath of Schwann, or from the remains of old fibres, or 
from both, by the assumption that thfe axis-cylinders growing from the proximal 
end convey a stimulus from the nerve-centres to the distal portion and thereby make 
possible the development of new fibres, I regard as unsuccessful, and hold to the 
above-given view. I am further of the opinion that the medullary sheath is not 
formed by the cells of the sheath of Schwann, but represents a product of the 
axis-cylinders. According to Nissl, Marineseo, and others (see Barbaeci, l. c.) 
there occurs, after severing of a nerve, degeneration in the corresponding ganglion- 
cells with disintegration of the Nissl’s bodies, and this may lead to the destruction 
of individual cells. Later, progressive changes with new-formation of chromatin 
take place, and may lead to hypertrophy of the cells (Marinesco) ; these changes 
reach their maximum in about ninety days, after which time there is a return to 
the normal condition. 
The regenerative new-formation of the tissues of the eye has repeatedly 
been an object of research. According to Wolff, Miiller, and Kochs the lens of 
tritons may regenerate, after removal, by proliferation of the epithelium of the inner 
layer of the iris. According to Rothig, the same thing occurs in the trout. Gonin 
observed in rabbits, after the lens had been removed in such a manner that the 
capsule and some of the equatorial lenticular fibres and epithelium of the anterior 
wall were left behind, that there occurred proliferation of this epithelium, leading 
to the union of the anterior and posterior walls through cells resembling connective- 
tissue cells. A new-formation of lenticular fibres from these cells does not take 
place. Remains of the lenticular fibres may form a rudimentary, useless lens, which 
in young animals may become somewhat enlarged through the growth of the fibres. 
Randolph obtained somewhat better results in guinea-pigs. In the human eye sim- 
ilar formations are seen after removal of the lens, and are known under the name 
of “ Krystallwulst ” (Baas'). According to Franke, Kriickmann, and Stoewer, the 
sclera possesses but slight power of proliferation. Wounds of the same are healed 
chiefly through proliferation of the choroid and episcleral tissue. 
According to Baquis, there occurs, in the injured retina of the rabbit, division 
of both ganglion and neuroepithelial cells. According to Kriickmann, the pigment- 
epithelium is capable of extensive regeneration, but neuroepithelium, on the other 
hand, is not again formed. 
Literature. 
(Regeneration of the Elements of the Central Nervous System.) 
Bardeen: The Histogenesis of the Cerebrospinal Nerves. Am. J. of Anat., iv., 
19°3. 
Borst: Regenerationsfahigkeit des Gehirns. B. v. Ziegler, xxxvi., 1904. 
Grunert: Regenerationsfahigkeit d. Gehirns. Arb. a. d. path. Inst. Tubingen, 
ii., 1899. 
Monti et Fieschi: Guerison des bless, des ganglions sympathiques. Arch ital. 
de Biol., xxiii., 1895. 
Stroebe: Heilung v. Riickenmarkswunden. Beitr. v. Ziegler, xv., 1894; Histol. 
d. degen. u. regen. Processe im centralen Nervensystem. Cbl. f. allg. Path., 
1895 (Lit.). 
Tedeschi: Regen. d. Gewebe d. Centralnervensystems. Beitr. v. Ziegler, xxi., 
1897. 
Tirelli: Proc. repar. dans le ganglion intervertebral. Arch. ital. de Biol., xxiii., 
1895. 
Tschistowitsch: Heilung von Hirnverletzungen. B. v. Ziegler, xxiii., 1898. 
Vitzou: La neoform, des cell, nerveuses dans le cerv. du singe. Arch, de phys., 
ix., 1897. 
Barbacci: Die Nervenzellen (Verand. nach Nervendurchschneid.). Cbl. f. a. 
Path., x., 1899 (Lit.). 
Bethe: Allg.,Anat. u. Phys. des Nervensystems, Leipzig, 1903. 
Forssmann: Ursache der Wachsthumsrichtung d. periph. Nervenfasern. Beitr. 
v. Ziegler, xxiv., 1898; Neurotropismus. Ib., xxvii., 1900. 
Galeotti u. Levi: Neubildungen nerv. Elem. im regen. Muskelgewebe. Beitr. 
v. Ziegler, xvii., 1895 (Lit.) 
(Regeneration of the Peripheral Nerves.) 234 
THE PROGRESSIVE CHANGES. 
Huber: A Study of the Operative Treatment for Loss of Nerve Substance in 
Peripheral Nerves. Jour, of Morph., vol. xi., 1895. 
v. Kolliker: Die Entwickelung der Nervenfasern. Anat. Anz., xxv., 1904. 
Neumann: Degeneration u. Regeneration nacli Nervendurchschneidung. Arch, 
d. Heilk., ix., 1868; Nervenquetschung u. Nervenregeneration. Arch. f. 
mikr. Anat., xviii., 1880; Axencylindertropfen. Virch. Arch., 158 Bd., 1898. 
Nissl: Veriind. d. Ganglienz. d. Fac. n. Ausreiss. d. Nerven. A. Zeit. f. Psych., 
48 Bd. 
Peterson: Peripheral Nerve Transplantation Amer. Jour, of Med. Sc., 1899. 
Stroebe: Degeneration u. Regeneration periph. Nerven. Beitr. v. Ziegler, xiii., 
1893; Obi. f. allg. Path., vi., 1895 (Zusfass. Ref. iib. Regen. d. Nerven u. d. 
Endapparate). 
Vanlair: Arch, de biol. de van Beneden et van Bambeke, 1882-85; Arch, de 
phys., x., 1882; vi., 1885; viii., 1886; Compt. rend, de 1’Acad. des sciences, 
1885; Sur l’innervat. indirecte de la peau. Ib., 1886; De l’organisat, des drains 
de caoutchouc, etc. Revue de Chir., 1886; La suture des nerfs, Bruxelles, 
1889; La persistance de l’aptitude regeneratrice des nerfs. Bull, de l’Acad. 
Roy. de Belgique, 1888; Rech. chronometriques sur la regen. des nerfs. 
Arch, de phys., vi., 1894. 
Wieting: Regen. periph. Nerven. Beitr. v. Ziegler, xxiii., 1898. 
(Regeneration of the Tissues of the Eye.) 
Baquis: fitude exper. sur les retinites. Beitr. v. Ziegler, vi., 1888. 
Gonin: Regen. du cristallin. Beitr. v. Ziegler, xix., 18% (Lit.). 
Kochs: Regen. d. Organe bei Amphibien. Arch. f. mikr. Anat., 49 Bd., 1897. 
Kriickmann: Pigmentzellen der Retina. Arch. f. Ophthalm., 48 Bd., 1899. 
Muller: Regen. der Linse bei Tritonen. Arch. f. mikr. Anat., 48 Bd., 1896. 
Randolph: The Regeneration of the Crystalline Lens. Johns Hopkins Hosp. 
Rep., ix., 1900. 
Schimkowitsch: Linsenregen. bei Amphibien. Anat. Anz., xxi., 1902. 
Stoewer: Heilungsvorg. bei Wunden d. Auges. Arch. f. Ophthalm., 46 Bd., 
1899. _ 
Wolff: Linsenregeneration bei Tritonen. Biol. Cbl., xiv., 1896; An. Anz., xviii., 
1900; Regen. d. Urodelenlinse. A. f. Entwickelungmech., xii., 1901. 
III. The Results of Transplantation and Implantation of Tissues and 
Organs. 
§ 87. The local regeneration of tissue is, as mentioned in the last 
part, often but slight, so that losses of tissue may be followed by 
permanent defects, and in place of the original structures there may 
appear only cicatrical tissue of lesser value. Consequently, many 
attempts have been made, through transplantation and implantation 
of tissue, to improve the healing-process; such attempts have in part 
been successful. At the same time they have thrown light on the 
individual life of the tissues and on the behavior of the organism 
toward implanted living tissue. 
The most successful results have been obtained in the transplantation 
of tissues which remain connected with their nutrient vessels, since, at 
the point of union the transplanted portion and the fixed tissues grow 
together in essentially the same manner as do the edges of an incised 
wound. This method is utilized most frequently in plastic operations on 
the surface of the body, but it also finds application in internal surgery. 
Transplantations of tissues completely freed from their basement- 
structures have been successfully performed. The cells of the epi- 
dermis are able to live for the longest time. Ciliated epithelium may 
be preserved for days and still show movements of the cilia. Next 
to the surface-epithelium stand the connective tissues, other tissues 
quickly die, the cells of the brain and kidney within a few hours after TRANSPLANTATION OF TISSUES. 
235 
obstruction to the blood supply. According to the investigations which 
have been made up to the present time the tissues of the skin, periosteum, 
inter-articular cartilages, muscle and cartilage most easily preserve their 
vitality. Morpurgo found cells of the periosteum to be capable of repro- 
duction after seven to eight days. The vessels, tendons, and neurilemma 
appear to be even more resistant. 
Transplantations of skin give the best results, and were first recom- 
mended by Reverdin and Thiersch for the healing over of open wounds 
Fig. 156.—Skin-graft four and one-half days old (formalin, haematoxvlin, picrofuchsin). 
a, Deep layer of the corium; b, proliferating granulation-tissue; c, boundary of proliferating 
zone; d, e, transplanted portion of skin; f, desquamation of the horny layer; g, vascular offshoots 
and granulation-tissue extending into the transplanted connective tissue. X 107. 
and have since been extensively used for this purpose. The material 
used consists of pieces of skin taken from the same individual or from 
another person. Ordinarily, strips of skin removed by means of a sharp 
knife are used, and include the tips of the papillse and the upper layers of 
the corium. Epithelium in connection with a thicker layer of the corium 
may also be successfully transplanted, and in injuries large portions of 
skin which have been completely torn off may be again joined to the 
deeper tissues on the same spot from which they were removed. 
The transplantation may be made either on a fresh wound or on one 
showing proliferation. The strips of skin are held in place by mechanical 
means. The pieces of skin become fastened to the surface of the wound 
by coagulated blood or lymph. In successful cases union with the under- 
lying tissue takes place in about eight days. 
The nourishment of the transplanted pieces (Fig. 156, d) is obtained 236 
THE PROGRESSIVE CHANGES. 
from the fluids which exude from the underlying tissues. Later, there 
begins in the latter vascular connective-tissue proliferation (b, c), and 
the transplanted portion becomes penetrated from below by new blood- 
vessels (g) and by fibroblasts, so that it finally becomes interspersed 
with granulation tissue. Under favorable conditions the old vessels may 
again become opened through the ingrowth of new vessels. 
The behavior of the transplanted portion varies in individual cases. 
A part of the transplanted tissue is always lost (/). Other cells, both 
epithelial and connective-tissue, proliferate and produce new tissue. 
The outcome of a successful transplantation is the covering over of 
the area with epithelium and corium. Through the latter it is possible 
for the cicatricial area to possess papillae. To what extent the superficial 
layers of the cutis arise from the graft or to what extent from the tissue 
upon which it is planted, cannot be determined. If the papillary bodies 
are preserved, a portion of the tissue may be formed from immigrating 
fibroblasts. After a time the transplanted area comes to contain nerves. 
The tactile sense is first restored (Stransky), later the sensibility to pain 
and temperature. New elastic tissue also develops, as in ordinary scars, 
from the ends of old fibres. 
Besides skin-transplantations, there have been attempted transplanta- 
tions of almost all the tissues: periosteum, bone-marrow, bone, muscle, 
nerves, thyroid, pancreas, adrenals, mammary gland, mucous glands, 
ovary, testis, etc.; also of tissue-combinations, for example, a rat’s tail 
from which the skin has been stripped. Embryonal tissue has also been 
transplanted in a variety of ways. Finally the attempt has been made 
to transplant tissues from one animal to another of different species. 
Such transplantations have been made on open wounds, in the sub- 
cutaneous tissues, peritoneal cavity, glandular organs and lungs, either 
by direct operative procedures or by the introduction of the tissue into 
the blood-stream. 
The results of these experiments may be summed up as follows: 
In all transplanted tissues there first occurs degeneration, and a part 
of the tissue dies. After a time there usually results proliferation of the 
remaining portion, which may lead to new-formation of tissue. Con- 
nective-tissue cells form new connective tissue; periosteum and end- 
osteum form bone or connective tissue; muscle-cells, new muscle; carti- 
lage, new cartilage; surface epithelium, new epithelium (epithelial cysts). 
Of the glands the thyroid, mucous glands, and mammary glands may 
form new glandular tissue; such new-formation does not take place in 
the case of the kidney, liver, testis, and ovary. Of the liver only the 
epithelium of the bile-ducts proliferates. Only in the transplantation of 
the ovary into the peritoneal cavity of the same animal can the ova 
ripen and pregnancy occur (Knauer, Ribbert, Gregorieff). The tissues 
of young individuals in general show a greater capacity for proliferation 
than those of old ones. In the transplantation of complicated tissues, 
for example, the skinned tail of a rat, all the tissues may produce new 
tissue and the whole may grow. 
Embryonal tissue can likewise grow after transplantation and become 
differentiated; cartilage, which in later life shows but little power of 
proliferation, is longer preserved and shows further growth, while the 
delicate soft tissue-formations easily die. 
After a time there occurs in almost all transplanted tissues, as well 
as in tue revdy formed tissue, a retrograde change, and they are finally METAPLASIA. 
237 
destroyed through the ingrowth of tissue from the neighborhood. The 
time at which this occurs varies with different tissues, and is dependent 
partly on the character of the tissue, and partly on surrounding con- 
ditions. Implanted surface-epithelium can remain permanently, and give 
rise to epithelial cysts. Portions of thyroid, mammary gland, and pan- 
creas are preserved for a long time. Cristiani found pieces of thyroid 
intact two years after implantation. The majority of tissues, however, 
disappear in a few months. In glands which are not capable of 
proliferation the gland-cells die first. If all of the implanted piece is 
not destroyed it may become encapsulated. 
Tissue of different species, when transplanted, does not grow, but is 
destroyed or encapsulated, sometimes quickly, sometimes slowly. 
According to published observations, the implantation of tissue does 
not lead to the formation of permanent tissue except in transplantation of 
skin. Nevertheless, such implantation may have a transitory or perma- 
nent value. The implantation of thyroid or pancreas may for a time 
check the harmful consequences of the loss of these glands. Through 
implantation of tissue into a defect temporary filling of the latter may 
be produced, and the neighboring tissues are thus permitted to proliferate 
for a longer time, and to form a greater amount of new tissue along the 
framework afforded by the implanted portion, and so to close the defect 
completely. Bone (not connected with nutrient vessels) when implanted 
into a part of the skeleton is absorbed (equally so whether living or dead 
bone is implanted), and is replaced by new bone arising from the neigh- 
boring periosteum and endosteum. In this way there may be better heal- 
ing of the defect; implantations of bone or cartilage may also be made 
use of in other tissues, for the stimulation of more abundant production 
of tissue for the purpose of filling tissue-defects. 
The transplantation of nerves has never resulted in the new-formation 
of nerve from the transplanted piece. The attraction which the prod- 
ucts of disintegration of a nerve (Forssmann) exerts on the axis-cylin- 
ders growing into a wound may be utilized to direct the course of grow- 
ing nerves into certain channels. 
IV. Metaplasia. 
§ 88. Metaplasia is that process by which a tissue is changed into an- 
other closely related without the intermediation of embryonic or granula- 
tion-tissue. Metaplasias play an important role in the development of indi- 
vidual connective-tissue formations, particularly in bone, cartilage, and 
marrow-tissue. Through proliferation of the periosteum or endosteum 
there is produced ordinary fibrillated connective tissue which later under- 
goes metaplasia into osteoid tissue, bone, or cartilage. In the metaplasia 
of connective tissue into osteoid tissue there occurs without further cell- 
proliferation condensation of the ground-substance (Fig. 157, a, b) which 
leads by gradual transformation to an osseous ground-substance (r) 
staining red with carmine or eosin or fuchsin. Deposit of lime-salts 
(Fig. 158, c) completes the process of metaplasia into true bony trabeculce. 
In the metaplasia of connective tissue into cartilage the ground-sub- 
stance becomes thicker but more clear and stains less intensely (Fig. 
159, c) than the connective tissue (b). The cells increase in size and 
lie in round spaces. Such changes may be observed in the periosteum 
and endosteum as the result of traumatic or infectious processes or in 238 
THE PROGRESSIVE CHANGES. 
the new-formation of fibrous tissue associated with tumor formations 
(Figs. 157 and 159). In wounds of the trachea which are first closed by 
scar-tissue, cartilage may be later developed by proliferation of intact 
perichondrium and metaplasia into cartilage (Fig. 160, b). 
If normal or pathological new-formed cartilage becomes penetrated by 
Fig. 157.—Periosteal formation of bone in a case of metastatic carcinoma of a rib. (Haema- 
toxylin, picric acid, fuchsin.) a, Fibrillated connective tissue; b, connective tissue undergoing 
condensation; c, fully developed bone, x 300. 
blood-vessels the ground-substance may undergo solution and the carti- 
lage cells form reticular connective tissue with branched processes in the 
interstices of which certain cells gather, so that the whole takes on the 
character of bone-marrow; by taking up fat it may be transformed into 
adipose tissue (Figs. 161, b, c, and 162, /). If, in the vascularization of 
cartilage, trabeculae of cartilage re- 
main, these may be transformed into 
osteoid tissue (Fig. 162, /) which 
when stained with hsematoxyh.n and 
eosin takes an intense red stain, while 
the unchanged cartilage stains blue. 
Through the deposit of lime-salts it 
may later be changed into bone. In 
chronic inflammation of the joints, 
cartilage may be transformed into 
ordinary fibrillated connective tissue, 
particularly when its free surface is 
covered with connective tissue. 
The metaplastic processes thus de- 
scribed are connected with preceding 
proliferations and may be associated 
with further appearances of pro- 
liferation. But there are metaplasias which have no connection with any 
proliferative change, or are only associated with it at a later period; thus 
myxomatous becomes changed into adipose tissue when the star-shaped 
tissue-cells become round through the taking up of fat, while the mucoid 
Fig. 158.—Formation of bone from con- 
nective tissue (alcohol, hematoxylin). Cross- 
section through a bone trabecula in process 
of formation; from an ossifying fibroma of 
the periosteum of the upper jaw. a, Con- 
nective tissue; b, thickened tissue, forming 
the groundwork of the new bone; c, deposits 
of lime-salts; d, connective-tissue cells; di, 
bone-cells, x 180. METAPLASIA. 
239 
ground-substance disappears. Lymphadenoid tissue may, after disap- 
pearance of the lymphoid elements, be changed into adipose tissue 
through the absorption of fat droplets by the cells of the stroma. Through 
Fig. .159.—Periosteal formation of cartilage in metastatic carcinoma of a rib. (Haema- 
toxylin, picric acid, fuchsin.) a, Fibrillated connective tissue; b, connective tissue undergoing 
condensation; c, fully developed cartilage, x 300. 
Fig. 160.—Healed tracheotomy wound in the cricoid cartilage, fifty-two days old. (Formalin, 
haematoxylin, and eosin.) a, Old cartilage; b, b, connective tissue arising from the perichondrium 
undergoing metaplasia into cartilage. X 60. 240 
THE PROGRESSIVE CHANGES. 
the disappearance of fat, adipose tissue may take on the appearance of 
mucoid tissue, and occasionally comes to contain mucin. 
In the change of connective tissue into myxomatous tissue the fibrillae 
Fig. 161.—Metaplasia of cartilage into reticular tissue, in arthritis fungosa (alcohol, haema- 
toxylin). a, Hyaline cartilage; b, tissue consisting of branched cells; c, cartilage-cells, set 
free by the liquefaction of the basement-substance of the cartilage, and becoming transformed 
into cells of mucous tissue. X 400. 
Fig. 162.—Metaplasia of cartilage into osteoid tissue, in a callus fourteen days old (Muller’s 
fluid, picric acid, haematoxylin, carmine), a, Hyaline cartilage; b, marrow-spaces; c, blood-vessel; 
d, cellular, e, fibrocellular marrow; f, osteoid tissue; g, osteoblasts; h, cartilage-cells freed through 
the disappearance of the ground-substance; i, proliferating cartilage-cells in opened capsule; 
k, proliferating cartilage-cells in closed capsule, x 200. 
vanish and there appears in their place a jelly-like mucus. If sufficient 
numbers of lymphoid cells collect in connective tissue and there occurs 
at the same time disappearance of the connective-tissue fibres, while METAPLASIA. 
241 
the connective-tissue cells unite through their processes to form a reticu- 
lum, lymphadenoid tissue is developed. 
Epithelial metaplasia occurs most frequently in chronically inflamed 
mucous membranes, for example, uterus, urethra (gonorrhoea), nose 
(ozaena), and trachea, cylindrical being transformed into pavement 
epithelium. 
This change occurs in the following manner: after repeated loss 
of epithelium the regenerating epithelium changes its character. In 
mucous membranes possessing stratified pavement-epithelium the 
upper layers may show cornification, not only in places which nor- 
mally possess pavement-epithelium, as the tongue and cheeks, but 
also in those possessing transitional epithelium (the urinary tract), 
or cylindrical epithelium (nose, ureters, and gall-bladder). In con- 
nection with this phenomenon should be mentioned the fact that 
epithelial tumors arising in mucous membranes possessing transi- 
tional or cylindrical epithelium may bear the character of squamous- 
cell tumors. 
Literature. 
{Metaplasia.) 
Dietz: Plattenepithelkrebs d. Gallenblase. V. A., 164 Bd., 1901. 
Hansemann: Studien iib. Specificitat, Altruismus u. Anaplasie d. Zellen, Berlin, 
1893. 
Kischensky: Plattenepithelkrebs der Nierenkelche. B. v. Ziegler, xxxi., 1901. 
Lubarsch: Die Metaplasiefrage. Arb. a. d. p. I. v. Lubarsch, Wiesb., 1901. 
Zeller: Plattenepithel im Uterus. Zeitschr. f. Geburtsh., xi., 1885. CHAPTER VII. 
Inflammation. 
I. The Early Stages of Acute Inflammation. 
§ 89. Under the designation inflammation are grouped phe- 
nomena which represent a combination of pathological processes, 
consisting of tissue-degenerations and tissue-proliferations, and of 
exudations from the blood-vessels. Degenerations of tissue and patho- 
logical exudations initiate the process; with these tissue-proliferation is 
sooner or later associated, the latter leading in the further course of the 
process to compensation for the disturbance — that is, to healing. The 
proliferation of tissue may, therefore, be regarded as regenerative, but 
such new-formation of tissue may be in excess of that which is useful 
to the body. The tissue-degenerations and proliferative processes de- 
scribed in the previous chapters appear for the greater part as participat- 
ing factors in inflammation; the inflammatory process acquiring its char- 
acter through the combination of tissue-degenerations and tissue-pro- 
liferations rvith pathological exudations. 
Injury of tissues containing blood-vessels produces changes which con- 
stantly bear at some time during their course the character of an inflam- 
mation. The formation of scar tissue, the healing of transplanted tissues, 
as briefly described in the last chapter, always take place through proc- 
esses that are essentially inflammatory in nature. 
Exudation in acute inflammation is constantly associated with 
hyperccmia, which appears even before the beginning of exudation, and 
hence ushers in the latter. As a result of the combination of hypersemia 
and exudation the inflamed tissue becomes reddened and swollen. When 
situated on the surface of the body the increased flow of warm blood 
from the deeper tissues causes local increase of temperature. If the in- 
flamed tissue contains sensory nerves, pain will be produced as the result 
of the mechanical effects of the exudate. 
Redness, swelling, increased warmth, and pain are phenomena 
which even in ancient times were regarded as the signs of inflamma- 
tion ; rubor, tumor, calor, and dolor were designated by Celsus the 
cardinal symptoms of inflammation. To these four was then added 
a further symptom, functio laesa, altered function of the inflamed tissue. 
The causes of inflammation lie in mechanical, thermal, bacterial, 
electrical, or chemical influences. The common characteristic of all these 
injurious agencies is the production, in the first place, of local tissue- 
degeneration, which, when of a certain extent and intensity, is associated 
with disturbances of the circulation and exudation from the vessels. The 
causes of inflammation are not specific; any injurious agent may excite 
inflammation if its action is sufficiently intense to cause certain disturb- 
ances of circulation in association with tissue-degenerations, but not so 
intense as to destroy the tissue and stop the circulation. 
The majority of the causes of inflammation reach the body from 
the outside, but excitants of inflammation may be formed within the body. CAUSES OF INFLAMMATION. 
243 
Bacteria which have penetrated into the tissues often form in their proto- 
plasm or from substances present in the body products which are capable 
of exciting inflammation. Moreover, substances that excite inflammation 
may arise in the organism without the aid of parasites; particularly as 
the result of the death of large masses of tissue from any cause, or 
when in metabolic processes abnormal products are deposited in the tis- 
sues. 
The causes of inflammation may act on the tissues from portions of 
the body accessible from without, or from the lymph and the blood; 
and we may, therefore, distinguish ectogenous, lymphogenous, and 
haematogenous inflammations. Through the spread of inflammation to 
neighboring tissues there arises inflammation by continuity; as the re- 
sult of transportation through the lymph or blood stream of an agent 
causing inflammation, there are produced metastatic inflammations. If 
injurious substances are discharged through the excretory organs, 
excretory inflammations may arise. 
When local injury to tissues has reached such a degree as to produce 
the exudation characteristic of inflammation, there is an associated 
hyperaemia, as a result of which the blood flows through the dilated 
vessels with increased velocity. After a short time, lessening of the 
speed of the circulation leads to abnormal slowing of the current. 
The disturbances of circulation, which find expression in hyper- 
aemia, may be due to stimulation or paralysis of the vasomotor system 
or to direct action on the vessel-walls, particularly the arterial walls, 
leading to dilatation of the lumen. Although these disturbances fre- 
quently precede the inflammatory exudation, they do not belong ex- 
clusively to the process of inflammation, but often occur without being 
followed by inflammatory exudation. Further, they may be absent dur- 
ing the course of an inflammation. The circulatory disturbances charac- 
teristic of inflammation are shown only when slowing of the blood-cur- 
rent and exudation from the blood-vessels set in. Slowing of the blood- 
stream and exudation are dependent on a change in structure, an alter- 
ation of the vascular walls, through which there results lasting dilata- 
tion of the vessel and adhesion of the blood to the vessel-wall, causing 
increase of frictional resistance and increased permeability of the vessel- 
wall. In the capillaries the persistent dilatation is in part the result of 
relaxation of the connective tissue surrounding the capillaries, inasmuch 
as the thinness of the capillary walls makes this tissue bear the greater 
part of the blood-pressure resting upon them. 
The tissue-lesion which leads to disturbances of circulation and exu- 
dation usually affects all parts, but under certain conditions may be 
limited to the vessel-wall, particularly in hematogenous inflammation, 
in which the injurious agent acts from the blood. However, the tissue 
adjoining the capillary walls must soon become involved. The tissue- 
changes brought about by the excitants of inflammation are sometimes 
slight, and even on microscopic examination are not recognizable at all 
or with difficulty; at other times they are so severe that they may be 
easily recognized on macroscopic examination. The latter is particularly 
true when some time has elapsed after the action of the injurious agent. 
During the further course of the inflammatory process there are often 
added to the lesions produced directly by the causes of inflammation 
other tissue-changes, which are brought about by disturbances of circu- 
lation and the collection of exudate in the tissues. 244 
INFLAMMATION. 
If in any tissue the cause of inflammation has led to that alteration 
of the vessels which is the requisite antecedent for the formation of an 
exudate, and if as a result of this alteration there is slowing of the 
blood-stream, the capillary circulation becomes irregular, due either to 
complete or transitory stasis in different areas. In this event the white 
blood-corpuscles often remain clinging to the vessel-walls while the red 
blood-cells are carried on, and there arises in the capillaries a more or 
less marked increase of white blood-corpuscles as compared to the red. 
Fig. 163.—Inflamed human mesentery (osmic-acid preparation). a, Normal trabecula; 
b, normal epithelium (endothelium); c, small artery; d, vein with leucocytes arranged peri- 
pherally; e, white blood-cells which have emigrated or are emigrating; f. desquamating endo- 
thelium; fi, multinuclear cells; g, extravasated red blood-cells, x 180. 
In the veins, in which there can be distinguished in the normal circu- 
lation an axial red stream and a peripheral plasma-zone free from cells, 
greater or less numbers of leucocytes pass over into the plasma-zone, 
when the slowing of the circulation has reached a certain degree. Still 
greater slowing of the current leads to the passing over of blood-plates 
and red cells, and finally the distinction between axial-stream and peri- 
pheral zone may be entirely lost. 
When leucocytes pass over into the peripheral zone they either roll 
along or cling to the wall of the vein, either to roll on again or to remain 
attached. If this leads to marked accumulation of leucocytes along the 
vein-walls, the condition is known as marginal disposition of white cor- 
puscles (Fig. 163, d). 
Following the accumulation of the leucocytes in the capillaries and 
the marginal disposition in the veins there occurs emigration of leucocytes 
(Fig. 163, d, e) from the vessels involved, and at the same time fluid 
escapes from the vessels into the tissues. 
The emigration of white corpuscles is an active process, and is ac- 
complished through the amoeboid movement of the cells; to a certain 
extent it occurs under normal conditions. The cause of the marked emi- EXUDATION. 
245 
gration seen in inflammations is doubtless a change in the vessel-walls, 
which favors the clinging of the cells to the walls and their passage 
through the latter. According to investigations by Arnold, Thoma, and 
others, the leucocytes pass out through the lines of cement-substance 
between the endothelial cells; and in the alteration of the vessel-wall due 
to inflammation localized defects occur as the result of widening of these 
lines. The emigration is accomplished by the leucocytes sending a 
process through the vessel-wall, the remainder of the cell-body flowing 
after the process, until finally the entire cell is outside the vessel. Ar- 
rived here the leucocytes remain for a while in the immediate neigh- 
borhood of the point of diapedesis, but then wander farther, the direc- 
tion being determined partly by mechanical stimuli, partly by chemotaxis 
— that is, the repulsion or attraction exerted by chemical substances in 
the tissue-juices. Possibly chemotactic influences exert an action even 
on the leucocytes in the capillaries or in the peripheral zone of the veins. 
The cells emigrating from the vessels are almost exclusively polynuclear 
leucocytes, but lymphocytes may accompany them. Polynuclear leucocytes, 
passing out in great numbers and accumulating in the adjacent tissues, 
are known as pus cells. 
The pouring-out of fluid exudate, whose composition differs more or 
less from that of normal tissue-lymph, and is characterized by a relatively 
high albumin-content, is a process also to be referred to alteration of the 
vessel-wall. It takes place at the same time as the emigration of leuco- 
cytes, but may begin before this event, and may also occur in cases in 
which the emigration of leucocytes does not take place at all, or remains 
within narrow limits. The composition of the exudate varies, but it may 
be assumed that the albumin-content is higher the greater the damage to 
the vessel-walls. If the extravasated fluid contains fibrinogenic sub- 
stances separation of fibrin and coagulation occur. 
If the alteration of the vessels is of high degree, or if at the same 
time there is marked stasis, red blood-cells may pass out of the vessels 
(Fig. 163, g) with the fluid, either by rhexis or diapedesis. According to 
Thoma and Engelmann rhexis of red cells occurs particularly in those 
places where leucocytes have previously passed through the vessel-wall. 
Since red cells are not motile, their escape must be regarded as a passive 
process performed under the influence of pressure. 
The escape of blood-plates may take place both in exudates rich in 
cells and those containing few, but occurs particularly in exudates with 
an abundance of fibrin and red blood-cells. 
Tissue-proliferation — that is, division of cells and nuclei — is first 
recognizable about eight hours after the action of the injurious agent; 
and in many cases appears later. In other words, tissue degeneration 
and exudation from the vessels precede proliferation, assuming, of course, 
that the inflammation does not arise in a tissue which is already in a 
state of proliferation. 
The clinical significance of the term inflammation (inflammatio, phlogosis) has 
changed but little in the course of time, since the cardinal symptoms of inflammation 
set forth by Celsus, and accepted by Galen, are recognized as such at the present 
day. Nevertheless, the views regarding the differentiation of the essential from the 
unessential in the symptom-complex of inflammation and the accurate determination 
of the true nature of the process have differed greatly. A comparison of the 
expressions concerning these points made by the more modern writers (Virchmv, 
von Recklinghausen, Cohnheim, Ponfick, Samuel, Thoma, Neumann, Strieker, 246 
INFLAMMATION. 
Heitsmann, Grawits, Leber, Metschnikoff, and others) shows that no single writer 
defines inflammation in the same way as any other, or interprets in exactly the same 
way any one of the individual phenomena of inflammation. Ponfick designates as 
the cause of inflammation the disturbance of equilibrium in the tissues, “but hesi- 
tates to designate retrogressive changes as an indispensable attribute of the inflam- 
matory process, and doubts wholly that they should be regarded as the point of 
departure and the chief feature of the process.” I am of the opinion that “ a dis- 
turbance of the tissue-equilibrium ” is nothing more than a degenerative change of 
tissue, and regard Ponfick’s statement, though directed against my definition, as 
harmonizing with my views. Moreover, I once again emphasize the fact that the 
alteration of the vessels is a necessary requisite for exudation, and that this altera- 
tion is nothing else than a tissue-degeneration. 
It was formerly believed that hypersemia was the essential symptom of inflam- 
mation. Rokitansky held that every inflammation was characterized by dilatation 
of the capillaries, slowing of the blood-stream, and by stasis caused by thickening 
of the blood through the effusion of serum and adhesion of the red blood-cells to 
one another. Henle, Stilling, and Rokitansky attributed dilatation of the vessels 
and slowing of the circulation to paralysis of the nerves of the vessels, the cause 
of which, according to Henle and Rokitansky, is increased stimulation of the sen- 
sory nerves; while according to Stilling, the cause lies in paralysis due to the in- 
flammatory irritant. Eisemann, Heine, and Briicke sought to attribute the circu- 
latory disturbances to primary spasm of the vessels brought about by irritation of 
sensory nerves, which produces behind the contracted portions of the vessels slow- 
ing of the current, irregular circulation, and finally stasis. Vogel, Emmert, Paget, 
and others, on the other hand, attributed dilatation of the vessels and stasis) to ab- 
normal attraction of the blood by the tissues. Against these views it must be 
maintained that the disturbances of circulation produced by contraction or dilatation 
of the vessels introduce or accompany those leading to exudation, and may exert a 
modifying influence on the course of inflammation, but do not form an essential 
part of the process, and may be entirely wanting, or may appear without the 
accompaniment of an inflammatory exudate. 
The recognition that the formation of the exudate is to be referred to injury 
of the vessel-walls we owe chiefly to Cohnheim, whose investigations were com- 
pleted by Samuel, Arnold, Thoma, Bins, and others. Cohnheim also showed that 
in inflammation the colorless corpuscles emigrate, and form an essential constituent 
of the exudate. 
Dutrocliet (“Rech. anatomiques et physiologiques sur la structure interne des 
animaux et des vegetaux et sur leur motilite,” Paris, 1842, p. 214) and Waller 
(Philo soph. Magas., xxix., 1846, pp. 271, 398) as early as 1842 and 1846, respectively, 
described the escape of colorless corpuscles from the blood-vessels. These observa- 
tions had, however, fallen into oblivion until Cohnheim, in 1867, rediscovered the 
phenomenon. 
According to researches of Schklarezvsky (P Auger’s Arch., Bd. i.), the peri- 
pheral disposition of the leucocytes in the veins is purely a physical phenomenon. 
If fluids, in which are suspended finely powdered substances of different specific 
gravity, are made to flow through tubes, it will be found that at a certain degree of 
retardation of the current, the bodies of lighter specific gravity pass over into the 
peripheral zone and at a more marked retardation the heavier bodies also enter this 
zone. 
For the emigration of the white corpuscles, it is necessary, according to Bins, 
Thoma, and Lavdowsky, that they be capable of motion and of adhering to the 
vessel-wall. According to these observers, the emigration of the white blood-cells 
is not a passive, but an active process. If the amoeboid power of the white cells be 
lessened by means of irrigation of the mesentery with a 1.5-per-cent, solution of 
salt (Thoma), or if the energy of these cells be lowered by means of quinine or 
iodoform (Bins, Appert, Kerner), there results inhibition of emigration. On the 
other hand, Pekelharing believes that quinine, oil of eucalyptus, and salicylic acid 
cause contraction of the veins, lessen the permeability of their walls, and thereby 
hinder the passing-out of white cells. This view is rejected, however, by Dissel- 
horst, who observed dilatation of the veins after irrigation of the tissues with 
quinine, carbolic acid, salicylic acid, and mercuric chloride. As there occurs in 
this case retardation of the current after transitory acceleration, without emigra- 
tion of the leucocytes collected in the peripheral zone; and as, on the other hand, 
leucocytes from blood-vessels that have been irrigated for an hour with quinine 
still retain complete vitality (Eberth), Disselhorst is of the opinion that the drugs EMIGRATION. 
247 
mentioned so change the inflamed vessel-wall that adhesion of the leucocytes roll- 
ing along the wall either cannot occur at all or only with difficulty. 
It is probable that a lesion of the vessel-wall is not necessary for the emigra- 
tion of leucocytes (Thoma). Since vasomotor disturbances of circulation can pro- 
duce migration (von Recklinghausen, Thoma), it is probable that all conditions 
necessary for this process are furnished by slowing of the blood-stream with 
peripheral disposition of the colorless corpuscles and the ability of the leucocytes 
to perform amceboid movements and to adhere to the vessel-walls. It is possible 
that differences in the water-content of the tissues (Thoma) exert some influence, 
since an increased amount of water causes increased amoeboid movement. It is also 
possible that the presence in the tissue-fluids, of substances having active cherno- 
Fig. 164.—Recent purulent meningitis (Muller’s fluid, haematoxylin). a, Arachnoid; b, sub- 
arachnoideal tissue; c, d, desquamated endothelium; e, pus-corpuscles, x 300. 
tactic properties causes emigration of those leucocytes in the peripheral zone that 
are adherent to the vessel-wall. 
According to the investigations of Arnold, Thoma, and Engelmann, there is 
present between the edges of the endothelial cells a soft cement-substance which 
suffers a change in the circulatory disturbance associated with cell-migration. This 
change may sometimes, but not always (Lowit), be recognized, on histological 
examination, in the form of numerous circumscribed widenings of these inter- 
cellular areas (Engelmann). If leucocytes pass through these places in great 
numbers the cement-substance becomes still more permeable, and lymphocytes and 
red cells escape in rapid succession (Thoma). 
The inflammatory disturbances of circulation and the formation of exudates 
may be most easily followed in the transparent membranes of cold-blooded animals, 
particularly in the mesentery, or the extended tongue or web of the frog. In the 
frog’s mesentery, which has been spread out on a suitable glass plate, circulatory 
disturbances and inflammation develop simply through exposure to the air and the 
resulting evaporation; in the case of the tongue and web, it is necessary to cauterize 
in order to produce inflammation. By the employment of suitable apparatus the 
circulation of the blood and the formation of the inflammatory exudate may also 
be observed under the microscope in the thin membranes of mammals (mesentery 
of rabbit, wing-membrane of bat), and observations thus made harmonize wholly 
with those made on the frog. 
The modern conception of inflammation is that it is a pathological complex 
essentially adaptive, protective, and reparative, called into action by a primary tis- 
sue-lesion. For a presentation of this view see Warthin, Chapter on Inflammation, 
“American Practice of Surgery,” Vol. I. 
§ 90. The cellular and fluid exudate from the vessels collects first 
in the immediate neighborhood (Fig. 164. e), but soon spreads in the 
lymph-spaces and thus forms a tissue-infiltrate (Figs. 165, b; 168, p). 248 
INFLAMMATION. 
When the exudate is abundant it may infiltrate tissue that has not been 
injured by the inflammatory irritant. This infiltration may be so marked 
Fig. 165.—Haematogenous staphylococcus myositis (alcohol, haematoxvlin-eosin). a, Transversely 
cut muscle-bundles; b, purulent; c, seropurulent, partly coagulated exudate, x 45. 
Fig. i66.—Section through the border of a blister caused by a burn (alcohol, carmine), a, 
Horny layer; b, rete Malpighii; c, normal papillae; d, swollen cells, some of whose nuclei are 
still visible though pale, while others have been destroyed; e, interpapillary epithelial cells, the 
deeper ones intact, those of the upper layers are drawn out longitudinally and in part are 
swollen and have lost their nuclei; f, total liquefaction of the cells; g, interpapillary cells, with- 
out nuclei, swollen and raised from the cutis; h, total degeneration of interpapillary cells which 
have been raised from the cutis; k, coagulated exudate (fibrin) lying beneath the uplifted 
epithelium; i, flattened papillae infiltrated with cells. x 150. 
that new disturbances of circulation and nutrition are produced, and the 
area of tissue-degeneration and inflammatory exudation becomes in- 
creased in extent. EXUDATION. 
249 
The fluid exudate may be partly absorbed by the tissue-elements, so that 
they become swollen, separated from their surroundings (Fig. 164, c, d), 
and contain drops of fluid (d) which are commonly designated vacuoles. 
Fig. 167.—Parenchymatous hepatitis (Flemming’s solution, safranin). a, Fiver-capsule; b, liver* 
rods showing fatty degeneration; c, liver-cells showing total degeneration, x 300. 
Fig. i68.—Mucous catarrh of a bronchus (Muller’s fluid, aniline-brown), a, Ciliated epi- 
thelium; ai, deeper cell-layers; b, goblet-cells; c, cells showing marked mucous degeneration; 
cJt mucoid cells with mucoid nuclei; d, desquamated mucoid cells; e, desquamated ciliated cells; 
/, layers of drops of mucus; fi, layer consisting of thready mucus and pus-corpuscles; g, duct 
of mucous gland filled with mucus and cells; h, desquamated epithelium of the excretory duct; 
i, intact epithelium of the duct; k, swollen hyaline basement-membrane; l, connective tissue of 
the mucosa, infiltrated with cells in part; m, dilated blood-vessels; n, mucous Hand filled with 
mucus; m, lobule of mucous gland without mucus; o, wandering cells in epithelium; p, cellular 
infiltration of the connective tissue of the mucous glands, x no. 250 
INFLAMMATION. 
There also occurs solution of tissue-elements in the exudate (Fig. 166, d, 
f) and of connective tissue cells, and intercellular substances. In this way 
brain and muscle tissue, as well as ordinary connective tissue, which have 
been killed as the result of injury, may become completely liquefied in 
the course of inflammation. 
If dead cells become satu- 
rated with lymph containing 
fibrinogen, and if fibrin-fer- 
ment is formed, the liquefac- 
tion of the infiltrated tissue 
may be preceded by coagula- 
tion, and the cells become 
changed into homogeneous 
masses without nuclei, or 
partly into granular and 
fibrillar masses. 
If the exudate — for ex- 
ample, in a muscle — lies in 
the supporting tissue, while 
the parenchyma suffers but 
little change, the inflammation 
is designated interstitial in- 
flammation (Fig. 165, b). If, 
on the other hand, degenera- 
tion of the parenchyma — 
e.g., the epithelium of the kid- 
ney tubules, the liver-cells 
(Fig. 167, b, c), or the con- 
tractile substance of muscles 
— is the most prominent 
feature of the process, the 
condition is called parenchy- 
matous inflammation. 
When the seat of inflam- 
mation is the surface of an 
organ it is termed superficial 
inflammation (Fig. 168). If 
the exudate gains access to the 
surface and escapes mixed 
with desquamated portions of 
tissue (Fig. 168, d, e, /, 
fiy ffy h)> the inflammation is 
called catarrh. If the pour- 
ing out of fluid exudate on 
the surface of skin or mucous 
membrane is hindered by 
a horny epithelial layer (Fig. 166, a), and if beneath this there are 
circumscribed collections of fluid, in which the deeper and softer 
layers of the epithelium dissolve (Fig. 166,d,f,g,h), the lesions produced 
are called vesicles and blisters. The exudate from serous surfaces 
collecting in the body cavities are termed inflammatory effusions, 
and may reach such size as to distend the affected cavity and com- 
press the organs contained in it. 
Fig. 169.—Purulent desquamative catarrh of the 
trachea in measles (alcohol, hematoxylin, eosin). 
a, Layer of. pus-corpuscles and desquamated epi- 
thelium; b, intact deepest layer of epithelium; c, 
basement-membrane; d, hyperoemic and infiltrated 
connective tissue of the mucosa; e, infiltrated sub- 
mucosa with mucous glands, x ioo. EXUDATION. 
251 
It is customary to express the occurrence of inflammation by adding 
the termination “itis” to the Greek name of the organ. Thus are formed 
the terms endocarditis, myocarditis, pericarditis, pleuritis, peritonitis, en- 
cephalitis, pharyngitis, keratitis, orchitis, oophoritis, colpitis, metritis, 
hepatitis, nephritis, amygdalitis, glossitis, and gastritis. The ending 
“ itis” is sometimes affixed to the Latin names, for example, conjuctivitis, 
tonsillitis, vaginitis, etc. To denote inflammation of the serous covering 
■of an organ or of the tissues immediately about it the prefixes “peri” 
Fig. 170.—Caharrhal secretion of different mucous membranes. A, Secretion from mucous 
membranes with columnar cells; B, from the mouth; C, from the bladder. i, Round cells 
(pus-cells); 2, large round cells with bright nuclei, from the nose; 3, mucoid columnar cells 
from the nose; 4, spirillum from the nose; 5, mucoid cells with cilia, from the nose; 6, goblet-cells 
from the trachea; 7, round-cells with spherules of mucus from the nose; 8, epithelial cells con- 
taining pus-corpuscles, from the nose; 9, fatty cells from a chronic catarrh of the pharynx and 
larynx; 10, cells containing carbon pigment, from the sputum; 11 and 12, squamous epithelium 
from the mouth; 13, mucoid pus-corpuscles; 14, micrococci; 15 bacteria; 16, leptothrix buccalis; 
17, spirochaete denticola; 18, superficial, 19, middle layer of bladder epithelium; 20, pus-cor- 
puscles; 21, schisomycetes. X 400. 
and “para” are placed before the Greek names with the termination 
“ itis” Thus are formed the words perimetritis, parametritis, periproct- 
itis, paranephritis, perihepatitis, etc. 
For certain forms of inflammation special names are used, for ex- 
ample, inflammation of the lungs is called pneumonia, and inflammation 
of the palate and tonsillar regions, angina. 
§ 91. Local tissue-degeneration and exudation vary in different cases, 
and there may accordingly be distinguished different forms of inflam- 
mation. 
If the exudate consists essentially of fluid, while the cellular con- 
stituents are insignificant, it is called a serous exudate; circumscribed 
collections of clear fluid beneath the horny layer of the epidermis 
with liquefaction of the soft layers of the epithelium lead to the 
formation of vesicles and blisters (Fig. 166, d, /). 252 
INFLAMMATION. 
When the exudation of fluid on a mucous membrane is associated with 
mucoid degeneration of the surface epithelium (Fig. 168, b, c, cr), and 
of the mucous glands (n), the con- 
dition is termed mucous catarrh (d, 
f, flf g). If marked desquamation 
of the epithelium, with or without 
mucoid change, occurs (Fig. 169, a), 
the condition is termed desquamative 
catarrh; such a process may occur 
not only on mucous membranes, but 
also in the air vesicles of the lungs, 
in the kidney-tubules, etc. If pus- 
corpuscles are present in the exudate 
it may be spoken of as purulent 
catarrh; in which condition the 
exudate becomes white or yellowish- 
white, milky or creamy. 
The form and character of the 
cells of a catarrhal secretion vary with 
the location and the variety of catarrh 
(Fig. 170). Bacteria are often 
present in the cells of the exudate 
(Fig. 170, 4, 14, 15, 16, 17, 21). 
If in a fluid exudate there is depo- 
sition of fibrin, serofibrinous exu- 
dates are formed, and are often desig- 
nated croupous. These occur chiefly 
on the surface of serous and mucous 
membranes, and in the lungs; but 
masses of fibrin may be formed in 
tissues infiltrated with exudate, as 
well as in lymph-vessels. 
On mucous membranes fibrinous 
exudates form whitish patches, which sometimes lie loosely, at other 
times are attached. In the serous cavities fibrinous coagula float in the 
fluid portion of the 
exudate, or are de- 
posited on the surface. 
Such deposits consist 
of thin films or gran- 
ules which give to the 
surface a cloudy, 
lustreless, rough, or 
granular appearance; 
or of larger yellowish 
or yellowish-red, firm 
membranes, which im- 
part a felted or villous 
appearance (cor vil- 
losum). In the lung, 
croupous inflammation leads to filling of the alveoli with a coagulated 
mass, in consequence of which the lung acquires a firm consistence. 
Fig. 171.—Acute hemorrhagic fibrinous 
inflammation of the trachea, caused by 
vapor of ammonia (Muller's fluid, hema- 
toxylin, eosinl. a, Superficial layer of the 
connective tissue of the mucosa, with 
greatly dilated blood-vessels and extrava- 
sated red blood-cells; b, deep layer of epi- 
thelium raised up in toto; c, desquamated 
epithelial cells; d, hemorrhagic fibrinous 
exudate with radiating, crystal-like masses 
of fibrin, in part proceeding from small, 
colorless spherules, x 300. 
Fig. 172.—Croupous membrane from the trachea, a, Section 
through membrane; b, uppermost layer of the mucosa in- 
filtrated with pus-corpuscles (d) ; c, fibrin threads and granules; 
d, pus-corpuscles. x 250. EXUDATION. 
253 
On mucous surfaces the formation of croupous membranes takes place 
when the epithelium is desquamated and the connective tissue, at least in 
part, is exposed; but tissues covered with epithelium may become the 
seat of fibrinous deposits extending from denuded areas. The desquama- 
tion of epithelium may follow gradually, at other times rapidly through 
Fig. 173.—Section from an inflamed uvula covered with a stratified fibrinous membrane, 
from a case of diphtheritic croup of the pharyngeal organs (Muller’s fluid, hsematoxylin, eosin). 
a, Surface layer of coagulum, consisting of epithelial plates and fibrin and containing numerous 
colonies of cocci; b, second layer of coagulum, consisting of fine-meshed fibrin network enclos- 
ing leucocytes; c, third layer of coagulum, lying upon the connective tissue, consisting of a 
wide-meshed reticulum of fibrin enclosing leucocytes; d, connective tissue infiltrated with cells; 
e, infiltrated boundary layer of the connective tissue of the mucous membrane; f, heaps of red 
blood-cells; g, widely dilated blood-vessels; h, dilated lymph-vessels filled with fluid, fibrin and 
leucocytes; i, duct of a mucous gland distended with secretion; k, transverse section of a gland; 
l, fibrin reticulum in the superficial layer of connective tissue, x 45. 
the lifting up of whole layers of epithelium (Fig. 171, b), which are either 
well preserved or degenerate or necrotic, and infiltrated with exudate 
(Fig. 173, a). . . 
The deposition of fibrin may begin under the raised epithelium with 
the formation of fine needle-like forms (Fig. 171, d) ranged radially about 
a centre, in which at times there lies a small body, or blood-plate. Soon 
there form threads (Figs. 172, c; 173, b, c) which enclose variable numbers 254 
INFLAMMATION. 
of leucocytes and red cells. The arrangement of the threads is usually 
reticular, but the thickness of the network and the size of the meshes 
vary. When there is unequal development of the fibrin threads, the prin- 
cipal strands sometimes lie parallel with the surface of the mucous mem- 
brane (Fig. 172, c), sometimes perpendicular to it (Fig. 173, c). Thick 
fibrinous membranes frequently show distinct stratification (Fig. 173, a, 
b, c), indicating that their formation has occurred in successive layers. 
When a mucous membrance becomes the seat of fibrin deposit, the un- 
Fig. 174.—Croupous tracheitis. Section through the connective tissue of the mucosa 
(carmine and fibrin-stain. a, b, c, d, Blood-vessels with fibrin precipitates; e, oedematously 
swollen connective tissue with leucocytes; f, connective tissue with fibrin-threads, x 500. 
derlying connective tissue is more or less hyperaemic (Fig. 173, g), cede- 
matous and swollen, infiltrated with leucocytes (Figs. 173, d, e; 174, e), 
and usually contains thready fibrin precipitates (Figs. 173, ]; 174, /). 
Often the tendency to precipitation of fibrin is manifested in the blood- 
vessels (Fig. 174), at times these contain tangled threads and rods (Fig. 
174, b), at other times fibrin-needles grouped in stellate forms or clusters 
(a, c, d), which proceed from blood-plates, or radiate from portions of 
the vessel-wall where the endothelium is lost. Likewise, fibrin-threads 
may be found in dilated lymph-vessels, in association with fluid and 
cellular exudate (Fig. 173, h). 
On serous membranes deposits of fibrin appear in granular and 
thready, or in thick, homogeneous masses, or even in the form of 
ribbon-like bands. Here also the epithelium is exfoliated at the point of 
deposition or preserved in patches and covered with fibrin. The con- 
nective tissue of serous membranes in croupous inflammation is more 
or less infiltrated, and may contain leucocytes and fibrin, both in the 
congested vessels and in the connective-tissue spaces (Fig. 175, c). 
More marked exudations on serous membranes produce thick, felted 
deposits, the elements of which consist of thready fibrin and EXUDATES. 
255 
pus corpuscles (Fig. 175, d, e), as well as micro-organisms (&). An 
abundance of pus corpuscles gives to the exudate a fibrinopurulent char- 
acter, the deposits becoming whitish in color. 
Fibrinous exudates in the lungs are characterized by a more or less 
close network of fibrin (Fig. 
176, b), in whose meshes and 
in the immediate neighbor- 
hood of which lie leucocytes 
mingled with red blood-cells 
{e), and desquamated epi- 
thelium. In the early stages 
there are occasionally found 
globular, wreath-shaped pre- 
cipitates of fibrin joined to- 
gether in rows. 
In the kidneys fibrin may 
occur in the form of fine 
threads or hyaline masses in 
the tubules and glomerular 
capsules. In lymph nodes 
fibrin-threads are formed in 
the lymph-channels. 
Haemorrhagic exudate 
— that is, an exudate con- 
taining large numbers of red 
cells — occurs in connection 
with the exudation of fibrin. 
The exudate of croupous 
pneumonia contains a larger 
or smaller number of red 
blood-cells (Fig. 176, c), and 
in fibrinous pericarditis and 
pleuritis great numbers of 
red cells may escape from 
the vessels. Haemorrhagic 
inflammations occur not in- 
frequently in the central 
nervous system, in lymph 
nodes, in the skin and kid- 
neys. In the last case the 
blood escapes from the 
glomerular vessels. 
Serous, fibrinous, and 
serofibrinous inflammations 
are caused by thermal and 
chemical influences, as well 
as by bacteria; but are most 
frequently the result of in- 
fection, particularly with the 
Diplococcus pneumonice 
(Fig. 176, b) and the Bacil- 
lus diphtheria. The former 
causes croupous inflamma- 
Fig. 175.—Fibrinopurulent diplococcus pleuritis in a 
- three-year-old child (formalin, fibrin-stain), a, Inflamed 
pleura; b, diplococci; c, fibrin; d, e, fibrinopurulent 
exudate, x 500. 256 
INFLAMMATION. 
tions of the lungs and pleura, the latter fibrinous inflammations of the 
throat, palate, and respiratory passages. 
Fig. 176.—Croupous pneumonia. Red hepatization of the lung (alcohol, carmine, fibrin-stain). 
a, Infiltrated alveolar septa; b, fibrinous exudate; c, red blood-cells, x 200. 
Fig. 177.—1 ulent bronchitis, peribronchitis, and peribronchial bronchopneumonia in a 
child one year and three months old (Muller’s fluid, hiematoxylin, eosin). a, Purulent, b, mucoid 
bronchial contents; c, c 1, bronchial epithelium infiltrated with round cells and partly desquamated 
d, infiltrated bronchial wall with greatly dilated blood-vessels; e, infiltrated peribronchial and 
periarterial connective tissue; f, alveolar septa, in part infiltrated with cells; g, fibrinous exudate 
in the alveoli; h, alveoli filled with exudate rich in cells; alveoli filled with exudate containing 
few cells; k, cross-section of a pulmonary artery; l, bronchial, peribronchial, and interacinous 
vessels showing marked congestion, x 43. PURULENT INFLAMMATION. 
257 
§ 92. When the inflammatory exudate is made up chiefly of leuco- 
cytes, infiltration (Figs. 165, b; 177, d, e, f) may be so marked that the 
structure of the tissue is obscured. If polynuclear leucocytes or pus-cells 
are present in large numbers in the exudate on a mucous membrane or 
Fig. 178.—Section of a smallpox pustule (injected haematoxylin preparation), a, Horny 
layer; b, stratum mucosum of the epidermis; d, cutis; e, smallpox pustule; f, cavity of the pock, 
containing at /, pus-corpuscles; g, interpapillary remains of epithelium infiltrated with pus- 
corpuscles; h, papillary bodies infiltrated with cells; i, umbilication with thin pock cover; t'i, edge 
of the pock, the roof at this point consisting of the horny and transitional layers, x 25. 
wound, so that the exudate is white or yellowish-white in color and of a 
milky or creamy consistence, it is called pus; such an inflammation is 
designated purulent (Fig. 177; a). Persistent marked secretion is termed 
blennorrhcea. Collections of pus in the body-cavities — for example, 
Fic. 179.—Embolic abscess of the intestinal wall with embolic purulent arteritis, and embolic 
aneurism in cross-section (alcohol, fuchsin). a, b, c, d, e, Layers of intestinal wal’l; f, remains 
of arterial wall, cross-section; g, embolus, surrounded by pus-corpuscles lying within the dilated 
and partly suppurating artery; h, parietal thrombus; i, periarterial purulent infiltration of the 
submucosa; k, vein showing marked congestion, x 28. 258 
INFLAMMATION. 
the pericardial, pleural, or joint cavities — give rise to purulent effusions 
or empyemata. If in a blister arising through liquefaction of epithelium 
below the horny layer of the epidermis there takes place marked col- 
lection of leucocytes, the fluid becomes turbid, and the vesicle is changed 
into a pustule (Fig. 178, fff). 
When leucocytes collect in a tissue in such numbers as to give it a 
white, gray-white, or yellowish-white color the process is known as 
Fig. i8o.—Suppuration and necrosis of the mucosa of the large intestine in dysentery 
(Muller’s fluid, hrematoxylin, eosin). Section through the mucosa (a) and submucosa (b) of 
the large intestine; c, muscularis; d, interglandular, di, subglandular infiltration of the mucosa; 
e, focus of infiltration in the submucosa; f, infiltrated upper glandular layer undergoing desquama- 
tion; g, ulcer with infiltrated base. X25. 
purulent infiltration. This may be followed by liquefaction and abscess- 
formation (Fig. 179, i)—that is, the formation of a circumscribed 
cavity filled with pus. 
When purulent infiltration involves the superficial parts of an organ 
—for example, a mucous membrane (Fig. 180, d, f, g)—the process leads 
to localized loss of substance — an ulcer. The formation, through 
suppuration, of duct-like excavations gives rise to fistulous tracts. 
If an accumulation of pus-corpuscles is associated with abundant 
collection of fluid, the exudate is spoken of as seropurulent. The rapid 
spread of purulent or seropurulent inflammation over wide areas — for 
example, through extensive areas of subcutaneous or submucosal tissues 
— is known as phlegmon (Fig. 181, c, d). This often leads to the forma- 
tion of pus-cavities, in which lie shreds of disintegrating tissue infiltrated 
with pus. 
The association of serous exudation and fibrin precipitation with 
suppuration leads to the formation of fibrinopurulent exudates (Fig. 
175, d, e) ; effusions into the body-cavities, meningeal exudates, croupous 
exudates on mucous surfaces and in the lungs, and phlegmons may 
bear this character. It is to be noted, however, that with increase of 
suppuration the formation of fibrin becomes decreased, and coagula 
already present dissolve. Fibrin-masses infiltrated with pus are white and 
easily torn. 
Suppurations and the associated formation of abscesses and ulcers are 
in the majority of cases caused by bacteria, most frequently by the CAUSES OF SUPPURATION. 
259 
Staphylococcus pyogenes aureus, Streptococcus pyogenes, and the Gono- 
coccus; but suppurations due to Actinomyces, Bacillus anthracis, Bacillus 
mallei, or the Bacterium coli commune, are not rare. Staphyloccoci gen- 
erally produce localized inflammations; streptococci, on the other hand, 
phlegmonous. The presence of certain bacteria (Bacillus phlegmones 
emphysematosa, Frankel; Bacillus acrogenes capsulatus, Welch) may 
cause the formation of gas (gas- 
phlegmon). Suppuration is sometimes 
ectogenous, sometimes lymphogenous or 
hsematogenous; in the last case it bears 
the character of an embolic process 
(Fig. 179). 
Of the chemical substances which, 
when introduced into the tissues, pro- 
duce liquefaction resembling suppura- 
tion may be mentioned mercury, oil of 
turpentine, petroleum, five- to ten-per- 
cent. solutions of silver nitrate, creolin, 
digitoxin, dilute croton-oil, and steril- 
ized cultures of various bacteria, in 
which the bacterial proteins are the 
active agents. The liquefactions thus 
produced differ from those of infection, 
in that they heal more easily, do not 
spread in the tissues, or give rise to 
metastases, and their products when 
inoculated possess no virulence. 
§ 93. Suppurative inflammation al- 
ways leads to tissue-necrosis; but this 
necrosis is submerged in and obscured 
by the liquefaction and dissolution 
which form the characteristic feature of 
suppuration. In other circumstances 
necrosis may occur, recognizable even 
to the unaided eye, and is not followed 
by suppuration, but is characterized by 
the fact that the necrotic portions re- 
main unchanged for a long time, and 
ultimately are removed through seques- 
tration, sloughing, or absorption. Since 
necrosis in such a case forms the 
chief feature, the condition may be 
appropriately designated necrotic in- 
flammation. 
Necrosis associated with inflammation may be caused by caustic 
chemicals, high or low temperatures, ischaemia, and infection (typhoid 
fever, diphtheria, dysentery, and tuberculosis).. 
Necrosis of tissue may appear as the immediate effect of injury, exu- 
dation following, being confined to the region adjoining the necrosis; 
this is especially the case after the action of corrosive substances, high 
temperature, and ischaemia. In other cases, inflammation is first es- 
tablished, the infiltrated tissue later becoming necrosed. In tuberculous 
Fig. 181.—Phlegmon of the subcutaneous 
tissue with formation of a vesicle through 
oedema (Muller’s fluid, hematoxylin, eosin). 
a, Corium; b, epidermis; c, infiltrated, fat 
tissue; d, focus of pus; e, cellular foci in 
corium; f, subepithelial vesicle due to 
oedema, x 30. 260 
INFLAMMATION. 
infection necrosis occurs, as a rule, after proliferation has existed for 
some time. 
Necrotic inflammations are most frequently seen in mucous mem- 
Fig. 182.—Necrosis of the epithelium of the epiglottis (Muller’s fluid, haematoxylin). a, 
Living epithelium with well-stained nuclei; b, necrotic epithelium with nuclei not staining; 
c, leucocytes lying in the epithelium; d, hyperaemic, inflamed, and infiltrated connective tissue. 
X 300, 
branes, and are sometimes called diphtheritis, particularly those caused 
by infection. The necrosis may first affect the epithelium, which loses 
its nuclei (Fig. 182, b) 
and acquires a granular 
appearance. If white 
opaque patches are formed 
on the mucous membrane, 
as in the pharynx in diph- 
theria, the condition may 
be spoken of as epithelial 
or superficial diphtheritis. 
Usually, however, the des- 
ignation diphtheritis is ap- 
plied only to necroses in 
which the inflamed and in- 
filtrated connective tissue 
(Fig. 183, a), becomes 
converted into a granular 
mass without nuclei, or 
into a homogeneous mass 
containing fibrin, in which 
the structure of the tissue 
can no longer be recog- 
nized. 
Diphtheritic sloughing 
of a mucous membrane is 
observed particularly often 
in the intestine (Fig. 183), 
but occurs also in the 
Fig. 183.—Bacillary diphtheritis of the large intestine 
in dysentery (alcohol, gentian violet). a, Necrotic 
portion of the glandular layer of the mucosa, infiltrated 
with bacilli; b, intact inflamed mucosa; c, muscularis 
rnucosse; d, submucosa; e, colonies of bacilli; f, glands 
with living epithelium; g, glands with necrotic epithe- 
lium and bacilli; h, connective tissue infiltrated with 
cells; i, blood-vessels, x 80. NECROTIC INFLAMMATION. 
261 
vagina, the descending urinary passages, and the region of the throat, 
where the tonsils are especially affected, etc. The necrotic tissue forms 
white, or grayish white sloughs, which are surrounded by reddened and 
inflamed tissue. If some time has elapsed since its formation, and if 
liquefaction at the 
boundary between 
the living and dead 
tissues has oc- 
curred, with sepa- 
ration of the latter, 
the necrosed parts 
form loosely at- 
tached or free de- 
posits lying on the 
surface, consisting 
at times of small 
flakes, at other 
times of larger 
sloughs. 
Diphtheritis of 
mucous membranes 
may be associated 
with croupous de- 
posits (Fig. 184, 
c, d), so that the 
area of necrosis 
(d) may be covered 
with fibrin (c). 
Wound-granulations may necrose in the same way as inflamed mucous 
membranes; such may therefore be called wound-diphtheritis. 
Acute tissue-necroses caused by infection occur in internal organs, 
notably in typhoid fever, in the lymph nodes (Fig. 185), spleen and 
bone-marrow, and are characterized by 
the formation of opaque grayish-white, 
yellowish, or dirty-gray sloughs. Not 
infrequently fibrinous collections are 
seen in the necrotic tissue (Figs. 184, d; 
185). 
In the necrosis caused by tuber- 
culosis, destruction of tissue occurs 
gradually, and bears the character of 
caseation. 
When an inflammatory focus con- 
tains bacteria which excite putrid de- 
composition of albuminoid bodies, the 
inflammation may take on the character 
of putrid gangrene; the tissue may dis- 
integrate into a dirty gray or black, tinder-like mass which gradually 
dissolves and gives off an extremely disagreeable odor. Gas-bubbles are 
sometimes developed in the focus. (See § 92.) 
Fig. 184.—Section of the uvula in pharyngeal diphtheria with 
croupous deposits (alcohol, aniline brown), a, Normal epithelium; 
b, connective tissue of the mucous membrane; c, reticulated fibrin; 
d, connective tissue of mucosa infiltrated with coagulated fibrin and 
round cells, and partly necrotic; e, blood-vessels; f, haemorrhage; 
g, clumps of micrococci, x 75. 
Fig. 185.—Diphtheritic necrosis within a 
swollen mesenteric lymph-gland, in typhoid 
fever (alcohol, fibrin-stain). Fibrin net- 
work between the necrotic ceils, x 300. 262 
INFLAMMATION. 
II. The Termination of Acute Inflammation in Healing. 
§ 94. Should acute inflammation occur in any tissue, sooner or later 
processes arise whose object is restoration of the damaged tissue, and may 
therefore be regarded as processes of repair. These consist in the 
cessation of pathological exudation and its replacement by normal secre- 
tions, the removal or absorption of exudate and of necrotic tissue, and 
restoration of destroyed tissue. If the exciting cause of the inflammation 
is still present in the tissue and active, it must be removed or rendered 
inert. 
The repair of the vessel-walls is brought about through restoration 
of the blood-supply, so that the nutrition of the vessels becomes normal. 
If the alteration is slight, restoration may take place in a time that may 
be measured in minutes and hours. 
When the exciting cause of the inflammation acts at some length — as 
in the case of bacteria which live and multiply in the tissues, and if there 
Fig. i86.—Phagocytes from granulation tissue with included leucocytes and fragments of 
same (sublimate, Biondi’s stain), a, Round, b, spindle, fibroblast with leucocytes; c, d, e, fibro- 
blasts containing remains of leucocytes, x 500. 
has been, for example, necrosis of the vessel-walls, complete restoration 
is hindered or prevented entirely. 
The absorption of exudate occurs in many cases easily and quickly, 
in that it is taken up by the lymph-stream, eventually by the blood. This 
takes place most rapidly in serous exudates, in many places fibrinous 
exudates may also be removed, but only when the coagula liquefy. For 
example, coagulated exudate in the lung may be liquefied and made cap- 
able of absorption through the action of a proteolytic enzyme (Muller) 
that arises most probably from the leucocytes. The absorption of exu- 
dates is often aided by phagocytes, that is, through amoeboid cells taking 
up corpuscular substances and destroying them. Thus, large mononu- 
clear cells (macrophages) may take up polynuclear leucocytes (Fig. 186, 
a, b) and digest them (c, d, e). In the same manner red blood-cells and 
their disintegration-products may be disposed of (Fig. 96). Firmer 
fibrinous exudates such as are formed on serous membranes, and large 
collections of pus, offer considerable resistance to absorption. In many 
cases absorption is accomplished by the substitution for the exudate of 
embryonic tissue which later becomes changed into connective tissue. 
The sequestration and absorption of necrosed tissue, with the ex- 
ception of dead epithelium, which may be quickly accomplished, require a 
length of time which varies according to the nature, situation, and 
extent of the lesion. In general, inflammation persists as long as 
necrotic tissue is present. Superficial necrosed tissues may be cast off 
after sequestration from the living. In deep-seated necroses in which HEALING OF ACUTE INFLAMMATION. 
263 
the tissue does not undergo total liquefaction, absorption is slow, and is 
brougli about through grauual substitution of living tissue for the dead. 
Phagocytosis often takes place in the absorption of necrotic tissue. 
The regeneration of tissue in inflammatory lesions is dependent on 
the degree and extent of degeneration, on the nature of the tissue, and 
on the mode of action of the agent exciting the inflammation. 
If the tissue-cells of the inflamed area are but slightly degenerated, 
they are quickly restored when the nutrition becomes normal. If single 
cells are lost but the organization of the whole is not disturbed, there can 
take place in certain tissues renewal of cells through regenerative growth 
of remaining cells. This is particularly true of different forms of con- 
nective tissue, surface epithelium, the cells of lymph nodes, etc., while 
ganglion-cells and heart-muscle possess little or no power of regeneration 
(see Chapter VI.). Extensive destruction of tissue with solution of 
continuity, wounds, fractures, suppuration, necrotic inflammations, etc., 
produce proliferations which are sufficient to close the defect, but do not 
lead to restoration of the normal tissue, rather to the formation of tissue 
of lower grade, which in its earliest stages is known as granulation tissue, 
in its mature form as cicatricial tissue, the whole process being included 
under the title of productive inflammation. 
The phenomena of proliferation begin in inflamed tissues, at the 
earliest after eight hours, but are first clearly recognizable after from 
twenty-four to forty-eight hours. 
In general, they appear more rapidly the milder the inflamma- 
tion and the more quickly as exudation is overcome or diminished. 
Suppuration, necrosis, and gangrene hinder proliferation and retard 
repair, or at least confine the reparative processes to neighboring 
tissues. 
Every tissue capable of proliferation furnishes formative cells for 
tissue of its own kind or for one closely related to it. On the other 
hand, newly developed tissue-cells may become mixed with the exudate, 
degenerate, and die. Thus not all cells developed through proliferation 
fulfil their function of producing new tissue. 
The removal of the exciting cause of inflammation takes place 
differently in different cases, and depends on the nature of the cause. 
Many traumatisms and thermal influences act for a short time, and 
have no further influence on the course of the inflammation. Sub- 
stances acting chemically may be taken up by the tissue-juices and 
made inert, or excreted, while others remain locally active for a long 
time. Insoluble bodies in the form of dust which have penetrated into 
the tissue, for example, into the lungs, are for the greater part taken up 
by phagocytes and carried away (see § 21) and either deposited or re- 
moved from the body. Of the bacteria exciting inflammation, many die 
as the result of bactericidal substances formed in the diseased area (see 
§ 31). The destruction of bacteria takes place partly in the tissue-fluids 
and partly by phagocytosis, the bacteria being taken up by the cells alive, 
or, having first been killed, are then digested. Of the bacteria causing 
inflammation, many live and produce new generations which in turn 
cause new inflammation, often in such a way that in the first focus the 
inflammation may subside and healing take place, while in the neighbor- 
hood, or even in distant regions, metastatic inflammations develop. 
On account of the differences in the nature and behavior of the 
exciting cause of inflammation, as well as in the course of tissue-degen- 264 
INFLAMMATION. 
eration, exudation, and healing, it is easy to understand that the whole 
course may vary greatly in different cases, and that all the possibilities 
cannot be reviewed. At the same time it is not difficult to comprehend 
the decline of the different forms of inflammation, since the whole proc- 
ess is always made up of the same factors—that is, tissue-degeneration, 
exudation, and proliferative processes, the last of which are intended to 
counterbalance the disturbances caused by the first two. 
The phenomenon of chemotaxis, that is, the attraction or repulsion of motile 
cells by chemical substances soluble in water, was first observed by Strahl and 
Pfeffer, who carried out observations on the myxomycetes, infusoria, bacteria, 
spermatozoa, and zoospores. Investigations by Leber, M assart, Bordet, Boris sow, 
Gabritschewsky, and others have shown that the leucocytes likewise are attracted 
by chemical substances (positive demo taxis) or are repelled by them (negative 
chemotaxis). In particular do products of fission-fungi {Leber, Massart, Bordet, 
Gabritschezvsky), or bacterial proteins, even in great dilution (according to Buchner, 
pyocyaneus protein acts even in a three-hundred-fold dilution), possess positive 
chemotactic action. According to Buchner, this property is also shown by gluten- 
casein from wheat-gluten and legumin, aleuronate, glue from bones, and alkali 
albuminates from peas, while ammonium butyrate, trimethylamin, ammonia, leucin, 
tyrosin, urea, and skatol show negative chemotaxis. 
III. Inflammatory New-formation of Tissue; Healing of Wounds and 
Substitution of Exudates and Tissue-necroses by Connective 
Tissue. 
§ 95. The inflammatory proliferation of tissue is essentially a re- 
generative process. Not rarely hyperplastic proliferations of con- 
Fig. 187.—Isolated cells from a wound-granulation (Muller’s fluid, picrocarmine). a, Mono- 
nuclear, ai, polynuclear leucocytes; b, different forms of mononuclear fibroblasts; c, fibroblast 
with two nuclei; c 1, multinuclear fibroblast; d, fibroblasts in the stage of connective-tissue forma- 
tion; e, fully developed connective tissue, x 500. 
nective tissue fail to accomplish this purpose and cause new injury; 
this is especially the case when persistent infection or the residues of 
acute inflammation (exudates, abscesses, necroses) keep up a chronic 
condition of inflammation. GRANULATION TISSUE. 
265 
The inflammatory new-formations of tissue may be distinguished 
from simple regeneration by the fact that they are accompanied by 
circulatory disturbances and pathological exudations, especially by im- 
migration of lymphocytes and leucocytes, and that these have a modifying 
action on the course of the process. 
The granulation tissue formed during inflammation is an em- 
bryonic tissue arising through cell proliferation and infiltrated with 
Fic. 188.—Scar fifteen days old (Maximow, 1. c.). a, Fibroblasts; b, polymorphous lympho- 
cytes (polyblasts); c, unchanged lymphocyte (polyblast), x 500. 
leucocytes and lymphocytes. In the beginning it consists essentially 
of cells and of new-formed blood-vessels which at first find support in 
the ground substance of the tissue from which they pass out, but soon 
form a ground substance for themselves. 
The cells of granulation tissue are proliferated tissue-cells (Fig. 
187, b, c, d), polynuclear leucocytes (at) and mononuclear lymphocytes 
(a). Tn 'most cases the proliferated cells are derivatives of fibrous con- 
nective tissue, and are known as fibroblasts. Granulation tissue, how- 
ever, may contain derivatives of other tissues, for example, of perios- 
teum, marrow-tissue, and muscle, in the form of osteoblasts, chondro- 
blasts, and sarcoblas-ts, which are able to form bone, cartilage, and muscle, 
respectively. Further, newly formed epithelium may occur in glands, 
while in mucous membranes and in the skin new-formed surface epi- 
thelium may be found in or on the granulation tissue. The fibroblasts 
of granulation tissue are large polymorphous cells, with clear nuclei 
(Fig. 187, b), and may possess long processes. Young forms without 
processes resemble epithelial cells and are therefore called epithelioid 
cells. With the help of their processes they can push into the tissue 
spaces, but usually show no lively amoeboid movements. 
In the development of granulation tissue the fibroblasts form con- 
nective-tissue fibrillae, a portion of the protoplasm taking on a fibrillar 
appearance, or first becoming homogeneous and then producing fibrillae 
(Figs. 187, d, e; 188, a; 189, a). 266 
INFLAMMATION. 
The polynuclear leucocytes of granulation tissue (Fig. 187, a) are 
not capable of further development and either wander farther or die, 
particularly those which collect on the surface or in abscesses. If 
bacteria are present (streptococci, staphylococci, gonococci, anthrax- 
bacilli, etc.) the leucocytes may act as phagocytes (micro phages) and aid 
in the destruction of the bacteria. 
The lymphocytes and mononuclear leucocytes of granulation 
tissue arise from the blood, or are attracted from the lymphoid depots 
Fig. 189.—Tissue from a scar sixty-five days old (Maximow, 1. c.). a, Fibroblasts; b, bi, 
spindle-formed lymphocytes (polyblasts), with elongated nuclei embedded in the tissue; c, plasma 
cell. X 500. 
and mingle with the cells of the exudate. Many of them die, as do 
the polynuclear leucocytes; or, on the other hand, may change into 
various cell-forms; from this they may be designated polyblasts. 
Enlargement of the protoplasm and enlargement and clearing of the 
nucleus give them the character of epithelioid cells; usually they are 
smaller than fibroblasts and their nuclei stain darker (iron-haematoxylin 
or methylene blue). By sending out pseudopodia they may assume 
various forms (Fig. 188, b). On the surface of smooth foreign bodies 
they may form an epithelial-like deposit or covering. 
In the development of cicatricial tissue polyblasts, it is held, may be 
embedded as permanent elements in the form of spindle cells which are 
to be distinguished with difficulty or not at all from ordinary connective- 
tissue cells (Fig. 189, b, b-f). Occasionally they assume a character cor- 
responding to that of the so-called klasmatocytes of Ranvier (Fig. 190, 
b), that is, they form spindle or branched cells, coarsely granular, show- 
ing many vacuoles and often containing granules staining metachro- 
matically (polychrome methylene blue). Further, among the polyblasts 
of granulation tissue may be included the so-called plasma-cells (Figs. GIANT CELLS. 
267 
189, c; 190, c), that is, round or irregularly formed cells having an 
eccentric nucleus and a bright central and dark granular periphery. 
The polyblasts are those cells which show the greatest activity in granu- 
lation tissue as phagocytes, and not only take up bacteria but disintegrat- 
Fig. 190.—Plasma cells and klasmatocytes within scar tissue, forty days old (Maximow, l. c.) 
a, Fibroblasts; b, klasmatocytes; c, plasma cells; d, blood-vessel, x 500. 
ing or dead red cells and leucocytes (Fig. 186), and destroy or carry them 
away. 
They also have an inclination to form multinucleated giant-cells 
by continuous division of the nuclei in the same cell, usually by 
amitosis, rarely by karyokinesis, and syncytial forms, the latter, through 
confluence of cells lying in close contact. This is frequently observed 
Fig. 191.—Dog’s hair encapsulated in the subcutaneous tissue (alcohol, Bismarck brown), a, Hair; 
b, fibrous tissue; c, proliferating granulation tissue; d, giant-cells, x 66. 
when foreign bodies or necrotic portions of tissue lie in the 
granulation tissue (Fig. 191, d) ; such multinucleated cells are there- 
fore designated foreign-body giant-cells. Soluble substances, for ex- 
ample, catgut sutures or necrotic muscle-substance, can be gradually 
dissolved by them. 
The presence of foreign substances in the form of the bodies of 
bacteria (tubercle-bacilli and lepra-bacilli) can also lead to their 
formation, 268 
INFLAMMATION. 
The blood-vessels of granulation tissue arise through offshoots 
from old vessels (see Fig. 140), which show proliferative processes 
early in the inflammatory state, (a), and in the formation of granu- 
lation tissue take on very lively proliferation. The young granula- 
tion tissue, as a result, becomes permeated by blood-vessels, so that 
it acquires a red appearance. During the transformation of granu- 
lation into connective or scar-tissue, obliteration of vessels occurs 
and the scar becomes pale. 
The structure of granulation tissue, the origin and the fate of the cells 
contained in it, have been for decades the object of investigation and dis- 
cussion, and even to-day not all of the questions can be regarded as solved. It has 
been demonstrated beyond doubt, however, that the builders of cicatricial tissue, the 
fibroblasts, are derivatives of fixed connective-tissue cells; further, it is certain that 
the polynuclear leucocytes emigrate from the blood and undergo no further develop- 
ment. The origin of the small mononuclear cells which resemble lymphocytes and 
the mononuclear leucocytes of the blood is still a matter of dispute, as is also the 
role which they play in the granulation-tissue. 
Even in the year 1876, on the ground of ex- 
perimental investigations, I expressed the 
opinion that they were capable of development 
into epithelioid cells and that at the time of 
their formation and transformation they exert 
phagocytosis and take up other cells and digest 
them and that they can become changed into 
permanent elements of cicatricial tissue. I 
have demonstrated that under special condi- 
tions they form syncytial giant-cells. 
Maximow, through investigations carried on 
in my laboratory in 1901-1902, has confirmed 
the view that the mononuclear leucocytes and 
lymphocytes, after passing out from the blood- 
vessels, may undergo further development, and 
has demonstrated that in cicatricial tissue they 
take on the appearance of klasmatocytes, 
plasma-cells, and mast-cells, also appearances 
similar to those of ordinary fixed connective-tissue cells, so that finally differentia- 
tion of the two original cell-forms is no longer possible. They also change to fixed 
connective-tissue cells, but do not produce, as I formerly assumed, the fibrillary 
ground-substance. 
With reference 'to the varied forms which these cells show, Maximow has 
designated them polyblasts. 
The differentiation of the different cell-forms as given above, rests essentially 
on differences in the structure of the protoplasm. Plasma cells (Unna) or the 
“kriimelzellen ” (von Mars chalk o) are mononuclear, round or oval, at times elongated 
cells that stain intensely with methylene blue and possess an eccentrically placed 
nucleus showing a chromatin network and five to eight chromatin granules. At 
the periphery of the cell the protophasm is more densely clumped, so that there is 
formed a lighter area surrounding the nucleus. The klasmatocytes (Ranvier) are 
spindle shaped, branched or stellate cells with blunt or swollen ends and a granular 
protoplasm that often contains little vacuoles. The mast-cells (Ehrlich) are round 
or flat or spindle-shaped cells, with numerous distinct coarse granules that, with the 
basic aniline stains, show an intense metachromatic reaction. 
Cells of the character of lymphocytes, plasma-cells, and mast-cells occur in 
normal tissue and are regarded by some as tissue cells and by others as ceills 
arising from the blood. The correct view is probably that which regards them as 
different stages of development of a mesenchymal group of cells to be separated 
from the tissue-building fixed cells, and to this group there should be added 
the polynuclear leucocytes and eosinophile cells. Certain stages of development 
are present in the blood, others are found in the tissue, partly in special tissue- 
formations (lymphadenoid tissue, bone-marrow), and partly in ordinary connective 
tissue. Under certain conditions it is possible that individual forms may pass into 
one another, for example, that lymphocytes may become transformed into plasma 
cells and klasmatocytes into mast cells. 
Fig. 192.—Cross-section of blood- 
vessel from the deep layers of the skin, 
forty hours after painting the skin of 
a rabbit with tincture of iodine (Flem- 
ming’s solution, safranin). a, Endo- 
thelial cells with mitoses; b, bi, leuco 
cytes. x 350. HEALING OF WOUNDS. 
269 
§ 96. If on any part of the body there occurs an open wound, 
which does not become infected or otherwise seriously injured, the edges 
and base of the wound after twenty-four hours become deep red and 
somewhat swollen, and here and there small shreds of necrotic tissue 
may be seen. On the second day the gelatinous condition of the tissues 
is more apparent, the outlines of individual tissue-elements are effaced, 
and the color of the wound becomes grayish-red. From the second day 
on there appear over the wound small red papules, which increase in 
number and size, become con- 
fluent, and after two to three 
days form a granular surface. 
This is covered with more or 
less abundant secretion, which 
forms a gray, gelatinous layer, 
later becoming yellow and 
creamy. This layer consists 
of coagulable exudate and 
polynuclear leucocytes. 
The changes which the 
surface of the wound show in 
the first two days are de- 
pendent on local hypersemia, 
and the infiltration of cellular 
and fluid exudate, and on 
swelling and liquefaction of 
the tissue; as early as the sec- 
ond day there is proliferation 
leading to the development 
of wound-granulations, or 
granulation tissue (Fig. 193, 
a), consisting of fibroblasts 
and leucocytes, and wide ves- 
sels (c), among all of which 
there soon appears a fibrillar 
ground-substance. The leuco- 
cytes, which are mostly of the 
polynuclear form, are found 
in all the layers in fresh 
granulations, but heap them- 
selves particularly in the 
superficial strata, and, embedded in fibrin, cover the surface (b). The 
fibroblasts are found most abundantly in the deeper layers (Fig. 193, a), 
and it is here that the new-formation of connective tissue proceeds most 
actively. 
When a certain degree of fibrillse-formation has been reached, the 
process comes to a standstill, the fibroblasts with their nuclei remain as 
fixed connective-tissue cells (Fig. 187, e), and attach themselves to the 
surface of the fibrillse. The process has now reached its termination — 
granulation tissue has become scar-tissue. 
In open wounds of the skin, when infection does not disturb the 
course of healing, the formation of granulation tissue lasts until the 
wound is covered with epithelium. The regeneration of the latter pro- 
ceeds from the edges, the epithelium gradually pushing itself over the 
Fig. 193.—Wound-granulations from an open 
wound with fibrinopurulent covering (Muller’s fluid, 
haematoxylin). a, Granulation tissue; b, fibrinopuru- 
lent layer; c, blood-vessels, x 135. 270 
INFLAMMATION. 
granulations. With the formation of connective tissue the reproductive 
processes terminate, but transformation processes continue in the cica- 
tricial tissue for some length of time. Shortly after its formation the 
cicatrix is rich in blood and appears red; later it loses a portion of its 
vessels through obliteration, becomes pale, and contracts to much less 
than the original volume. Large scars of the skin show permanently a 
smooth surface, since the papillary bodies are not again formed or only 
imperfectly (Fig. 195, e). The scar remains for several months abnor- 
Fig. 194.—Healing of incised wound of skin united by suture (Flemming’s solution, safranin). 
Preparation made on the sixth day. a, Epidermis; b, corium; c, fibrinous exudate, in part 
haemorrhagic; d, newly formed epidermis, containing numerous division-figures, and with plugs 
of epithelium extending into the underlying exudate; e, division-figures in epithelium at a dis- 
tance from the cut; f, proliferating embryonic tissue, developing from the connective-tissue 
spaces, and containing cells with nuclear division-figures, and in part also vessels with pro- 
liferating walls; g, proliferating embryonic tissue with leucocytes; h, focus of leucocytes in 
deepest angle of wound; i, fibroblasts lying within the exudate, one showing a nuclear division- 
figure; k, sebaceous-gland; l, sweat-gland, x 70. 
mally rich in cells, but in time becomes poor in cells and firm in consistence. 
When the healing of a wound occurs in such manner that the defect 
is closed by granulation tissue visible to the naked eye, the process is 
designated repair by second intention (per secundam intentionem). 
Incised wounds of the skin, whose edges are united by sutures, grow 
together by first intention, and healing takes place in essentially the same 
manner as that of an open wound by second intention; but inflammation, 
proliferation, and new-formation of tissue are less prominent, partly 
because they take place below the skin, and partly because they are of less 
extent and intensity. 
The result of such a cut is hemorrhage together with more or less 
abundant exudation (Fig. 194, c), which glues the opposing wound-sur- HEALING BY FIRST INTENTION. 
271 
faces. Soon there arises inflammatory infiltration of the edges of the 
wound, which varies greatly in different cases, and when repair is aseptic 
never reaches a significant degree (g, h), attaining its maximum in from 
two to four days, diminishing from the fifth to the seventh day, and 
completely disappearing at or soon after the end of the second week. 
The inflammatory infiltration is usually greater in the neighborhood of 
the sutures than at the edges of the wound. 
As early as the second day regenerative processes begin in the con- 
Fig. i9s.—Cutaneous portion of a laparotomy cicatrix, sixteen days after the operation 
(Muller’s fluid, hematoxylin, Van Gieson’s). a, Epithelium; b, corium; c, subcutaneous fat 
tissue; d, scar in corium; e, new epithelial covering; f, scar in fat tissue, x 38. 
nective tissue and in the vessels, and lead, in the course of several days, 
to the formation of embryonic tissue at the edges of the wound (Fig. 194, 
/), partly extending into the wound itself (i) ; and gradually replacing 
the coagulum. This tissue is present in varying quantity in different 
parts of the wound (Fig. 194). After a time, varying according to the 
size of the wound, the thickness of the exudate, and the intensity of 
proliferation, the masses of embryonic tissue growing from the edges 
of the wound blend and young connective tissue joins the edges together, 
and at the same time extends into the old tissue, so that the boundary 
between old and new becomes indistinct. 
While connective tissue is being formed in the deeper parts of the 
wound, the epithelium on the surface is also being regenerated (Fig. 
194), and through continuous cell-divisions (d, e) forms a covering of 
many layers. 
The young connective tissue uniting the edges of the wound is distin- 
guishable for a long time from the neighboring older tissue through its 272 
INFLAMMATION. 
richness in cells (Fig. 195, d, /), and the finer fibrillation of its ground- 
substance; in large incised wounds of the skin there may be found in 
the scar, after the lapse of weeks or even months, slight evidence of 
proliferation and in- 
flammation. In general 
however, transforma- 
tion processes gradually 
occur in the scar, so that 
its tissues approach 
more closely to the nor- 
mal, and finally the 
place of incision can no 
longer be easily recog- 
nized. If the wound 
heals by the interposi- 
tion of abundant em- 
bryonic tissue, there 
may occur a defect of 
the papillary bodies 
(Fig. 195, e), so that 
the scar remains smooth. 
§ 97. When on the 
surface of an inflamed 
serous membrane (Fig. 196, a) there is an adherent layer of fibrin (&), 
beneath it granulation tissue is apt to form rapidly. The beginnings can 
be seen as soon as the 
fourth day and consist in 
the appearance of fibro- 
blasts (/) in the deepest 
layers of fibrinous mem- 
brane. These arise through 
proliferation of the con- 
nective-tissue cells of the 
affected part, and penetrate 
the fibrin. There follows 
soon of 
blood-vessels, and in the 
course of days or of weeks 
there is developed on the 
surface vascular embryonic 
or granulation tissue, 
which, when the overlying 
fibrin is compact, lifts this 
up in toto (Fig. 197, b, c) ; 
or penetrates the interstices 
of the fibrin-membrane 
(Figs. 196, f; 198, b, d), 
and in time replaces the 
fibrin. Remains of fibrin 
(Fig. 198, c) may, however, persist for weeks or months in the granula- 
tion tissue. 
In the formation of granulation tissue and the development of 
scar-tissue the epithelium (endothelium) of the serous membranes takes 
Fig. 196.-—Fibrin deposit and beginning formation of granula- 
ion tissue in a fibrinous pericarditis five days old (Muller’s fluid, 
haunatoxylin). a, Epicardium; b, fibrin-membrane; c, dilated, 
congested vessels; d, round cells infiltrating the tissue; e, lymph- 
vessel filled with cells and clots; f, fibroblasts within the deposit. 
X 150- 
Fig. 197.—Development of granulation tissue in the 
pleura, in bronchopneumonia and pleuritis of fourteen days’ 
duration (alcohol, Van Gieson). a, Hyperaemic, infiltrated 
pleura; b, very vascular granulation tissue; c, fibrin; d, 
pus-corpuscles, and granules of precipitated albumin, 
x 100. ORGANIZATION OF EXUDATES 
273 
no part, since it produces no 
fibroblasts. On the other 
hand, the products of the in- 
flammatory proliferation be- 
come covered later with 
epithelium. 
The result is the forma- 
tion of connective tissue, 
which leads either to thicken- 
ing of the serosa or to ad- 
hesion of opposing surfaces, 
so that the inflammation may 
be designated adhesive. The 
result in individual cases de- 
pends on the amount of fibrin 
and the situation of the 
affected organ, and its condi- 
tion during the process of 
healing. 
Small deposits of fibrin, 
limited to one surface of the 
serous membrane, lead to 
thickenings of the serosa, 
which, becoming pale with the 
obliteration of vessels, are 
finally represented by so- 
called milk-spots or tendinous 
spots. The glueing together 
of two serous layers by abundant fibrin leads to an adhesion through the 
formation of connective tissue. In the case of a smaller amount of fibrin, 
and repeated rubbing of the 
membranes upon each other, 
there develop loose membran- 
ous or stringy adhesions, which 
still permit the serous sur- 
faces to move upon one an- 
other. Very large amounts 
of fibrin may permanently re- 
sist absorption and usually 
become calcified. 
Coagulated exudates in 
the lungs may become lique- 
fied and absorbed, but it 
sometimes happens that their 
removal is associated with 
connective-tissue proliferation 
and induration of the lung. 
The proliferation proceeding 
from the lung tissue leads to 
thickening of the septa (Fig. 
199, a, b) or extends into 
the exudate in the alveoli in 
Fig. 198.—Formation of granulation tissue in the 
fibrinous deposits of a pericarditis several weeks old 
(Muller’s fluid, haematoxylin, eosin). a, Epicardium; 
b, deposit on the epicardium, consisting of granulation 
tissue (d), and fibrin (c). x 40. 
Fig- J99-—Intraseptal and intra-alveolar formation of 
connective tissue in the lung (alcohol, haematoxylin). 
a, Thickened fibrocellular alveolar septum, in part in- 
filtrated with round cells (b) ; c, fibrinocellular exudate 
in the alveoli; d, intra-alveolar formative cells; e, strand 
bfoXeSd?11 ?r2°oo.asts: 9’ intra'aIveolar newly formed 274 
INFLAMMATION. 
the form of embry- 
onic tissue (d, e) 
which later may con- 
tain newly formed 
blood-vessels (g). 
Masses of coagula 
within blood-vessels, 
called thrombi, give 
rise, in case no in- 
fection occurs, to in- 
flammatory prolifera- 
tion of the vessel- 
wall, a proliferating 
vasculitis. This pro- 
cess corresponds ex- 
actly to the inflam- 
matory proliferation 
of serous membranes. 
It is immaterial 
whether thrombosis 
has been caused by a 
preceding inflamma- 
tory process or by 
other conditions, inas- 
much as the mere presence of the coagulum is sufficient to cause inflam- 
mation and tissue-proliferation. 
Fig. 200.—Development of embryonic tissue in a thrombosed 
femoral artery of an old man, three weeks after ligation (alcohol, 
haematoxylin). a, Media; b, elastic limiting membrane; c, intima, 
thickened through older inflammatory processes; d, coagulated 
blood; e, cellular infiltration of the media, f, of the intima; g, 
round cells, partly in the thrombus, partly between it and the 
intima; h, different forms of fibroblasts, x 300. 
Fig. 201.—Periphery of a healing pulmonary infarct (Muller’s fluid, haematoxylin, eosin). 
«, Blood-extravasate changed into a yellowish granular mass; b, necrotic alveolar septa without 
nuclei; c, newly formed connective tissue; d, vascular granulation tissue within the alveoli; e, 
fibroblasts within alveoli containing the residue of the haemorrhage; f, artery; g, vascular con- 
nective tissue formed within the artery at the place of the embolus, x 40. ORGANIZATION OF NECROTIC TISSUE. 
275 
The first change introduced in the substitution of the thrombus by 
connective tissue is the appearance of fibroblasts (Fig. 200, h), which arise 
from the vessel-wall, and later, with the aid of vessels growing in from 
the vessel-wall and its neighborhood, form embryonic tissue, which ulti- 
mately changes into connective tissue. The complete substitution of an 
obturating thrombus leads to obliteration of the vessel-lumen by vascular- 
ized connective tissue (Fig. 201, g) ; the substitution of a parietal throm- 
bus, on the other hand, results in the formation of fibrous thickening of 
the vessel-wall. As the result of imperfect substitution or liquefaction 
of the part not substituted, strands and threads of connective tissue cross 
the lumen of the ves- 
sel. Calcification of 
portions of thrombi 
not replaced by con- 
nective tissue leads to 
the formation of ves- 
sel-stones (arterio- or 
phleboliths). 
Necrotic tissue 
which cannot be se- 
questrated and dis- 
charged externally, 
is also replaced by 
vascular connective 
tissue, which be- 
comes converted into 
scar-tissue; this sub- 
stitution takes place 
in the same manner as 
in fibrinous exudates 
and thrombi. The 
requisite condition is 
that the necrotic tis- 
sue shall contain no 
substances (bacteria) 
which hinder tissue- 
proliferation. In gen- 
eral it is immaterial 
how the necrosis has 
occurred, or whether 
the necrotic tissue is free from or infiltrated with exudate or blood. 
The change leading to healing consists in the production of granu- 
lation tissue, which grows toward the necrotic tissue (Fig. 201, 
c, d), and finally replaces it. If this process is not disturbed large 
tissue-necroses (for example, a haemorrhagic infarct of the lung) 
may in the course of weeks or months disappear and be replaced by con- 
nective tissue. It may also happen, however, that certain tissues resist 
absorption, or that the development of granulation tissue stops so early 
that remains of the necrosed tissues persist and become calcified. 
When, as the result of inflammation or ischaemia, only the more sensi- 
tive elements die—for example, epithelial or muscle cells — while the 
connective tissue remains intact, the absorption of necrotic portions takes 
Fig. 202.—Fibroid area in heart-muscle. Section through a 
muscle-trabecula which has undergone fibroid change (Muller’s 
fluid, hrematoxylin). a, Endocardium; b, cross-section of normal 
muscle-cells; c, hyperplastic connective tissue rich in cells; d, 
atrophic muscle-cells in hyperplastic connective tissue; e, dense 
connective tissue, poor in nuclei and containing no muscle-cells; 
f, vein, in whose neighborhood muscle-cells are still preserved; 
g, small blood-vessels; h, small-cell infiltration, x 40. 276 
INFLAMMATION. 
place quickly, and there is formed in a short time a scar of connective 
tissue (Fig. 202, e), in which specific tissue-elements are lacking. 
Pus is quickly absorbed from small abscesses, and the defect is closed 
by granulation and scar tissue. Large amounts of pus may be absorbed 
from the body-cavities and from the lungs. 
Abscesses cause in their immediate neighborhood granulation tissue 
which leads to the formation of a limiting, so-called pyogenic or abscess- 
membrane. The abscess-cavity may become obliterated through absorp- 
tion of the pus and union of the 
walls of the cavity; the abscess 
finally heals and leaves a scar. 
Incomplete absorption may lead 
to thickening of the pus and cal- 
cification of the residue. If the 
pus does not become inspissated, 
the abscess may persist and in- 
crease in size by exudation from 
its walls. 
Empyemata may heal in 
similar manner to abscesses 
through the absorption of pus. 
The tissues enclosing the pus 
produce granulation- and scar- 
tissue, which may reach a con- 
siderable size when absorption is 
delayed (Fig. 204). When in- 
completely absorbed, calcification 
may occur. 
Foreign bodies, so far as 
they are absorbable and exert no 
specific influence on their sur- 
roundings, are dissolved, and re- 
placed by connective tissue in the 
same way as are tissue-necroses 
or fibrin masses. If they pos- 
sess accessible interstices, these 
may be penetrated by granulation 
tissue. If not absorbed, they be- 
come encapsulated. 
Fig. 203.—Necrosis of fifteen years’ duration 
in the lower part of the diaphysis of the femur. 
a, Sequestrum; b, c, edges of the opening in the 
thickened bone (alcoholic preparation). Reduced 
one-third. 
IV. Chronic Inflammations, 
§ 98. Inflammation is essentially an acute process, but various con- 
ditions may cause the phenomena of tissue-degeneration and exudation 
to persist, and inflammation then becomes chronic. 
The causes of chronic inflammations are to be sought in the fact that 
in an acute inflammation changes occur which prevent healing. When 
masses of necrotic tissue are not completely absorbable, such as large 
pieces of bone, they may become sequestrated, but persist as sequestra for 
years (Fig. 203, a), and keep up inflammation. Following a large, super- 
ficial defect of the skin, such as results from a burn, granulation tissue CHRONIC INFLAMMATION. 
277 
develops, but months may pass before the wound is covered with epithe- 
lium from the edges and 
the process brought to a 
close. 
A further cause of 
chronic inflammation is 
constantly repeated injury. 
For example, frequently 
repeated inhalation of dust 
may cause chronic inflam- 
mation of the lungs; re- 
peated rubbing of the skin 
may cause chronic inflam- 
mation of the part affected; 
pathological alterations of 
the stomach contents may 
cause chronic inflammation 
of the stomach. In canals 
or reservoirs, such as the 
gall-bladder, the ducts of 
the pancreas, etc., concre- 
tions may give rise to last- 
ing tissue-lesions. 
Unfavorable nutritive 
conditions — e. g., marked 
congestion — may enable 
external influences that, 
under normal conditions, 
produce no inflammation 
at all or one soon subsiding, 
to set up ulcerative pro- 
cesses showing no tendency 
to heal. In this manner, 
for example, chronic ulcers 
of the leg may arise. 
A frequent cause of 
chronic inflammation is 
furnished by infections, 
particularly bacteria and 
moulds, which multiply in 
the body and constantly 
give rise to irritation. The 
inflammations which they 
cause are distinguished by 
the fact that they lead to 
connective-tissue prolifera- 
tions and that they usually 
show a progressive char- 
acter, and form secondary 
deposits through the lymph- 
and blood-vessels. 
Finally, chronic intoxi- 
cations form a cause. These 
Fig. 204.—Changes in the pleura and lung after a 
purulent pleuritis lasting six months (alcohol, orcein). 
a, Thickened lung tissue with gland-like alveoli, and 
elastic fibres in the newly formed connective tissue; 
b, thickened pleura; c, newly formed connective tissue 
without elastic fibres; d, granulation tissue covered 
with pus; e, elastic limiting membrane of the pleura; 
f, elastic fibres. X 46. 278 
INFLAMMATION. 
affect chiefly the kidneys and liver, and may be attributed either to the 
continued introduction through the gastro-intestinal tract, lungs, or skin of 
substances harmful to the organs directly concerned or to others; or 
injurious substances may be produced in the body itself, through dis- 
turbances of metabolism. 
The forms of chronic in- 
flammation are determined 
partly by their causes, partly 
by the character of the tissue 
affected. 
Chronic inflammations 
characterized by hyper- 
plastic formations of con- 
nective tissue are found in 
serous membranes, lungs, and 
skin, but may occur in other 
tissues. Chronic pleuritis, 
caused by exudates which are 
with difficulty absorbable, or 
by chronic infections, lead to 
extensive scar-likc thickenings 
(Fig. 204, b, c), on the pleura 
(c) and in it (h). Moreover, 
induration of the lung (&)may follow infectious inflammations, or may 
be caused by the continued inhalation of stone dust, the latter character- 
ized by the formation of fibroid nodules (Fig. 205, a), or by diffuse 
induration (c) Continued irritation of the orifices of the urogenital 
apparatus, through the discharge of secretions (chronic gonorrhoea), 
frequently leads to the forma- 
tion of pointed condylomata 
(condylomata acuminata), in 
which inflamed and infiltrated 
papillae grow out with their 
vessels (Fig. 206, a, b) and 
divide into branches. 
Frequently repeated or 
continued slight inflammations 
of the skin and subcutaneous 
tissue, due to mechanical 
lesions, parasites, or other 
irritation, may, if they reach a 
considerable extent, give rise 
to diffuse hyperplasia of con- 
nective tissue, known as 
elephantiasis. 
Inflammatory prolifera- 
tions of the periosteum and bone-marrow, which give rise to pathological 
new-formations of bone or hyperostoses (Fig. 207), may be caused both 
by non-specific irritations — for example, by inflammations which run 
their course in the neighborhood of chronic ulcers — as well as by specific 
infections — for example, svphilis or tuberculosis. 
Fig. 205.—Section of a stonecutter’s lung with fibroid 
nodules (alcohol, picrocarmine). a, Group of fibroid 
nodules; b, normal lung tissue; c, thickened lung tissue 
still containing bronchi, vessels, and a few alveoli. X 9. 
Fig. 206.—Condyloma acuminatum (injected prepara- 
tion). a, Enlarged branching papillae; b, epidermis, 
x 20. CHRONIC INFLAMMATION. 
279 
Chronic catarrhs of mucous membranes are caused by specific infec- 
tion (gonorrhoea, tuberculosis), by non-specific injuries (concretions, 
pathological changes in the gastric or intestinal contents), and by con- 
tinued disturbances of circulation (congestion). 
Chronic abscesses usually arise from acute abscesses, and have the 
same etiology; but may develop gradually and are then caused by such 
infections as tuberculosis and actinomycosis. They are usually limited by 
a connective-tissue membrane lined on the inside 
by granulation tissue, and may increase in size 
Trough secretion of pus from the abscess-wall, 
md through destruction of the wall and neigh- 
boring tissue. Progressive extension toward 
he deep parts leads to the formation of bur- 
rowing abscesses. Their increase in size is 
dways to be ascribed to persistence of infection. 
Perforation into neighboring tissues leads to 
secondary infective inflammations. 
The tuberculous and actinomycotic forms 
bf chronic abscesses are distinguished by the 
specific character of the pus and by the peculiar 
structure of the abscess-membrane (see Tuber- 
culosis and Actinomycosis, Chapter X.). 
Chronic ulcers are caused chiefly by spe- 
cific infections (tuberculosis, syphilis, glanders), 
but non-specific agents may lead to chronic 
ulcerative processes in tissues which are 
especially susceptible. Thus chronic congestion 
in the vessels of the leg may have such an effect 
that ulcers arising through any influence may be 
prevented from healing under the mechanical 
conditions in which the leg finds itself. Like- 
wise peculiar qualities of the stomach contents 
may hinder the healing of an ulcer of the 
stomach. If healing begins at one edge of an 
ulcer while ulceration advances at other parts, 
the ulcer is known as serpiginous. The exces- 
sive development of granulation tissue in an 
ulcer leads to the production of the condition 
known as exuberant granulation, or “ proud 
flesh; ” dense thickening of the edge and base 
gives rise to the form known as indolent ulcer. 
Chronic proliferations of granulatibn 
tissue — i. e., granulations which persist with- 
out becoming changed into connective tissue — 
occur in various specific infections, notably in 
tuberculosis, syphilis, leprosy, glanders, rhino- 
scleroma, and actinomycosis. Since the granu- 
lations in these infections form fungoid proliferations and tumor-like 
formations, they are often called fungous granulations or infectious 
granulomata. All these show certain structural and other peculiarities 
which enable us to recognize their specific nature (see Chapter X.). It 
should be noted, however, that the etiology of some of the granulomata is 
still unknown. 
Fig. 207.—Periosteal hyper- 
ostosis of the tibia, at the base 
of a chronic ulcer of the leg. 
Reduced two-fifths. 280 
INFLAMMATION. 
Chronic inflammations in which atrophy of specific tissue is asso- 
ciated with hyperplasia of connective tissue, occur particularly often in 
the mucous membrane of the gastro-intestinal tract, and in the kidneys 
and liver. 
In the intestinal canal the cause may lie in specific infections (dysen- 
tery) as well as in non-specific irritations; the latter dependent on some 
abnormal property of the contents of the canal. The epithelial elements 
may undergo necrosis with persistent desquamation, the connective tissue 
being unaffected; or they may necrose and disintegrate at the same time 
as the connective tissue on which they rest. The result is a mucous mem- 
Fig. 208.—Section through the mucosa of an atrophic large intestine, (alcohol, alum-carmine). 
a, Glandular layer decreased to one half its normal height; b, muscularis mucosa; c, submucosa; 
d, muscularis; e, total atrophy of the mucosa, x 30. 
brane (Fig. 208) which either contain no glands (e) or only rudimentary 
ones (a). 
In the liver and kidneys the chronic inflammations which lead to 
atrophy and induration, and whose results are respectively known as 
cirrhosis of the liver and indurated or contracted kidney, are hsemato- 
genous diseases, in so far as they do not depend on disturbances in the 
efferent passages (obstruction, inflammation of pelvis of kidney, formation 
of concretions), and are caused partly by infections and partly by 
intoxications. They may begin as acute inflammations or insidiously, and 
are characterized by atrophy and degeneration of glandular tissue, hyper- 
plasia of connective tissue, cellular infiltration, formation of granulation 
tissue, obliteration of old vessels, and the formation of new vessels. In 
the liver new bile-ducts are often encountered, which, however, for the 
greater part do not functionate. CHAPTER VIII. 
Tumors. 
I. General Considerations. 
§ 99. A neoplasm, or autonomous new-growth, atypical blastoma, 
or tumor in the commonly accepted sense, is a new-formation of tissue, 
apparently arising and growing independently, having an atypical struc- 
ture, inserted uselessly into the organism, possessing no function of serv- 
ice to the body, and showing no typical termination to its growth. The 
atypical character of a tumor is shown in its external appearance as well 
as in its internal organization in that it departs more or less in structure 
from that of a normal organ or tissue. When this departure is slight, the 
structure of the tumor approaches closely to that of the hypertrophies; 
in fact, there are cases in which the difference in structure is so slight 
that it becomes difficult to decide whether an excessive new-growth of 
tissue is to be classed as tumor or hypertrophy. 
Tumors may develop in any tissue of the body which is capable of 
growth, and arise through proliferation of tissue-cells, associated with 
new-formation of blood-vessels. Not infrequently leucocytes and lym- 
phocytes emigrate into the tumor, and exudative processes and inflamma- 
tory proliferations may take place in it or its neighborhood, but these 
phenomena form no essential part of the development of the tumor. 
The processes of cell-division and of new-formation of blood-vessels 
are the same as those described in §§ 80 and 82 — i. e., division of cells 
takes place by karyomitosis, and new vessels are formed from buds given 
off by old vessels. The mitoses are for the greater part typical (Fig. 
209, b), but there are also atypical forms, such as asymmetrical divisions, 
nuclear figures with abnormally large chromatin masses (so-called giant 
mitoses), pluripolar mitoses, nuclear fragmentation, and direct seg- 
mentation. 
In their fully developed condition tumors are often well defined from 
surrounding tissues, but in some cases may pass into the neighboring tissue 
without any sharply defined border of transition. Further, an entire organ 
may become transformed into a tumor, or large portions of tissue not 
sharply outlined from their surroundings may take on the character of a 
tumor. Through the disintegration of tumor tissue ulcers frequently 
arise. 
The difference between the structure of a tumor and that of normal 
tissue is usually recognizable macroscopically, but there are tumors which 
so closely resemble the tissue from which they arise that the difference 
can be made out only through more careful examination. 
The circumscribed tumors are usually nodular (Figs. 210, d; 212; 213, 
a). The size of the individual nodules varies, according to the kind of 
tumor and the stage of development, from miliary and submiliary nodules 
to masses weighing ten to twenty kilograms or more. When situated on 
the surface of an organ nodular tumors not infrequently take on the form 
of a sponge (Fig. 210, d) or of a polyp, and are accordingly designated 
fungoid or polypoid tumors. When a new-growth on the surface of a 282 
TUMORS. 
mucous membrane or the skin leads to enlargement and branching of the 
papilke, or if new papillae are formed, there arise warty, verrucose, and 
papillary tumors or papillomata (Fig. 211). Further development of the 
papillary structure may lead to dendritic branching and the formation of 
a cauliflower mass. 
Tumors usually develop from small beginnings; rarely do they arise 
from centres extending diffusely through an organ. Growth may be rapid 
or slow, sometimes with periods of quiescence, or it may be suspended for 
years, and then suddenly become active. 
The structure of the tumor is determined by the tissue from which it 
takes its origin; and although true tumors always show a certain atypical 
character, yet they retain certain characteristics of the parent tissue. 
According to their structure and genesis tumors may be broadly 
Fig 209.—Tissue from a carcinoma of the breast, containing numerous division-figures in 
different phases of mitosis (Flemming’s solution, safranin). a, Stroma; b, epithelial plugs. 
X 500. 
divided into three groups: 1, connective-tissue tumors; 2, epithelial 
tumors; 3, teratoid tumors and cysts. It should be noted, however, that 
there are many forms of tumors which, according to one’s point of view, 
may be classed as belonging to two, or even to all three groups. 
The connective-tissue tumors or tumors arising from the support- 
ing-tissues, often called histoid tumors, consist of tissues which in struc- 
ture correspond to mature or to embryonal connective tissue, and take 
their origin from mesodermal tissues. Ordinarily there are included in 
this group tumors arising from glia cells, and muscle-tumors, since these 
in structure resemble the connective-tissue tumors more than they do the 
epithelial. 
The differences in type of conn'ective-tissue tumors are dependent on 
the character of the ground-substance and cells. When such tumors are 
rich in cells and the ground-substance is only slightly developed, they ac- 
quire a soft consistence and are classed with the sarcomata. Through 
combination of different forms of connective tissue mixed connective- 
tissue tumors arise. GENERAL CONSIDERATION OF TUMORS. 
283 
The epithelial tumors are composed of cells derived from surface or 
glandular epithelium, and vascularized connective tissue forms a frame- 
work in which the tumor cells lie in definite groups. Inasmuch as this 
arrangement gives to the tumors a structure suggesting that of a gland, 
they are often called 
organoid tumors, in con- 
tradistinction to the his- 
toid or connective-tissue 
tumors. It should be 
noted, however, that 
there are also included 
in the connective-tissue 
group of tumors certain 
varieties (endothelio- 
mata) which have an 
organoid structure. 
The cells which give 
the epithelial tumors 
their special character 
arise from the ectoderm 
or entoderm, and from 
the glands developing 
from the same, or from 
the mesodermal epithe- 
lium of the pericardium, 
and of the pleural and 
peritoneal cavities, or 
of the glands arising 
from this layer (kid- 
neys, sexual glands, 
adrenals). Tumors hav- 
ing the last-named origin often show more or less distinctly the character 
of the parent tissue. 
Very soft epithelial or connective tissue tumors are designated medul- 
lary. 
Combinations of epithelial hyper- 
plasia and proliferations of connective 
tissue which exceed the ordinary 
amount of supporting tissue or bear a 
sarcomatous character, lead to the 
formation of epithelial mixed tumors. 
Teratoid tumors and teratoid 
cysts form a group which is char- 
acterized by the fact that they contain 
various sorts of tissue derived from 
all three germ-layers (teratoid mixed 
tumors), or by the presence of certain 
tissues in regions where they do not 
normally occur. Tumors, therefore, 
which according to their structure may he placed in one or the other 
groups, may be considered as teratomata on account of their situation. 
Further, there are included in the group of teratoid tumors certain for- 
mations which according to their structure, origin, and physiological rela- 
tions ought not to be classed with the tumors. 
Fig. 210.—Fungoid carcinoma of the endometrium of the 
posterior wall of the uterus, a, Body of the uterus; b, cervix; 
c, vagina; d, tumor. Two-thirds natural size. 
Pia alI._Papi„ary artenonla o{ „Mum 
Natural size. 284 
TUMORS. 
Tumors usually develop singly; but it also happens that within a 
certain tissue system there may appear coincidently or in succession 
a great number of tumors of the same kind, so that it must be assumed 
that conditions requisite for their development were present in different 
parts of the same system at the same time. At times there develop in 
different organs of the same individual two entirely different varieties of 
tumors, which stand in no relation to each other, and whose coincident 
appearance is accidental. 
The determination of what should be included under the term tumor is 
hardly possible; consequently the designation tumor is applied to many different 
formations which, according to their etiology, genesis, and life-characteristics, have 
not the same significance. The idea of tumor is, therefore, differently conceived by 
different authors. I regard it as advisable, as based on the life-characteristics of 
the tissue-formations which we are about to consider, to exclude from the class of 
tumors all hyperplastic proliferations, and cysts which arise through the reten- 
tion of secretions, and which show no independent new-formation of tissue. 
Further, according to my view, there should be separated from the true tumors all 
proliferations of tissue due to the presence of parasites or to infection, particularly 
the granulomata of tuberculosis, syphilis, leprosy, etc. Should it be proved that 
some of the new-growths now included with the true tumors are caused by infec- 
tion, they should likewise be excluded from the category of true tumors. 
The above classification of tumors is based on their microscopic char- 
acter and histogenesis. 
Tumors are in no sense useful to the organism as many tissue-hypertrohies 
may be. Tumor-tissue does not possess the specific activity of that from which 
it springs. It happens, indeed, that in certain tumors there occur processes of 
secretion which correspond to normal secretions — epithelial tumors may produce 
mucous or horny or colloid material (thyroid tumors), or bile-pigment (liver- 
tumors), even in metastatic nodules — but from these facts we can conclude only 
that, in many tumors which do not differ too greatly in structure from the parent 
tissue, the cells may retain, to a certain degree, and for a number of generations, 
the functional capacities of the parent tissue. There is, however, no basis for 
believing that new useful tissue is formed as in the case of hypertrophy from in- 
creased labor; the products are for the chief part of no use to the body, and though 
perhaps in special cases the iodine-containing colloid produced by malignant tumors 
of the thyroid may be made use of, such a function must surely be of much less 
value than that of the normal tissue. 
The tumors springing from the mesodermal epithelium of the serous membranes 
or of the glands arising from these, are included in the group of epithelial tumors. 
This is justified by the fact that such tumors correspond in their structure and 
clinical behavior to the epithelial tumors of the ecto- and entoderm. I have also 
considered the question whether it would not be advisable (as Hansemann has 
proposed) to class among the epithelial tumors — i. e., the adenomata and carcino- 
mata—■ those tumors which have a framework of connective tissue, the spaces of 
which are filled, in a manner suggesting epithelial tissues, with cell nests arising 
from the proliferating endothelium of the blood- and lymph-vessels. Aside from 
the similarity in the structure of these tumors with the ordinary adenomata and 
carcinomata, there may be taken in favor of this view the anatomical fact that 
the endothelium of the blood- and lymph-vessels is often designated mesodermal 
epithelium. Against such a grouping of the endothelial with the epithelial tumors 
it may be urged that, aside from the general acceptance of the term endothelioma, 
the behavior of the endothelium of the blood- and lymph-vessels under patho- 
logical conditions is different from that of epithelium, and that in many tumors it 
is impossible to separate the products of the growth of the endothelium of blood- 
and lymph-vessels from the products of proliferation of connective-tissue cells. 
Literature. 
(Development of Tumors.) 
Adami: Classification of Tumors. Jour, of Path, and Bact., 1902. 
Paget: Lectures on Tumors, 1852. 
Senn: Pathology and Surgical Treatment of Tumors, 1895. ETIOLOGY OF TUMORS. 
285 
Wells: Multiple Primary Tumors. Jour. Path, and Bact., 1900 (Lit.). 
White: The Definition, Terminology, and Classification of Tumors. Jour, of 
Path., vi., 1899; Pathogenesis of Tumors. J. of Path., vii., 1901. 
Williams: The Principles of Cancer and Tumor Formation, London, 1889. 
See also §§ 100 and 101. For an admirable presentation of the entire sub- 
ject of Tumors, see Ewing, Neoplastic Diseases, 1919. 
§ 100. The cause of tumors is unknown. In the majority of cases, 
however, the conditions under which the new-growth appears can be as- 
signed, and we may accordingly establish different groups. 
In the first group may be included those tumors arising from congenital 
local malformations of tissue. They develop in uterine life, and are 
Fig. 212—(Bellevue Hospital.) Primary carcinoma of the gall-bladder with secondary 
infiltration of the substance of the liver, showing the presence of a large ga’.l-stone in the lumen 
of the gall-bladder. 
present at birth, or in extra-uterine life, during the period of growth or 
later, in which case trauma not infrequently gives the immediate occasion 
for the beginning of the tumor. 
To this group belong many osteomata, chondromata, angiomata, 
gliomata, fibromata (of the nerves and skin), and adenomata. Further, 
many teratoid tumors and cysts are to be included, inasmuch as they repre- 
sent either remains of foetal structures, transpositions or monogerminal 
inclusions of embryonic tissue, implantations of rudimentary portions of 
a twin embryo (bigerminal implantations), or the results of disturbances 
of the earliest stages of the development of the ovum. 
A second group develops after traumatic injuries of tissues; it has 
been reckoned that in about seven to fourteen per cent of cases a trau- 
matic origin can be assigned; particularly in sarcoma, carcinoma, and 
osteoma. It may be a single injury, a stab, a blow, crushing fracture, etc., 
or repeated mechanical irritation, such as rubbing, etc. 
In a third group the development of the tumor follows inflammation, 
particidarly granulation tissue with subsequent cicatrization. The inflam- 286 
TUMORS. 
mation and ulceration may be caused by non-specific as well as by specific 
agents. For example, cancer of the gall-bladder (Fig. 212), develops 
almost invariably only in gall-bladders which contain stones, and are 
consequently the seat of chronic inflammation. In the stomach, cancer 
may develop in the edge of an ulcer or in the resulting scar and also in 
a mucous membrane which has suffered severe changes as the result of 
previous inflammation. In the skin and in the mucous membranes of the 
pharynx and larynx cancers occasionally arise in the base of a tubercu- 
lous or syphilitic ulcer or in the scar of such a process. 
In a fourth group the development of tumors appears to owe its origin 
to unequal atrophy of the elements which make up a tissue, so that certain 
hindrances to growth are removed or lessened. Not mechanical resistance 
alone, but influences dependent on chemical conditions, should be con- 
sidered in this connection. Certain epithelial proliferations (cancers) 
develop in old age, or in organs which after a period of increased activity 
become atrophic. For example, the development of cancer of the skin 
may be explained on the ground that the connective tissue undergoes 
retrogression leading to relaxation, while the epithelium is still possessed 
of full power of proliferation. At the same time the chemical composition 
of the connective tissue may be altered. 
It cannot be doubted that the etiology of tumors is not always the same, as 
shown by the variety of conditions under which they arise. 
It is difficult to say what is the nature of the influence which excites the cells 
to the production of an atypical tissue. We are at first inclined to think of the same 
causes which underlie hypertrophy and regeneration of tissue, also of stimuli which 
increase the formative activity of cells, or of lessening or removal of hindrances 
to growth. But it still remains a problem why there should not be formed typical 
tissues which would so fit into the organization of the body that they would be of 
service. In the attempt to explain this phenomenon, many writers have sought and 
would recognize as the cause the presence of parasites (see Etiology of Car- 
cinoma) ; but our present knowledge does not in any way justify us in attributing 
the development of true tumors to the influence of parasites. On the contrary, the 
development and life-history of tumors, and the formation of metastases, which 
arise through the multiplication of living tumor-cells transported in the lymph- or 
blood-stream, speak against the hypothesis of the parasitic nature of tumors. 
Cohnheint advanced the theory that all true tumors arose from the persistence 
of foci of embryonal tissue. Neither the results of clinical observation nor of 
anatomical investigation speak in favor of such a theory. 
Ribbert is of the opinion that the cause of the proliferation which leads to 
tumor-formation is to be found in separation of cells or cell-groups from their 
organic relations, such separation occurring as the result of intra-uterine disturb- 
ances of development or later under the influence of external agencies. Neverthe- 
less, such transplantations or separations of cell-groups take place frequently in 
intra-uterine life, or after trauma, after ulceration, in scars and in infectious 
granulomata, without subsequent development of a tumor. These transplantations 
of tissue constitute only one of the predisposing causes of tumor-formation; some 
other factor is necessary to excite the atypical progressive tissue-proliferation —• 
i. e., the development of the tumor. The development of a tumor is, therefore, 
in no wise dependent upon transplantation of tissue; rather the tumor-proliferation 
takes its origin in cells which are normally situated; this may be actually demon- 
strated particularly in epithelial tumors. 
Our knowledge of the causes of tumor-development at the present time may be 
summed up as follows: Inherited and acquired conditions of certain cells and cell- 
groups, which assert themselves in a tendency to increased formative activity with 
the production of atypical tissue, lead to the formation of tumors. In many cases 
this proliferation is prepared for, favored, and excited by the transplantation of 
cells and cell-groups, but often also through changes in the neighborhood of the 
cells concerned. No general scheme applicable to the development of all tumors 
can be given. On the contrary, the conditions vary not only with the different 
forms of tumors, but with individual cases of the same tumor-type. Moreover, GROWTH OF TUMORS. 
287 
it should not be forgotten that the formations which we class as tumors do not 
all possess the same significance, and that many more properly might be classed 
with other phenomena of growth (malformations). 
§ 101. When once a tumor has arisen and has reached a certain stage 
of development it may become quiescent, and remain for a life-time 
without undergoing further change. This is true particularly of those 
which are regarded as local tissue-malformations; but tumors which 
Fig. 213.—Section through primary cancer of the liver (a), with multiple metastases (b) within 
the liver itcelf. Three-sevenths natural size. 
first develop in later life may come to a standstill after attaining a certain 
size. 
The growth of a tumor takes place independently, and in many 
cases continues until death. 
From the surrounding tissues the tumor acquires its blood-vessels and 
hence its food material, but may besides glow independently — i. e., 
through increase of the cells which form the elements of the tumor. In 
many cases the tumor increases in size through interstitial expansive 
growth, and the neighboring tissue is crowded or pushed aside. In other 
cases the tumor grows by infiltration and forces its way into the inter- 
cellular spaces of the neighboring tissue, so that new areas are brought 
under the influence of the tumor. In this way the cells of the invaded 
tissue are often excited to proliferation, and enlargement takes place 
through appositional growth. 
The characteristic feature of growth by infiltration consists in 
involvement of the tissues of the organ that lie in the neighborhood of 
the primary tumor. Further, the tissue of neighboring organs may become 
involved by the tumor through contiguity. If tumor-cells gain entrance 
into the great body-cazities they may spread over the serous surfaces and 
lead to the development of secondary tumors. 288 
TUMORS. 
If, in the process of infiltration, a tumor gains entrance to a lymph- or 
blood-vessel — an event which is likely to occur in carcinoma and sarcoma 
—• and if tumor-cells capable of proliferation are transported through the 
lymph or blood, tumor-metastases arise — that is, secondary or daugh- 
Fig. 214.—Periglandular lymph-vessel (in the axillary region) filled with cancer-cells arising 
from a primary carcinoma of the mammary gland (Muller’s fluid, haematoxylin). a, Cancer- 
cells; b, wall of lymph-vessel. X 300. 
ter tumors which are not directly connected with the original focus of 
growth. The daughter-tumors may develop first in the organ primarily 
affected (Fig. 213, b), but usually involve other organs as well; in the case 
of rupture into lymph-vessels the lymph nodes are first affected; in rupture 
Fig. 215.—Metastatic development of cancer in the branches of the portal vein and liver- 
capillaries (Miiller’s fluid, hsematoxylin, and eosin). a, Liver tissue; b, plugs of cancer-cells 
in the portal vein; c, cancer-cells in the capillaries, x 100. 
into blood-vessels, those organs to which the blood carries the living cells. 
The direction of transportation is usually that of the lymph- or blood- 
stream, but retrograde transportation not infrequently occurs, particularly 
in the lymph-vessels, the lumina of which are easily obstructed by tumors. METASTASIS OF TUMORS. 
289 
The development of daughter-tumors takes place from transported 
cells. In lymphatic metastasis the lymph-vessels (Fig. 214, a) are in- 
vaded by tumor-cells which are deposited at a distant point, this is followed 
by proliferation and metastatic nodules develop. It not infrequently hap- 
pens that the lymph-vessels are uniformly distended by the groivth (Fig. 
214, a), without the formation of nodules, or at least only small swellings 
develop along the course of the lymph-vessels. In metastasis into lymph 
nodes the latter become swollen, forming nodules of smaller or larger size, 
Fig. 2 i 6.—Metastatic sarcoma of the liver from a primary sarcoma of the parotid (Flem- 
ming’s solution, safranin, picric acid). o,_ Liver-rods; b, sarcoma tissue developing within the 
vessels; c, isolated tumor-cells in the liver-capillaries; d, liver-cells which have undergone 
atrophy and fatty degeneration. x 150. 
and the structures of the node are gradually replaced by tumor tissue. 
In metastasis through blood-vessels the development of the secondary 
tumor begins with the deposit of tumor-cell emboli in artery, capillary, or 
vein, and the vessels (Figs. 215, b, c; 216, b, c) may eventually be filled 
and dilated by proliferating tumor-cells. The tissue in which the tumor- 
embolus develops may remain passive, and the specific tissue-elements —• 
gland-cells (Fig. 216, d) and muscle-cells — may vanish as the result of 
pressure atrophy. Later, the blood-vessels and connective tissue may take 
part in the development of the secondary tumor. 
In the further course of development the secondary nodule is usually 
sharply circumscribed from its surroundings and grows by expansion. It 
not infrequently happens, however, that the infiltrative growth persists, 
and under these conditions widespread diffuse tumors develop, particu- 
larly in the bone-marrow and the liver (Fig. 216). 
The number of lymphogenous and hsematogenous metastases varies 
greatly in different cases. At one time the metastases may be confined 
to one organ, at other times they may be scattered through several. In 
rare cases cells of the original tumor may be spread through the entire 
body, so that in diverse organs — glands, muscles, skin, etc. — larger and 
smaller nodules appear in quick succession. This phenomenon is possible 
when tumor-nodules break into blood or lymph vessels and the tumor 
cells are thus enabled to spread throughout the body and to lodge and grow 
in different parts (carcinomatosis, sarcomatosis*melanomatosis, etc.). 290 
TUMORS. 
If a living bit of tumor (carcinoma, sarcoma) capable of forming 
metastases is transplanted from one animal into the tissues of another 
animal of the same species, it sometimes happens that it will develop in 
the second animal. In man, tumor particles may be transplanted during 
operations from one part of the body to another and there grow (im- 
plantation metastasis), or rupture of an encapsulated tumor may be fol- 
lowed by secondary implantations in neighboring surfaces, e. g., in cer- 
tain ovarian tumors rupture may be succeeded by extensive implantation 
metastases in the peritoneum. 
Side by side with progressive proliferation of tissue there frequently 
occur in tumors retrogressive changes, particularly in rapidly growing 
and infiltrating cellular tumors, in which 
fatty and mucous degeneration, necrobi- 
otic processes, and haemorrhages may 
take place to such marked degree as to 
bring about extensive destruction of the 
tumor tissues. This disintegration is 
due to the fact that the tumor grows 
into or compresses the blood-vessels and 
obstructs them. If the cells are badly 
nourished they undergo necrosis and be- 
come dissolved through the action of 
proteolytic ferments. In nodular 
tumors the destruction of tumor-cells, 
followed by softening or partial resorp- 
tion of the products of degeneration, 
leads to local areas of umbilication. 
Often ulcers may thus be formed; in 
carcinomatous tumors of mucous mem- 
branes the parts growing above the sur- 
face often undergo disintegration. In 
slowly growing tumors of hard con- 
sistence extensive retrograde changes 
do not usually occur. 
The necrosis and disintegration of a 
tumor rarely terminate in cure. This 
event is most likely to happen when a 
polypoid new-growth becomes totally 
necrotic (for example, as a result of 
twisting or tearing of its pedicle) and 
is thrown off. In the majority of 
tumors showing a tendency to retro- 
gressive changes and disintegration, while the older portions are dying 
the growth advances at the periphery, and new tissues are progressively 
attacked. 
If the tumor is completely extirpated, cure may be brought about. 
This is most easily accomplished in slowly growing and sharply circum- 
scribed tumors which increase by expansion. In infiltrating tumors it is 
difficult to determine the boundary of the growth, since this may extend 
far beyond the point where macroscopic change is apparent. Conse- 
quently, in such cases, recurrence sooner or later takes place in the scar, 
and (Fig. 217, a) arises from portions of the tumor remaining in the tis- 
sues. Such recurrences behave exactly like the primary tumor, and may 
femur?™, FungSd 
tumor arising from the bone-marrow; b, 
C' metastasis‘ 0ne'ha,f FIBROMA. 
291 
form metastases (Fig. 217, c). In those cases in which recurrence in the 
scar following operation is long delayed, it is possible that this circum- 
stance depends on the fact that in the affected area the conditions favor- 
ing tumor development again occur. 
According to their clinical and anatomical characteristics tumors may 
be classed as benign and malignant. Benign tumors are generally re- 
garded as those which grow slowly and by expansion and do not form 
metastases; malignant, those which shozv complete emancipation from the 
normal laws of proliferation, grow quickly and by infiltration, easily 
undergo degenerative changes and form metastases. 
The malignant tumors, on the whole, coincide with those forms which 
are known as carcinoma and sarcoma. It must, however, be borne in 
mind that the malignancy of a tumor depends not only on its character, 
but also on its location (local malignancy). A benign tumor takes on 
malignant character as soon as its presence interferes with the functions 
of vital organs. Hence every tumor of the brain or meninges becomes a 
dangerous affection at the moment when it gives rise to disturbances of 
the cerebral functions. Under certain conditions such benign tumors as 
fibromata of the uterus become destructive, or locally malignant, as soon 
as they reach such size as to displace and compress neighboring organs. 
After a tumor has existed for a certain period there frequently results 
marked lowering of the general nutrition, marasmus, which is designated 
tumor-cachexia. This occurs oftenest in association with the malignant 
growths known as cancer and sarcoma; and may depend, in part at least, 
on the great demands made on the food supply by the rapid growth of the 
tumor, particularly if there are metastases. A still more important cause 
may be that the tumor interferes with the ingestion of food. In cancer of 
the oesophagus, stomach, and intestine the function of the affected organ 
is interfered with, and the entrance and assimilation of food may be 
entirely prevented or nearly so. Further, it should be borne in mind ’that 
through degeneration of the tumor and from resulting ulcers large amounts 
of albuminous material are lost; and that through putrid decomposition 
there may arise substances which, when absorbed, act injuriously on the 
organism. Finally, the pain which is often felt in a tumor may rob the 
patient of sleep. Whether the tumor itself produces substances harmful 
to the organism is unknown, but is, however, not improbable. 
Metastases occasionally occur with benign tumors, chondromata, myo- 
mata, and adenomata. Of these, the metastases in the bones of thryoid tumors are 
of special importance; they occur when no carcinomatous proliferation can be 
demonstrated in the thyroid, so that it would seem probable that under certain 
conditions even the cells of a normal or hypertrophic tissue may be transported 
into the bone-marrow and there proliferate. 
II. The Different Forms of Tumors. 
I. Tumors Derived from Connective Tissue or the Supporting 
Framework. 
(a) Fibroma. 
§ 102. A fibroma is a tumor composed of fibrous connective tissue. 
It occurs most frequently in the form of nodules, which are sharply cir- 
cumscribed from the surrounding tissues, and usually involve but a por- 
tion of the affected organ. Rarely an entire organ (ovary) may become 292 
TUMORS. 
changed into a single tumor-mass. On a free epithelial surface and on 
mucous membranes a fibroma may appear in the form of a papilloma or 
polyp. 
According to the character of the connective tissue of which it is com- 
posed, the consistence of a fibroma may vary greatly. Often it is hard 
and tough, creaking under the knife, and showing on its surface a white, 
tendon-like, shining tissue (desmoid) ; but in other cases the growth may 
be soft, flaccid, the cut surface 
more uniformly grayish-white and 
somewhat translucent. In still 
other cases the individual strands 
of connective tissue are white and 
shining, but the tumor as a whole 
has a looser structure and is cor- 
respondingly flaccid. 
Between the hard and soft 
growths there are all possible tran- 
sition-forms, and even in one tumor 
different parts may possess differ- 
ent characteristics. Under the mi- 
croscope the hard fibromata appear 
to be composed chiefly of thick 
bundles of coarse fibres (Fig 218, a, b), in which lie scattered a larger or 
smaller number of cells. In the softer forms the bundles of fibres are 
more delicate (Fig. 219, a). If as a result of congestion or other cause 
clear fluid collects between the fibrillse, there is formed an ocdcmatous 
fibroma, whose bundles of fibres (Fig. 219, b) are pressed apart by the 
fluid, the tumor becoming softer and more translucent, finally resembling 
the tissue of the umbilical cord. 
Fig. 218.—Hard fibroma from lobe of the ear 
(alcohol, haematoxylin), a, Longitudinal section; 
b, transverse section of bundles of fibres. X 400. 
The soft fibroma, 
which presents a trans- 
lucent, grayish-white cut 
surface, is usually rich in 
cells; so that it is possible 
by teasing to isolate nu- 
merous slender spindle- 
shaped forms with term- 
inal fibrils. The inter- 
cellular substance is cor- 
respondingly less in 
amount, the fibrillse more 
delicate and arranged in 
finer bundles. Sections 
of such fibromata, when 
stained, appear rich in 
nuclei (Fig. 220, b). 
Fibromata develop from proliferating connective-tissue cells, and it 
is usually possible to find in the tumor areas which are richer in cells than 
others, and in which the cells appear not only as small spindle cells, but 
as round cells, or as short, thick spindles, or even as stellate cells. The 
transformation of the newly formed cellular tissue into connective tissue 
takes place in the same way as that described under FTyperplasia of Con- 
nective Tissue. New-formation of elastic fibres is usually wanting, but 
Fig. 219.— Section of an cedematous fibroma of the uterus 
(osmic acid, glycerin). a, Closely lying fibres; b, fibres 
pressed apart by fluid; c, spindle-shaped cells; d, swollen 
round cells; e, blood-vessel. X 200. FIBROMA. 
293 
at times does occur, particularly in the neighborhood of the blood-vessels. 
Fibromata may appear in any part of the body which contains any 
form of connective tissue. They occur most frequently in the nerves, 
skin, periosteum, fascia, mammae, and mucous membrane of the nose; 
more rarely in the ovary, intestinal tract, etc. In the mammary gland 
the development of the fibroma takes place particularly around the cana- 
liculi (Fig. 220, b), which become surrounded by connective tissue rich in 
cells. 
Fibromata do not form metastases, but often occur as multiple tumors, 
especially in the nerves and skin (see Neurofibroma, § 111). Moreover, 
Fig. 220.—Fibroma pericatialiculare mammae (Muller’s fluid, alum carmine, eosin). a, Gland- 
tubules; b, newly formed pericanalicular connective tissue rich in cells; c, connective tissue poor 
in cells, x 35. 
it is not uncommon to see in a tumor several centers of growth — that is, 
the mass of the tumor is made up of several nodules or bands held to- 
gether by ordinary connective tissue (Fig. 220, b). Fibromata are malig- 
nant only through size and position. 
Fibromata may undergo mucous or fatty degeneration or may soften 
and disintegrate, so that cavities are formed in them. They may also 
break down and give rise to ulcers. Their blood-supply varies greatly, at 
times being scanty, at other times abundant. Occasionally the blood-ves- 
sels are ectatic, so that the tissue is interspersed with wide channels and 
clefts, from which blood escapes when the tumor is incised and examined 
in the fresh state. In other cases dilated lymph-channels are seen. 
Keloid is the designation applied to a hard, nodular, or flat and 
banded, or stellate growth of the skin, which in its fully developed state 
consists of dense fibrous tissue without elastic fibres. The direction of 
the fibres is often at right angles to the surface of the skin, or at least 
does not accord with that of the normal fibres. It usually develops after 
injuries or inflammations (cicatrix-keloid), but may appear without such 
association (spontaneous keloid). The cause of keloid growth is not 
known; the tendency to recurrence after removal, the multiple occurrence, 294 
TUMORS. 
and the fact that cases frequently occur in the same family (Hutchinson) 
speak in favor of some special predisposition on the part of the skin. 
(b) Myxoma. 
§ 103. A myxoma is a tumor which consists essentially of mucous 
tissue, and is made up of cells and a fluid or gelatinous intercellular sub- 
stance containing mucin. The cells are for the greater part polymorphous, 
with processes of varying length (Fig. 221) which anastomose with one 
another (Fig. 222, a). The tissue is markedly translucent, soft and the 
blood-vessels are easily seen through it. From the cut surface gelatinous 
or stringy masses which swell in water, may be obtained. 
No tumor is ever made up wholly of myxomatous tissue; the latter 
is usually combined with other forms of tissue, particularly with fibrous 
connective tissue, fat tissue, cartilage, and sarcomatous tissue. For this 
reason such tumors are designated fibromyxoma, lipomyxoma (Fig. 
224), chondromyxoma (Fig. 227, c), and myxosarcoma (Fig. 222). 
Mucous tissue may develop 
from fibrous connective tissue 
through the collection of a 
mucin-containing fluid between 
the fibrillse and the gradual dis- 
appearance of the latter. Adi- 
pose tissue may pass over into 
myxomatous tissue through the 
disappearance of fat from the 
fat-cells and the appearance of a 
mucin-containing gelatinous sub- 
stance between the cells, during 
which process the fat becomes 
broken into droplets (Fig. 224, 
b, c), while the cells themselves 
become smaller and star-shaped 
(d). Cartilage may also be- 
come transformed into mucous 
tissue through mucoid degenera- 
tion of the basement-substance 
and change of form of the cells 
(Fig. 227, c, d). Myxosarco- 
mata (Fig. 222) arise either 
through local increased activity 
of cell-proliferation in myxomata or through a collection of mucoid sub- 
stance between the sarcoma cells. 
Myxomata, myxofibromata, and myxolipomata develop most fre- 
quently in the connective tissue of the periosteum and endosteum, skin, 
heart, fascia, and sheaths of the muscles, as well as in the fat tissue of 
the subcutaneous and subserous tissues. Myxochondromata occur par- 
ticularly in the parotid, and constitute the most common form of tumor 
found there. 
These forms are all benign tumors, which rarely produce metastases. 
Myxosarcomata, on the other hand, have characteristics of malignancy, 
and may form metastases. 
„ , ... 
Fig. 221.—Cells from a myxoma of the periosteum 
of the femur (gold preparation), x 400. LIPOMA. 
295 
(c) Lipoma. 
§ 104. A lipoma is a tumor consisting of adipose tissue (Fig. 223). 
These tumors are sometimes soft, almost fluctuating, sometimes firm, 
usually nodular and lobulated, and often attain great size. 
Fig. 222.—Section of a myxosarcoma (Muller’s fluid, carmine, glycerin), a, Myxomatous tissue; 
b, strands of cells; c, fibrous tissue, x 225. 
Histologically, the tissue of a lipoma resembles the fat-lobules of 
the subcutaneous panniculus (Fig. 223), although the tendency to form 
typical grape-like clusters of fat-cells is wanting. If, as not infrequently 
happens, mucous tissue is formed in connection with the fat tissue, or if 
the latter, following disappear- 
ance of its fat, becomes changed 
into myxomatous tissue, the 
tumor is designated lipomyxoma 
(Fig. 224) ; if there is an abun- 
dance of fibrous tissue present, it 
is called lipofibroma or fibro- 
lipoma. 
Calcification, necrosis, gangrene, 
and sloughing are not infrequent in 
lipomata of large size. These 
tumors do not produce metastases, 
but are often multiple. Complete 
disappearance of a lipoma does not 
take place even in extreme emacia- 
tion of the host. 
Lipomata are sometimes ob- 
served in new-born children — for 
example, as tumors developing in 
or over the cleft-formations of spina bifida — but occur much more 
frequently in later years. The most common seats of these 
growths are the subcutaneous tissues of the back, buttocks, neck, 
axilla, abdomen, and thigh; they are also found in the intermuscular 
Fig. 223.—Lipoma of shoulder region, with 
relatively small fat-cells (Muller’s fluid, hema- 
toxylin). x 300. 296 
TUMORS. 
connective tissue, subserous fat tissue, in the kidneys, intestine, mammary 
gland, under the aponeurosis of the forehead, in the skin, fingers, joints, 
etc. They may occur as multiple growths symmetrically distributed. In 
man the formation of fat tissue about the neck and throat, leading to 
Fig. 224.-—Lipomyxoma of the back (Muller’s fluid, Van Gieson’s). a, Large fat-cells; 
b, c, fat-cells in which the fat is broken up into little droplets; d, mucous tissue; e, blood vessel. 
X 300. 
nodular and lobulated disfigurations of this region, occasions the 
designation fatty collar. The development of fat in these cases takes 
place in the subcutaneous tissue, in and under the fascia and between the 
muscles. Abnormal development of fat in an extremity may give rise to 
the condition known as lipomatous elephantiasis. 
There are at least two other varieties of lipomatosis that deserve mention, 
namely, Dercum’s syndrome and that of Frolich. The former, known as 
adiposis dolorosa, is characterized by symmetrical deposits of fat in various parts 
of the body, preceded or attended by pain and sometimes associated with asthenia 
and mental disturbances. The lipomatous masses involve the abdomen, chest, arms 
or legs, or may be localized on the limbs or trunk. The affection is more common 
in females. The few cases which have been investigated post-mortem have shown, 
among other things, in addition to the lipomatosis, interstitial neuritis, changes in 
the thyroid gland and sometimes in the pituitary. The syndrome of Frolich or 
dystrophia adiposo-genitalis is a condition of obesity which occurs in connection 
with tumors of the pituitary and is associated with hypoplasia of the genital 
organs and infantilism. Lyon (Archives of Internal Medicine, 1910) has con- 
tributed an admirable paper on the subject of lipomatosis. He includes (1) Der- 
cum’s syndrome, (2) simple adiposity, (3) solitary multiple or symmetrical nod- 
ular circumscribed lipomatosis, (4) diffuse symmetrical lipomatosis, including the 
so-called “ fat neck,” (5) neuropathic oedema, pseudo-oedema and pseudo-lipoma, 
and (6) the syndrome of Frolich. He believes that all of these conditions are 
merely different expressions of the same morbid process. 
In addition to the forms already described, there are lipomata composed of 
proliferating embryonal fat cells which display a disposition to invade surrounding 
tissues ahd thus to become diverted in the direction of malignancy. Still another 
but rare variety of lipoma consists in a combination of adult and embryonal fat 
cells supported in a reticulum of connective tissue and1 associated with the presence 
of reactions of newly formed or dilated capillary or other small vessels (lipoma CHONDROMA. 
297 
cavernosum). A patient at Bellevue Hospital presented these growths in the sub- 
cutaneous tissue literally by dozens. 
There is a large group of chronic productive inflammatory lesions characterized 
by the infiltration of greater or less numbers of embryonal fat cells. Sometimes 
these are so numerous and so closely packed or so widely distributed through the 
tissues as to suggest neoplasmic transformation. Such changes are not uncommonly 
encountered in productive inflammatory lesions in the breast, the walls of the 
gall-bladder and intestine, the interstitial tissues of the bone marrow, occasionally 
in the kidney in chronic interstitial nephritis and particularly in tissues which are 
normally rich in fat, such as the omentum and mesentery (Symmers and Fraser, 
Arch. Internal Medicine, 1917). 
Extensive hyperplasia of embryonal fat cells is sometimes to be seen in maran- 
tic infants. In such a case investigated by myself at the New York Hospital, em- 
bryonal fat cells occurred in such enormous numbers as to suggest the presence of 
a new growth. They were distributed, however, through those regions where fat 
is normally encountered and consisted of bright cherry-red nodules composed of 
embryonal fat cells lying in a network of capillary vessels. 
(d) Chondroma. 
§ 105. A chondroma or enchondroma is a tumor consisting essen- 
tially of cartilage. The amount of connective tissue covering its surface 
or accompanying the blood-vessels into its interior, is so slightvas to fall 
completely into the background when compared with the cartilage. 
Chondromata develop chiefly in those places where cartilage is 
normally found — that is, in the osseous system or in the cartilages of 
the respiratory tract; but also 
occur in tissues which nor- 
mally possess no cartilage — 
Fig. 225. 
Fig. 226. 
Fig. 225.—Periosteal chondroma of a digital phalanx, seen in longitudinal section. a, 
Chondroma; b, phalanx. Natural size. 
Fig. 226.—Section from a chondroma of the ribs (haematoxylin, carmine), a, Cartilage rich 
in small cells; b, cartilage rich in large cells, x 80. 
for example, in the salivary glands, particularly the parotid, and 
in the testicles, rarely in other organs. In bones which develop 
from cartilage, chondromata arise from cartilaginous remains that persist 
after ossification; but more often take their origin from the periosteum 
and endosteum (Fig. 225). They form tumors which vary greatly in 
size. The small ones are usually spherical (Fig. 225) ; the larger ones 
nodular or lobulated. The individual nodules are often separated from 
one another by connective tissue. Not infrequently they are multiple, 
particularly in the skeleton, where they sometimes may be found literally 
by dozens. 298 
TUMORS. 
The tissue of an enchondroma most often presents the characteristics 
of hyaline cartilage (Fig. 226), more rarely that of reticular or fibrous 
cartilage. At the peri- 
phery of the tumor the 
cartilage passes over into 
connective tissue, which 
forms a kind of perichon- 
drium. 
The number, size, 
form, and grouping of 
the cartilage cells vary 
greatly in different cases 
and in different parts of 
the same tumor. Many 
enchondromata are cellu- 
lar (Fig. 226), others 
poor in cells, many con- 
tain large cells, others 
small cells, or both large 
and small cells. 
The cells are some- 
times surrounded by a so- 
called capsule, at other 
times not; sometimes they 
lie in groups inside the 
mother-capsule, at other times they are more regularly distributed. All 
varieties of cartilage normally occurring in the body are found in 
Fig. 227.— Chondromyxosarcoma parotidis (alcohol, 
carmine), a, Cartilage; b, sarcomatous tissue; c, myxo- 
matous tissue; d, cartilage in process of liquefaction and 
being converted into sarcomatous and myxomatous tissue. 
X 80. 
Pig. 228.—Periosteal chondroma of the calcaneus, with areas of calcification (Miiller’s fluid, 
hsematoxylin). a, Hyaline cartilage; b, c, calcified cartilage, x 225. CHONDROMA. 
299 
enchondromata. Accordingly the cells vary in form; the majority 
showing the familiar spherical form, but spindle and stellate cells are not 
rare, particularly in the neighborhood of the connective-tissue bands 
Fig. 229.—Osteochondroma of the humerus (alcohol, picric acid, hrematoxylin, carmine. 
a, Hyaline cartilage; b, bone; c, cartilage which is becoming converted into bone; d, blood- 
vessel. x 250. 
which divide the tumor into nodules or surround it as a whole. Cartilage, 
the perichondrium, endosteum, periosteum, and different forms of con- 
nective tissue may form the matrix of enchondromata. Chondromata 
arising from the surface of 
cartilage or bone are 
known as ecchondroses. 
The tissue of enchon- 
dromata frequently suffers 
retrogressive metamor- 
phoses. The ground-sub- 
stance in large tumors 
shows a tendency to un- 
dergo, in localized areas, 
mucoid degeneration and 
liquefaction, the first (Fig. 
227, c), giving rise to 
chondromyxoma, liquefac- 
tion of the ground-sub- 
stance with destruction of 
cells forming cyst-like col- 
lections of fluid. In other 
cases the cartilage may be- 
come calcified Fig. 228, 
b, c), or true bone may be formed (Fig. 229, c, b), so that the tumor 
must be termed an osteochondroma. Through marked proliferation of 
cartilage cells sarcomatous tissue may be developed, the tumor becoming 
changed to a chondrosarcoma (Fig. 227, b). 
Fig. 230.—Ivory-like exostosis of the parietal bone. Natural 
size. 300 
TUMORS. 
The enchondromata are, on the whole, benign tumors, although me- 
tastases are not unknown. 
In the region of the spheno-occipital suture, in the median line of the clivus, 
there is not infrequently found a small tumor which either lies beneath the dura, 
or at its highest point breaks through this membrane and penetrates into the 
arachnoid and pia. The tumor consists of bladder-like cells, resembling plant- 
cells. Cartilage and bone tissue may be associated with the peculiar tumor tissue, 
and for this reason Virchow regarded the growth as a chondroma arising from 
remains of the spheno-occipital cartilage and characterized by vacuolar degenera- 
tion of the cells. The peculiar character of the tissue, however, favors the view 
advanced by Muller, and supported by Ribbert, that , the growth is a product of 
proliferative activity of remains of the notochord, and the tumor has consequently 
been designated chordoma. Ribbert states that chordomata of small size are to 
be found in 2 per cent of all routine autopsies. At Bellevue Hospital we have never 
detected such a growth in over 6,000 autopsies. 
(c) Osteoma. 
§ 106. The term osteoma is applied to tumors which consist of 
osseous tissue. Such growths arise chiefly from the bones of the skeleton 
(Figs. 230, 231), but may de- 
velop elsewhere. 
A small circumscribed new- 
growth of bone attached to old 
bone is called an osteophyte; 
when of a large size an exostosis. 
Circumscribed formations of 
bone inside of bones are known 
as enostoses. New-growths of 
bone not attached to old bone are 
classed as follows: movable 
periosteal exostoses, which have 
their seat in the periosteum but 
are separated from the bone; 
parosteal osteomata, lying near 
the bone; disconnected osteo- 
mata, which are situated some 
distance from the bone, in the 
muscles, and tendons; and, 
finally, heteroplastic osteomata, 
which occur in other organs, in 
the lungs, mucous membrane of 
the trachea, in the skin, arteries, 
mamma, etc. 
Excrescences on the teeth, 
consisting of cement-substance, 
are known as dental osteomata; 
those consisting of dentine, as 
odontomata. 
According to their structure, 
osteomata may be divided into 
hard osteomata (osteoma durum) (Fig. 230) and spongy forms (osteoma 
spongiosum or medullare) (Figs. 231, 232). The former consist of 
firm, compact tissue resembling the cortical portion of long bones, and 
possess narrow nutrient canals; the latter are made up of delicate bony 
Fig. 231.— Exostosis carti- 
laginea of the upper diaphysis of 
the tibia. Reduced about one- 
half. OSTEOMA. 
301 
trabeculae and wide medullary spaces (Fig. 232), and resemble the struc- 
ture of spongy bone. 
The surface is sometimes regular and smooth, and the tumor presents 
the form of a cone (Fig. 230), sphere, or pedunculated button; or it 
may be rough, and nodular, without resemblance to form (Fig. 231). 
The first variety occurs most frequently as exostoses on the skull (Fig. 
Fig. 232.— Osteoma of the dura mater (alcohol, picric acid, hematoxylin, carmine). X 40. 
230) ; the latter as spongy exostoses and disconnected and heteroplastic 
osteomata, such as are sometimes encountered in the falx of the dura 
mater (Fig. 232). 
Osteomata may occur as single or multiple tumors, the latter being 
relatively common. The ivory-like exostoses of the cranium and the 
osteomata of the dura mater are frequently multiple, and circumscribed 
bony growths often appear in great numbers on the bones of the extremi- 
ties and trunk. In such cases the epiphyseal ends of the bones and the 
points of insertion of tendons, or both, are favorite sites. It is probable 
that such growths are to be referred to an inherited predisposition of the 
part to over-growth, or to disturbances in the development of the skeleton. 
The bony plates and spicules, which occasionally develop in the lung or in 
the mucous membrane of the air-passages, may occur in large numbers.. 
The development of bone in osteomata and osteoid growths takes place 
partly through osteoblasts, as described in § 83, and partly through meta- 
plasia of formed tissues (§ 88). The matrix is formed from the connec- 
tive tissue of the periosteum, or from that of the tissue from which the 
osteoma arises; or from the perichondrium or endosteum. If an exostosis 
develops in such manner that cartilage is formed from the proliferating 
periosteum or endosteum and if from this cartilage bone is developed, 
it is called a cartilaginous exostosis (Fig. 231); when the exostosis is 
formed directly from the proliferating periosteum without an intermediate 
stage of cartilage, it is known as a connective-tissue exostosis (Figs. 230, 
and 232). 302 
TUMORS. 
The combination in the same tumor of connective tissue and bone in 
relatively equal proportions is known as an osteofibroma. This is a com- 
mon tumor of the osseous system. The abundant production of bone in a 
chondroma leads to the formation of an osteochrondroma (Figs. 229, and 
233) ; these tumors are usually found in the long bones. The new-growth 
may develop in the periosteum (Fig. 233, c) or endosteum (a, b). 
Abundant formation of bony trabeculae (/, h, k) in the cartilage (e, g, i) 
gives to the tissue a 
hard consistence. 
Many new-growths 
of bone are not tumors 
in the strict sense, but 
malformations of the 
skeleton resulting from 
excessive growth, or 
inflammatory hyper- 
plasias. Many osteo- 
phytes and exostoses, 
parostoses and the dis- 
connected osteomata 
(bone formation in 
lymph-n odes and 
lungs) are best in- 
terpreted as malforma- 
tions. The bony plates 
not infrequently found 
in the falx of the dura, 
and which have a 
normal bone-marrow 
(Fig. 232), are to be 
regarded as misplaced 
portions of the skele- 
ton. According to 
Ziegler the formations 
known as rider’s bone 
and drill-bone, which 
are found in the ad- 
ductors of the thigh 
and in the deltoid muscle, as the result, respectively, of riding and the 
repeated shouldering of arms, are to be regarded as tumors which arise 
on a congenital basis, in that the connective tissue of the muscle shows 
characteristics which ordinarily belong only to the periosteum and bone- 
marrow. The so-called myositis ossificans■—a peculiar disease of the 
muscles, characterized by progressive ossification of their connective 
tissue during childhood — is to be similarly interpreted. 
There are two varieties of ossifying myositis — one local, the other 
widespread and progressive. The local variety, as already indicated, is 
associated with frequently repeated injuries, but occasionally follows 
single blows or other mechanical influences, producing rupture of muscle 
fibres succeeded by haemorrhagic and exudative inflammation. This 
gradually goes over into a chronic productive lesion attended by prolifera- 
tion of the interstitial connective tissue which then, through a process of 
metaplasia, becomes transformed into bone. The progressive variety of 
Fic. 233.— Osteochondroma of the humerus (alcohol, picric 
acid, hsmatoxylin, carmine), a, Cortical portion of the humerus; 
b, medullary cavity; c, periosteal deposit of bone; d, normal 
Haversian canals; e, dilated Haversian canals filled with cartilage, 
containing newly formed bone at f; a, cartilage with bone- 
trabeculae h, formed by the periosteum; i, cartilage with newly 
formed bone-trabeculae, arising from the endosteum; k, l, old 
bone trabeculae; m, remains of marrow-tissue. Pocket-lens mag- 
nification. ANGIOMA. 
303 
myositis ossificans is extremely rare and involves groups of muscles in 
various parts of the body leading, in advanced cases, to almost complete 
locking of the skeleton. The majority of cases are associated with con- 
genital malformations of various sorts, notably supernumerary fingers 
and toes, microdactyly, dwarfing of the lower jaw, etc. Histologically 
this form is likewise characterized by overgrowth of the connective tissues 
between the muscles, followed by metaplasia into bone. 
There is a well defined clinical condition attended by the appearance 
of multiple exostoses in various parts of the body, sometimes to the 
extent of dozens or even hundreds. These exostoses are most frequently 
found in the growing ends of diaphyses of long bones where membrane 
and cartilage formation come into juxta-position. Arthur Keith, who 
has carefully studied the condition, believes that it should be removed 
from the category of tumors, the exostoses being secondary formations 
which serve to mask a remarkable disorder of growth characterized by 
the fact that, as bone is being laid down within the growth disk in the 
epiphyseal line in cartilage, a covering of fibroblastic bone is being depos- 
ited by the overlying periosteum. Keith suggests that the condition be 
placed among the disorders of growth known as diaphyseal aclasis. 
(/) Hcemangioma and Lymphangioma. 
§ 107. Under the term angioma are grouped tumor-like formations in 
which blood-vessels or lymph-vessels constitute the striking feature. 
Vascular growths arising from blood-vessels are called haemangiomata, 
or angiomata in the restricted sense; those arising from lymph-vessels are 
Fig. 234.—Teleangiectasis of the panniculus adiposus of the abdominal wall (formalin, hae* 
matoxylin, eosin). a, Blood-vessels filled with blood; b, adipose tissue, x 80. 
designated lymphangiomata. Of the haemangiomata there may be dis- 
tinguished four varieties : hcemangioma simplex, hcemangioma cavernosum, 
hcemangioma hypertrophicum, and angioma arteriale racemosum. 
Haemangioma simplex is a vascular formation in which, in a ground 
tissue of normal occurrence in the body, there is an abnormal increase in 
the number or size of the capillaries and veins. 304 
TUMORS. 
Such formations occur most frequently in the skin and subcutaneous 
tissue. They are usually congenital, but increase in size after birth. 
They are designated vascular naevi, and are often found in places where 
fetal clefts have closed (fissural angiomata). In many instances it is 
scarcely permissible to speak of them as tumors, since the skin may show 
no tumor-like elevation. Teleangiectases of the skin and subcutaneous 
tissue, presenting either as circumscribed growths or as flat, occasionally 
nodular thickenings, may with propriety be termed tumors. The smooth 
ncevus vasculosus, on the other hand, appears as a superficial substitution 
of the skin by another tissue. The color of the affected skin is bright red 
Fig. 235.—Dilated capillaries of a teleangiectatic tumor of the brain, isolated from a portion of 
tumor by means of shaking, x 200. 
(ncevus flammeus) or bluish-red (nccvus vinosus). The line of demarca- 
tion between normal and affected skin usually is not a sharp one; around 
the edge and in the neighborhood of the area of discoloration there are 
often found circumscribed red spots appearing as outrunners of the 
process. 
The red color is due to dilated blood-vessels in the corium or in the 
subcutaneous fat tissue (Fig. 234, a) ; and cases occur in which large areas 
of subcutaneous adipose tissue present a red appearance as a result of the 
pathological development of blood-vessels. More rarely than in the skin 
and subcutaneous tissues, there occur similar angiomata in other places: 
in glands (mamma), bones, brain (Fig. 235), and spinal cord and their 
membranes. Not infrequently, on the other hand, there are found 
analogous vascular changes in tumors, for example, in gliomata or 
sarcomata. 
If the vessels, which are usually abundant, are isolated, it becomes 
evident that the capillaries and small veins (angioma simplex venosum), ANGIOMA. 
305 
are more or less dilated. The dilatations (Fig. 235) are spindle-shaped 
or cylindrical, saccular or spherical, and different forms of dilatation may 
be combined in a variety of ways. T he dilated vessels are united by 
capillaries of normal size or of moderately increased calibre. The walls 
of the vessels are thin — 
in comparison with nor- 
mal capillaries they are 
slightly thickened. 
Haemangioma caver- 
nosum is a vascular 
formation consisting of 
spongy tissue, whose 
structure suggests that 
of the corpus caver- 
nosum or spongiosum of 
the penis (Figs. 236, and 
237). Through filling of the spaces with blood they present a bluish-red 
or dark red color. 
The cavernous angioma, like the angioma simplex, occurs chiefly in 
the skin (Fig. 236, c) and subcutaneous tissues. At times it forms a small 
bluish-red spot; at other times, a smooth, elevated (Fig. 236), or slightly 
Fig. 236.— Angioma cavernosum cutaneum congenitum (Mul- 
ler’s fluid, luematoxylin). a, Epidermis; b, corium; c, cavernous 
blood-spaces, x 20. 
Fig. 237.— Angioma cavernosum hepatis (Muller’s fluid, hematoxylin, eosin). a, Liver tissue; 
b, angioma, x ioo. 
nodular bluish-red wart (verruca vasculosa). Extensive development of 
cavernous tissue in the subcutaneous or intermuscular connective tissue 
may produce large tumors or elephantiasis-like disfigurations of portions 
of the body (elephantiasis hccmangiomatosa). 
Within the body the cavernous angioma is found most commonly in 
the liver (Fig. 237, a, b), but may develop in other organs; kidney, spleen, 306 
TUMORS. 
intestine, bladder, bones, muscles, uterus, brain, etc. In the liver it 
appears in the form of sharply defined, dark-red areas, varying in size 
Fig. 238.—Angioma simplex hypertrophicum (formalin, haematoxylin). a, Vessels containing 
blood; b, empty and collapsed thick-walled blood-vessels rich in nuclei, x 100. 
from that of a pin-head to several centimetres in diameter. They replace 
the liver tissue, and are usually flush with the surface. 
The width of the blood spaces and the thickness of the limiting trabe- 
culae vary in different cases; the angioma may be rich in fibrous tissue 
that was formed in the beginning, or 
fibrous proliferations take place as 
sequelae to thrombosis. The blood 
spaces are lined with endothelium; at 
times smooth muscle-fibres may be 
demonstrated in their walls, and the 
interstitial tissue is often rich in elastic 
fibres (Briichanow). Usually no liver 
cells are found in the trabeculae. 
The cavernous angioma of the liver 
occurs in old individuals, as well as in 
infants and children, and not infre- 
quently is multiple. It is probably a 
local disturbance of development, 
which proceeds from the vessels of 
Glisson’s capsule or from the intra- 
a'cinoue capillaries, characterized by ab- 
normal multiplication of blood-vessels 
at the expense of other tissues. De- 
velopment is slow and limited; ordi- 
narily the liver-cells in the immediate neighborhood show no signs of 
degeneration. 
In the majority of cases hepatic angiomata are encountered as acci- 
dental findings at autopsy, and are solitary and small in size. In rare 
instances, however, they attain large dimensions or occur in such numbers 
as to replace no inconsiderable part of the liver substance. Occasionally 
Fig. 239.—Angioma simplex hypertro- 
phicum cutaneum et subcutaneum (alcohol, 
carmine). In the middle of the section is 
the duct of a sweat-gland cut transversely, 
x 200. ANGIOMA. 
307 
thrombosis may take place in them, subsequent organization resulting in 
partial or complete replacement by fibrous tissue. As a rule, hepatic 
Fig. 240.—Angioma cavernosum hypertrophicum (angioendothelioma) of the skull-cap (Mul- 
ler’s fluid, hematoxylin), a, Blood-vessel with flattened endothelium; b, blood-vessel with cubical 
and cylindrical endothelium, x 250. 
Fig. 241.—'Angioma arteriale plexiforme arteriae angularis et frontalis dext. et sin. 308 
TUMORS. 
angiomata are of no clinical significance whatever, although in a case 
investigated post-mortem at Bellevue Hospital, death occurred from rup- 
Fig. 242.— Weeping subepithelial lymphangioma of the skin (alcohol, carmine), a, Corium; b, 
epithelium c, d, lymph-spaces, x 14. 
ture of a small angioma of the under surface of the liver with the 
production of massive hsemorrhage into the abdomen. 
Haemangioma hypertrophicum occurs most frequently in the skin and 
subcutaneous tissues, where it forms circumscribed nodules. The altered 
Fig. 243.— Lymphangioma cavernosum subcutaneum (alcohol, alum-carmine), a. Ectatic lymph- 
vessels; b, connective tissue; c, adipose tissue; d, large blood-vessels; e, cellular areas. X 
200. 
vessels lie in the papillae and corium as well as in the subcutaneous tissue, 
and form tubes filled with blood (Figs. 238, a, and 239), the walls of 
which are thickened and cellular, or solid cords of cells (Fig. 238, b), 
which are either collapsed, thick-walled vessels, or possess no lumen 
whatever. ANGIOMA. 
309 
In very rare cases it happens that in angiomata, which from the calibre 
of the vessels bear the character of cavernous angiomata, there occurs 
hypertrophy of the vessel-walls; and this hypertrophy is due to the fact 
that the flat endothelial cells become changed into cubical and cylindrical 
cells (Fig. 240, b). Such a tumor may be classed as an angioma caverno- 
snm hvpertrophicum, or as a blood-vessel-endothelioma, or hcemangioitic 
endothelioma; the last term being in particular applicable when, as a result 
of the marked proliferation and multiplication of the endothelium, there 
are produced nests of large cells which fill 
the blood-vessels (compare Endothelioma, 
§§ 114 and 115). 
A cirsoid aneurism, or angioma 
arteriale racemosum, or angioma arter- 
iale plexiforme (Fig. 241), is a condi- 
dition in which the arteries of an entire 
vascular area are dilated, tortuous, and 
thickened, so that there is formed a con- 
volution of enlarged and thickened 
arteries. To the palpating finger they 
feel like a bunch of earth-worms. Many 
of these angiomata, which occur particu- 
larly on the head, and which may cause 
erosion of the cranial bones, arise from 
congenital defects; others appear to be 
acquired, and develop after traumatism, 
but it is possible that special conditions 
may have existed before the trauma. 
§ 108. Angioma lymphaticum or 
lymphangioma is a tumor the greater 
part of which is made up of dilated lymph- 
vessels. The following forms may be dis- 
tinguished : lymphangioma simplex or 
teleangiectasia lymphatica (Fig. 242); 
lymphangioma cavernosum (Fig. 243); 
lymphangioma cystoides; and lymphan- 
gioma hypertrophicum. The cavities of 
these tumors usually enclose a clear, light- 
colored lymph ; more rarely it is milky and 
contains lymphocytes. The walls consist 
of connective-tissue trabeculae of varying 
thickness and containing more or less in- 
voluntary muscle; the spaces are lined 
with endothelium. 
In lymphangioma simplex (Fig. 242) the lymph-vessels of a more or 
less extensive area are dilated and their walls for the greater part are 
thickened. In cavernous lymphangiomata the number of lymph-vessels 
is still greater, their spaces are larger, and the intervening tissue is less 
abundant, so that, even to the naked eye, the growth presents a spongy 
appearance. The cystoid lymphangiomata contain cysts varying in size 
from that of a pea to a walnut. The tissue between the dilated lymph- 
vessels consists, according to the location of the tumor, of connective tissue 
(Fig. 242), fat (Fig. 243, c), muscle, or lymphadenoid tissue may be en- 
closed (e), and may present evidences of active proliferation. 
Fic. 244.—Large hairy and pigmented 
naevus of back, buttocks, and thighs 
with scattered smaller pigmented spots 
ever the remaining portions of the body. 
(After Rohring.) (Reduced from orig- 
inai.) 310 
TUMORS. 
Lymphangiomata are sometimes congenital; at other times they appear 
at a later period of life. 
The congenital forms occur as ectasias of lymph-vessels, and are found 
in the tongue {macroglossia), palatal arch, lips (macrocheilia), skin {ncevus 
lymphaticus), subcutaneous tissue, in the neck {hygroma colli congenitum), 
vulva, etc. The lymphangiomata of the skin spread over more or less 
extensive areas, and form either smooth or irregular elevations. If the 
blood-vessels are numerous the growth may have a red color. The rupture 
of dilated lymph-vessels lying immediately beneath the epithelium (Fig. 
242, d) may give rise to lymphorrhoea. The extension of cavernous lymph- 
vessels over large areas of the skin and subcutaneous tissue gives rise to 
Fig. 245.— Lymphangioma hypertrophicum. Section through a small, soft, smooth wart (formalin, 
hsematoxylin, eosin). x 40. 
elepliantiasis-like disfigurations of the part affected. Not infrequently the 
intervening connective tissue takes part in the hypertrophic growth. 
In rare cases chyle-containing growths (chylangiomata) are found in 
the intestinal wall or mesentery. Cystic lymphangiomata are occasionally 
found in the peritoneum. 
Hypertrophic lymphangiomata represent peculiar changes of the skin, 
which are either congenital or develop in early youth. Included in this 
general group are pigmented moles, lentigines, freckles, and fleshy warts. 
The pigmented moles, nccvi pigmentosi, or benign melanomata, form 
large or small smooth areas which are not elevated above the surface of 
the skin (ncevus spilus), or prominent warty growths (ncevus prominens, 
ncevus verrucosus). When covered with hair, as frequently is the case, 
they are called hairy moles (ncevus pilosus). They are usually light 
brown or dark brown, or even black (Fig. 244) ; and are usually covered 
by epidermis of normal thickness, rarely by hypertrophic epithelium. 
They are usually small, but may be as large as the palm of the hand, or 
may even cover a large part of the body surface. 
Lentigines appear at any time after birth, and on any part of the body 
surface; when once formed they remain for life. They form sharply 
circumscribed yellow to brownish-black spots closely resembling the little 
pigmented nsevi; and vary in size from a pinhead to that of a lentil. 
Freckles or ephelides are small, irregularly outlined, serrated, pale- 
brown spots, which are not elevated above the surface of the skin. ' They ANGIOMA. 
311 
occur in young individuals, particularly on the face, hands, and arms, 
rarely on other portions of the body; and may remain permanently or 
disappear after a longer or shorter time. The pigmentation is favored 
by exposure to sunlight. 
Fleshy moles (verruca carnece) are non-pigmented, circumscribed, 
smooth (Fig. 245) or slightly irregular, or rough and papillary (Fig. 247) 
prominences, over which the epidermis is at times normal, at other times 
somewhat hypertrophic (Fig. 247, a). 
In all the pathological formations just described the connective-tissue 
framework encloses collections of cells, either in round or cord-like masses 
Fig. 246.— Lymphangioma hypertrophicum. Rounded summit of a large, soft, smooth wart 
(formalin, haematoxylin, eosin). Sharply outlined cell-nest in corium. X 250. 
(Figs. 245, 246, 247, d, dj), which lie partly in the papillae and partly in 
the corium; and are the more abundant the more the growth projects 
above the surface. In the pigmented varieties the cells of the cell-nests 
may contain pigment in the form of brown or yellow granules, or the 
pigment may lie in or between the connective tissue cells of the fibrous 
portions of the growth. 
The cells of the nests are relatively large (Fig. 246), possess abundant 
protoplasm, and a bright, bladder-like nucleus. Their position and appear- 
ance justify the assumption that they represent proliferation of the endo- 
thelial cells of the lymph-vessels. In rarer cases similar formations arise 
from blood-vessels (hsemangioma hypertrophicum). Accordingly, it 
would seem proper to class these growths with the endotheliomata, but 
their limited growth makes their classification as lymphangiomata more 
appropriate (see § 114). The cell-nests of hypertrophic lymphangioma 
may spread more diffusely through the tissues (as is the case with the 
hypertrophic hsemangioma), so that the pecuhar structure of the growth 
may be lost. 312 
TUMORS. 
Unna, Kromayer, Delbanco, and Marchand hold that the cell-nests of nsevi 
are of epithelial origin, and represent misplaced portions of surface epithelium; 
Kromayer goes so far as to assume metaplasia of epithelium into connective tissue. 
Preparations showing the first stages of the development of naevi are not accessible 
to me; but a borough study of naevi and fleshy warts of a later stage does not show 
any connection between the cell-nests and epithelium; and consequently I hold — 
Fig. 247.— Section through two papillae of a papillary fleshy wart (alcohol, carmine), a, 
Thickened horny layer of the epidermis; b, epithelial pearls; c, rete Malpighii; d, nests and strands 
of cells in the papillae; di, nests and strands of cells in the reticular layer; e, connective tissue, 
x 50. 
notwithstanding the investigations of others—'that the view given above harmonizes 
with the anatomical nature and clinical behavior of these growths, both in their 
fully developed condition as well as when they undergo malignant transformation. 
That the cell-nests lie close to the epithelium is no proof of genetic relationship, 
since the ordinary lymphangiomata also lie close to the epithelium (Fig. d). 
According to investigations by Jadassohn and Lanz the cellular warts can be trans- 
planted from one individual to another by an intra-epidermoidal inoculation of 
cell-masses. 
(g) Myoma. 
§ 109. A myoma is a tumor consisting of newly formed muscle-fibres.. 
According to the nature of the muscular elements, myomata are divided 
into leiomyomata formed of unstriped muscle, and rhabdomyomata com- 
posed of striped muscle. 
The leiomyoma, or myoma Icevicellulare, occurs frequently in the 
uterus, more rarely in the tubes, uterine ligaments, labia majora, muscu- 
laris of the gastro-intestinal tract and urinary passages; and may form 
spherical, nodular tumors of varying size. In rare cases it is also found 
in the skin and subcutaneous tissues, forming nodules occasionally reach- 
ing the size of a pigeon’s egg. Leiomyomata occur as single or multiple MYOMA. 
313 
tumors; and may appear in childhood, or even during intrauterine life 
(Marc). 
In muscular organs the new-growth proceeds from the muscularis, 
and forms bundles of muscle-fibres (Fig. 248) which are interwoven in 
such fashion as to present a variety of pictures according to the direc- 
tion in which the bundles are cut. Myomata of the uterus may contain 
uterine glands, and those developing in the dorsal wall near the angles of 
the tubes, or in the inguinal region, may include gland-tubules from the 
Wolffian body (von Recklinghausen) ; such tumors may be designated 
Fig. 248.— Myoma of the uterus (Muller’s fluid, haematoxylin, eosin). x 300, 
adenomyomata. They are distinguished from ordinary myomata, which 
are circumscribed, by the fact that their boundaries are not sharply 
defined. Eventually some of the glands may become cystic from accumu- 
lation of secretions. According to Ricker, Pfannenstiel, and others, 
uterine myomata as well as those of the vaginal vault may contain epithe- 
lial tubes, which probably owe their origin to inclusions of portions of the 
duct of Muller. In the skin and subcutaneous tissue the formation of 
muscle-fibres proceeds from the muscularis of the vessels (Fig. 249), 
which become thickened (a), and give rise to free strands of muscle-fibres 
(b). Pathological new-formation of blood-vessels may be associated with 
that of muscle (a), so that tumors arise which are designated angiomyo- 
mata (Fig. 249). According to Jadassohn and others, multiple myomata 
of the skin may take their origin from the arrectores pilorum or from 
the muscle-cells of sweat-glands. 
A certain amount of connective tissue always takes part in the forma- 
tion of a myoma, and often assumes such importance that the tumor is 
called fibromyoma or myofibroma. The majority of uterine myomata 
are fibromyomata. The fibrous portions of the tumor appear glistening 
white, the muscular portions reddish-white or reddish-gray. The spindle- 
shaped muscle-fibres may be isolated by teasing a bit of the tumor or by 
maceration in nitric-acid solution or potassium hydroxide. In longitudinal 
sections the muscle-fibres are recognized by their rod-shaped nuclei (Figs. 
248, 249), as well as by the arrangement of the cells in bands or strands. 314 
TUMORS. 
In cross-section the muscle-cells appear as small flattened cells containing 
in their centres the transversely cut nuclei (Fig. 248). 
The leiomyomata are benign tumors, but often reach large size, and 
sometimes undergo sarcomatous transformation and set up metastases. 
The muscle-cells themselves may multiply or the intermuscular connective 
tissue take on sarcomatous proliferation. In fibromyomata of the uterus 
fatty degeneration may lead to softening or to the formation of cystic 
Fig. 249.—Angiomyoma subcutaneum dorsi (alcohol, haematoxylin, eosin). a, Cavernous 
blood-vessels; b, strands of muscle cut longitudinally; c, same cut transversely; d, connective 
tissue; e, artery with hypertrophic muscularis; f, groups of lymphoid cells, x 46. 
cavities. Calcification and bone-formation may also occur. Through 
degeneration and atrophy of the muscle-fibres a myofibroma may become 
transformed into a fibroma. 
By far the greater number of tumors composed of smooth muscle 
tissue originate in the uterus, and it is estimated that between 1 and 2 
per cent, eventually undergo malignant transformation (Kelly and Cullen). 
This may be brought about in one of two ways: first, by the development 
of genuine sarcomata from the connective tissue of the interstitium, and, 
second, by direct transformation of the muscle fibres, or mesodermal ele- 
ments, into cells whose histology and vegetative vagaries correspond to 
the form and behavior of the cells of an autonomous malignant growth. 
Strictly speaking, this latter type of tumor should not be classified among 
the sarcomata, but as a malignant myoma. For practical purposes, how- 
ever, most writers on the subject employ the term myosarcoma to designate 
a malignant tumor which develops either from the connective tissue frame- 
work or from the smooth muscle elements of a leiomyoma. In still other 
quarters it is maintained that the proliferation of muscle cells occurs 
primarily in the walls of the blood-vessels with which the tumor is 
provided. RHABDOMYOMA. 
315 
In addition to the familiar uterine leiomyomata, smaller but histologi- 
cally identical tumors occasionally are to be observed at autopsy or opera- 
tion, either singly or in numbers, lying in the musculature of the stomach, 
intestine, gall-bladder and elsewhere. In the autopsy experience at 
Bellevue Flospital they occur in less than 1 per cent, of cases and the 
individual tumors rarely exceed a centimetre in diameter, projecting, as 
a rule, beneath the serous surface, sometimes into the lumen. They are 
apt to be regarded as interesting but otherwise negligible. As a matter of 
fact, there is evidence to show that these apparently insignificant growths 
undergo malignant transformation with a degree of frequency which 
entitles them to notice as factors of clinical importance. 
Rhabdomyoma, or myoma striocellulare, is a rare tumor com- 
posed of striated muscle-fibres, which in part are fully developed 
and in part undeveloped. When well developed the muscle-fibres 
form multinuclear bands of varying width, which present cross- 
Fig. 250.—Cells from a rhabdomyoma. (After Ribbert and Wolfensberger.) a, b, c, c, Striated 
fibres of varying thickness; d, slender nucleated fibre without striation; e, spindle-cell with 
longitudinal striation; f, spindle-cells with longitudinal and transverse striation; g, spindle-cells, 
without striation, with elongated processes; h, i, round cells with concentric and radial striation. 
striation (Fig. 250, a, b, c), and also longitudinal striation (e, /). The 
undeveloped forms consist of narrow bands without transverse striations 
(d) ; spindle-cells with long-drawn-out thread-like processes without 
transverse striation (g) or with partial striation (/) ; or round cells of 
different sizes, which present either radial or concentric fibrillation or 
striation (h, i). Besides these there are cells which possess no special 
characteristics, so that it is impossible to determine whether they are young 
muscle or connective-tissue cells. The bands as well as the spindles are 
usually arranged in interlacing bundles. It is not possible definitely to 
demonstrate sarcolemma on the surface of the fibres; but various delicate 
membranes have been described which probably are to be regarded as 
a rudimentary sarcolemma. 
Rhabdomyomata of the heart are peculiarly constructed in so far as 
they do not consist of transversely striated muscle-fibres, but are made up 
of a network in which lie spider-like cells, whose processes are partly free, 
and partly continuous with the connective tissue reticulum. According to 316 
TUMORS. 
Seiffert, these are to be regarded as enlarged embryonal muscle-cells, 
which have formed no transversely striated covering. 
Rhabdomyomata occur in the kidney, testicles, uterus, vagina, bladder, 
heart, subcutaneous tissue, oesophagus, etc., and form nodular, or, if on 
a mucous membrane, papillomatous and polypoid tumors. They develop 
from striped muscle, possibly from smooth muscle (uterus). 
If a tumor contains only a few cells which can be definitely recognized 
as muscle-fibres, while the majority of the cells have no specific character, 
the tumor is ordinarily designated rhabdomyosarcoma. 
(/i) Glioma and Neuroglioma Ganglionare. 
§ 110. A glioma is a tumor which develops from the cells of the sup- 
porting tissue of the central nervous system (neuroglia). In the brain 
gliomata form tumors which are not sharply defined from normal brain- 
substance, but pass into the latter by insensible gradations. At times they 
appear as local swellings of the brain, and only the difference in color 
and consistence and the disappearance of contrasts between the different 
elements of the brain, give evidence that a tumor is present. In the 
spinal cord they arise most 
frequently in the neighbor- 
hood of the central canal, 
and may extend over a 
large portion of the cord. 
Their appearance varies 
greatly; sometimes they 
are light-gray, somewhat 
translucent, and similar in 
color to that of the cortex, 
and moderately firm in con- 
sistence ; at other times 
they are grayish-white, 
dense, and firm; again they 
are not infrequently gray- 
ish-red or dark red and 
sharply circumscribed from 
the surrounding brain, and 
traversed by numerous 
large vessels. Gliomata 
well supplied with blood 
often contain haemorrhagic areas. Fatty degeneration, softening, and 
destruction of the tissue are of common occurrence. 
A fully developed glioma shows under the microscope a network of 
delicate fibrillae (Fig. 251, B), in which are imbedded numerous short oval 
nuclei. About the nuclei there is scanty protoplasm, to be distinguished 
only with difficulty. When examined in the fresh state or after macera- 
tion it may be seen that these nuclei belong to cells (astrocytes) which are 
characterized by fine processes extending in all directions, and often 
branching (Fig. 251, A). By proper staining the connection between 
some of the fibres may be demonstrated (Fig. 252). 
The cells are similar to normal glia-cells; but are frequently larger, 
occasionally more plump, and may possess two, three, or four nuclei. 
A preponderance of cells with slight development of processes leads to 
Fig. 251.—'Glioma cerebri. A, Cells isolated by teasing 
;nd stained with carmine. B, Section from same glioma 
after hardening in Muller’s fluid (Bismarck brown). X 350. GLIOMA. 
317 
the formation of medullary gliomata; more marked formation of pro- 
cesses and of fibrillated ground-substance gives rise to hard forms. As 
the result of proliferation of the perivascular connective tissue gliosarco- 
mata may be formed. 
In gliomata developing in the neighborhood of the ependyma, the 
ependymal epithelium may share in the proliferation, and the surface of 
the tumor becomes covered with a layer of ependyma. Epithelial in- 
growths resembling ducts may be formed, so that the tumor takes on the 
character of an adenoma (neuro-epithelioma adenomatosum gliomatosum). 
A similar appearance may be pro- 
duced when misplaced portions of the 
medullary canal lie in the glioma. 
Proliferations arising from the 
epithelium of the choroid plexus bear 
the character of epithelial growths. 
Neuroglioma ganglionare (Fig. 
253) is a tumor of the central 
nervous system, composed of hyper- 
plastic glia-tissue, ganglion-cells, and 
nerve-fibres, and forms poorly defined 
swellings of large portions of the 
brain, or circumscribed, nodular en- 
largements of smaller portions. To 
the naked eye the structure of the 
brain may appear to be preserved, 
though the difference between cortical 
and medullary substance is less distinct than normal, and the tissue 
throughout is white or grayish-white, or spotted gray and white, and 
more or less increased in consistence. 
The main portions of these masses consist of glia-tissue containing 
nerve-fibres (d) and ganglion-cells (a, b, c), or cells resembling ganglion- 
cells, not only in the cortical tissue, but in the white substance. 
Probably all of these formations are to be regarded as the result of 
disturbances of development — that is, as local malformations character- 
ized by pathological development of neuroglia (gliomatosis) and by devel- 
opment of neuroblasts, probably also of spongioblasts, into ganglion-like 
cells (a) such as are not normally found in the brain. 
The term glioma is also applied to certain tumors of the retina occur- 
ring during childhood. These growths are evidently to be referred to 
disturbance in the development of the retina. They form cellular, soft, 
white or reddish tumors, the greater part of which consists of small, 
round or irregular cells poor in protoplasm, resembling the cells of the 
stratum granulosum. Some of them possess smaller or larger processes. 
These cells are best preserved in the neighborhood of the blood-vessels; 
in other portions of the tumor they often show retrograde changes. The 
tumor may also contain ganglion-cells, cylindrical cells, and rosette and 
ribbon-like cell-formations, regarded as aggregations of rods and cones. 
Wintersteiner has designated the tumor neuroepithelioma. 
The glioma of the retina often shows areas of necrosis in its central 
portion. In its growth it may break into the retrobulbar space, or forward 
through the cornea and sclera; it recurs after operation, and gives rise to 
metastases. 
Fig. 252.— Section of a glioma of the cere- 
brum, with astrocytes (Muller’s fluid, haema- 
toxylin, Mallory’s method.) X 500. 318 
TUMORS. 
The neuroblastoma is a malignant tumor composed of undifferentiated 
nerve cells or neuroblasts, and arises most often in the medulla of the suprarenal 
capsule, but occasionally in other parts of the body. Histologically, the tumor is 
characterized by the presence of rosettes made up peripherally of cells with richly 
chromatic, rounded nuclei, surrounding tangled masses of fibrillated or homogene- 
ous material staining pinkish with eosin, the latter representing the remains of 
cell fibrils. In certain cases the fibrils are absent or poorly developed, rosettes can- 
not be seen, and the richly nucleated character of the growth in these circum- 
stances may lead to the diagnosis of sarcoma. The condition is not common. It 
occurs oftenest in children, in whom there are two symptomatic groups; one at- 
tended by an abdominal mass with secondary exophthalmus, ecchymosis of the 
lids, infiltration of the bones of the skull and of the regional lymph nodes; the 
other by rapidly increasing distention of the abdomen due to neoplasmic infiltration 
Fig. 253.— Section from a nodular neuroglioma ganglionare of the central convolution of the 
cerebrum (Muller’s fluid, Weigert’s stain). A, Portion of tissue rich in ganglion cells. B, Portion 
of tissue containing nerve-fibres. C, jelly-like portion, a, Ganglion-cells arranged in groups; b, 
scattered ganglion-cells; c, ganglion-cells with two nuclei; d, nerve-fibres with medullary sheath; 
e, glia-cells; f, blood-vessel, x 275. 
of the liver unattended by ascites or jaundice . (Wright, Journal Experimental 
Medicine, 1910; Hutchison, Quarterly Journal of Medicine, 1917; Pepper, Ameri- 
can Journal Medical Sciences, 1901.) 
With reference to the origin of neuroglia and ganglion-cells from the ectoderm, 
various writers class the different forms of gliomata with the epithelial tumors. 
In so far as ependymal proliferations resembling epitheliomata and adenomata (§§ 
118, 119) are concerned, such a classification is justified. The ordinary gliomata, 
however, show a structure resembling that of the other connective-tissue tumors, 
so that it is more proper to class them with the latter. 
(i) Amputation Neuroma, Neurofibroma, and the True Neuroma. 
§ 111. The tumors designated neuromata occur most frequently on 
the ends of amputated nerves, where they form more or less prominent 
swellings, either circumscribed or blending into the surrounding tissue, 
and are familiarly known as amputation-neuromata (Fig. 254, b). The 
development of these neuromata is to be referred to changes taking place 
after the nerves have been severed; during the development of connective 
tissue in the stump the axis-cylinders of the proximal portion of the NEUROMA. 
319 
nerve divide and grow longitudinally, so that the scar is penetrated by 
nerves which at first have no sheaths, but are soon surrounded by medul- 
lary sheaths. The number may be so large as to permeate the connective 
tissue in all directions (Fig. 254, b). The process is an example of use- 
less regenerative proliferation. 
Another form of so-called neuromata are those growths developing 
spontaneously along the course of nerves; and consist of increase in the 
connective tissue of the nerve, usually of 
the outer, more rarely of the inner layer of 
the endoneurium. 
At the point of tumor-grov. th the nerve- 
bundles become surrounded by a more or 
less thick layer of connective tissue, which 
is usually loose, more rarely dense (Fig. 
255, b, d), or the bundles may be split into 
individual fibres (c). Occasionally the 
perineurium takes part in the proliferation. 
In large nerve-trunks the epineurium may 
be affected in association with the endo- 
neurium and perineurium of individual 
bundles, although the process is most fre- 
quently confined to the endoneurium. 
These tumors are not true neuromata, 
but neurofibromata or fibromata nervo- 
rum. They are usually multiple, and may 
extend through the entire peripheral nerv- 
ous system, but are more often limited to a 
definite area of nerve-distribution. In rare 
cases they occur in the nerve-roots and 
spinal cord. The nodules are sometimes 
situated along the course of the nerve- 
trunks, sometimes on the finer branches, 
most frequently of the cutaneous nerves; 
and in the skin form numerous, large or 
small nodules, for the greater part of soft 
consistence, to which the designation multi- 
ple fibromata of the skin is applied. The 
smallest nodules can be seen only with the 
microscope; the majority vary in size from 
a pea to that of a hazel-nut. Individual 
tumors may reach the size of a man’s fist, 
the nerve-fibres being lost in the tnass of 
connective tissue. Atrophy of the fibres 
may be caused by the increasing connective 
tissue, the fibres finally vanishing. In addi- 
tion to the formation of circumscribed nodules there may occur diffuse 
thickening of the nerves from hypertrophy of their connective tissue. 
Moreover, there may be associated hypertrophic proliferation of the con- 
nective tissue of the skin and subcutaneous tissue, leading to elephantiasis- 
like thickenings. 
A third form of false neuroma is the cirsoid or plexiform neuroma, 
which is characterized by the development in the domain of one or more 
nerve-branches of tendril-like, twisted or interwoven, thickened and 
Fig. 254.—Amputation-neuroma of 
the sciatic nerve (nine years after am- 
putation of the nerve). Longitudinal 
section, a, Nerve; b, neuroma; drawn 
from a preparation which had been 
hardened in Muller’s fluid, x 3. 320 
TUMORS. 
nodular nerve-strands (Fig. 256). When examined in detail this forma- 
tion is also found to depend on fibromatosis of the nerves (Fig. 255), the 
proliferation of the endoneurium resulting partly in diffuse and partly 
Fig. 255.— Nerves from an elephantiasis-like cirsoid neuroma of the cheek and lower jaw 
(Flemming’s solution, safranin). a, b, INerves, the.outer layers of whose endoneurium have under- 
gone marked proliferation; the nerve-fibres lie in the axial portion; c, nerve with markedly 
proliferated endoneurium and separated nerve-fibres; d, thickened nerve with a small strand of 
nerve-fibres at the left end; e, loose connective tissue, rich in nuclei and containing fat, lying 
between the nerves. X 7. 
in nodular thickening. In ad- 
dition, it may be found that the 
nerves of the affected area are 
lengthened and tortuous, and 
at the same time increased in 
number. In these circum- 
stances the condition must be 
regarded as one of true neu- 
roma, or neuroma associated 
with fibromatosis. The nerves 
for the greater part are medul- 
lated (neuroma myelinicum). 
It is difficult to determine to 
what extent non-medullated 
nerves are present in such 
formations, but cases have been 
reported in which the nerve- 
fibres were largely of the non- 
medullated variety (neuroma 
amyelinicum). Cirsoid neuro- 
mata occur on the head, trunk, 
and extremities, and give rise 
to elephantiasis-like disfigura- 
tions. 
Fig. 256.— Cirsoid neuroma of the sacral region. 
(After a drawing by P. Bruns.) The nodular, twisted, 
and interwoven nerves are in part free (a), and in 
part (b) covered by connective tissue. Natural size. SARCOMA. 
321 
True neuromata consisting of nerve-fibres and ganglion-cells (neu- 
roma gangliocellulare verum) are rare; but the occurrence of such 
growths cannot be doubted. They form tumors varying in size from a 
millet-seed to that of an apple, and consist of connective tissue, non- 
medullated and medullated nerve-fibres, and ganglion-cells which resemble 
those of the sympathetic ganglia. 
Neither the neurofibroma nor the true neuroma forms metastases, but 
cases occur in which neurofibromata take on a sarcomatous character 
and thus become malignant. 
(k) Sarcoma. 
§ 112. A sarcoma is a connective-tissue tumor whose cellular elements, 
either because of their number or size, predominate over the intercellular 
substance. Sarcomata are closely related to undeveloped connective tissue, 
and may be compared with embryonal tissue. 
Sarcomata develop either in previously normal tissue belonging to the 
connective-tissue group — in the skin, subcutaneous or intermuscular con- 
nective tissue, periosteum, spinal cord, meninges, connective tissue of 
glands, etc.— or in some preexisting connective-tissue tumor, as a fibroma, 
myoma, chondroma, hypertrophic lymphangioma, etc. The transforma- 
tion of the parent tissue into tumor tissue takes place through the multi- 
plication of existing cells. The division of cells takes place chiefly by 
mitosis, and mitoses are the more abundant the more rapid the growth of 
the tumor. In addition to typical mitoses there are frequently observed 
atypical forms, nuclear fragmentation, and, more rarely, segmentation. 
Fully developed sarcomata form more or less sharply circumscribed 
growths. They may appear in any portion of the body where connective 
tissue is present; but are found in certain tissues more frequently than in 
others. Thus, they are found much oftener in the skin, fascia, intermus- 
cular connective tissue, bone-marrow, periosteum, brain, and ovaries, than 
in the liver, intestines, and lungs. 
The development and form of the cells vary greatly in different 
sarcomata. The intercellular substance is sometimes scanty, soft, and 
delicate; at other times abundant and resembling the ground-substance of 
mature connective-tissue. 
The amount of intercellular substance has a marked influence on the 
consistence and color of the tumor. The medullary forms are soft and 
cellular, and poor in intercellular substance; on section they present a 
marrow-like white or grayish-white surface. The hard, dense forms, on 
the other hand, are poor in cells and rich in fibrous intercellular substance; 
they pass by insensible gradations into transition-forms known as fibro- 
sarcomata. The cut surface of a sarcoma presents a nearly uniform 
appearance, provided retrograde changes or differences in the blood- 
content do not interfere; sometimes the vessels are numerous, large, and 
ectatic (teleangiectatic sarcoma). Usually the vessels have walls easily 
distinguishable from the tumor tissue; but the tumor-cells may form the 
vessel-wall. Retrograde changes — fatty degeneration, mucous degenera- 
tion, necrosis, haemorrhage, gangrene, ulceration — are of frequent occur- 
rence in sarcomata. 
The sarcomata may be divided into three classes. The first includes 
simple sarcomata — tumors of the type of embryonal connective tissue, 
showing more or less uniform distribution of cells without the formation 
of distinct groups of cells. The second class includes sarcomata which 322 
TUMORS. 
show special arrangement and grouping of the individual elements, so that 
growths arise which are similar to the epithelial tumors. The third class 
is characterized by secondary changes in the cells, intercellular substance, 
and blood-vessels. 
The etiology of sarcoma is not simple. It occurs more frequently in 
youth than in old age. Some sarcomata develop even in embryonal life. 
Occasionally trauma appears to be an exciting cause. A parasitic origin 
has not been demonstrated (see Etiology of Carcinoma). Usually only 
one primary tumor is formed, but multiple primary sarcomata sometimes 
occur, particularly in the skin, bone-marrow and lymphoid depots. The 
softer tumors give rise to metastases. 
§ 113. The simple sarcomata include medullary forms and those of 
Fig. 257, 
Fig. 258. 
Fig. 257.— Section through the edge of a sarcoma of the intermuscular connective tissue of 
the cervical muscles (alcohol, carmine), a, Transverse section of normal muscle; ai, transverse 
section of an atrophic muscle-fibre; b, round cells of the sarcoma, between the muscle-fibres; c, 
fully developed tumor; d, lymphocytes, x 300. 
Fig. 258.—Section from a lymphosarcoma of the nasal mucous membrane (alcohol, carmine). 
firmer consistence, which pass by insensible transition into fibrosarcomata 
and fibromata. According to the character of the cells, several forms may 
be distinguished. 
The small round-cell sarcomata are soft, quickly growing tumors, 
which develop particularly in the connective tissue of the skeletal muscles, 
and in the skin, testicles, ovaries, and lymph-nodes. On section they 
appear milky-white, and occasionally present caseous or softened areas. 
When scraped the cut surface yields a milky fluid. Their structure is 
simple; the tumors consist almost wholly of round cells and blood-vessels 
(Fig. 257, c). The cells are small, they possess little protoplasm, and have 
spherical or slightly oval, rather large, bladder-shaped nuclei (c), which 
appear to be more highly developed than the nuclei of lymphoid cells. 
Between the cells lies a scanty amount of fibrogranular intercellular 
substance. The vessels traverse the growth in the form of thin-walled 
canals. If such a tumor growing in muscle be examined at its periphery 
it appears as an aggregation of round cells (Fig. 257, b, c) in the inter- 
muscular connective tissue. Not infrequently lymphoid cells lie near 
the tumor-cells, the nuclei of the former (d) staining more intensely than 
those of the tumor-cells. SARCOMA. 
323 
A second form of round-cell sarcoma is designated lymphosarcoma 
or sarcoma lymphadenoides; it imitates the structure of a lymph-node, 
in that the stroma supporting the lymphoid cells consists of a vascular 
Fig. 259. 
Fig. 260. 
Fig. 259.— Section from a fungoid large round-cell sarcoma of the skin of the leg (carmine 
preparation), x 400. 
Fig. 260.— Section from a sarcoma of the mamma with cells of different shapes (alcohol, 
Bismarck-brown), a, Connective tissue; b, sarcoma tissue; c, small cells; d, cells with hyper- 
trophic nuclei; e, multinuclear cells, x 300. 
reticulum (Fig. 258, a) composed of branching and anastomosing cells (b). 
According to the amount of reticulum, the lymphosarcomata may be 
divided into soft and hard forms. In the denser varieties the reticular 
framework may take on the appearance of ordinary fibrous connective 
Fig. 261.—(Bellevue Hospital.) Massive spindle cell sarcoma of breast (weight 25 lbs.). 324 
TUMORS. 
tissue. Special forms of round-cell sarcoma arising in the bone-marrow 
are known as myelomata. 
Lymphosarcomata arise most frequently in the lymph-nodes and the 
adenoid tissue of the mucous membranes and of the spleen, but are found 
in other places. 
Large round-cell sarcomata, the cells of which are larger than those 
of the forms just described, appear in the same places as do the small 
round-cell variety, and closely resemble the latter. The cells possess 
abundant protoplasm and large, bladder-like, oval nuclei (Fig. 259). 
Many of the cells have two nuclei, some more than two. Between the 
round cells there lies a reticulated sub- 
stance (Fig. 259), as well as spindle- 
shaped and branched cells, which 
form a supporting alveolar network. 
Fig. 262.— Spindle-cells from a large spindle-cell sarcoma of the cheek (teased preparation) 
X 400. 
Fig. 262. 
Fig. 263. 
Fig. 263.— Cells from a myelogenous giant-cell sarcoma of the tibia. (Haematoxylin.) x 400. 
In other forms of large round-cell sarcomata the tumor-cells are 
unequal in size (Fig. 260), and at the same time there are mingled with 
them elongated or irregularly shaped cells, so that the tumor may be 
regarded as a sarcoma with polymorphous cells. The nuclei likewise 
vary in size (Fig. 260), and (e) may be present in large numbers (multi- 
nuclear giant-cells). 
The large round-cell sarcomata and the polymorphous-cell variety are 
on the whole less malignant than the small-cell, but they also give rise to 
metastases. 
Spindle-cell sarcomata belong to the most commonly occurring tumors. 
As a rule, they are firmer than the round-cell varieties, but medullary 
forms also occur. On section they present a grayish-white or yellowish- 
white, translucent surface, which may be more or less reddened according 
to the degree of vascularity. Medullary tumors whose cells have under- 
gone fatty degeneration may possess a pure white color. In general, 
these sarcomata are more benign than the round-cell varieties, but their 
character in this respect varies according to location and their richness 
in cells. SARCOMA. 
325 
According to the size of the cells there are distinguished large 
spindle-cell and small spindle-cell sarcomata. The cells lie with their 
flat sides approximated, and are grouped in bundles, which, in section, are 
cut longitudinally, transversely, and obliquely — evidence that they are 
interwoven in different directions. 
The arrangement in bundles is often striking; in other cases it is 
wanting; and the spindles for considerable distances run in the same 
direction. Sometimes the direction of the spindles is determined by that 
of the blood-vessels — that is, individual bundles form sheaths about the 
blood-vessels. 
Between the spindles there is often but scanty intercellular substance, 
or it may not be possible to demonstrate it at all. In other cases it may 
Fig. 264.— Giant-cell sarcoma of the upper jaw (Muller’s fluid, haematoxylin). x ioo. 
be more abundant, and show a fibrillar character. Such varieties are 
dense and hard. They represent the connecting-link between sarcomata 
and fibromata, and are designated fibrosarcomata. 
Sarcomata with polymorphous cells are also found among the 
spindle-cell forms; and contain spindle-shaped, pyramidal, prismatic, 
stellate, and various irregular forms (Fig. 263). 
Both in polymorphous- and spindle-cell sarcomata there may be 
numerous giant cells (Figs. 260, 263, and 264), and the designation giant- 
cell sarcoma is applied to these tumors. They arise particularly from 
the bones, but may also occur in other places. 
If a sarcoma develops in preexisting new growths there may be 
formed mixed tumors, known as myxosarcoma (Fig. 222), chondrosar- 
coma (Fig. 227), myosarcoma, etc. 
Lymphosarcoma is essentially a growth of regional distribution and anatomi- 
cally may be divided into five groups, (a) involving regional collections of super- 
ficial lymph nodes, as in the neck, axilla and groin, (b) implicating the lymphoid 
structures of the thorax, notably the remains of the thymus gland and the lymph 
nodes at the root of the lung, (c) involving the lymphoid tissues of the abdomen, 
including the stomach, intestines, spleen and lymph nodes, (d) diffuse infiltration of 
tissues, especially the paired organs, and (e) leukosarcoma, which is characterized 326 
TUMORS. 
by the formation of lymphoid tumors in peculiar situations, such as the uterus, 
breast, skin, etc., the growths pouring lymphocytes into the blood in such quan- 
tities as to constitute a form of leukemia. In the same category certain pathologists 
are inclined to place chronic lymphatic leukemia and its companion lesion, pseudo- 
leukemia. The implication of paired organs in lymphosarcoma is well shown by the 
lesion first fully described by Mikulicz, which is characterized by infiltrative over- 
growth of the lymphoid cells in the stroma of the lachrymal glands, and is mani- 
fested by symmetrical enlargement of the outer two-thirds of the upper lids, fol- 
lowed by symmetrical invasion of the parotid and submaxillary glands. There is 
also a form of symmetrical conjunctival lymphosarcoma. In still another variety, 
lymphosarcoma brings about symmetrical neoplasmic infiltration of other paired 
viscera, such as the mammary gland, ovaries, testicles, suprarenal capsules and 
kidneys. In three cases of the latter description encountered at Bellevue Hospital, 
the kidneys were enormously increased in size, due to the infiltration of hordes 
of lymphocytes associated with lymphosarcomata in other parts of the body. 
Fig. 265.—(Bellevue Hospital.) Changes in the spleen in Hodgkin’s disease, the whitish 
areas representing nodular formations, the histology of which corresponds to that found in 
the lymph nodes and elsewhere. 
At this point may be mentioned another peculiar process involving lymphoid 
tissues, namely, the so-called Hodgkin’s disease, Clinically it often resembles 
lymphosarcoma, pseudo-leukemia and even true chronic lymphatic leukemia, but 
histologically it is distinctive. It is characterized by multiple, discrete enlargement 
of regional lymph nodes, notably those of the neck, axilla and groin, followed by 
similar changes in the lymph nodes of the thorax and abdomen. The lymphoid 
structures in the spleen are likewise changed and the organ becomes markedly en- 
larged and nodulated; the liver may be similarly riddled. Histologically the changes 
in the lymph nodes and elsewhere are characterized by diffuse overgrowth of con- 
nective tissue with varying degrees of hyperplasia of the lymphoicl cells, together 
with numbers of mononuclear and multinuclear giant cells, eosinop'hiles and eosino- 
philic myelocytes, the composite histological picture being not unlike that of a 
polymorphous sarcoma. The cause of the disease is totally unknown. In certain 
quarters it is regarded as a variety of tuberculosis, but this origin has never been 
demonstrated, in spite of much investigation. It is possible that Hodgkin’s disease, 
like the lymphosarcomata and multiple myelomata, represents a peculiar reaction 
to stimuli acting on functionally related tissues at the same or approximately the 
same time, the first effect of which, in Hodgkin’s disease, is to promote hyper- 
plasia of the lymphoid cells, and that the peculiar giant cells and the eosinophiles 
and eosinophilic myelocytes are derived from the bone marrow and are filtered out PSEUDO-LEUKAEMIA; MYELOMATA. 
327 
by the hyperplastic lymph nodes. Clinically the disease first shows itself, as a 
rule, by enlargement of the cervical or other superficial groups of lymph nodes. 
There are, in addition, well defined varieties of Hodgkin’s disease in which the 
changes are first manifested in other parts, as the thymic remains, the peribronchial 
lymph nodes, spleen, intestinal lymph follicles, etc. 
Cohnheim (Virchow’s Arch., 1865) described a disease under the title of 
pseudo-leukemia, characterized by marked hyperplasia of lymph nodes in various 
parts of the body but without increase in the number of circulating lymphocytes. 
Ihis latter fact distinguishes it at once from chronic lymphatic leukemia, which 
presents virtually identical changes in the lymphoid tissues, but, in addition, is at- 
tended by enormous numbers 
of lymphocytes in the blood. 
Clinically, pseudo-leukemia 
cannot be distinguished from 
Hodgkin’s disease except by 
microscopic examination of 
excised lymph nodes. From 
true leukemia it is at once 
differentiated, of course, by 
examination of the blood. In 
many quarters the term 
pseudo-leukemia still is erro- 
neously employed as a 
synonym for Hodgkin’s dis- 
ease. 
The neoplasmic disease 
described under the caption 
of multiple myelomata is 
characterized by foci of 
growth arising in different 
parts of the marrow system 
at approximately the same 
time, the individual tumors 
springing from certain primi- 
tive cells of the blood-form- 
ing series, variously de- 
scribed as lymphoblasts, neu- 
trophilic myelocytes, erythro- 
blasts, plasma cells and 
myeloblasts. It is highly 
doubtful, however, if there 
are myelomata composed of 
each of these varieties, but 
that all myelomata are made 
up of myeloblasts — in other 
words, the tumor is a myelo- 
blastoma. The disease is 
rare. It occurs apparently 
exclusively in individuals 
over thirty-five years of age, 
oftenest in men, and pursues 
a rapidly fatal course. The 
bones involved are those with 
red marrow, notably the vertebrae, sternum, ribs, skull, scapulae and ileum, and 
are exquisitely tender. Spontaneous fractures are common. The Bence-Jones 
albumose frequently is found in the urine in these cases. A notable feature of 
the myeloma consists in a tendency on the part of the growth to confine itself 
to the marrow system, although it may bring about continuate infiltration of 
adjacent structures by direct erosion of the bony casement. Genuine metas- 
tasizing myelomata are extremely rare, but do occur, cases having been recorded 
by Christian and Symmers, the metastases occurring in tissues having no relation 
either to bone marrow or to the extramedullary hemopoietic system. In still 
another group of cases, myelomata of the marrow are associated with identical 
growths in such tissues as the tonsil, spleen, lymph nodes and liver, but in these 
localities the tumor cells spring from or are implanted in tissue which is function- 
Fig. 266.— (Bellevue Hospital.) Mixed spindle and 
giant cell sarcoma of the upper end of the tibia. 328 
TUMORS, 
ally related to bone marrow (autochthonous myeloma). Surgical intervention is 
sometimes necessary for the relief of mechanical symptoms, such as those produced 
by pressure on the spinal cord, but is otherwise hopeless. 
There is another variety of medullary bone disease that has been variously 
designated medullary giant cell sarcoma, giant cell myeloma, chronic hcemorrhagic 
osteomyelitis (Barrie), benign bone cysts, etc. It is of great surgical importance. 
Two forms of growth are recognized — solitary and multiple, the latter having 
been described by Martland. In both forms the histology is the same; the lesion 
consists of medullary formations, in or near the ends of long bones, that are com- 
posed of innumerable giant cells of the osteoclastic type, imbedded in richly vascu- 
larized fibroblastic tissue, poor in mitoses, and associated with haemorrhage and 
necrosis, the naked eye appearance of the growth being comparable to that of red- 
Fig. 267.— Section through an endothelioma of the pia mater and cerebral cortex, diffusely- 
spread over the surface of the brain and spinal cord (Muller’s fluid, hrematoxylin). a, Superficial 
pia; b, pia in a sulcus; c, cortex; d, e, endothelial proliferations in the pia sheaths of the cortical 
vessels; /, g, h, endothelial proliferations in the pia sheaths of the cortical vessels; i, longitudinal 
section through a vein. X 28. 
currant jelly. Growth is expansive and slow, often stretching over a period of 
years, and the individual nodules are localized and circumscribed by relatively 
intact bone and periosteum. Infiltration of surrounding tissues and metastasis have 
not been observed, there is no Bence-Jones proteinuria, and the growths are painless. 
Spontaneous fractures are common. Simple curettement usually suffices, although 
local recurrence may take place. The multiple variety described by Martland con- 
stitutes a pathological entity with a close clinical resemblance to the multiple myelo- 
blastomata already considered. It is obvious that differentiation of the two is 
important since, in Martland’s disease, surgical intervention offers a hope of cure, 
and, in the solitary form, is distinctly promising. In this connection it is to be 
recalled, however, that mixed spindle and giant-cell sarcomata occur in the medul- 
lary ends of certain bones, notably the femur and tibia, that they grow expansively 
and rapidly and not uncommonly metastasize, and that the histology of these 
growths may simulate that of the formations described by Barrie and by Martland. SARCOMA. 
329 
In such tumors, however, giant cells are less numerous and the stroma is more 
richly nucleated and poor in both intercellular substance and vascular channels, 
while mitotic figures are often discernible. When malignancy is fully established 
and flourishing, giant cells may be rare or wanting, the growth partaking of the 
nature of a pure spindle cell sarcoma. Three examples of this type of tumor have 
been encountered in the pathological laboratories of Bellevue Hospital in the past 
two years. In such cases, of course, amputation is imperative, all things else being 
equal. (Barrie, Annals of Surgery, 1913; Surgery, Gynecology and Obstetrics, 1914; 
Martland, Proceedings New York Pathological Society, 1915; Haussling and Mart- 
land, Annals of Surgery, 1916.) 
§ 114. Sarcomata which present an organoid structure appear as 
alveolar and tubular growths in which it is possible to distinguish a vas- 
cular connective-tissue stroma and strands or nests of cells. According to 
their genesis, these growths may be divided into two types: lymphangio- 
sarcoma and hcemangiosarcoma. There are, however, alveolar sarcomata 
which cannqt be included with the above-named types. 
The lymphangiosarcomata arise from proliferation of the endothelium 
of lymph-vessels and lymph-spaces. They may accordingly be designated 
Fig. 268.— Endothelioma durse matris (Muller’s fluid, hamiatoxylin). a, Connective-tissue 
stroma; b, small-cell focus; c, groups and strands of cells arising from the proliferation of 
lymph-vessel endothelium; d, endothelial cell-strand with a lumen; e, area of fatty degeneration 
in nest of endothelial cells; f, strand of cells, passing gradually, on the right, into the surround- 
ing connective tissue, x 25. 
lymphangioendotheliomata or as endotheliomata in the narrower sense. 
They may develop in previously normal tissue, or in preexisting tumor-like 
formations, such as the hypertrophic lymphangioma (pigmented moles 
and warts, see § 108), and from myxochondromata. The first occur par- 
ticularly in the meninges of the brain, and in the serous membranes of the 
great body-cavities, but may develop in other organs; the second are 
found chiefly in the skin; those arising from myxochondromata develop 
in the salivary glands, palate, and orbit. 
The endotheliomata of the meninges of the brain and spinal cord occur 
as nodular growths and as plaque-like proliferations; they develop through 
transformation of the flattened endothelium, which covers the connective- 
tissue of the subarachnoid tissue and pia, into cubical or cylindrical 
cells (Fig. 267, d, e). In consequence, the new-growth at first presents 
the appearance of gland-like formations; in the event of more active 330 
TUMORS. 
proliferation solid nests of cells are formed. Inasmuch as the pia is 
continued as a lymph-sheath about the cerebral vessels, there are formed 
around the latter strands of large epithelial-like cells (Fig. 267, f, g, h). 
Endothelioma of the dura mater arises through proliferation of the 
endothelium of the lymph-vessels, and leads, through filling of the latter 
with large cells, to the formation of anastomosing cords of cells (Fig. 268, 
c, d, e), which in places may contain a lumen. 
Endotheliomata of the pleura or of the peritoneum appear as flattened 
thickenings of the affected membrane, but scattered nodular elevations 
may occur. These growths are characterized by cords of large cells 
Pig. 269.— Endothelioma of the pleura (alcohol, haematoxylin). a, Proliferated and thickened 
pleural connective tissue; b, cell-strands, x ioo. 
(Fig. 269, b), which correspond to the course of the lymph-vessels in the 
serosa. 
Endothelioma of the mammary gland is a rare tumor and takes its 
origin from proliferation of the endothelium of the lymph-vessels and 
lymph-spaces (Fig. 270, b, c), and gives rise to the formation of large 
cords of cells (c) or of smaller cell-nests. The proliferating cells are 
marked by great variation in the size, character, and form of the nucleus 
and cell-body. 
Endothelioma of the skin, which arises from hypertrophic lymphan- 
gioma (warts and pigmented moles), resembles these in its general struc- 
ture, and also possesses cell-nests of varying size (Fig. 246). Further, 
there occur endotheliomata of the skin, which do not arise from warts, 
and may develop in great numbers (Spiegler, Mulert). 
The endothelial proliferations which arise in myxomata and myxo- 
chondromata form cords of cells of different shapes (Fig. 222, b) ; but it 
should be noted that in these cases similar proliferations may arise from 
the blood-vessels (Fig. 274, c, d), so that it is often impossible to decide as 
to the nature of the cell-strands. ENDOTHELIOMA. 
331 
The alveolar, tubular, or plexiform structure of the endothelioma is 
well marked only in the first stages of the tumor, and usually disappears 
with advancing growth. This is due to the fact that the endothelial pro- 
liferation extends, without sharp limits, into the neighboring connective 
Fig. 270.— Endothelioma of the mammary gland (alcohol, hematoxylin, eosin).. a, Con- 
nective tissue; b, enlarged cells in the connective-tissue spaces; c, strands of cells; d, diffuse cell- 
proliferation. x 300. 
tissue (Fig. 268, /) ; and to the circumstance that the connective-tissue 
cells take on proliferative activity similar to that of the endothelium, so 
that there is formed a diffuse, cellular new growth of the character of an 
ordinary sarcoma (Fig. 270, d). Accordingly, endotheliomata cannot be 
sharply distinguished from sarcomata. 
Fig. 271.—Blood-vessel endothelioma of the V'dnev (formalin. Ivrmatoxylin, eosin). a, 
Vessels filled with blood; b, vessels filled with proliferated endothelial cells, x 300. 332 
TUMORS. 
The similarity in structure between endothelionrata and carcinomata raises the 
question whether it would not be expedient to class the former as endothelial cancers. 
The structure of these tumors would certainly justify such a classification, but I 
Fig. 272.— Section through a nodular angiosarcoma of the thyroid (Flemming’s solution, 
safranin). a, Transversely cut vessels; b, perivascular cylinders of cells cut transversely and 
showing numerous mitoses; c, granular masses, with scattered cells, between the cell-cylinders, 
x 73- 
consider it better to avoid the use of this term. In the first place, the term 
endothelioma is in general use and is entirely appropriate, and the introduction of 
the term endothelial cancer would easily give rise to confusion; by the term cancer 
Fig. 273.—Angiosarcoma of the testis (Muller’s fluid, haematoxylin, eosin). a, Perivascular 
masses of closely packed cells; b, areas poor in cells; c, hyaline lumps; d, hyaline masses con- 
taining blood; e, seminiferous tubules; f, large vein. X 80. H2EMANGIOSARCOMA. 
333 
in general is understood an epithelial tumor, and it does not seem desirable to 
introduce two types of cancer — an epithelial and an endothelial. 
I have classed as endotheliomata those tumors of the serous membranes which 
are characterized by the formation of cell-cords in the lymph channels, on the 
assumption that these arise from the endothelium of the lymph-vessels and lymph- 
spaces. I must admit, however, that I do not consider this assumption entirely 
justified, in spite of the concurring statements of a number of authors. The pos- 
sibility of their development from the epithelium of the serosa is not excluded 
Fig. 274.— Chondrofibroma of the parotid with angiosarcoma (Muller’s fluid, hematoxylin, 
eosin). a, Areas of cartilage; b, dense sarcoma tissue; c, blood-vessel; d, cell-strands arising 
from blood-vessels, and in part containing a hyaline substance, x 80. 
{Benda), and if such an origin could be proved, the question would arise whether 
it would not be better to class these tumors with the carcinomata, since the corre- 
sponding tumors of the kidneys and ovaries, whose gland-cells arise from peritoneal 
epithelium, are classed with the epithelial tumors. 
§ 115. The haemangiosarcomata represent a group of organoid sar- 
comata in which blood-vessels constitute a characteristic feature. 
One form of hsemangiosarcoma is the hemangioendothelioma, a tumor 
which arises, either from preexisting blood-vessels or from those newly 
formed in hemangiomata, active proliferation giving rise to blood spaces 
lined with cubical or cylindrical endothelium (Fig. 271, a), or to canals 
completely filled with such cells (&). According to the number of blood- 
containing vessels the tumor is dark-red, pale, grayish-white or yellowish- 
white. 
A second form of hemangiosarcoma (occasionally called peritheli- 
oma), arises through proliferation of the outer layers of the blood- 
vessel walls and their immediate surroundings, so that the vessel-lumina 
are surrounded by a more or less thick mantle of cells (Fig. 272, b). In 
typical cases the tumor-tissue consists almost wholly of a tangle of blood- 334 
TUMORS. 
vessels (Fig. 272, a), whose walls are banked by a thick layer of cells, 
which often reach to the endothelium. The cellular tubes sometimes run 
an isolated course, at other times anastomose, so that twistings and inter- 
Fig. 275.—(Bellevue Hospital.) Melanoma of instep. 
weavings result (plexiform angiosarcoma). Between the cell-strands the 
remains of the original tissue (Fig. 273, b) may retain characteristic 
formations, for example, glands (e). 
Should more active prolifera- 
tion of the perivascular mantle of 
cells occur, and if these become 
confluent (Fig. 273) the tumor 
passes into an ordinary sarcoma. 
This change almost invariably oc- 
curs in larger tumors of this kind. 
Flsemangiosarcomata occur in 
various organs: testicles, kidneys, 
salivary glands, bones, brain, 
mamma, thyroid, skin, carotid 
gland, coccygeal gland, ovaries, and 
liver. 
Lymphangiosarcomata and 
hsemangiosarcomata cannot always 
be sharply differentiated from each 
other, and tumors occur to which 
both designations may be applied 
with propriety. The perivascular 
endothelial proliferation in the sub- 
stance of the brain associated with 
endothelioma of the pia (Fig. 267, 
/, g, h) also justify the application of the term hjemangiosarcoma. 
Fig. 276.—Alveolar melanotic sarcoma of the 
skin (alcohol, haematoxylin). a, Mononuclear, 
ai,_ multi-nuclear sarcoma cells; b, pigment-con- 
taining cells; e, stroma with blood-vessels and 
pigment. X 300. 
Borst, in his work on tumors, has separated the endotheliomata (lymphangio- 
and hsemangio-endothelioma) from the sarcomata, and has attempted to class them 
as a special form of neoplasm. In so far as typical microscopic pictures are 
concerned, such a separation is possible, but the endotheliomata in general do not 
show so typical a structure that they can be distinguished from ordinary sarcomata. MELANOSARCOMA. 
335 
Further, it is by no means determined that endothelial cells of lymph spaces and 
vessels do not take part in the formation of sarcomata. It seems to me, therefore, 
better to consider the endotheliomata as a form of sarcoma. 
§ 116. Sarcomata which acquire a peculiar character through 
special products of the cells or through changes in their ground-sub- 
stance are to be found both among the simple and organoid forms. 
The chief types in this class are the melanosarcoma, osteosarcoma, osteoid 
sarcoma, the petrifying sarcoma, psammoma, and sarcomata containing 
hyaline formations. 
Melanosarcomata occur in tissues which contain pigmented connec- 
tive-tissue cells — chromatophores. They develop most frequently in the 
Fig. 277.—Melanotic sarcoma of the skin (alcohol, carmine, eosin). a, Sarcoma tissue rich 
in cells; b, cell-nests; c, pigment-cells; d, blood-vessels with hyaline walls, x 300. 
choroid of the eye and in the skin. In the latter situation they arise 
chiefly from pigmented moles. They belong to the malignant sarcomata, 
grow into neighboring tissues, and give rise to extensive metastases. The 
fully developed tumor is in whole or part smoky-gray, black or brownish- 
black, the color being due to the presence of round, angular, fusiform, and 
branched cells, which are filled with yellowish-brown pigment granules 
(Figs. 277, b, e; 278, c). In the alveolar forms both the large cell-nests, 
as well as the cells of the supporting framework, may contain pigment. 
It is often abundant in the neighborhood of the blood-vessels (Figs. 
276, e; 277, d), although the pigment is not hsemosiderin. 
The metastases are likewise more or less pigmented (Fig. 278) ; 
the smallest ones may consist largely of pigmented cells (c, d). Cases 
occur in which numerous organs, the skin, muscles, pia, serous mem- 
branes and adipose tissue (Fig. 278) are spotted black through the 
formation of metastases. 336 
TUMORS. 
There is scarcely an individual who does not possess one or more skin moles, 
and every skin mole is a potential source of a milignant melanoma. The mole is 
Fig. 278.— Metastasis of a melanotic sarcoma of the skin in the mesentery of the small in- 
testine (formalin, alum-carmine), a, Peritoneum; b, fat tissue; c, sarcoma nodule; d, isolated 
chromatophores. X 280. 
a vice of development characterized, even in the resting state, by a histological 
grouping of chromatophores that bears a striking resemblance to a malignant 
Fig. 279.— Endosteal osteosarcoma of the humerus. (Formalin, nitric acid, hematoxylin, 
and eosin). a, Old bony trabecule of the spongiosa; b, sarcomatous proliferation arising from 
the endosteum; c, Ci, new-formed bone; d, blood-vessel. X 80. MELANOSARCOMA. 
337 
tumor. In fact, the number, formation and chromatic richness of the cells in 
many instances are such that a given microscopic field (Fig. 245) might readily 
be mistaken for a tumor with established malignant qualities instead of an appar- 
Fig. 280.—Sarcoma ossificans. (Formalin, nitric acid, hcematoxylin, and picrofuchsin.) 
a, Sarcoma tissue; b, new-formed bone; c, areas of transition, x 40. 
ently trivial congenital malformation of the skin. If left alone the skin mole may 
never occasion trouble, in fact, the vast majority maintain an attitude of innocent 
quiet. If, however, it is exposed to frequent irritation or, as not infrequently hap- 
Fig. 281.— Osteoid sarcoma of the ethmoid bone (Muller’s fluid, hrematoxylin, eosin). a, Sarcoma 
tissue; b, osteoid tissue; c, old bone-trabeculx; d, vascular fibrous tissue, x 45. 
pens, it is deliberately subjected to ligation, escharotics, caustic salves, and the 
like, either at the hands of the host himself or of ignorant meddlers, it may develop 
into a growth of surpassingly vicious qualities. Moreover, malignant transformation 338 
TUMORS. 
may occur soon after interference, or it may be postponed for months or years- 
In one of the Bellevue Hospital cases general melanomatosis followed the removal 
of a skin mole after the lapse of thirteen years. In other words, the skin mole 
should be left to its own devices, or, if removal is considered advisable, it should 
be done by a surgeon at the sacrifice of a considerable sweep of apparently healthy 
skin and subcutaneous tissue. 
Osteosarcomata or ossifying sarcomata occur chiefly in connec- 
tion with the skeleton and are characterized by the formation of bone in 
sarcomatous tissue. The new bone arises at times from a homogeneous 
Fig. 282.—Petrifying large-cell sarcoma of the tibia (Muller’s fluid, hematoxylin, eosin). 
a, Polymorphous tumor-cells; b, alveolar stroma; c, trabecule of stroma containing small calcareous 
concretions; d, petrifying trabeculae of the stroma. X 330. 
ground-substance Fig. 279 (c, cx) formed between the tumor-cells (b) 
which is either connected (q) with the old bony trabeculae (a) or arises 
independently (c), or at other times from coarsely fibrillated connective 
tissue (Fig. 280, c) which gradually becomes condensed (b) and, taking 
up lime-salts, is transformed into 
bone. 
Osteoid sarcomata develop in 
the endosteum and periosteum, and 
are characterized by thickening of 
the ground-substance in certain 
areas, forming trabecula of osteoid 
tissue (Fig. 281, b). Such tumors 
are closely related to the osteosar- 
comata, but differ from them in the 
absence of lime-salts. 
Petrifying sarcomata likewise 
occur most frequently in connec- 
tion with the skeleton, and are char- 
acterized by the development be- 
tween the tumor-cells of a ground- 
substance (Fig. 282, c), through 
calcification (d) of which the tumor 
tissue becomes hardened, although 
no typical bone is formed. 
Fig. 283.—Section from a psammoma of the 
dura mater (alcohol, picric acid, haematoxylin, 
eosin). a, Hyaline nucleated spherule inclosing 
calcareous concretion; b, calcareous concretion 
with hyaline non-nucleated border, inclosed in 
fibrous connective tissue; c, calcareous concretion 
surrounded by hyaline connective tissue; d, 
spicule of lime in the connective tissue; e, spicule 
with three concreitions. X 180. PSAMMOMA. 
339 
Psammomata or sand tumors are sarcomata or fibro-sarcomata of 
the dura, inner meninges, or pineal gland, which contain concretions of 
lime-salts in greater or less abundance. Some of these concretions are 
Fig. 284.— Myxo-angiosarcoma of the parotid, with hyaline formations (Muller’s fluid, hae- 
matoxylin, eosin). a, Myxomatous tissue; b, cell-strands inclosing hyaline spherules; c, hyaline 
spherules in myxomatous tissue; d, blood-vessels with proliferating endothelium and hyaline 
spherules. X 90. 
similar in structure to the normal brain-sand, the basis of their formation 
being concentric layers of cells which have previously undergone hyaline 
degeneration (Fig. 283, a, b, c). Occasionally the chalky spherules lie 
inside individual cells and represent hyaline products of the cells that 
Fig. 285.— Papillary epithelioma or ichthyotic wart of the skin (Muller’s fluid, haematoxylin, 
eosin). a, Corium; b, enlarged papillary body; c, laminated horny layer, x 25. 
have become calcified. Others are of the nature of spicules (d), and 
arise through the deposit of lime-salts in connective tissue or blood- 
vessels which have undergone hyaline degeneration. 
Psammomata usually form round nodules, and are often multiple. 340 
TUMORS. 
Sarcomata with hyaline formations (the myxosarcomata excepted) 
arise as follows: Either the cells form hyaline products, or they them- 
selves become converted into such, or the fully developed connective 
tissue and the blood-vessels undergo hyaline degeneration. These changes 
may take place in simple sarcomata as well as in endotheliomata and 
haemangiosarcomata; but occur more frequently in the latter (Figs. 280, b; 
274, d; 284). The hyaline masses form spherules, or club-like forms, or 
cords, or net-like or cactus-like figures. They push the cells apart, and 
often reduce them to narrow strands. Billroth has designated such 
Fig. 286.—(Bellevue Hospital.) Papillary epithelioma of back. 
tumors cylindromata. In endotheliomata hyaline degeneration may be 
associated with the formatin of laminated masses of flattened cells around 
a nucleus, like the layers of an onion. 
Hyaline degeneration of the vessel-walls and connective-tissue bundles 
results in thickening, (Fig. 277, d), sometimes uniformly and some- 
times irregularly distributed. Hyaline products of cells have a tendency 
to assume spherical form (Figs. 269, b; 274, d; 284, c, d). The disintegra- 
tion of larger cell-masses with hyalinisation leads to the formation of 
spherules, strands, or branching structures. 
If, in endotheliomata and angiosarcomata, the cord-like masses of 
cells in the lymph- or blood-vessels become converted into hyalin, struc- 
tures arise which resemble glands containing colloid (Fig. 284, d) and 
have often been mistaken for such. THE EPITHELIAL TUMORS. 
341 
2. The Epithelial Tumors. 
(a) General Remarks. 
§ 117. The epithelial tumors are new growths in the formation of 
which vascular connective tissue and cells derived from surface or 
glandular epithelium take part. The distribution of epithelium and con- 
nective tissue follows, in a general way, the normal arrangement of 
these tissues, the connective tissue forming a basement structure covered 
with epithelium (skin and mucous membranes), or a stroma, in the 
meshes of which the epithelial cells are distributed in gland-like array. 
The imitation of skin structure leads to the formation of papillary 
new-growths; that of mucous membrane, to more of less sharply cir- 
cumscribed nodules or to extensive superficial thickenings of tissue. 
Fig. 287.— Senile horny wart of forehead, from a woman eighty-four years of age (alcohol, 
haematoxylin, eosin). a, Corium; b, epithelium; c, atrophic sebaceous glands with development 
of horny epithelium in their ducts; d, hypertrophic horny layers; e, enlarged papillae, x 15. 
According to the physical characteristics and arrangement of the epi- 
thelial cells, as well as the clinical behavior of these tumors, epithelial 
new-growths may be divided into two groups; one including papillary epi- 
theliomata, adenomata, and cystadenomata; the other carcinomata and 
cystocarcinomata. The first group is characterized clinically by the 
benign character of the growths, which are sharply circumscribed and 
form no metastases. The second group includes new-growths which in- 
filtrate and give rise to metastases. The two groups, however, are not 
sharply separated, as papillary epitheliomata and adenomata may, through 
changes in the mode of reproduction and spread of the epithelial cells, 
become changed into carcinomata. 342 
TUMORS. 
(b) Papillary Epithelioma, Adenoma, and Cystadenoma. 
§ 118. A papillary epithelioma is a new-growth composed of a 
framework of connective-tissue papillae covered with epithelial cells. In 
structure, therefore, it is similar to the papillae of the skin; but the papillae 
are, as a rule, higher and often branched, and the epithelial covering 
thicker. 
The papillary epithelioma of the skin occurs in the form of warty 
protuberances, which consist of slender papillae (Fig. 285), covered with 
epithelium, the superficial layers 
of which show marked cornifica- 
tion (ichthyotic warts and horny 
warts). These warts may ap- 
pear during childhood (ichthy- 
otic warts) or in old age (ver- 
Fig. 288.— Papillary epithelioma of the larynx, a, Epiglottis; b, ossified cricoid cartilage; c, 
thyroid cartilage; d, trachea; e, f, papillary proliferations. Natural size. 
Fig. 288. 
Fig. 289. 
Fig. 289.—’Papillary epithelioma of the urinary bladder, a, Epithelioma; b, c, enlarged prostate; 
d, thickened bladder-wall. Five-sixths natural size. 
ruca senilis'). The first-named represents a local malformation of the 
skin (Fig. 285) ; while the latter is due to pathological proliferation and 
cornification of the epithelium (Fig. 287, c, d) followed by outgrowth of 
the papillae at the periphery. Excessive cornification o>f epithelium over 
hypertrophic papillae, giving rise to cylindrical or conical masses of cells 
in which the horny layers lie at right angles to the surface, leads to the 
formation of a cutaneous horn or cornu cutaneum (Figs. 112, 113). EPITHELIOMA. 
343 
Papillary epitheliomata of mucous membranes occur as warty, nodu- 
lar formations (Fig. 288, e, /), or as long, slender papillary excrescences 
(Fig. 289, a), which, springing from a narrow base, are often repeatedly 
branched. The former variety is found especially in the larynx, more 
rarely in the nose and urinary bladder; the latter in the urinary bladder 
and pelvis of the kidney, vaginal portion of the uterus, and rarely in the 
ureters, gall-bladder, and biliary passages. 
In both varieties the excrescences are formed of slender, connective- 
tissue papillae (Fig. 290) which contain blood-vessels, and are covered 
by a thick layer of epithelium the character of which corresponds in 
Fig. 290.—’Papillary epithelioma of the urinary bladder (alcohol, hsematoxylin, eosin). x 35. 
general to that of the part in which the growth occurs, although papillo- 
mata covered with stratified squamous cells are sometimes seen in regions 
that normally possess cylindrical epithelium (nose, trachea). 
Papillary epitheliomata in cysts, or so-called papillary cystomata, 
occur most frequently in cysts of the ovary and of the mammary gland, 
more rarely in the skin. Within the cyst are formed small, warty ele- 
vations or cauliflower-like outgrowths, which may fill the entire cyst- 
cavity. 
Papillary epitheliomata of the surface of the ovary appear in forms 
similar to those of the urinary bladder, but are rare. Papillary epithelio- 
mata of the cerebral ventricles rise in part from the telse choroidese. 
It is difficult to draw a line between papillary epitheliomata and other 
formations. Inflammatory proliferations of the skin and mucous membranes — 
pointed condylomata—which develop on the external genitals under the influ- 
ence of chronic irritation (compare Fig. 246), so closely resemble epitheliomata 
that their inflammatory origin forms the only point of difference. If the con- 
nective-tissue framework of the papillary outgrowth is developed to a greater 
extent than the epithelium, the tumor may be classed with the papillary fibro- 
mata, and it becomes a question of individual standpoint as to which designa- 
tion shall be employed. Intermediate forms can be designated as papillary 
fibroepitheliomata. Finally, the benign papillary epitheliomata may pass into 
carc'nomata. either through the growth of epithelium at the base of the papillae 344 
TUMORS. 
into the underlying connective tissue, or through extension of the proliferating 
surface epithelium into neighboring organs (as in the papillary epitheliomata of the 
ovary). 
Among the epitheliomata may be classed those formations known as 
cholesteatomata or pearl tumors, which in part are caused by inflammation, and 
in part represent misplaced embryonal tissue. The most striking characteristic 
of the cholesteatoma is the formation of glistening white pearls, which consist 
of thin, scale-like epithelial cells pressed closely together, and which often 
inclose cholesterin. These tumors are found most frequently in the descending 
urinary passages, the cavities of the middle ear, and the pia of the brain; rarely 
in the spinal cord. 
Pathological cornifications, with the formation of glistening white scales 
and pearls, occur in the urinary passages, particularly in the course of chronic 
inflammations. In the tympanic cavity, mastoid antrum, and external auditory 
canal, the cholesteatomata appear as yellowish-white or bluish-white nodules, vary- 
ing in size from a cherry-stone to that of an egg, and presenting an onion-like 
laminated structure. Through pressure on neighboring bone they may cause its 
disappearance. In chronic inflammatory conditions they arise as a product of 
squamous epithelium which has penetrated from the external ear through openings 
in the ear-drum into the cavities of the middle ear and has replaced the cylindrical 
epithelium. It is probable that in rare cases they arise from epidermoidal cells 
which during the period of embryonic development have found their way into the 
cavities in question. 
The intracranial cholesteatomata are found at the base of the brain (rarely in 
the spinal canal), in the region of the olfactory lobe, tuber cinereum, corpus cal- 
losum, in the choroid plexus, in the pons, medulla oblongata, and cerebellum. In 
these regions the cholesteatomata appear on the surface as silk-like, shining nodules 
of varying size which extend more or less deeply into the brain-substance. The 
nodules are single, but cholesteatoma-masses may become separated and be displaced 
into neighboring tissue. According to Bostrom, it is always possible to demonstrate, 
at some point, a connection between the pia and the cholesteatoma, where the 
scales composing the cholesteatoma take their origin from a cell-layer lying on 
vascular connective tissue, the cells throughout bearing the character of epidermoidal 
cells. The cholesteatomata of the pia may therefore be designated as epitheliomata 
or as epidermoids (Bostrom) ; and their origin may be explained by the assumption 
that in the early period of development epidermal germs are misplaced into the 
primordium of the pia. 
§ 119. The adenomata are usually nodular tumors with sharply de- 
fined borders; and are situated in glands, or in the skin or mucous mem- 
branes. In the latter situations they frequently appear as polypi elevated 
above the surface. They may also occur in the form of papillary pro- 
liferations (Fig. 211). The absence of any tendency to grow by infiltra- 
tion or to produce metastases stamps these tumors as benign. 
The chief characteristic of the adenoma is the formation of new 
glands, which depart more or less from the typical glands of the affected 
organ. According to their structure adenomata may be classed as tubular 
or acinous; but the two forms cannot be sharply separated. Through the 
formation of papillary excrescences on the inner walls of the gland- 
spaces there is formed an adenoma papilliferum. Adenomata develop in 
apparently normal tissue, malformed tissue, in tissues altered by disease 
(chronically inflamed mucous membrane, cirrhotic liver, contracted kid- 
ney), or from remains of foetal structures. The new-formation of glands 
is dependent on proliferation of glandular epithelium similar to that occur- 
ring in regeneration of normal gland-tissue. The beginning of the 
adenomatous process may be recognized by changes in the form and 
staining, of the cells. This is particularly true of the stomach and in- 
testine, in which adenomatous proliferations often develop in connection 
with chronic inflammatory and ulcerative processes. The change of 
normal gland-cells into high cylindrical cells may occur contemporane- ADENOMA. 
345 
ously or successively in a number of glands and is followed by cell-pro- 
liferation and new-formation of glands. 
The cause of the new-formation of gland-tissue in normal organs is 
Fig. 291.—Adenoma tubulare (glandular polyp) of the intestine ('alcohol, alum-carmine) 
a, Transverse section, b, longitudinal section of gland-tubules; c, stroma rich in cells, x 90. 
unknown. Glandular new-formations developing in tissues which have 
been altered by inflammation, and which lead to tumor-like growths, may, 
in the beginning, bear the character of a regenerative or hyperplastic new* 
Fig. 292.—Adenoma tubulare of the stomach in an atrophic mucosa (formalin, alcohol, hsema- 
toxylin, eosin). a, Mucosa; b, muscularis mucosae; c, submucosa; d, muscularis; e, serosa; f, 
adenoma. X 14. 
formation, and for this reason the adenomata cannot be sharply differ- 
entiated from regenerative and hyperplastic proliferations. 
Tubular adenomata represent the most common form. They occur 346 
TUMORS. 
particularly in mucous membranes (Fig. 291,292,/) provided with tubular 
glands (intestine, uterus) ; but are also found in the breast (Fig. 293), 
liver, ovary, and not infrequently in the kidneys. They are characterized 
Fig. 293.—Adenoma mammae tubulare (alcohol, alum-carmine), a, P>ranched and dilated glandular 
spaces cut longitudinally; b, same, cut transversely; c, stroma. X 27. 
by the formation of simple and branched tubules (Figs. 291, a, b; 292, f; 
293, a, b) lined by columnar or cubical epithelium and form nodular 
tumors varying in size from a pea to that of an apple or a man’s fist, or 
even larger. 
Fig. 294.'—Adenoma mammae alveolare (alcohol, alum-carmine), a, Terminal alveoli; b, gland- 
ducts; c, connective-tissue stroma. X 27. 
The alveolar adenomata arise from glands (mamma, ovary, thyroid, 
sebaceous glands) ; and are characterized by the formation of numerous 
terminal berry-like alveoli (Fig. 294, a), as well as ducts (b). ADENOMA. 
347 
Papillary adenomata (Fig. 295, a) arise through the formation in 
the tubules of an adenoma of elevations of epithelium into each of 
which a connective-tissue papilla grows. 
Fig. 295.— Developing papillary adenoma of the kidney. (Alcohol, haematoxylin, picrofuchsin.) 
a, b, Fully developed tumor-tissue; c, d, early stages of development of the tumor, x 150. 
Fig. 296.— Fibroma intracanaliculare mammae (fibro-adenoma papilliferum) (alcohol, alum- 
carmine). a, Dense, intercanalicular growth of fibrous tissue; b, pericanalicular tissue rich in 
cells; c, d, e, nodular intracanalicular connective-tissue proliferations cut longitudinally; f, intra- 
canalicular proliferations cut transversely. X 23. 348 
TUMORS. 
The stroma of an adenoma is at times well developed, at other times 
but slightly. Consequently adenomata may be divided into hard (mam- 
mary gland) and soft varieties (kidney, liver, ovary, testicle). Marked 
development of the connective tis- 
sue leads to the formation of fibro- 
adenomata or fibrous adenomata. 
Such forms occur most frequently 
in the mammary gland. 
If, as happens not infrequently 
in the mammary gland, the con- 
nective-tissue proliferation in an 
adenoma is not of diffuse character, 
but takes place more particularly 
around the canaliculi (see Fig. 
220), the tumor is designated 
fibroma pericanaliculare. If, as the 
result of more marked local pro- 
liferative activity on the part of the 
connective tissue (Fig. 296, c, d, 
e), an ingrowth of papillae (c) 
into the gland-spaces takes place, 
the resulting tumor is known as a 
fibroma intracanaliculare. 
Fig. 297.—Section of a cystadenoma ovarii pa- 
pilliferum (Muller’s fluid, hsematoxylin). x 40. 
Adenomata cannot be sharply differentiated from tumor-like glandular hyper- 
trophies on the one hand, and carcinomata on the other. For example, in the heal- 
ing of intestinal ulcers regenerative processes in the glands may be so active as 
to give rise to polypoid formations, which may be called glandular hypertrophies 
or adenomata, according to the individual standpoint. Likewise, different names 
may be applied to the glandular polypi which occur so frequently in the uterus. 
Fig. 298.—-Adenocystoma of the bile-passages in the first stages of development (alcohol, hsema- 
toxylin). a, Liver tissue; b, adenoma tissue in the periportal connective tissue, x 90. CYSTADENOMA. 
349 
The carcinomatous nature of a new-growth resembling an adenoma (see § 121) 
is generally made evident by more marked epithelial proliferation and by infiltrative 
growth. There are, however, adenomata having a single layer of columnar cells, that 
grow by infiltration (particularly in the intestine), and assume the character of 
malignant tumors. They should accordingly be classed with the carcinomata, and 
must be designated adenocarcinoma. On the other hand, there are also adenomata 
with marked atypical epithelial proliferation (mamma, endometrium), which — 
for a long time at least — do not show any malignant characteristics. 
§ 120. A cystadenoma or adenocystoma is an adenoma zvhose gland- 
spaces have undergone cystic dilatation through the accumulation of secre- 
tions. Such tumors are usually composed of numerous cysts, and are, 
therefore, designated multilocular cystomata. According to the char- 
acter of the wall there may be distinguished a simple and a papilliferous 
cystoma. 
Small amounts of secretion are often seen in the ordinary adenomata 
Fig. 299. 
Fig. 300. 
Fig. 299.— Section of a portion of a multilocular adenocystoma of the ovary. Reduced about 
one-sixth. 
Fig. 300.— Section through an adenocystoma of the testis of a four-year-old boy. Natural size. 
(Fig. 291), and the spaces of both simple and papillary adenomata are 
often so wide (Figs. 293, a; 296) that they attract the eye on cross-section 
of the growth. In cystadenomata cyst-formation is the predominating 
feature. 
The early stages of the cysts are represented by gland-tubules of vary- 
ing shape (Figs. 297 and 298, b), that lie in a more or less richly de- 
veloped connective-tissue stroma. Through the accumulation of secre- 
tion these tubules become gradually dilated so that numerous small cysts 
(Fig. 297), or both large and small cysts (Figs. 300-303) are formed. 
Often the relationship is such that the tumor may consist of a few large 
cysts in which smaller cysts occur; or there may be found, by the side of 
large cysts, (Fig. 301, c) portions of tissue which contain only small 
cysts (e) or even appear solid — that is, consisting of tissue the glands 
of which are not dilated. 350 
TUMORS. 
All the different varieties of cystomata may develop in the ovaries 
(Fig. 299), testicles (Fig. 300), liver (Figs. 298 and 301), kidneys 
(Fig. 302), and the mammary glands. 
In the ovaries cystomata not infrequently develop coincidently on 
both sides, and may be associated with dermoid formations. Adenocys- 
tomata of the testicles not infrequently inclose in their stroma foci of 
cartilage or other tissue, so that such growths should be classed with 
the teratomata (§ 128). 
The epithelial lining of cystomata is usually composed of simple colum- 
nar cells, but may be ciliated, cubical, or flattened. 
The cyst-contents usually consist of clear, often ropy fluid, which con- 
tains a mucin-like substance (pseudomucin, see § 59). This is a product 
Fig. 301.— Multilocular adenocystoma of the liver, seen in section, a, Liver parenchyma; b, 
membranous margin of the left lobe; c, d, large cysts; e, group of smaller cysts, separated from 
each other only by connective tissue; f, portal vein; g, hepatic artery. Two-thirds natural size. 
of the epithelial lining in which goblet-cells are found (Fig. 304, c). Not 
infrequently the fluid contains whitish flakes, the products of cells which 
have undergone fatty degeneration; or it may be more or less reddish 
or brownish from previous haemorrhage. Abundant secretion in multiple 
cysts may lead to tumors of enormous size; in the ovary, for example, 
they may reach a weight of from ten to twelve kilograms or more. 
The papillary adenocystomata constitute a common variety. They 
are characterized by the fact that sooner or later papillary excrescences 
develop in glands which have undergone cystic dilatation. 
In the adenocystomata of the ovary such excrescences are usually 
slender and delicate, forming villous-like (Fig. 303) or cauliflower 
elevations, which fill a larger or smaller part of the cysts. Minute papil- 
lary elevations, extending over an extensive area of the inner surface 
of the cyst-wall, may give to the latter a velvety appearance similar to that CYSTADENOMA. 
351 
of a mucous membrane. If the excrescences develop in cysts of small 
size, they may fill these, and the tissue may take on the appearance of a 
medullary tumor. 
Larger papillse are always more or less branched (Fig. 304), and 
consist of a cellular stroma (a), whose surface is covered with tall cells 
(c) of the character of goblet-cells. The contents of the cysts consist of 
ropy mucus (d) mingled with desquamated cells which have undergone 
mucous degeneration. In rare cases the connective tissue of the papillse 
Fig. 302.— Cystoma of the kidney, cut transversely. Eleven-fourteenths natural size. 
may undergo mucous degeneration (Fig. 305, a, b), and swell to a marked 
degree, and finally become changed into myxomatous spheres covered with 
epithelium. 
Adenocystomata of the liver, testicles, and kidneys usually form no 
papillse, or at most small ones. In the papillary adenocystomata of the 
mammary gland the excrescences are broad a«d plump (Fig. 306), as 
are those of the papillary adenomata (1H ig. 296). Accordingly, on cross- 
section the cyst-spaces are found to be filled with polypoid proliferations 
of various forms (Fig. 306), which are flattened through mutual pres- 
sure, and give to the cut surface a laminated appearance. 
Since in these tumors the connective-tissue elements predominate over 
the epithelial, these growths are often classed with the connective-tissue 
tumors, and designated, according to the character of the connective 
tissue, cystofibroma, cystomyxoma, or cystosarcoma. When showing a 
structure of leaf-like layers they receive the name of sarcoma phyllodes. 352 
TUMORS. 
The papillary adenocystomata show a certain degree of malignancy. 
The papillary proliferations may break through the cyst-wall in such 
tumors of the ovary and mammary gland; in the latter situation they may 
break through the skin. Papillary ovarian cystomata in this way give 
rise to metastases in the peritoneal cavity. 
Polycystic degeneration of the kidneys is an affection which leads, during 
embryonal development, to the formation of innumerable cysts throughout both 
organs, and frequently is associated with the presence of cysts in the liver and 
other anomalies of growth. The occurrence of renal cysts in these circumstances 
is apparently due to the fact that the kidney is developed from two primordia, one 
giving rise to the glomeruli and convoluted tubules and the other to the straight 
and collecting tubules. Failure of the two primordia properly to unite permits 
cystic distention of the glomerular capsule and of the convoluted tubules. 
Fig. 303.—Portion of a papillary adenocystoma of the ovary, seen in section. (Drawn from a 
specimen hardened in chromic acid.) Four-fifths natural size. 
In one group of cases polycystic degeneration of the kidneys is encountered 
during intrauterine life and there are instances in which distention of the cysts had 
reached such a stage as to interfere with birth. In another group of cases the child 
is born with well developed polycystic kidneys and dies shortly after birth. In 
still another group, however, the individual attains adult life. The condition is not 
common. For example, in 6,500 autopsies at Bellevue Hospital, polycystic degen- 
eration of the kidneys was encountered in four cases only. All of them were in 
adults. It seems that in certain cases the individual is born with cystic kidneys in 
which the amount of secreting substance, however, is compatible with life, but 
that, as time goes on, the gradual distention of the cysts so reacts on the inter- 
vening kidney tissue as to cause pressure atrophy. In the Bellevue Hospital cases, 
the patients, toward the end, passed remarkably small quantities of urine and died 
with symptoms of uraemia. Histologically, polycystic degeneration of the kidneys 
may, I think, be classified among the cyst-adenomata. 
(c) Carcinoma and Cystocarcinoma. 
§ 121. The carcinomata are malignant epithelial tumors characterized 
by infiltrative growth and the formation of metastases. 
They develop: 
(1) In skin, mucous membranes and glands, all of which appear pre- 
viously to be normal. CARCINOMA. 
353 
(2) In skin, mucous membranes, and glands, which have already suf- 
fered changes. 
(3) In papillary epitheliomata, adenomata and adenocystomata. 
(4) From the remains of foetal epithelial structures, and from epi- 
thelial tissues which have been misplaced through disturbances of de- 
velopment, and have already developed into pathological formations. 
(5) From the epithelial tissues of the chorionic villi and placenta. 
The outstanding characteristic of a carcinoma is represented by atypical 
proliferations of epithelium which sooner or later penetrate the bor- 
dering tissue. This phenomenon is usually accompanied by proliferation 
Fig. 304.— Cystoma papilliferum ovarii (Muller’s fluid, hasmatoxylin, eosin). a, Stroma with 
papillae; b, gland-tubule with small papillae; c, high cylindrical epithelium; d, mucus-containing 
cells, within the cyst-spaces, x 150. 
of connective tissue. The invaded tissue is sooner or later destroyed by 
the growth. In the stroma of the carcinoma there may occur new-forma- 
tion of other tissue, for example, bone. 
The cause of the atypical growth of epithelium is not known; it 
can only be said that certain conditions favor such growth. For example, 
old age predisposes to the development of carcinomata of the skin, inas- 
much as in this period of life the connective tissue of the skin undergoes 
atrophy and becomes looser in structure, while the epithelium, at least 
in part, continues to increase (formation of coarser hairs on the nasal 
septum, lobes of the ears, and in the eyebrows). Likewise carcinomata 
of mucous membranes and glands usually appear in later years, although 
they may occur earlier in life, even in childhood. 
A further predisposition to the development of carcinoma is found in 
regenerative processes following the destruction of surface epithelium and 354 
TUMORS. 
glandular tissue. These occur most frequently in old inflammatory proc- 
esses, particularly in the mucous membrane of the intestinal tract, gall- 
bladder, and uterus, and in glands and in the skin. In the stomach the 
round ulcer may form the starting-point of a cancer. In the first place 
the regenerative proliferations following injury may form the basis 
for malignant proliferation. In addition an important role is played by 
snaring-off and misplacement of epithelial cells into the neighboring 
altered connective tissue, as in the healing of ulcers, the growth of epi- 
thelium over granulation-tissue, and in tuberculosis, and other chronic 
infective granulomata, both in the mucous membranes and skin and in 
glands. 
These predisposing factors may exist for a long time without giving 
rise to cancer. Something else must be added to cause unlimited atypical 
Fig. 305.— Papillary adenocystoma of the ovary with myxomatous degeneration of the con- 
nective tissue of the papillae (Muller’s fluid, haematoxylin). a, Fibrous stroma; b, papillae which 
have undergone myxomatous change; c, epithelium, x 80. 
proliferation of epithelium, and what this something is is unknown. 
Whether to be found in a bioplastic stimulus comparable to that of fertili- 
zation, or in chemical influences, or in the removal of influences that 
inhibit and regulate proliferation, cannot be stated. 
In recent years the opinion has been advanced that parasites cause 
carcinomatous and sarcomatous proliferations. But the majority of 
forms described as parasites (protozoa, especially sporozoa, and yeast- 
fungi) are not parasites at all, but degenerated nuclei and nuclear 
division-figures, or leucocytes inclosed in tumor-cells, or degeneration- 
products of such, or of cell-protoplasm, particularly keratohyalin and 
colloid, or epithelial hyalin and mucin. In the few cases in which true 
parasites are present in the tissues, this occurrence could well be a sec- 
ondary infection, in no way to be regarded as a cause of the tumor. In 
not a single case has it been proved that parasites are the cause of either 
carcinoma or sarcoma. 
Certain portions of the intestinal tract—the rectum, the flexures of the 
colon, the pylorus and cardia of the stomach, the oesophagus, pharynx, CARCINOMA. 
355 
tongue, and gums — are favorite seats for the development of cancer. 
Cancer may develop in any portion of the skin, but occurs more frequently 
on the lips and nose than on the remaining portions of the face; on the 
extremities, more frequently than on the trunk. Of the sexual apparatus 
the parts most commonly affected are the mammary gland and cervical 
portion of the uterus; less frequently, though relatively often, the ovary, 
testicles, body of the uterus, vulva, vagina, and penis. The liver, kidneys, 
bladder, trachea, bronchi, lungs and pancreas occupy a middle ground; 
while the larynx and gall-bladder are frequently affected. 
Cancer usually develops in the form of nodules, which are not sharply 
Fig. 306.— Papillary systoma or intracanalicular papillary fibroma of the breast, laid open by a 
longitudinal incision. One-half natural size. 
differentiated from the neighboring tissues; on the mucous membranes 
they are not infrequently elevated in the form of sponge-like, polypoid, 
or papillary grozvths. From the point of origin they spread by infiltrative 
growth of epithelial prolongations, and the nodules increase in size or 
there are formed diffuse superficial thickenings, as in the intestinal wall. 
The ovaries, testicles, uterus, kidneys, etc., may be partly or wholly, 
transformed into carcinomatous tissue. Often the boundaries of the 
organ originally affected are overstepped, and the epithelial infiltration ex- 
tends into neighboring tissues and organs. Thus, carcinoma of the 
mamma may infiltrate neighboring fat, skin, and muscle; carcinoma of the 
gums, the maxillary bone; carcinoma of the uterus, the vagina, para- 
metrium, bladder, and rectum; cancer of the gall bladder may involve the 
liver; one of the thyroid, the trachea; and one arising in the bronchi, 
the lungs, etc. 356 
TUMORS. 
The formation of metastases may take place through the lymph- or 
blood-vessels, and is of frequent occurrence by both routes. It leads to 
the development of secondary nodules in different organs; but it may 
happen that large lymphatic areas — for example, the lymphatics of the 
lung—'may be dilated by the new-growth, without the formation of cir- 
cumscribed nodules. The transportation of cancer-cells to the bone- 
marrow may lead to carcinomatous transformation of the marrow of an 
entire bone or of several bones. However, it should be noted that 
probably not every transportation of cancer-cells is followed by the de- 
velopment of a cancer, but that many transplanted cells die. 
The tissue of a carcinoma is sometimes white and soft, sometimes 
Fig. 307.—(Bellevue Hospital.) Rodent ulcer of forehead. 
firm and dense; but it is almost always possible to obtain from the cut 
surface whitish, cloudy fluid called cancer juice. Often the cut surface 
presents a tough, fibrous framework in the meshes of which the softer 
masses lie; and from which the latter may be squeezed out in the form of 
plugs or crumb-like masses which consist of atypically proliferating epi- 
thelial cells, so-called cancer-cells, which are found in a great variety 
of forms, and usually show degenerative changes, particularly fatty de- 
generation. A true secretion of cancer cells is usually not found; but 
cancers occur — particularly in the mucous membranes, ovaries, mammary 
glands, and thyroid — which produce mucin, pseudo-mucin, or colloid. 
The amount of secretion may be so abundant as to lead to the formation 
of cystocarcinoma. 
Retrograde changes often occur in cancers at an early stage. They 
are caused by the feeble vitality of the new growth, by circulatory dis- 
turbances, which may be due to filling of capillaries and veins by cancer- 
cells, and by external causes. These changes lead to destruction of certain 
portions of the tumor and the formation of cavities due to lique- CARCINOMA. 
357 
faction of the dead portions, so that, after resorption, the tissues sink 
in. Such depressed areas are seen particularly in cancer-nodules in the 
mammary gland, and in secondary nodules in the liver, lungs, and other 
organs, and are spoken of as umbilications. 
Retrograde changes often lead to destruction of tumor-tissue, and to 
the formation of ulcers. This occurs particularly in cancers of mucous 
membranes, but may also take place in carcinomata of the mammary 
glands and skin. In the latter situation the cancer may take on the appear- 
ance of a rodent ulcer. The edge of such ulcers is sometimes elevated and 
studded with nodules; at other times it is sharply defined and only 
slightly infiltrated. The base of the ulcer is sometimes fissured and 
ragged, and covered with necrotic tissue; at other times it is smooth. 
(Fig. 307.) 
Fig. 308.— Transverse section through a carcinoma of the lip (alcohol, haematoxylin, eosin). 
a, Corium, in a state of proliferation; b, epithelium; c, thickened horny layer; d, epithelial plugs 
extending into the corium; e, epithelial plugs with horny pearls, cut obliquely; f, enlarged papillae. 
X 12. 
The view that the cause of carcinoma and sarcoma is to be found in para- 
sites still finds adherents, although the investigations of recent years do not 
support it. Publications concerning cancer and sarcoma parasites have not been 
wanting, but in the majority of cases proof has been wanting that the supposed 
parasites were really living organisms; or, when living organisms (yeasts, 
rhizopods) have been cultivated from tumors, there has been no positive pi oof 
that they stood in causal relation to the neoplasm. The experiments, in particular, 
of Sanfelke, Wlaeff, Leopold, and Sjobring are far from convincing. 
It is worthy of note that nearly every author has found a different parasite 
and has not recognized the parasitic forms described by the others. This speaks 
against the interpretation of the findings. Moreover, in the majority of the forma- 
tions described as parasites another interpretation is possible. Some of them are 
degenerating leucocytes or the remains of such enclosed in cancer-cells; others are 
vacuoles, hyaline or mucoid products of the cancer-cells, or degenerating nuclei 
or cell-division figures, or fragments of these. Only rarely is it impossible to give 
a satisfactory interpretation of the findings, but this fact is not sufficient for 
ascribing a parasitic nature to the formations. The attempt to compare the “bird’s 
eyes ” of von Leyden, or the Plimmer’s bodies, to which they correspond, with the 
parasite found in the root-tumors of cabbage, the Plasmodiophora brassiere, and to 
regard these root-tumors as analogous to cancer, is, likewise, without justification, 
since the two diseases have scarcely anything in common. The plasmodiophora 
multiplies within the plant-cells and distends the latter. Only after the destruction 
of the affected cells does regenerative proliferation occur in neighboring cells. In 
cancer there is from the beginning an unlimited and infiltrative growth of tissue- 
cells. 
The natural history and clinical behavior of cancer are not such as to make it 
probable that it is of parasitic nature. The formation of cancerous tumors as a 358 
TUMORS. 
result of disturbances of development speaks against this view. The metastases 
develop from transported tumor-cells, and cell-inclusions are not necessary to their 
formation. The transplantation of cancer and sarcoma into animals of the same 
species, and the implantation-cancers occasionally observed after operation, are 
the result wholly of the transplantation of living tumor-cells, and cannot be used 
as arguments in favor of the parasitic theory. If protozoa are the cause of cancer 
we must assume, according to our present knowledge of these parasites, that a 
given species can find a suitable soil only in a certain variety of epithelium. Cases 
of transmission of cancer from man to man, occasionally cited as evidence, can be 
utilized hypothetically in support of the parasitic theory only when the cancer in 
the affected individual develops in the same mother-tissue. 
Fig. 309.— Beginning development of carcinoma in the vaginal portion of the uterus (alcohol, 
Bismarck-brown), a, Epithelium; b, connective tissue; c, surface epithelium growing into the 
deeper tissues; d, dilated glands; e, glandular epithelium growing out in form of plugs; f, cross- 
section of a gland, the cylindrical epithelium of which has become converted into stratified 
epithelium, x 45. 
§ 122. The development of carcinoma of the skin takes place most 
often from surface epithelium, and is characterized by growth of the inter- 
papillary portions into the deeper structures in the form of epithelial 
plugs (Fig. 308, d) which fill the connective-tissue spaces. The stratum 
corneum (c) may undergo hypertrophy along with the cells of the rete 
Malpighii, and penetrate into the deeper tissues with the epithelial plugs 
(d). The horny cells which get into the deeper tissues may form epi- 
thelial pearls (<?). CARCINOMA. 
359 
Besides the surface-epithelium, the epithelium of the hair-follicles and 
sebaceous glands may take part in the development of cancer; there 
Fis. 310.—’Developing adenocarcinoma of the large intestine (Muller’s fluid, haematoxylin, 
eosin). a, Mucosa with unchanged glands; b, glands showing carcinomatous change; c, carcino- 
matous areas in the submucosa, x ioo. 
are carcinomata of the skin which develop entirely from sebaceous glands, 
and should be classed with the adenocarcinomata. 
The connective tissue may remain passive during the ingrowth of 
epithelium, but sooner or later (Fig. 308, a), the papillae develop into long, 
Fig. 31 i.—Adenocarcinoma of stomach in process of development (formalin, alcohol, haema- 
toxylin, eosin). a, Mucosa; b, muscularis mucosae; c, submucosa; d, muscularis; e, serosa; f, g, 
adenocarcinoma. X 15. 360 
TUMORS. 
branched formations (/). In the proliferating connective tissue there are 
often found, in association with fibroblasts, leucocytes and lymphocytes. 
They become especially numerous in the event of tissue-destruction, and in 
such circumstances the proliferation of connective tissue acquires the 
character of granulation tissue. 
The origin of carcinomata from mucous membranes covered with 
squamous epithelium may be the same as that of cancer of the skin— 
that is, it is introduced by proliferation of surface epithelium (Fig. 309, 
a, c). If glands are present they may take part in the development of 
the cancer. It is a remarkable fact that in the formation of such a tumor, 
glands with cylindrical epithelium may furnish epithelial products which 
Fig. 312.— Developing cystocarcinoma of mamma (alcohol, hcematoxylin). Tumor of the size of 
a bean, a, Normal gland-tissue; b, proliferating gland- tissue, x ioo. 
correspond with those of the surface-epithelium. The epithelial pro- 
liferation may at first be intracanalicular and lead to diffuse thickening 
and stratification of the epithelium (Fig. ), or to the formation of ex- 
crescences (e). Later, the proliferating epithelium beaks into the con- 
nective tissue. The connective tissue behaves in the same manner as in 
cancer of the skin. 
The cylindrical-cell carcinomata of mucous membranes arise in the 
intestine from the tubular glands or from the crypts, the epithelium of 
which undergoes proliferation, and becomes stratified, while the glands 
dilate (Fig. 310, b). Later, the glands become changed into branching, 
atypical structures (c), which possess epithelium arranged in layers, and 
which grow into neighboring tissues. 
In the stomach the glands change their character (Fig. 311, /), and 
through continued growth infiltrate the submucosa (g), the muscularis 
(d), and the serosa (e). CARCINOMA. 
361 
The epithelium of the newly-formed glands stains more deeply with 
nuclear stains than normal epithelium. 
The connective tissue, as in cancer of the skin, sooner or later pro- 
liferates, and in connection with this there may occur emigration of leuco- 
cytes and lymphocytes. 
The development of cancer in glands — for example, in the mammary 
gland — likewise begins with epithelial proliferation, as the result of 
which the glands (Fig. 312, a) become widened and altered in form (b), 
while their lining epithelium becomes stratified (b). With breaking 
through of epithelium into neighboring tissue spaces, infiltration is begun. 
Fig. 313.— Tubular adenoma of mamma showing a beginning transition to carcinoma (for- 
malin, haematoxylin). a, Branching gland-tubules with simple epithelium; the pericanalicular 
connective tissue is proliferating and very cellular; b, c, gland-tubules, the epithelium of which 
is partly simple, partly stratified. X 100. 
According to the structure of the gland in which the cancer arises, and 
to the variety of the cancer itself, varying microscopic pictures are 
produced. 
The connective tissue of the gland through proliferation takes part in 
building up the tumor; in the early stages of development such prolifera- 
tion may be slight or wanting. 
The development of carcinoma in an adenoma or fibro-adenoma 
(Fig. 313, a) is likewise initiated by change in the character of the cells 
and by more active proliferation of the epithelium, in that simple epi- 
thelium becomes stratified (b, c). The ingrowth of epithelium into the 
connective tissue, which often occurs at a late stage, is a further sign of 
malignancy — that is, of carcinomatous transformation. 
The development of carcinoma from papillary epitheliomata takes 
place in the same manner as from the skin and mucous membranes; 
and is characterized by the infiltration of epithelium into the basement- 
tissue on which the epithelioma rests. 362 
TUMORS. 
The development of carcinoma from transplanted or misplaced 
epithelium or from remains of foetal structures proceeds in the same 
manner as that of carcinomata arising in surface or glandular epithelium. 
Carcinomatous proliferations of the cell-layer and the syncytium of 
the chorion, both of which arise from the foetal ectoderm, may occur in 
the chorion of young ova or in the placenta of older embryos, and in 
atypical cases are characterized by a mixture of the two forms of cells 
(Fig. 314). They grow into the neighboring uterine tissue, particu- 
larly the blood-vessels (c) and through the formation of thrombi may 
lead to extensive destruction of the tissues of the uterus, and give rise to 
metastases. Myxomatous degeneration of the chorion or placental villi 
(hydatid mole) appears to favor the development of such growths. 
Fig. 314.—Intravascular epithelial plugs of a placental carcinoma. 
The development and growth of carcinoma have been the object of search- 
ing investigation. All writers agree that the developing neoplasm, in so far as its 
epithelial elements are concerned, grows through its own resources and does not 
excite neighboring epithelium to proliferation. The neighboring tissue is com- 
pressed and infiltrated. On the other hand, differences of opinion exist concerning 
the beginning of cancer. According to Hauser, Krompecher, Petersen and Colmers, 
the development may be unicentric or multicentric, in the latter case starting in 
several places in the epithelium. Borrmann assumes a unicentric origin; in those 
cases in which the development apparently proceeds from several places he assumes 
that there is coincident development of several primary cancers. 
According to Hauser, Krompecher, and Petersen, with whom I agree, the de- 
velopment of carcinoma takes place from cells of the superficial epithelium, hair- 
follicles, glands, and gland-ducts. According to Borrmann, a developing carcinoma 
is a growing cell-complex, which existed as such before it began to grow; it is an 
isolated embryonal cell-complex. Squamous-cell cancers, although not all of them, CARCINOMA. 
363 
arise from extremely small cell-complexes that lie in the superficial epithelium, 
and probably become isolated during fcetal life through closure of a furrow or 
other anomaly of development. 
According to the first-named authors, the pathological new-formation has its 
origin from epithelium or at least takes its point of departure from it. According 
to Borrmann and Ribbert, the process begins with inflammatory changes in the 
connective tissue; in the skin these may be caused by retention and infection of 
the secretion of the sebaceous glands causing elevation and stretching of the 
epithelium. As the result of this stretching and accompanying hypersemia, the 
included fcetal cell-complex proliferates and grows into the deeper tissues. 
The independent proliferations of the fcetal ectoderm are usually designated 
chorioepithelioma (Marchand) in accordance with the view that they represent 
epithelial proliferation. There is no reason for not classing them with the carcino- 
Fig. 315.—(Bellevue Hospital.) Carcinoma of the kidney. 
mata, since they are characterized by epithelial proliferation which infiltrates neigh- 
boring tissues. The metastasis through the blood-vessels which characterizes the 
chorionic carcinomata occurs frequently in other carcinomata, for example, carcino- 
mata of the stomach. 
To a certain extent the character of the parent tissue is preserved in cancer- 
cells, but careful examination shows in all cases that there is a certain amount of 
change both in their morphological and in their physiological character (anaplasia). 
This is shown in changes in the form and structure of the cells, their behavior 
toward stains, in altered position and arrangement of cells, and in their relations 
to surrounding tissues. 
The traumatic displacement of surface-epithelium in wounds may lead to the 
formation of so-called traumatic epithelial cysts — that is, cysts varying in size 
from a hemp-seed to that of a nut, which are lined with epithelium, and, in case 
they arise from the epidermis, contain a pultaceous mass of desquamated epithelium. 
They occur most frequently after puncture-wounds of the volar surface of the 
fingers and in the hollow of the hand. 
§ 123. The structure of a carcinoma is determined by its origin. 
The manner in which the epithelium proliferates and the associated pro- 364 
TUMORS. 
liferation of connective tissue make it possible to distinguish a connective- 
tissue stroma which contains the blood-vessels, and nests and strands 
of cells—the so-called cancer-plugs—which are imbedded in the stroma. 
If the cancer grows into tissue having a special structure, the stroma may 
thus be provided with muscle-fibres, bone trabeculae, unchanged glandular 
tissue, etc.; but these tissues usually die after a time. In general, carci- 
noma possesses an alveolar structure, at times suggesting an imperfectly 
developed acinous gland, at other times a tubular gland, so that it is 
possible to distinguish acinous and tubular types. When the cell-plugs 
are solid the growth may be called carcinoma solidum or merely carci- 
Fig. 316.— Horny cancer of the tongue (Muller’s fluid, haematoxylin, eosin). a, Epithelial plugs 
with epithelial pearls; b, stroma. X 100. 
noma. The presence of a lumen in the cell-plugs gives to the growth an 
appearance resembling the adenomata, and warrants the designation carci- 
noma adenomatosum or adenocarcinoma. 
The type of carcinoma is to a degree dependent on the parent-tissue, 
and the cells may still show the characteristics of the parent epithelium. 
Squamous-cell carcinoma may occur wherever there is squamous epi- 
thelium, and cylindrical-cell carcinomata in mucous membranes having 
cylindrical cells. Cornification takes place in carcinomata of the skin, 
mucoid degeneration in those of mucous membranes, while the formation 
of colloid occurs in those arising from the thyroid. Departures from this 
rule are common, in that the epithelial cells may remain at a less highly 
differentiated stage, so that the type of cell concerned may not be de- 
veloped to its fullest; or it may happen that the cells lose their original 
character and take on others. For example, colloid-like substances may 
be formed in cancers of the skin, mucous may be produced in mammary 
cancers, or squamous-cell carcinomata may develop in mucous mem- 
branes possessing cylindrical epithelium (gall-bladder) or in those having 
transitional epithelium (pelvis of kidney). 
(1) Squamous-cell cancers develop in the skin and in mucous mem- 
branes covered with squamous cells. They occur, therefore, in the CARCINOMA. 
365 
external skm, mouth cavity, pharynx, oesophagus, larynx, vaginal portion 
of the cervix, vagina, and external genitals. In rare cases they may 
develop in mucous membranes possessing cylindrical epithelium — for ex- 
ample, in the trachea 
and gall-bladder, or in 
the remains of foetal 
structures, such as the 
branchial clefts, and 
dermoids. 
The flat-cell cancer 
is characterized by the 
formation of relatively 
large cell-nests (Fig- 
316, a) of irregular 
shape; but often forms 
small strands of cells. 
The epithelial cells show 
the character of strati- 
fied squamous epithel- 
ium with the formation 
of prickle-cells, but on 
account of their multi- 
plication in the tissue- 
spaces are usually poly- 
morphous, and no lon- 
ger manifest typical 
characteristics. Often 
the formation of keratohyalin and cornification takes place in the large 
epithelial plugs which have penetrated the deeper tissues. The cells 
which have undergone horny change become arranged in concentric 
Fig. 317.— Carcinoma of the skin, with delicate cellular 
network and areas of hyaline connective tissue. (Alcohol, 
hsematoxylin.) x 80. 
Fig. 318.—Adenocarcinoma recti tubulare (alcohol, alum-carmine), a, b, Epithelial gland-tubules; 
c, ci, stroma; d, collections of leucocytes in the gland-tubules, x 65. 
laminae resembling those of an onion (Fig. 316, a). Such cell-nests are 
known as epithelial pearls or horny bodies, and occasion the designation 
of horny cancer. If, instead of cornification, the central portions of the 366 
TUMORS. 
cell-nests undergo necrosis and liquefaction, the carcinoma may take on an 
adenoma-like structure. 
Besides typical flat-cell cancers there often occur in the skin and in 
mucous membranes possessing squamous cells, carcinomata having epi- 
thelium persisting at a lower stage of development, so that the cell- 
strands remain slender and delicate, and consist of small epithelial cells of 
different forms (Fig. 317) that do not change into prickle and horny cells. 
Such cancers are called basal-cell carcinomata, since they develop from 
the layer of basal cells. The cell-cords are usually solid, but through the 
Fig. 319.—Adenocarcinoma fundi uteri, a, Strorrn; b, cancer-plugs; c, isolated cancer-cells. 
x 150. 
production of hyaline products in the centre of the cell-masses they may 
take on an adenomatous appearance. 
(2) Cylindrical-cell carcinomata develop chiefly in mucous mem- 
branes possessing cylindrical epithelium — intestines, stomach, respiratory 
tract, body of the uterus, and gall-bladder, but occur in glands — ovary, 
mammary gland, liver, etc.— as well as in the cerebral ventricles. Such 
tumors exhibit, at least in the early stages of development, the character 
of carcinoma adenomatosum or adenocarcinoma (Figs. 310, 311, 318), 
in that they form epithelial structures which consist of tubules lined by 
simple or stratified epithelium. More active proliferation of the epithelial 
cells finally leads to the formation of compact cell-nests possessing no 
lumen (Fig. 319). 
The stroma of cylindrical-cell carcinomata is usually poorly developed; 
and the tumor consequently bears the character of a soft cancer, carci- 
noma medullare. Nevertheless the cancer tissue may in some cases 
possess a firm consistence. CARCINOMA. 
367 
(3) The carcinoma simplex occurs most frequently in glands, but 
may develop in mucous membranes and skin. The cell-nests are irregu- 
larly shaped (Fig. 320), round (Fig. 321), or elongated or fusiform (Fig. 
322). These variations occasion the terms carcinoma acinosum (Fig. 
Fig. 320.— Carcinoma simplex mammae (alcohol, haematoxylin). a, Stroma; b, cancer-plugs; c, 
isolated cancer-cells; d, blood-vessels; e, small-cell infiltration of the stroma. X 200. 
321) and carcinoma tubulare (Fig. 322) as distinguishing types of corre- 
sponding character. It should be noted, however, that different types 
may be present in the same tumor (Fig. 323, e, f, g), since the character 
of the cell-nests depends partly on their manner of growth and partly on 
Fig. 321.—Acinous carcinoma of the mammary gland with large nests of cells (Muller’s fluid, 
haematoxylin). x 100. 
that of the connective-tissue stroma in which they develop. At the seat 
of origin the cell-nests may have a variety of shapes (e) ; in adipose 
tissue they are rounded (/) ; in the unyielding connective tissue of the 
skin they are small and fusiform (o'). 368 
TUMORS. 
Abundant development of cell-nests in a delicate connective-tissue 
stroma leads to the formation of carcinoma medullare. Marked devel- 
Fig. 322.— Tubular scirrhous cancer of the mammary gland (Muller’s fluid, haematoxylin). 
a, Area with well-developed elongated nests of cells; b, portion of tumor in which the cell-nests 
have for the greater part disappeared. X ioo. 
opment of stroma with the formation of relatively few cancer-cells gives 
rise to a hard tumor, called carcinoma durum or scirrhus (Fig. 322). 
Fig. 323.—'Section through a segment of a carcinoma of the breast (alcohol, hrematoxylin). 
a, Nipple; b, tissue of gland; c, skin; d, gland-ducts; e, carcinomatous masses occupying the place 
of the gland tissue; f, carcinomatous infiltration of fat tissue; g, portion of skin infiltrated with 
carcinoma; h, nests of cancer-cells in the nipple; i, normal gland-lobule; k, small-cell infiltration 
of the connective tissue. Magnified by hand-lens. 
The hard variety of cancer owes its origin to the fact that cell-nests 
are few and small, while the stroma is abundant and hard. Such tumors CARCINOMA. 
369 
are formed especially when epithelial proliferation infiltrates into hard 
connective tissue, for example, in the mammary gland and skin, but the 
Fig. 324.— Mucoid carcinoma of the mammary gland (Muller’s fluid, haematoxylin, eosin). 
a, Normal gland tissue; b, c, early stages of carcinomatous proliferation with beginning formation 
of mucus; d, larger cell-nests with masses of mucus; e, f, carcinoma tissue showing marked 
mucous degeneration, x 30. 
same characteristics may be exhibited in newly-formed connective tissue. 
In the course of time a cancer becomes harder by reason of the destruc- 
tion of its epithelial cells (Fig. 322, b), while the connective tissue increases 
Fig. 325.— Early stages of development of a mucoid carcinoma of stomach, arising in an 
atrophic mucosa (formalin, alcohol, haematoxylin, eosin). a, mucosa; b, muscularis mucosae; c, 
submucosa; d, muscularis; e, serosa; f, g, mucoid cancer. X 9. 370 
TUMORS. 
in amount. An originally soft cancer may become hard through shrink- 
age of the cancer tissue with corresponding induration of the connective 
tissue. Carcinomata of the mammary gland, stomach, and intestine 
often show secondary 
hardening, and in such 
tumors cancer-cells may 
be almost entirely re- 
placed by fibrous over- 
growth. 
(4) The chorion- 
carcinoma or malignant 
chorio-epithelioma is 
distinguished from other 
carcinomata by a mix- 
ture of cell-forms (Fig. 
314) belonging to 
t h e foetal ectoderm. 
Such a combination is 
not everywhere present, 
and does not occur 
where single cells or 
cell-groups penetrate the blood-stream or are transported passively. The 
conditions favoring development within the blood-vessels are found when 
fluid and coagulated masses of blood lie between the tumor-cells. 
(5) Cancers characterized by peculiar secondary changes arise 
through the formation of special 
products by the cancer cells, or 
through metamorphoses of the 
same, or through changes in the 
stroma. 
Mucoid or gelatinous cancer — 
carcinoma mucosum (C. gclatino- 
sum, C. colloides)—is that form 
of carcinoma in which the epithelial 
cells produce mucus (mucin or 
pseudomucin) or a colloid-like 
gelatinous substance. Such pro- 
duction of mucus occurs particu- 
larly in cancers of the intestine, 
stomach (Fig. 325), and mam- 
mary gland (Fig. 324) ; and may 
be manifest in the earliest stages of 
the development of the tumor 
(Figs. 324, b, c; 325, f, g), so 
that the mucoid products of the 
cells collect in the centre of the cell- 
nests after the manner of a gland- 
secretion. Later the border of cells surrounding the mucoid material is 
broken through, the cells pushed aside, separated from the underlying 
structures, and crowded toward the centre of the mucus-containing 
alveolus (Fig. 324, d, e, /). Ultimately, the epithelial cells are wholly 
destroyed. 
Fig- 326.—Carcinoma mucosum mammas (alcohol, harnia- 
toxylin). a, Stroma; b, cancer-plugs; c, alveoli without cancer- 
cells; d, cells containing spherules of mucus. X 200. 
Fig. 327.— Carcinoma with hyaline drops 
within the cell-nests (Carcinoma cylindroma- 
togum). a, Cell-nest without; b, cell-nest with a 
few hyaline spherules; c, cells which have been 
reduced to strands arranged in a network, as the 
result of the formation of numerous hyaline 
spherules, x 150. CARCINOMA. 
371 
In intestinal cancers the formation of mucin takes place in goblet-cells, 
which are similar to the goblet-cells occurring in normal conditions. In 
cancer of the breast the mucus appears in the form of droplets within the 
cancer-cells (Fig. 326, d), and becomes free by escaping from the cell, or 
through destruction of the cell 
itself. 
Through the development 
of mucoid or colloid-like 
masses in the cancer-cell nests, 
the latter may become studded 
with hyaline drops, and acquire 
a mesh-like appearance (Fig. 
327). Such formations were 
formerly designated cylindro- 
mata. Should it be thought 
desirable to retain this nomen- 
clature, such a tumor might be 
designated carcinoma cylindro- 
matosum; but it seems un- 
necessary to separate these 
growths from the mucoid and 
colloid carcinomata. 
When the cancer-cells attain an extraordinarily large size, for example, 
in flat-cell cancers or in cancers of the breast, the tumor may be termed 
carcinoma gigantocellulare. If the enlargement of the cells is not due 
to increase in the protoplasm, but to swelling of the cells or to collection 
Fig. 328.—.Enlarged hydropic cancer-cells, from a 
carcinoma of the mammae (Muller’s fluid, Bismarck- 
brown). a, Ordinary cancer-cells; b, hydropic cells 
containing drops of fluid; c, swollen nucleus; d, swol- 
len nucleolus; e, wandering cells. X 300. 
Fig. 329.— Carcinoma myxomatodes ventriculi (Muller’s fluid, hnematoxylin). a, Cancer- 
plugs; b, connective-tissue stroma; c, stroma of myxomatous tissue; d, cancer-cells which have 
undergone mucous degeneration, x 200. 
of fluid in the cells and their nuclei (Fig. 328), the cells are designated 
physalides (carcinoma physaliferum). 
Myxomatous degeneration may occur in portions of a cancer, so that 
the cancer-cells become separated by myxomatous stroma (Fig. 329, c). 
Such growths may be called carcinoma myxomatosum. 372 
TUMORS. 
Hyaline degeneration of the connective tissue occurs in different 
forms of cancer, but is usually confined to small areas. 
Deposits of lime-salts in carcinomata occur as masses similar to those 
in psammomata. The concretions may form either from the cells or in 
the connective tissue. They are observed particularly in papillary adeno- 
mata and carcinomata of the ovary, and in cancers of the mammary gland. 
There also occur more extensive calcifications, which may lead to com- 
plete petrifaction; tumors showing such changes occur in the skin and 
Fig. 330.—Adenosarcoma malignom of the kidney, from a child seven years of age (formalin, 
haematoxylin, eosin). a, Tissue with gland-tubules; b, sarcoma-like tissue. X 300. 
subcutaneous tissues, in the form of sharply defined, hard, rounded 
nodules. Some of these tumors are to be classed with the carcinomata, 
others represent calcified adenomata of the sebaceous glands. 
If, at the same time with development of the epithelial new-growth, 
there occurs marked proliferation of the connective tissue, leading to the 
formation of cellular tissue, there arise tumors which may be designated 
adenosarcoma or sarcocarcinoma. Typical examples occur in the kid- 
neys (Fig. 330, a, b), forming medullary tumors, the origin of which is 
probably to be referred to disturbance of development of the kidney. 
Such tumors show a varying structure in different parts, at one time of 
adenomatous or carcinomatous character, at another time sarcomatous. 
The metastases of such tumors exhibit a similar character. 
The tumor of the kidney referred to by Ziegler as adeno-sarcoma was care- 
fully studied by Wilms and frequently goes by his name or under the designation of 
embryoma. It is a composite tumor which occurs most frequently in the kidneys of 
infants and children, the growths reaching enormous size and frequently metastasiz- 
ing to distant parts. Most of them are unilateral, but bilateral growths are by no 
means unknown. The majority occur in children under twelve years of age, but 
examples have been recorded in adults. In fact, it is safe to say that an over- 
whelming majority of all tumors of the kidney encountered in individuals under 
twelve years of age belong in the category of the so-called Wilms’ embryoma. They 
are made up of a mixture of tissues in which cartilage, smooth muscle, osteoid and 
myxomatous connective tissue are associated with complex arrangements of epithe- 
lial cells, the latter presenting a striking histological resemblance to the tubules CARCINOMA. 
373 
of the developing kidney. (Fig. 330.) Unlike the so-called hypernephromata, the 
composite tumors of the kidney seldom cause hematuria and are recognized, as a 
rule, by their rapid growth and massive size. Hedren, of Stockholm (Ziegler’s 
Beitr., 1907), was able to collect only 90 cases from the literature and to add 
five from his own experience. In the past 15 years I have seen five cases in New 
York City; three from the service of Bellevue Hospital, one from the New York 
Hospital and one from an independent source. Of these five tumors, attention 
was directed to one as a result of the microscopic examination of a small nodule 
removed from the subcutaneous tissues between the scapulae, subsequent examina- 
Fig. 331.—(Bellevue Hospital.) Massive recurrent Wilms’ embryoma of left kidney. The 
tumor, when removed, weighed 37 pounds. 
tion of the abdomen revealing a large embryoma of the left kidney. Surgical 
removal of these growths is sometimes followed by recovery. 
Spontaneous healing of carcinomata does not take place, but many of them 
grow slowly, and many processes within cancers may be interpretated as local 
attempts at healing. In this category belong degenerative processes in the cancer- 
cells that lead to their death and dissolution, so that in large areas (for example, in 
cancer of the stomach) there may be found hyperplastic masses of connective 
tissue, but no cancer-cells. It is probable that in the destruction of the cells pro- 
teolytic ferments play a role. The occurrence of calcification in a cancer depends 
on previous death of cells. Further, the fact that transported cancer-cells (com- 
pare § 125) do not always give rise to daughter-tumors, but frequently die at the 
place where they lodge, may be interpretated as a healing process. 
Various authors (Becher, Petersen, Schwarz, Orth) also look on the occurrence 
of giant-cells in tumors as a process of healing; it would be more correct, how- 374 
TUMORS. 
ever, to say that in the course of certain retrograde processes giant-cells appear. 
The cause of the retrogression lies not in the giant-cells; they appear only under 
certain conditions, and especially when in cancers elements of certain kinds, corni- 
Fig. 332.—Cystocarcinoma papilliferum mammae, a, Stroma; b, smooth-walled. cysts; c, 
cysts containing papillary proliferations; d, cysts entirely filled with papillary proliferations; 
e, small, encysted papillary growths; f, adenomatous proliferations; g, papilla of the mamma. 
Reduced about one-third. 
fied cells in particular, come in contact with connective tissue. They are foreign- 
body giant-cells, and their occurrence is to be regarded as secondary to retrograde 
processes. 
Fig. 333.—Cystocarcinoma papilliferum ovarii (Muller’s fluid, haematoxylin). a, Stroma; 
b, epithelium; c, d, papillae, x 72. 
§ 124. The cystocarcinomata represent a form of tumor which 
stands in the same relation to cancer as the cystadenomata to the adeno- 
mata. The majority of cancers form no demonstrable secretion, but there 
are certain varieties, particularly in the group of adenocarcinomata, in 
which the epithelial cells produce mucus or colloid (thyroid) ; and in CARCINOMA. 
375 
adenocarcinomata of the liver secretion of bile has been observed. In 
cystocarcinomata the mucous secretion of the epithelium may lead to the 
formation of large spaces filled with fluid. Cystocarcinomata occur 
chiefly in the ovary and mammary gland, usually bearing the character of 
cystocarcinoma papilliferum (Fig. 332), in that the cyst-spaces, in 
certain parts or throughout, are partially (b, c) or wholly (d, e) filled 
with papillary proliferations. These excrescences possess a soft, medul- 
lary appearance, and when developed in great numbers give to the tumor 
a marrow-like character. 
Both the cyst-wall and the papillary proliferations, which branch in 
the same manner as those of the papillary cystadenomata, are covered 
with a thick, stratified layer of epithelium (Fig. 333, b, c, d; 334, c). The 
Fig. 334.—Papillary cystocarcinoma of the mamma with papilla? which have undergone 
myxomatous degeneration (Muller’s fluid, haematoxylin, eosin). a, Dense connective tissue; 
b, myxomatous papilla?; c, proliferating epithelium, arranged in several layers, x 73. 
papillae are usually slender (Fig. 333, c, d), hut through myxomatous 
degeneration of their connective tissue may attain large size (Fig. 334, b). 
Through total myxomatous degeneration of the connective tissue of the 
papillae the latter may become converted into mucous cysts surrounded 
by epithelium. If at the same time the epithelial layers of neighboring 
papillae become confluent, the epithelium finally comes to represent a 
stroma which incloses balls of mucus. 
The metastases of cystocarcinomata may have the character of cauli- 
flower-like, papillary growths. This is particularly the case when ovarian 
tumors of this nature spread throughout the peritoneal cavity. Other 
metastases show the characteristics of ordinary carcinomata. 
§ 125. Growth by infiltration and involvement of surrounding tis- 
sues takes place during the early stages of development (§ 122), 
through penetration of the epithelial elements into the neighboring tissue 
in the form of connected plugs or cords of cells. Not infrequently there 
appear in the tissue-spaces single epithelial cells that multiply and form 
strands or masses of cells. In the growth of a tumor into neighboring 376 
TUMORS. 
organs, the connective-tissue stroma (Fig. 335, d) surrounding the cell- 
nests breaks into the neighboring tissue (a) and replaces it. Such infil- 
tration occurs to the most marked degree in carcinomatous invasion of 
cartilage (a) and bones. 
The formation of metastases, which takes place more frequently in 
carcinoma than in any other form of tumor, is the natural result of its in- 
filtrative mode of growth. In the process of infiltration the cancer-cells 
break into the lymph-vessels (Fig. 214), and are carried to the lymph- 
nodes. In both places there results multiplication of the transported 
Fig. 335.—Colloid-containing cancer of thyroid infiltrating the thyroid cartilage (alcohol, 
hiematoxylin, eosin). a, Cartilage; b, cancer-tissue; c, colloid; d, cancer-tissue growing into 
the cartilage. X 85. 
cancer-cells (Figs. 214, a; 336, d). In lymph-nodes the lymphadenoid 
tissue becomes replaced by cancer tissue; the lymphocytes vanish, and 
the connective tissue of the lymph-nodes serves as a framework for the 
cancer. 
The development of cancer in lymph-channels is limited to filling and 
distention of the lymph-vessels by cancer-cells (Fig. 214) or it may lead 
to the formation in this situation of daughter-nodules. 
The epithelial obstruction of lymph-vessels is often extensive; and 
through blocking of individual lymph-channels or of the thoracic duct 
itself, retrograde metastasis of cancer-cells may be caused. For example, 
in cancer of the stomach the lymph-vessels of the mesentery and the 
thoracic duct, and those of the lungs, or even of the upper extremities, 
may become the seat of metastatic growths. Through the thoracic duct 
cancer-cells may be carried into the blood-stream. 
The epithelial proliferation involves blood-vessels not less frequently 
than lymphatics; the invasion of veins by cancer-cells is to be re- 
garded as a common phenomenon. In consequence die vessel becomes CARCINOMA. 
377 
filled with cancer-cells, and at a later stage is converted into cancer-tissue, 
the framework of which is formed through proliferation of constituents 
of the vessel-wall. 
If cancer-cells pass from the thoracic duct or from a vein into the 
Fig. 336.—Section from an enlarged axillary gland, with beginning development of cancer 
(alcohol, h;ematoxv!in). a, Germ-centre of a lymph-node; b, lymph-sinuses; c, artery; d, nests of 
cancer cells, x 60. 
circulation hccmatogenous metastases are formed. In carcinoma of 
the stomach and intestine cancer-cells are often carried through the portal 
vein into the liver (Fig. 215, b, c). The thoracic duct and the systemic 
veins permit transportation of cancer-cells to the lungs. In fact, the 
Fig. 337. 
Fig. 338. 
Fig. 337.—Metastatic collection of young cancer-cells within a liver-capillary, arising from 
a primary adenocarcinoma of the stomach (alcohol, hsmatoxylin). x 300. 
Fig. 338.—Metastatic development of cancer within the liver-capillaries, arising from a 
primary carcinoma of the pancreas (alcohol, carmine). Both connective tissue and nests of 
carcinoma cells have developed within the capillaries, x 250. 378 
TUMORS. 
lungs are frequently the seat of metastases which do not develop into 
nodules visible macroscopically. Frequently microscopic groups of can- 
cer-cells embedded in thrombi are found. A part of these metastases, 
through proliferation of the tumor-cells, develops into daughter-nodules, 
and the lungs may contain numbers of these. The transported cells may 
die, and there occurs proliferation of connective tissue in the vessel-wall, 
leading to organization of the thrombus. In other cases the cancer-cells 
increase within the vessel-lumen without forming large nodules. 
When cancer-cells enter the systemic circulation distribution to various 
Fig. 339.—Carcinomatous metastases in the upper layer of the uterine mucosa, in universal 
carcinomatosis following carcinoma of the mamma (formalin, hiematoxylin and eosin). a, 
Muscularis of the uterus; b, normal mucosa; c, nests of cancer-cells in the vessels between the 
uterine glands; d, upper layer of the mucosa densely infiltrated with nests of cancer-cells; e, 
uterine epithelium; f, ulcerated area. (Blood-clots containing cancer-cells were found in the 
uterus.) X 100. 
organs occurs, although many of the cells die. The favorite seats of 
secondary development of cancer are the liver, lungs, lymph-nodes and 
bones. Occasionally development of carcinoma may take place in all the 
organs of the body; the resulting condition is called carcinomatosis. 
The secondary cancer-foci develop first intravascularly (Figs. 337, 338, 
and 339, c). In the beginning the neighboring tissues are but little 
changed. Later there occur tissue-degenerations (Fig. 339. /) and con- 
nective-tissue proliferations (Figs. 338, 340, c, d), the newly formed 
connective tissue serving as the stroma for the developing cancer-nodule. 
The amount of connective tissue varies greatly, and is dependent on the 
parent-tissue in which the tumor develops and on the variety of cancer. 
The most marked connective-tissue proliferation occurs in metastases in CARCINOMA. 
379 
bones (Fig. 340), particularly when there is diffuse growth of carcinoma 
through the bone. With destruction of old bone the carcinoma may form 
an abundant fibrous stroma in which osteoid tissue or new bone may be 
produced in large amount. It would appear that certain carcinomata 
produce substances that excite marked proliferation of the periosteum and 
endosteum. 
As has already been mentioned in § 101, carcinomata may sometimes 
be transplanted to individuals of the same species, and after operations 
implantation-carcinomata may develop. 
Recurrences after removal of the tumor by operation are common in 
cancers, and in advanced cases can scarcely be avoided. They arise 
Fig. 340.—Metastatic development of cancer in the diploe of the shr.ll-cap in primary car- 
cinoma of the stomach (formalin, hiematoxylin, eosin). a. Marrow-tissue; b, nest of cancer- 
cells; c, proliferated endosteum with nests of cancer-cells; a, fully developed area of carcinoma, 
x 40. 
usually from remains of the primary tumor or from metastases already 
present in the body in the immediate neighborhood or in distant organs. 
In rare cases the conditions favoring growth of cancer may again arise 
in the neighborhood of the scar, so that after several years a new cancer 
develops. 
Recurrences and metastases of chorionic carcinomata occasionally grow 
extremely rapidly so that in a few days tumors of considerable size may be formed. 
The dark-red color shows even to the naked eye that blood is largely concerned in 
their make-up, and the microscopic examination demonstrates that the rapid in- 
crease in size is in large measure due to the haemorrhages caused by the development 
of the tumor. The epithelial masses may form a relatively small part of the bulk of 
the growth. 
Chorion carcinomata, that is, the epithelial cell-masses characteristic of these 
tumors, have been repeatedly observed outside the uterus, in various organs and in 
cardiac thrombi without any tumor of the uterus having been demonstrable. This 
phenomenon may be explained by the fact that the epithelial cells of the chorion or 
of the hydatid mole, that is, of mvxomatous chorionic villi, may be transported 
through the blood-stream and proliferate without the development of a tumor at 
the placental site. 380 
TUMORS. 
3. The Teratoid Tumors and Cysts. 
§ 126. Under the head of teratoid tumors and cysts may be grouped 
those tumor-like growths which are characterized by the fact that the 
tissue-formations of which they are composed do not occur normally at 
the site in question (heterotopous growth), or at least do not normally 
appear there at the time at which they are found (heterochronous growth). 
Part of the teratoid tumors and cysts classed as teratomata, are composed 
of a variety of tissues. 
The teratoid tumors and cysts may be divided, according to their 
structure and origin, into three groups : (1) The simple teratoid tumors; 
Fig. 341.—(Bellevue Hospital.) Recurrent carcinoma of the breast. 
(2) the simple teratoid cysts; (3) the complex teratomata, which contain 
tissues derived from all the germ-layers. 
The heterotopous tissue-growths, which are classed with the teratoid 
tumors, may occur in various organs, but are more frequently found in 
certain regions than in others. Among the common tumors of this class 
are the chondromata and chondromyxomata of the salivary glands and 
testicle, osteomata of the muscles, lipomata of the pia mater, adenosarco- 
mata of the kidney containing muscle, and the adrenal tumors 
found in the kidney. Among those occurring more rarely are the chon- 
dromata and osteomata of the skin or of the mammary gland, rhabdomyo- 
mata of the testicle, etc. 
The occurrence of tissue-formations in regions in which such tissues 
are not normally present can be explained in part by the assumption that TERATOMA. 
381 
cells or groups of cells have not undergone normal differentiation into 
definite tissue-forms, but retain the capacity of forming different kinds 
of tissues. Nevertheless, in many cases the explanation is to be sought 
rather in germinal aberration or misplacement of tissue, in that in early 
embryonic life cells of one organ find their way into the primordium of 
another organ, or that, later, tissues in process of development or already 
formed are displaced from their normal position. The first process can 
be inferred only from the subsequent appearance of pathological tissue- 
formations; the latter, on the other hand, may at times be recognized, 
later on, in the anatomical relations. Thus, in the retrograde changes 
occurring in hernias of the sacral portion of the spinal cord, adipose and 
muscle-tiSsue may find their way into the spinal canal and the arachnoidal 
sac and grow around the nerves. Arnold observed transposition of fat- 
tissue, gland-tissue, cartilage, and neuroglia at the lower end of the trunk, 
in a myelocyst with complete absence of the lumbar, sacral, and coccygeal 
portions of the spinal column. He also found in a lipomatous teratoma 
of the frontal region that the intracranial portion of the tumor communi- 
cated with the extracranial through a defect in the cranium. 
The teratoid cysts may be divided into two great groups: the ecto- 
dermal, and the entodermal and mesodermal epithelial cysts. 
The ectodermal cysts vary in size from a pea to that of a man’s fist. 
Their walls present ectodermal characteristics, in that they consist of a 
smooth connective-tissue membrane, covered with stratified squamous 
cells — the so-called epidermoids; or the cyst walls present all the char- 
acteristics of skin — that is, papillae, sebaceous glands, hair follicles, hairs 
and sweat-glands, and often subcutaneous fat — the so-called dermoids 
or dermoid cysts or dermatocysts. 
The cyst-contents consist of desquamated horny cells, or of a com- 
bination of such cells, fat, and hair. 
Epidermoids and dermoids are found chiefly in the skin and subcuta- 
neous tissues, in the form of growths containing a pultaceous material, 
and resemble tumors caused by the retention of secretion in sebaceous 
glands. They are also found at the sides of the neck and in the median 
line above or below the hyoid bone; in the thoracic cavity, particularly in 
the mediastinum, in the peritoneal cavity (rarely), pelvic cellular tissue, 
coccygeal region, and in the raphe of the perineum. Finally, they appear 
within the cranium, in the dura or hypophysis. Of frequent occurrence 
are the intracramal formations known as cholesteatoma or pearl tumors. 
These growths vary in size from a pea to that of an apple; they form 
spherical or nodular tumors, having a white satiny surface, and consist 
of thin, non-nucleated, scale-like cells, arranged in closely crowded laminae. 
They are invariably situated at some point on the pia, and at such places 
the vascular pia is covered with stratified squamous cells, which in the 
course of years produce the delicate epithelial scales of which the tumor 
is composed. The neighboring brain tissue and the arachnoid, which 
may extend over the growth, are not concerned in the formation of the 
horny scales. In rare cases cholesteatomata contain sebaceous material 
and fine hairs in addition to horny scales and cholesterin. In these cases 
there may be found here and there on the pia dermal structures, i. e., skin 
containing sebaceous glands and hair-follicles, from which sebaceous 
material and hairs arise. The simple cholesteatomata may be designated 
epidermoids, those containing hair as dermoids. Cholesteatomata occur 
at the base of the brain, in the neighborhood of the olfactory lobe, tuber 382 
TUMORS. 
cinereum, corpus callosum, choroid plexus, pons, medulla oblongata (rarel}' 
in the spinal cord), and in the cerebellum. 
The dermoids and epidermoids probably owe their origin to transplan- 
tation of epithelial germs to the sites in question. In the epidermoids 
probably only embryonal epithelial cells are transplanted; in dermoids 
embryonal dermal tissue is also transplanted. The intracranial cholestea- 
tomata originate probably in early implantation of epidermal cell groups 
in the pia. Mediastinal dermoids probably depend on disturbances of 
development of the thymus, which arises from the ectoderm. The der- 
moids on the sides of the neck arise from remains of the branchial clefts, 
Fig. 342.—Adenoma-like isolation in the submucosa of a portion of the mucous membrane 
of the small intestine, giving rise to a ridge-like prominence of the mucosa 2. cm. in length 
(alcohol, haematoxylin). From a child six weeks of age. a, b, c, Normal intestinal wall; d, e, 
portions of mucosa included within the submucosa; f, mucous tissue rich in cells, x 35. 
particularly the second; those hanging from the hyoid bone or lying 
beneath it are probably to be regarded as remains of the ductus thyreo- 
glossus. Dermoids of the pelvic cellular tissue may be explained as 
arising from epithelial inshoots from the perineum. 
Simple entodermal and mesodermal epithelial cysts are character- 
ized by a lining of cylindrical cells, which are often ciliated. They occur 
most frequently in the broad ligament and tubes. They are also found 
in other portions of the peritoneal cavity, in the intestine, in the neigh- 
borhood of the trachea and bronchi, in the lungs, pleura, neck, tongue, 
vagina, glandular organs, etc. They form cysts varying in size from a 
pin-head to that of a man’s head. 
The occurrence of these cysts may be explained in most cases by the 
persistence of foetal glands or canals or by separation through con- 
striction of portions of entodermal or mesodermal epithelial tubes. 
In the neck remains of the internal branchial clefts, in the posterior 
portions of the tongue the remains of the ductus thyreoglossus or of TERATOID CYSTS. 
383 
epithelial buds and glands developing from the same, in the oesophagus 
and respiratory tract snared-off portions of the intestinal canal or of 
the air-passages, or remains of the communication between alimentary 
tract and air-passages, may form the foundation for the development of 
such cysts. In the broad ligament, uterine wall, and tubes, the cysts arise 
from remains of the Wolffian duct and the duct of Gartner; in the tubes, 
cervix, portio vaginalis, vagina, and hymen they arise from the remains 
of the latter; in the peritoneal cavity from snared-off portions of the 
intestine (enterocysts), or from portions of the urachus (urachus-cysts). 
Within glands—for example, the liver or kidneys — portions of tubules 
Fig. 343.—Adenoma-like remains of the Wolffian body, within the uterine musculature 
(formalin, alcohol, haematoxylin, eosin). a, Muscle tissue; b, glandular tissue; c, sections of 
vessels, x 100. 
may become constricted during the period of development, and develop 
into cysts (adenocysts). 
Cysts located in the central nervous system or its immediate neighbor- 
hood— for example, at the lower end of the trunk — may arise from 
the medullary canal (myelocysts), in the latter place also from remains of 
the hind-gut (enterocysts). 
The origin of cysts lined with cylindrical epithelium can, as a rule, 
be determined only from their position and the character of their walls, 
but in the majority of cases the origin can usually be ascertained beyond 
doubt. The diagnosis can be made with relative assurance when the 
misplacement of the separated portion is slight (Fig. 342, d, e), and when 
the formation still shows the character of the mother-tissue. 
The significance of ectodermal, entodermal, and mesodermal cysts is 
dependent on their position, size, and the secondary changes which occur 
in them. Their size varies from a pin-head to that of a man’s head. 
Among secondary changes—aside from inflammation — may be men- 
tioned the development of adenomata and carcinomata. For example, 
remains of the Wolffian body in the dorsal wall of the uterus near the 384 
TUMORS. 
angles of the tubes, or in the broad ligament in the inguinal region, may 
give rise to adenomata, cystadenomata (Fig. 343, b), or adenomyomata. 
Dermoids may be the seat of development of a squamous-cell cancer 
(branchiogenic and subcutaneous carcinoma) ; while from separated por- 
tions of the intestinal mucous membrane (Fig. 342) cylindrical-cell carci- 
nomata may take origin. Cysts, cystadenomata, and carcinomata may 
Fig. 344.—Section through a prominence in a mutilocular dermoid (alcohol, nitric acid, 
haematoxylin, eosin). a, at, 02, Epidermis; b. corium with sebaceous glands; c, sinus lined with 
squamous epithelium; d, sinus lined with cylindrical epithelium; e, tubular glands; f, fat-tissue; 
fir. bone; h, teeth; i, brain-tissue with corpora amylacea; k, ovarian tissue, x 5. 
develop in the jaw from misplaced portions of the epithelial primordia of 
the teeth. 
§ 127. Complex teratomata occur most frequently in the sexual 
glands, in the form of dermoid cysts and as solid tumors associated with 
multiple cyst-formation. The first occur particularly in the ovary, the 
latter in the testicles. 
The so-called dermoid cysts of the ovary form rather thick-walled 
cysts, varying in size from a pea to that of a man’s head, and are filled 
with fatty material and hair. At some point in the wall there will 
be found extending into the cyst-cavity a villus-like, nodular, flat- TERATOID CYSTS. 
385 
tened, or septum-like prominence, covered with hairs and often studded 
with teeth. The upper layers of this prominence contain the char- 
acteristic structures of the skin (Fig. 344, a, a1} a2, b), namely, hair- 
follicles with hairs, sebaceous and sweat-glands; subcutaneous fat is 
usually present (/). In the deeper layers are found tissue-formations, 
such as cysts and tubes lined with ciliated columnar epithelium (d), bone 
(g), cartilage, teeth (/t), muscle-tissue (heart-muscle [Ivatsurado]), 
brain-tissue (i), nerves, groups of ganglion-cells, mucous glands, intestinal 
mucosa, and thyroid tissue, as well as pigmented formations resembling 
the rudimentary tissues of the eye. The remaining portion of the wall 
of the dermoid is either covered with cylindrical epithelium or is bare; 
if hairs are present in this portion, they are the result of secondary 
implantation, and may be surrounded by granulation-tissue, often by 
giant-cells. If in association with the cysts containing fat and hairs there 
are also found cysts filled with serous or mucoid fluid, the latter may be 
explained as arising through dilatation of spaces which are lined with 
cylindrical cells. More frequently, however, they represent formations 
resulting from cystic degeneration of neighboring ovarian follicles or of 
adenomatous new-growths. The ovary may be entirely destroyed by 
the dermoid; but remains of its tissue are often present (k). In rare 
cases several dermoids may develop coincidently in one ovary; a double- 
sided occurrence is seen in about fifteen per cent, of all cases. Ovarian 
dermoids are observed most frequently in individuals of middle age, but 
occur in children. 
The most characteristic feature of ovarian dermoids is that they 
contain elements of all three germ-layers, and that a certain order in the 
arrangement of the different elements is observed. The derivatives of 
the ectoderm and mesoderm, in particular the skin and its appendages, 
also bone and teeth, and often brain substance, are developed to the great- 
est extent; while entodermal formations, cylindrical-cell tubules, and 
mucous glands are developed to a less degree, and lie concealed in the 
deeper parts of the growth. The structure of the growth as a whole 
gives the impression of a rudimentary embryo with unequal development 
of ecto- and entodermal tissue; such tumors have been appropriately 
designated embryomata (Wilms). 
The solid teratomata of the ovary are more rare than dermoid cysts. 
They form tumors composed of a confused mixture of tissue-formations, 
e. g., epidermis, epithelial pearls, hairs, sebaceous glands, sweat-glands, 
tubules, and cysts lined with ciliated epithelium, acinous glands, connec- 
tive tissue rich in cells, adipose tissue, muscle, cartilage, and bone. In 
rare cases teeth, intestine, thyroid and brain tissue of rudimentary char- 
acter may be present. 
Since these formations contain elements of all three germ-layers, and 
are distinguishable from the dermoids only through lack of orderly ar- 
rangement of the different tissues, and through the more rudimentary 
development of the individual tissues, they may likewise be classed with 
the embryomata. Because of lack of structural organization approach- 
ing that of the human embryo, Wilms has designated these formations 
embryoid tumors. 
Since the embryoma contains elements of all three germ-layers, in 
more or less orderly arrangement, the genesis of such a tumor may be 
explained by the assumption of development from an ovum. Bonnet 
regards it as probable that in the development of a fertilized ovum, in 386 
TUMORS. 
the early stages of division, a blastomere (or several) may be delayed in 
division and later give rise to an independent formation containing ele- 
ments of all germ-layers, or that (Marchand) a fertilized polar body finds 
its way between the blastomeres of a developing ovum, and later develops 
within the embryo. The first assumption seems more probable, and the 
embryomata of the ovary may consequently be regarded as rudimentary 
unioval twin malformations (§ 128), which are to be placed in the same 
category with the foetal inclusions of other organs. That the ovaries 
Fig. 345.—Congenital adenocystoma (teratoma) of the testicle with pigmentation and forma- 
tion of cartilage (Muller’s fluid, hsematoxylin). a, Connective-tissue stroma; b, simple cubical 
epithelium; c, stratified cylindrical epithelium; d, stratified ciliated cylindrical epithelium; e, 
pigmented epithelium lining gland-tubule; f, pigmented connective-tissue cells; g, cartilage in con- 
nective tissue; h, cartilage lying in a gland-tubule. (Section taken from tumor pictured in 
Fig. 300.) x 100. 
(and testicles) form the favorite seats of such growths is probably 
dependent on the fact that the urogenital primordium in its earliest stage 
forms relatively such a large part of the embryonal primordium (Bonnet), 
or that the blastomeres, from which the sexual glands later arise, more 
easily than others take on special development, that may lead to the 
formation of a rudimentary twin. 
The teratomata of the testicle occur most frequently as adenocystoma, 
chondroadenoma, chondrosarcoma, adenomyosarcoma, cystosarcoma, cys- 
tocarcinoma, etc. In some cases the formation of cysts with fluid con- 
tents is the most striking feature of the tumor (Fig. 300) ; in other cases 
cysts are found only in certain parts of the growth; and in still other TERATOID CYSTS. 
387 
cases the tumor may be solid throughout. These growths may reach the 
size of a child’s head. They may be present at birth, but develop more 
frequently in adult life, and grow rapidly. 
The lining of the cysts is, a3 a rule, of entodermal character, but may 
vary in one and the same cyst (Fig. 344). Simple cubical (Fig. 344, b) 
and cylindrical epithelium either with or without cilia, as well as stratified 
ciliated (d) and pigmented epithelium (e), may be found. 
Ectodermal tissue is present in scanty amount, and is limited to pig- 
mented epithelium or to scattered groups of cells showing cornification; 
or it may be absent, or, at all events, cannot be demonstrated in tumors of 
large size. Besides the cysts, mucous glands may be found. 
Of the connective-tissue substances, fibrous tissue, myxomatous tissue, 
Fig. 346.—Teratoma (adenomyosarcoma) of the testicle (formalin, hrematoxyliri, eosin), 
a, Cellular tissue with bands of muscle; b, gland-tubule, x ioo. 
cartilage (Fig. 345, g, h) and occasionally muscle (Fig. 346, a), fat tissue, 
and more rarely bone, are present. 
The teratomata of the testicle may contain tissue-formations corre- 
sponding in structure to the malignant chorio-epitheliomata, characterized 
in particular by syncytial formations. 
Teratomata of the character of dermoids, containing, as in the ovarian 
dermoids, such structures as skin, brain tissue, cranial and tracheal tissues, 
and more rarely teeth and structures resembling the eyes, are of rare 
occurrence in the testicles, but are found both in children and adults. 
To what extent the different teratomata of the testicles are to be 
classed with the embryomata, or to what extent they can be explained 
by the assumption of tissue-implanations at later stages of embryonal 
development, cannot be stated. When elements of all the germ-layers 
are present in the tumor, the assumption is justified that the growth 
belongs to the embryomata or embryoid tumors, and that it has arisen in 
the same manner as the ovarian dermoids. The occurrence of syncytial 
formations is in favor of this assumption. The presence of single tissue- 388 
TUMORS. 
formations—for example, cartilage or muscle — in tumor-formations of 
a more simple character, may be explained on the ground that such tissues 
find their way into the testicle during embryonal development. 
The proliferations of chorio-epilhelial character found in teratomata of the 
testicles are believed to depend on the development of foetal membranes, and that 
the myxomatous tissues present in such tumors represent the chorionic stroma. 
According to Marchand and Risel, they are to be regarded only as products of 
the foetal ectoderm having the same histogenetic significance as the other ectodermal 
structures of the teratoma. It is yet to be determined to what extent corresponding 
ectodermal formations occur in teratomata or other organs. Pick found them 
in a teratoma of the ovary in a nine-year-old girl. Further, it is to be noted 
that syncytial formations occur in tumors (angiosarcoma, endothelioma) having 
nothing to do with foetal ectoderm. It cannot, therefore, be regarded as positive.y 
determined that the syncytial formations in teratomata of the testis actually corre- 
spond to chorio-epitnelioma. W las sow believes that the chorio-epitheliomatous 
proliferations observed by him in tumors of the testis, and designated epithelioma 
syncytiomatodes, are to be regarded as derivatives of incompletely developed epithe- 
lium of embryonal gland tubules. 
§ 128. Complex teratoid cysts and solid teratomata are found, out- 
side the sexual glands, in the same regions as the simple teratoid cysts, 
but show a predilection for the region of the coccyx. The complex char- 
acter of the cysts is shown by the presence in the wall of cartilage, bone, 
fat tissue, mucous glands, smooth and striped muscle fibres, nerve-tissue, 
and tissue of sarcomatous or carcinomatous nature. Dermoid cysts may 
contain teeth, and ciliated epithelial cysts. The solid teratomata occur 
as hairy polypi (nose, throat, and mouth) —tumors covered with hairy 
skin, and consisting of adipose tissue, muscle fibres, cartilage, bones, teeth, 
and cysts. Another group consists of kidney-tumors which, in addition 
to tubular glands, inclose sarcomatous tissue, cartilage, fibrous, adipose, 
and muscle tissue, in rare cases ectodermal tissues. In the vagina and 
cervix uteri of children there occur tumors, for the greater part of a race- 
mose character, which, in addition to connective tissue, myxomatous tissue, 
round and spindle-cell tissue, contain smooth and striped muscle-fibres, 
and in rare cases cartilage. Finally, there occur tumor-like growths of 
complicated structure in the cranium, thorax, abdomen, urinary bladder, 
neck, lower jaw, and especially in the region of the coccyx. They contain 
connective tissue, adipose tissue, cartilage, bone, gland tissue, muscle, 
nerve and brain substance, as well as ectodermal and entodermal cysts. 
They may inclose rudimentary, or completely formed, or at least easily 
recognizable, portions of the body. 
Both the complex teratoid cysts and the solid teratomata are in many 
instances to be regarded as local disturbances of development character- 
ized by misplacement or separation of tissues by constriction in a 
single individual (monogerminal tissue-implantation, autochthonous tera- 
toma). The hairy polypi of the throat, the cystic or solid teratomata at 
the base of the skull or in the hypophysis may be explained by the assump- 
tion of misplacement of ectodermal tissue. The presence of cartilage and 
mucous glands in teratoid cysts of the mediastinum may be explained by 
the proximity of the trachea. The teratoid mixed tumors of the kidney 
may be explained by the assumption that, in addition to kidney-tubules 
and remains of the Wolffian body, products of the mesenchyma arising 
from the myotome undergo proliferation. The occurrence of squamous- 
cell formations in such tumors must depend on the fact that ectodermal 
tissue has found its way into the developing kidney. The presence of TERATOID CYSTS. 
389 
striped muscle-fibres and cartilage in tumors of the vagina and uterus is 
explainable by implantation of myotome or of sclerotome; although many 
hold that striped muscle may be formed from unstriped. Wilms believes 
that the Wolffian duct and its development occasion implantations into 
the cervix and vagina. In teratomata of the coccygeal region the mani- 
fold character of these growths may be explained by the fact that portions 
of the terminal vertebrae, of the pelvis, and of muscular tissue, as well as 
remains of the neuroenteric canal, the hind-gut, and the medullary canal, 
take part in the formation of the tumor. In intracranial teratomata, as 
well as in simple dermoids, tissue-implantations probably form the basis 
for the growth. Moreover, there exists the possibility of another mode 
of origin for these growths — namely, the presence of a rudimentary 
twin, a bigerminal implantation. Such an assumption is well founded in 
those cases in which the teratoma contains fully developed or rudimentary 
parts of the body, or tissue-formations which cannot be explained by 
misplacement of the tissue elements of a single foetus at the spot in 
question. CHAPTER IX. 
Disturbances of Development and the Resulting 
Malformations. 
I. General Considerations Regarding Disturbances of Development 
and the Origin of Malformations. 
§ 129. After the copulation of sexual nuclei has taken place, the 
development of the embryo proceeds by progressive division of nuclei 
and cells, associated with which there arise in orderly manner special cell- 
complexes and differentiation of the same into tissues and organs. The 
multiplication of cells, as well as the development of individual cell- 
groups into organs and parts of the body, depends on intrinsic causes, and 
is determined by the characteristics which the embryo has received 
through inheritable paternal or maternal characteristics at the moment 
of union of the sexual nuclei, which are to be regarded as the carriers. 
It follows that the characteristics of the species as well as the peculiarities 
of the individual are predetermined in the germ, and the development of 
the embryo proceeds under the control of innate moulding forces. Never- 
theless, this development is not accomplished without the influence of 
environment, since the embryo receives its nourishment from the maternal 
organism, and is exposed to the mechanical influences of its membranes 
and of the uterus. These influences may operate to modify the develop- 
ment of the foetus. 
In every species of animal, man included, bodily shape and the con- 
figuration of organs conform to a type, which experience has shown con- 
stantly to recur, and which is therefore looked on as normal. If more 
or less marked departures from this type occur, the condition is designated 
congenital malformation. When departure from the normal is marked, 
so that the individual is grossly malformed, it is spoken of as a monster. 
According to usage, the term malformation is applied to anomalies in 
the form of the body as a whole, or to parts of it which present departures 
from the normal. 
A malformation affecting a single individual is known as a single 
malformation or single monster; one made up from two individuals is 
termed a double malformation or double monster. 
Malformations may owe their origin to intrinsic or extrinsic causes. 
As intrinsic causes may be considered such as exist in the germ. 
When such a malformation occurs in a family for the first time, it must 
be regarded as a primary germ-variation. This may be explained in one 
of two ways: either one or both of the sexual nuclei entering into union 
have been abnormal, or both have been normal, but from their union a 
variety has arisen which is to be regarded as pathological (cf. § 17). It 
is also possible that disturbances in the processes of fertilization can give 
rise to pathological variations. 
If a similar malformation has already occurred in the parent, the case 
may be regarded as one of inheritance. If the malformation appearing CAUSES OF MALFORMATIONS. 
391 
is a peculiarity which was not present in the parents, but did show itself 
in remote ancestors, while wanting in the intermediate links, the phenome- 
non is designated atavism. 
Only those malformations are inheritable which originally appeared 
as primary germ-variations. To such inheritable malformations belong 
increase in the number of the fingers and toes (polydactylism), malforma- 
tions of hands and feet, abnormal hairiness, harelip, and certain patho- 
logical conditions of the nervous system, for example, multiple fibromata 
of the peripheral nerves. 
Under extrinsic causes are to be considered concussion, pressure, 
disturbances in the supply of oxygen and nourishment, and infections. 
Concussions of the uterus in all probability directly damage the 
embryo at an early stage. At a later stage the effects of trauma are 
more often to be sought in tearing loose of the egg and in decidual hsemor- 
Fig. 347.—(Bellevue Hospital.) Polydactylism. 
rhages, whereby the nourishment of the embryo is disturbed. It is evident 
that haemorrhages from other causes, and changes in the maternal blood, 
as in infections, and pathological conditions of the uterus itself, have a 
harmful influence on the developing egg; yet these conditions probably 
lead more often to death of the foetus and expulsion of the egg than to 
the development of a malformation. Infectious diseases in the mother 
may be transmitted to the foetus and give rise to characteristic changes in 
the latter. Abnormal pressure from the uterus or its membranes may be 
exerted on the embryo, especially when there is deficient amniotic fluid; 
malformations of the extremities not infrequently show evidences of 
pressure having been exerted. 
In many malformations it appears that pathological conditions of the 
amnion exert a damaging influence on the embryo. 
This may be brought about through adhesions betzveen embryo and 
amnion, and by pressure of the amnion on the embryo. At the 
birth of the child adhesions may not infrequently be demonstrated, 
and their connection with the malformed parts is such as to leave no doubt 
that they stand in causal relation to the malformation. Such adhesions 
may give rise to malformations of the cerebral or facial (Fig. 348) por- 
tions of the head. Not infrequently extremities are snared off by amniotic 
bands (Fig. 349), amputated and absorbed. 392 
DISTURBANCES OF DEVELOPMENT. 
Some malformations are typical — that is, they always appear in the 
same form; others are atypical, so that astonishing anomalies may arise. 
Geoffroy St.-Hilaire (“Hist. gen. et partic. des anomalies de l’organization 
chez rhomme et les animaux,” Paris, 1832-37) discards entirely the teaching of a 
primary abnormality of the germ (Haller and Winslow), and attributes arrests of 
development purely to mechanical influences. Panum (“Untersuch. fiber de Entste- 
hung der Missbildungen,” Berlin, 1860) agrees with him on the whole, although he 
admits the possibility of a primary abnormality. lie produced malformations in 
hens’ eggs by temperature variations and by varnishing the shells. Dareste (“Re- 
cherches sur la production artificielle des monstruosites,” Paris, 1877) made similar 
Fig. 348.—Malformation of the face, caused by 
amniotic adhesion and pressure. Asymmetry of 
the face, a, Malformed nose; b, bi, rudimentary 
lid-clefts; c, ci, clefts in the upper lip and alveolar 
process of the upper jaw; d, intermaxillary bone 
with prominent lip; e, oblique facial fissure closed 
by scar tissue so as to form a groove. 
Fig. 349.—Hand stunted 
by amniotic adhesions; ring- 
finger snared off; middle and 
index fingers grown together 
and distorted. Reduced one- 
sixth. 
experiments and produced malformations due to arrested development by keeping 
the eggs in a vertical position, by varnishing the shells, by raising the temperature 
above 45° C., and also by irregular warming of the eggs. 
L. Gerlach, Fol, Warynsky, Richter, Roux, and Schultse have carried on ex' 
periments in this line, and have attempted, with partial success, to produce mal- 
formations in chicken-embryos through the localized influence of radiant heat, 
variations of temperature, varnishing of eggs, changes of position, injuries, removal 
of a portion of the white of the egg, and by agitation. Roux, experimenting on 
frogs’ eggs, found that, after destruction of one of the first segmentation-spheres, 
the other continued to develop and formed the half of an embryo, thus demon- 
strating that each of the first two segmentation-cells, corresponding in their posi- 
tion to the right and left body-halves, contains within itself material for the corre- 
sponding half of the body. But since the body-half which is wanting may later 
be replaced by subsequent development from the undestroyed half, and a whole 
structure be produced, each half must also possess the power of producing the 
other half. According to investigations by Herlitzka, Driesch, Morgan, Wilson, and 
others, the first two or even the first four segmentation-cells in tritons, teleosts, 
ascidians, and echinoderms possess the power of forming an entire embryo. CLASSIFICATION OF MONSTERS. 
393 
Schultze experimented on the eggs of amphibia; these normally always assume 
such a position that the darkly pigmented protoplasmic substance of lighter specific 
gravity lies above, the heavier clear protoplasm rich in yolk granules lies below. 
By placing the eggs in an abnormal position and preventing their return to the 
normal position malformations may be produced, the degree of malformation 
standing in direct relation to the size of the angle formed by the line of gravity and 
the abnormally-placed axis of the egg. By turning the egg through an angle of 
180° in the two-cell stage a double monster is regularly produced. The same turn- 
ing in the eight-cell stage causes complete cessation of development. These dis- 
turbances arise from displacements consequent upon sinking of the heavier and 
rising of the lighter constituents of the egg. 
According to the investigations of O. Hertwig, the eggs of axolotl, when kept 
in a 0.7-per-cent, solution of sodium chloride, undergo pathological development, 
which is confined to the central nervous system in the region of the head and 
trunk. If frogs’ eggs are left before fertilization for one to four days in the 
uterus of the dead female and are then fertilized, there are formed, besides normal 
embryos, various malformations due to defective development, for example, spina 
bifida. 
Recent studies have shown that monsters and malformations may be produced 
by Roentgen irradiation of fertilized ova or of either ova or spermatozoa before 
fertilization. Gilman and Baetjer found that the eggs of amblystoma developed 
abnormally under Roentgen irradiation, the embryos showing no mouths. Chicks 
developed in exposed eggs presented malformations of the occipital region and 
extremities and in the distribution of the feathers. Bardeen found that in frogs 
injury to the spermatozoa by Roentgen rays caused the development of monsters 
from eggs fertilized by such damaged spermatozoa. 
§ 130. Single malformations may be conveniently divided into five 
groups. 
Among monsters due to defective development may be classed those 
malformations in which the whole or a part of the body is small and 
imperfectly developed (hypoplasia), and those malformations character- 
ized by absence or stunting (agenesia or aplasia) of individual organs or 
parts of the body. 
If, in parts or organs which are normally formed by the union of 
primordia which are originally separated, such union should fail to take 
place, arrest of development may show itself in the form of clefts and 
reduplications. Thus imperfect development of the plates forming the 
anterior body-wall gives rise to clefts in the median line of the thorax 
and abdomen; failure of union of the maxillary processes of the first 
branchial arch with each other or with the nasal process of the frontal 
bone gives rise to clefts in the face. Defective union of the bilateral 
portions of the female genital tract results in more or less extensive 
reduplication of the uterus or vagina. 
When the primordia of two organs lie near to each other, these may 
become united to produce coalescence between organs or parts which nor- 
mally should be separated. For example, the kidneys may be united and 
the eyes merged into a single organ. 
Malformations due to excessive growth are characterized by abnormal 
size or increase in number of individual parts. For example, an extrem- 
ity or a portion of dne, as a finger, may reach abnormal size (partial giant 
growth), or the whole body may be involved in abnormal growth (general 
giant growth). Increase in number occurs particularly in the mammary 
gland, spleen, adrenals, and fingers, accessory or supernumerary organs. 
Among malformations due to abnormal disposition of organs are 
certain anomalies of the organs of the thorax and abdomen. Tn this class 
belongs the condition known as situs transversus — that is, transposition 
of the thoracic or abdominal organs, or of both. Various defects in the 394 
DISTURBANCES OF DEVELOPMENT. 
heart and great vessels may also be classed here, though it should be noted 
that these are more properly regarded as arrests of development. 
A fourth group of malformations includes those characterized by 
displacement of tissues and by persistence of foetal formations, as 
already mentioned in §§ 126 and 128. 
In the fifth group may be classed those malformations exhibiting a 
mixture of sexual characteristics, known as true and false hermaphro- 
ditism. True hermaphrodites possess both male and female sexual 
glands; false hermaphrodites are unisexual, but the remainder of the 
sexual apparatus does not correspond to the sexual gland, or there is 
simultaneous formation of organs belonging to both the male and female. 
Some of these malformations are arrests of development; others are to 
be regarded as cases in which from the original bisexual primordia the 
organs of both sexes have developed, whereas normally those of one sex 
undergo retrograde change, and persist only in rudimentary form. 
§ 131. Double monsters are malformations consisting of two indi- 
viduals; if both twins are developed (symmetrical twins) they are always 
of the same sex and are united to each other in the same portions of the 
body; the duplicated portions are usually equally developed, but unequal 
forms occur in which one twin is stunted in its development. Asymmetri- 
cal forms also occur in which one twin remains rudimentary and is 
dependent on the other for its nutrition (parasitic double monster). 
Often it is implanted in the other (see § 127). 
All double monsters arise from one egg and have a common chorion. 
In the formation of symmetrical double monsters two separate embryonal 
primordia are probably formed from one germinal vesicle, and in their 
growth blend with each other to a greater or less extent, but duplication 
or splitting may occur within a single primordium; this process occurs 
particularly in anterior reduplications and can be produced experimentally 
in animals. The genesis of rudimentary asymmetrical twins occurs in 
the manner described in § 127 (Teratomata). 
II. The Different Forms of Malformations in Man 
I. Arrests of Development in a Single Individual. 
(a) Arrest of the Development of the Entire Embryonal Primordium. 
§ 132. Arrest in the development of the entire embryo manifests 
itself in two ways. If the disturbance is marked, further development 
of the embryo is impossible, and it either dies at once or becomes stunted, 
and after a certain time perishes. If the disturbance is less severe there 
develops a normally formed foetus, but it remains small and stunted — 
that is, a dwarf is formed. 
A dead foetus in the majority of cases is expelled together with its 
membranes (abortion). In other cases the embryo for some cause re- 
mains stationary in development, the egg may stay for weeks or even 
months in the uterus and increase in size, and there arises disproportion 
between the size of the embryo and the .egg. The first changes after death 
are shown in swelling of the central nervous organs, leading to changes 
in the configuration of the head. Later there occurs infiltration of the 
tissues with wandering cells, the boundaries of the organs are indistinct, 
the entire embryo becomes cloudy and soft, and finally is completely 
dissolved. LITHOPAEDION. 
395 
When a foetus well advanced in development dies and remains in the 
maternal organism a lithopaedion may result. This occurs most fre- 
quently in extrauterine pregnancy, in which the embryo lies in the peri- 
toneal cavity, in a tube, or in an ovary. If the foetus dies at such an 
advanced stage of development that it cannot be absorbed, it may be 
carried in the maternal body for years. Not infrequently its form is 
Fig. 350.—-Lithopsedion, entirely inclosed in connective-tissue membranes (removed from 
abdominal cavity by operation two years after beginning of pregnancy). Extrauterine pregnancy 
caused by embryo breaking through the uterine portion of a tube into the abdominal cavity. 
Reduced to one-third. 
perfectly preserved (Fig. 350), and the foetus becomes inclosed in a con- 
nective-tissue membrane. In other cases the foetus, in time, becomes par- 
tially converted into a fluid mass, which contains osseous remains, fat, 
cholesterin, and pigment, and is surrounded by a fibrous capsule. Lime-salts 
are usually deposited in the newly formed membranes as well as in the 
portions of the foetus remaining, and for this reason the foetus is known 
as a “ stone-child ” or “ petrified child.” 
According to the condition of the foetus there may be distinguished 
three forms of lithopsedion. In the first the mummified foetus may be 
shelled out from the calcified membranes. In the second form the foetus 
becomes adherent to the membranes at various points which become calci- 
fied, while the other portions become mummified. In the third form the 
foetus is discharged into the peritoneal cavity, and becomes encrusted with 
lime-salts. 396 
DISTURBANCES OF DEVELOPMENT. 
(b) Defective Closure of the Cerebrospinal Canal and the Accompanying 
Malformations of the Nervous System. 
§ 133. Defective closure of the vertebral canal leads to malforma- 
tions. If the defect in the vertebral column is open so that at the bottom 
of the cleft the bodies of the vertebrae covered by membrane are seen, 
the malformation is termed rachischisis. When, at the site of the defect, 
there is a protruding sac, the malformation is designated spina bifida, or 
spina bifida cystica. 
Fig. 351.—Craniorachischisis with total absence of the brain and spinal cord. The base 
of the skull is covered with ragged membranous masses, the open spinal furrow with a delicate 
membrane (pia mater). Kypholordotic curvature and shortening of the spinal column. Reduced 
one-sixth. 
In rachischisis totalis (Fig. 351) the bodies of the vertebrae form a 
shallow groove opening posteriorly, usually covered by a thin, transparent 
membrane; in rare cases rudiments of the spinal cord are present in the 
form of whitish bands and lines. In this manner there occurs total or 
partial amyelia. The defect involves principally the motor tracts and 
centres, as well as the columns of Clarke and the lateral cerebellar tract, 
while the spinal ganglia are developed and may send sensory fibres into 
the membranous masses of the spinal groove. 
The delicate membrane which lines the furrow and covers the dura 
mater lying beneath it on the bones is the ventral portion of the spinal 
pia mater. A part of the nerve-roots may have undergone development, 
arising either from rudiments of the spinal cord or from spinal ganglia. 
Partial rachischisis usually involves the sacrolumbar or the upper 
cervical region, while the intervening portions of the vertebral column are 
only rarely the seat of malformations. The dorsal surfaces, with the 
overlying dura and pia mater, of the bodies of the vertebrae whose arches 
remain rudimentary are covered for the greater part by a mass of velvety, SPINA BIFIDA. 
397 
vascular tissue, which contains rudiments of the spinal cord (the area 
medullo-vasculosa, von Recklinghausen), though the amount of this tissue 
may be small or even wanting. To the outside of this layer, which is not 
everywhere equally abundant and which diminishes at the sides, there 
Fig. 352.—Spina bifida sacralis. (After Froriep and Forster.) A girl of nineteen years, born 
with a tumor the size of a pigeon’s egg over the upper sacral and lower lumbar regions, which 
enlarged from the sixth year on, while at the same time club-feet developed. 
comes a delicate, transparent, vascular membrane which represents the 
continuation of the pia mater covered with epithelium; and outside of 
this, a zone of epidermoidal tissue somewhat thinner than normal skin, 
and often covered with many hairs (zona dermatica), separating the 
reddened central area from the normal skin. 
Spina bifida cystica or rachicele occurs in three forms: myelomen- 
ingocele, meningocele, and myelocystocele. 
According to site there may be distinguished 
cervical, dorsal, lumbar, lumbosacral, and 
sacral spina bifida. In general, spina bifida 
is characterized by the development of a 
fluctuating tumor, which in most cases is 
visible (Fig. 352) on the posterior aspect 
of the spinal column (spina bifida pos- 
terior) ; but instances occur in which the 
sac projects anteriorly (spina bifida an- 
terior), and others in which it is so small 
that it is covered with normal skin and is 
not visible externally (spina bifida occulta). 
Myelomeningocele appears most fre- 
quently as spina bifida lumbosacralis, and 
forms a tumor varying in size from a nut 
to that of an apple and increasing in size 
after birth, in the region of the lower 
lumbar and upper sacral vertebra. It is 
covered by smooth or scar-like skin, or may 
be devoid of skin on its summit and there 
covered by a reddish, mucosa-like tissue 
(area medullovasculosa). The portion un- 
covered by skin may be drawn in, like a 
scar. In rare cases there may be no ex- 
ternal tumor (spina bifida occulta), the site 
of the cleft being indicated by more marked 
growth of hair or by a depression. 
On opening the sac, which is composed of arachnoid (Fig. 353, e), and 
pia (/, fx), while the dura (g) does not extend over the dorsal portion of 
the sac, it may be seen that the lower end of the spinal cord (&,) is drawn 
outward, and that the cavity of the sac is crossed by nerve-roots (i, it). 
Fig. 353.—Myelomeningocele sa- 
cralis in sagittal section, a little to the 
left of the median line. (After von 
Recklinghausen.) a, Skin; b, b i, 
spinal cord; c, area medullovasculosa; 
d, cranial; di, caudal polar groove; 
e, arachnoid; f, pia, somewhat sepa- 
rated from the arachnoid; fi, portion 
of pia mater turned over; g, dura 
mater; h, recurrent roots of the_fourth 
lumbar nerve; i, radix anterior; ti, 
radix posterior of the fifth lumbar 
nerve, running free through the 
arachnoid sac; k, sacral nerve-roots 
between the arachnoid and pia; l, 
filum terminale. 398 
DISTURBANCES OF DEVELOPMENT. 
Occasional nerve-roots (h) may also spring from the columns of the 
cord (&x) in its course through the sac. 
There is, therefore, accumulation of fluid in the meninges, hydro- 
meningocele, combined with prolapse of the spinal cord, myelocele. At 
the site of the protrusion the vertebral arches are defective; this defect 
may reach as far as the hiatus sacralis. Smaller defects may involve 
only one or two vertebrae. 
Dorsal and cervical meningoceles are more rare than the lumbosacral. 
The defect in the vertebral arch is usually confined to one or two verte- 
brae. The spinal cord is involved in the meningocele, in that portions of it 
are drawn outward in the form of a band or cone. 
Hydromeningocele spinalis arises from hernial protrusion of spinal 
arachnoid due to localized collection of fluid in the subarachnoid space. 
It may occur at the upper end of the spinal column in a cleft of the 
cervical vertebrae, at the same time with hernia of the brain in the oc- 
cipital region. More frequently, however, it occurs in the sacral region, 
where protrusion takes place either through a defect in the vertebral 
arches and bodies or through the hiatus sacralis, or between vertebral 
arches, or through intervertebral foramina. In the majority of cases the 
dura takes no part in the formation of the sac, although views differ on 
this point, and by many writers a dural sac is described. Through pro- 
gressive accumulation of fluid the sac may attain large size. Small men- 
ingoceles may be concealed in the deep tissues. 
According to the direction of the hernial protrusion there may be 
distinguished a meningocele posterior and a meningocele anterior, the 
latter taking place through defect in the bodies of the vertebrae. 
Myelocystocele or hydromyelocele (syringomyelocele) takes origin in 
dilatation of the central canal of the spinal cord, as a result of which a 
portion of the cord with its connective-tissue envelopes becomes converted 
into a cystic tumor. The dura is usually wanting over that portion of the 
sac protruding from the vertebrae. 
The wall of these sacs is formed of the inner spinal meninges, but is 
lined on the interior by cylindrical epithelium, and has at some part of its 
inner surface an area medullovasculosa — usually on the ventral side, 
rarely on the dorsal. The roots, if they are still preserved, spring from 
the ventral, rarely from the dorsal outer wall of the sac. The cavity itself 
is crossed neither by bands nor by nerves. 
Myelocystoceles occur, in the majority of cases, in lateral clefts of the 
vertebral column. They show a tendency to combine with defects and 
asymmetries of the bodies of the vertcbrce, and therefore with shortening 
of the trunk, which at times affects only the dorsal region, at other times 
also the lumbar region. Frequently there co-exists exstrophy of the blad- 
der and intestine. 
Myelocystoceles usually are covered only by skin, but are sometimes 
concealed deep in the soft parts. They may be combined with meningocele 
—- myelocystomeningocele. 
In cases of rachischisis there sometimes occurs division of the spinal 
cord into two parts (diastematomyelia), most often in total rachischisis, 
in which indeed only rudiments of the spinal cord are indicated. In partial 
rachischisis such division is rare, the separated strands of spinal cord are 
better developed, and the fibrous and bony coverings may, at the beginning 
or end of the cleft, send septa between them. Cases have occurred in 
which each cord-half possessed an H-shaped area of gray matter. RACHISCHISIS. 
399 
In the earliest embryonic period the medullary groove is formed by the de- 
velopment on both sides of the median line of wall-like elevations of the ectoderm 
which are designated medullary folds. Through the converging growth and union 
of the latter the medullary groove is closed and formed into the medullary canal. 
Thereupon the cell-masses (primitive vertebral plates) lying at the sides of the 
newly formed canal form an envelope about it, which gives rise to a membranous, 
non-articulated vertebral column. In this, at the beginning of the second month, 
there arise discrete cartilaginous areas from which, in the course of further de- 
velopment, the vertebral bodies and arches are formed, while between them the 
intervertebral discs and vertebral ligaments appear. The development of the car- 
tilaginous vertebrae is not completed until the fourth month, and up to this time 
the dorsal covering of the medullary tube consists of the united portions of the 
membranous vertebral column. The cartilaginous constituents of the vertebrae are 
in the course of development replaced by bone. 
The origin of rachischisis is to be referred to agenesia and hypoplasia of the 
medullary folds, which should form the medullary groove of the vertebral arches. 
The agenesia of the spinal cord is also to be dated from the very earliest period. 
Fig. 354.—Anencephatia et acrania. Reduced 
one-half. 
Fig:. 355.—Cranioschisis with Exencephalia. 
Whether it is a primary agenesia predetermined in the germ, or whether extrinsic 
influences, perhaps toxic substances (Hertwig), pressure from without, or the in- 
closure of foetal membranes, may have secondarily checked development or have 
destroyed parts already formed, it is difficult to determine; the symmetrical dis- 
tribution of the arrested development speaks in favor of the former view. 
In cases of spina bifida with hernial protrusion, local defects in the bony verte- 
bral column and defective development of the dura mater, which is usually wanting 
at the site of the protrusion, are to be regarded as the primary condition. The growth 
of the sac may be explained as due to congestive and inflammatory transudation, 
and the residue of inflammatory changes, such as thickenings and membranous ad- 
hesions, may often be demonstrated in.the pia. 
Von Recklinghausen refers the origin of myelocystocele and myelocystomen- 
ingocele to deficient growth in the long axis of the vertebral column, character- 
ized anatomically by shortness of the column, absence of vertebrae or parts of 
vertebrae, separation of wedge-shaped bony pieces from the bodies of the verte- 
brae, and by unilateral defects in the arches. The neural canal, then, in the course 
of normal development, becomes too long for the vertebral canal, and in conse- 
quence becomes curled or kinked, and there is a tendency to partial protrusion 
of the medullary tube at the point of sharpest bending. Marcland believes that 
this hypothesis is not applicable to all cases, and Arnold is also of the opinion that 
the causal relations between arrests of development in the muscle-plates and verte- 
bral primordium on the one hand, and those of the medullary canal on the other, are 
not constant, but that a variety of harmful influences may give rise to one or more 400 
DISTURBANCES OF DEVELOPMENT. 
of these anomalies. Lucksch emphasizes the effects of pressure as the cause of 
myeloschisis, but without excluding other causes. 
According to O. Hertwig, the ordinary spina bifida is an arrest of development 
depending on partially prevented closure of the blastopore (“ Urmundspalte ”). 
§ 134. Faulty de- 
velopment of the 
cranium and asso- 
ciated disturbances of 
cerebral development 
lead to those malfor- 
mations known as 
cranioschisis, acrania, 
hemicrania, microcep- 
halus, ancncephalus, 
exencephalus, micren- 
cephalus, and cephalo- 
cele. 
Acrania and hemi- 
crania or cranioschisis 
are the results of agen- 
esia or hypoplasia of 
the bony and mem- 
branous portions of the cranial vault, which arise as primary disturbances 
of development or as the result of harmful extrinsic influences on the 
cerebral primordium. 
In acrania both the bony portion and the skin of the cranial vault (Figs. 
354, 356) are wanting, the base of the skull being covered with mem- 
branous vascular tissue. 
If the defect in the cranial vault is associated with a similar defect in 
the vertebral arches, there is produced the condition known as craniora- 
Fig. 356.—Partial agenesia of the bones of the cranium in 
anencephalia. a, Defect; b, squamous portion of the occipital 
bone; c, parietal bone; d, frontal bone. Reduced one-fifth. 
Fig. 357.—Hydrencephalocele occipitalis. 
Fig. 358.—Encephalomeningocele nasofrontalis. 
chischisis (Fig. 351), in which the spinal column is usually shortened 
and bent, the head in consequence being drawn sharply backward and 
the face turned upward. Through bulging of the eyes with deficient de- 
velopment of the forehead, these malformations may resemble frogs 
(frog foetus). 
In hcmicrania the flat bones of the cranial vault have undergone more 
or less extensive development (Fig. 356, b, c, d) and form a cranial cavity, 
which is small, in that the flat bones of the vault are elevated but a short 
distance above the base of the skull. If the bones of the cranium DEFECTS OF CRANIUM. 
401 
have undergone imperfect development but unite with one another as 
under normal conditions, there is produced simple microcephalus, 
which may be present at birth or develop later, as the result of im- 
perfect development of the skull. 
Acrania and hemicrania ar'e often associated with total anenceph- 
alus, the base of the skull being covered by vascular connective tissue 
with no trace of brain tissue or only rudiments (area cerebrovasculosa). 
In other cases the meninges contain, besides cystic cavities and gland- 
like remnants of the medullary plate, brain-substance, which usually pro- 
trudes through the defect in the cranial vault, giving rise to exenceph- 
alus (Fig. 355). The hernial masses are inclosed by a soft membrane 
corresponding to the inner meninges, or are covered by skin. 
If the cranium presents partial defects, portions of the contents 
may protrude in the form of a sac. Such a condition is known as 
hernia cerebri or cephalocele (Figs. 357, 358). The dura mater is 
wanting over the extracranial portion of the sac. 
The size of the protruding sac varies; it may be so small as to be 
found only after careful examination, or it may be so large as to approach 
the brain in volume. If the arachnoid and pia 
protrude as the result of collection of fluid in 
the subarachnoid space, the hernia is desig- 
nated meningocele. If at the same time there 
is a protrusion of brain-substance, it is known as 
meningoencephalocele. A hernia of brain-sub- 
stance and pia without collection of fluid is an 
encephalocele; if the protruding brain-sub- 
stance contains a portion of a ventricle filled 
with fluid, it is designated hydrencephalocele. 
Cerebral hernias occur chiefly in the occipital 
region (hernia occipitalis), close above the fora- 
men magnum (Fig. 357), and at the root of 
the nose (hernia syncipitalis). In the latter 
region it may involve the frontal bone (hernia 
nasofrontalis), (Fig. 358), the ethmoid (hernia 
naso-ethmoidalis) or the lachrymal bone (hernia naso-orbitalis). More 
rarely hernias occur on the sides (hernia lateralis) or at the base of the 
skull (hernia basalis). The latter may bulge toward the nasopharynx 
(hernia sphenopharyngea), into the orbit (hernia spheno-orbitalis), or 
into the fossa sphenomaxillaris (hernia sphenomaxillaris). 
In central hernia the brain may be normal or malformed. As a result 
of marked stunting of development, particularly in the region of the fore- 
most of the three cerebral vesicles, the cerebrum may remain single, while 
at the same time deficient separation of the ocular vesicles takes place 
(cyclencephalia or cyclocephalia of St.-Hilaire). In severe grades of this 
form of maldevelopment only one eye may be formed, lying in the middle 
of the forehead, or two united eyes may be found in one orbital cavity — 
(Fig. 359), cyclopia, (or synophthalmus,) and arrhinencephalus. The 
nose is also stunted (Fig. 359) and forms a cutaneous tag attached above 
the eye, and devoid of bony foundation (ethmocephalia). 
When the eyes are separate, yet abnormally close together, the nose 
may be normal, though small at the root (cebocephalia). 
In more severe grades of these malformations the ethmoid bone and 
nasal septum may be wanting, and the upper lip and palate cleft in the 
Fig. 359.—Synophthalmos or 
cyclopia. 402 
DISTURBANCES OF DEVELOPMENT. 
median line, on one or both sides. In lighter grades the forehead is reduced 
in size and pointed. 
In the severe forms the cerebrum consists of a sac, occupying 
more or less of the cranial cavity and filled with clear fluid; at those 
points where the sac does not touch the cranial wall the intervening 
space is filled by fluid distending the subarachnoid space (h). In 
the less marked forms only individual portions of the brain are unde- 
veloped, those parts chiefly affected being the olfactory lobes and nerves, 
the corpus callosum, a part of the convolutions, etc. The optic thalami are 
often blended. The chiasm and the optic tract may be absent or present. 
The corpora quadrigemina (k), pons, medulla oblongata, and cerebellum 
(/) are usually unaffected. 
The spinal cord and brain arise from the medullary canal. In that portion that 
is to become the brain, the neural canal changes very early into three vesicles. 
The most anterior of these, the forebrain, throws out from its lateral portions the 
primary optic vesicles, while the middle portion grows forward and upward and 
divides into the telencephalon or forebrain, and the diencephalon or tweenbrain. 
From the former are developed the cerebral hemispheres, corpora striata, corpus 
callosum, and the fomix. From the tweenbrain are formed the optic thalami and 
the floor of the third ventricle. The second vesicle or midbrain forms the corpora 
quadrigemina, while the third vesicle divides into the isthmus, metencephalon, and 
myelencephalon, from which there are developed the pons, cerebellum, and medulla 
oblongata. 
The cerebral portion of the medullary canal becomes inclosed by the primitive 
vertebral plates of the head, which form the membranous primitive skull, the basal 
portions of which become cartilaginous in the second month of foetal life. In the 
third month the basal cartilage and the membranous vault begin to ossify. 
According to G. St.-Hilaire, Forster, and Panum, acrania and anencephalus are 
to be referred to abnormal accumulation of fluid in the cerebral vesicles, hydro- 
cephalus, occurring before the fourth month. Dareste and Peris oppose this view, 
and point out that in acrania the base of the skull is usually bulged inward and not 
pressed outward. They therefore seek the cause of acrania in pressure exerted 
on the cranium from without {Peris), due to abnormal tightness of the cephalic 
cap of the amnion, which retards the development of the cranium. Lebedeff seeks 
the cause of acrania is abnormally sharp bending of the body of the embryo, which, 
he thinks, occurs when the cephalic end of the embryo grows abnormally in the 
longitudinal axis, or in case the cephalic covering lags behind in its development. 
By sharp bending the change of the medullary groove into the medullary canal 
is thought to be hindered, or the canal after its formation is destroyed. From 
this could be explained the later absence of the brain, as well as of the mem- 
branous and osseous cranial covering. The cystic formations in the membranes 
lying on the base of the skull are, according to Lebedeff, formed from the folds of 
the medullary plate, which sink into the mesoderm and are snared off. 
Hertwig thinks it possible that chemical substances circulating in the blood 
or secreted from the wall of the uterus may destroy the primordium of the brain. 
According to K. and A. Petren, the spinal ganglia in anencephalus are always 
normally developed; on the other hand, the columns of Clarke, the lateral cere- 
bellar tracts, and the bundles of Gowers are either wanting or imperfectly de- 
veloped. Likewise the pyramidal tracts are wanting, while the anterior-horn gang- 
lion-cells and the anterior roots are developed. K. and A. Petren, therefore, regard 
the malformation as a system-defect in which neurones of the second order are 
not formed. 
(c) The Malformations of the Face and Neck. 
§ 135. The development of the face not infrequently suffers disturb- 
ances leading to more or less marked malformations, which may appear 
alone or in association with malformations of the cranium. If the frontal 
process and the maxillary processes of the first branchial arch remain in a 
rudimentary state or are destroyed, there persists at the site of the face an DEFECTS OF FACE AND NECK. 
403 
open sinus giving rise to the conditions known as aprosopia (absence 
of the face) and schistoprosopia (cleft face), which may be associated 
with defective development of the nose and eyes. 
More frequently than these large defects are smaller clefts involving 
the lips, alveolar process of the upper jaw, the upper jaw itself, and the 
hard and soft palates (Fig. 360), which are designated cheilo-gnatho- 
palatoschisis or “ wolf’s jaw.” This malformation gives rise to a com- 
munication between the mouth and the nasal cavity (Fig. 360). The hard 
palate is cleft in the part bordering on the vomer; the soft palate in the 
median line. In the alveolar process of the upper jaw the cleft runs be- 
tween the canine tooth and the outer incisor or between the outer and 
inner incisors. The malformation may be bilateral or unilateral. 
Not infrequently the cleft involves portions of the regions mentioned, 
Fig. 360.—Double cheilo-gnathopalatoschisis. 
(Wolf’s jaw.) 
Fig. 361.—Agnathia and synotia 
(After Guardan.) 
as the upper lip (harelip, labium leporinum), or the hard or soft palate. 
The lightest grades of this form of cleft-malformation are represented 
by a notch in the lips or by bifurcation of the uvula. 
Prosoposchisis or oblique facial cleft (Fig. 348) is the designation 
applied to a cleft running obliquely from the mouth to an orbit. It is 
usually associated with malformations of the brain. Three forms may be 
distinguished. The first is a cleft beginning in the upper lip as a harelip, 
passing into the nasal cavity, thence around the ala nasi toward the orbit, 
and even beyond the latter. The second form likewise begins in the 
region of a harelip, but extends outward from the nose toward the orbit. 
The third form extends from the corner of the mouth, outward through 
the cheek toward the canthus of the eye, and divides the superior maxillary 
process externally to the canine tooth. A transverse cleft of the cheek 
also occurs, passing from the corner of the mouth toward the temporal 
region. 
Median facial clefts (nasal cleft) run in the median line involving 
the nose, upper jaw, and also the lower jaw, and may extend as far as the 
sternum. The tongue may be cleft. The defect may extend even to the 
frontal bone and brain. 404 
DISTURBANCES OF DEVELOPMENT. 
All of the above-mentioned clefts may be confined to small portions 
of the regions mentioned, and may attain varying depths. 
If the development of the inferior maxillary process of the first 
branchial arch is retarded, the inferior maxilla is imperfectly developed or 
wanting, and there arise those malformations known as brachygnathia or 
agnathia (Fig. 361). The lower portion of the face appears as if cut 
away; the ears are sometimes brought so close as to touch (synotia). 
Uusually the superior maxillary processes are imperfectly developed; not 
infrequently the ear is malformed. 
Abnormal largeness of the mouth (macrostomia), abnormal smallness 
(microstomia) closure (atresia oris), and duplication of the mouth (dis- 
tomia) are all rare. 
When the embryonic external branchial clefts or internal branchial 
pockets fail to close, there persist fistulse opening externally or internally, 
or closed cysts. The former condition is known as fistula colli congenita. 
The mouths of the external fistulse are usually found at the side of the 
neck, more rarely nearer to or in the median line; those of the internal 
fistulae open into the pharynx, trachea or larynx. Often the remains of 
the branchial pockets form diverticula of the last-named organs. The 
fistulae are covered with mucous epithelium, sometimes ciliated, arising 
from the visceral branchial pockets, usually from the second. In rare 
cases there is a complete branchial fistula with both external and internal 
openings. 
Branchial cysts are sometimes lined with ciliated epithelium and con- 
tain fluid; they are called hydrocele colli congenita. At other times they 
possess an epidermoidal covering and inclose epidermoidal cell-masses. 
Cysts of the neck lying in the median line and reaching to the hyoid bone 
may develop from remains of the ductus thyreoglossus. 
The face and neck are developed in part from a single and in part from 
paired primordia. The latter are represented in the branchial or visceral arches 
growing from the lateral portions of the base of the skull ventrally in the 
primitive throat-wall. The single primordium, designated the frontal process, is 
a prolongation downward of the base and vault of the cranium, and is, in fact, 
nothing more than the anterior end of the skull. Between the individual branchial 
arches there are at a certain period cleft-like depressions known as the branchial 
pockets. 
The frontal process and the first branchial arch form the boundaries of the 
great primitive mouth-opening, which has a diamond shape. In the course of 
development the first branchial arch sends out two processes, the shorter of which 
applies itself to the under surface of the anterior portion of the head and forms 
the upper jaw, while from the longer one the lower jaw is developed. The frontal 
process, which forms the anterior boundary, gives rise to a broad prolongation of 
t*he forehead, and then pushes on two processes which are known as the lateral 
nasal processes. By further differentiation of the central portion of the frontal 
process proper, the septum narium is formed, which by means of two spurs, the 
inner nasal processes, produces the borders of the external nasal opening and the 
nasal furrow. The lateral nasal processes are the lateral portions of the skull, 
and later develop within themselves the ethmoid labyrinth, the cartilaginous roof, 
and the sides of the anterior portion of the nares. At a certain stage they form 
with the superior maxillary process a furrow running from the nasal furrow to 
the eye, the lachrymal fissure. 
In the beginning the mouth is a large sinus, but is soon separated into a 
lower and larger digestive and an upper and smaller respiratory portion. This 
separation is brought about by the development, from the superior maxillary pro- 
cesses of the first branchial arch, of the palatal plates, which from the eighth week 
on blend into each other and at the same time unite with the lower border of the 
nasal septum. The union of the anterior portions of the palatal plates takes place 
earlier than that of the posterior portions. DEFECTS OF THORAX AND ABDOMEN. 
405 
Through union of the contiguous portions of the frontal and nasal processes 
with the superior maxillary processes the cheek is formed and a continuous 
superior maxillary border, from which are developed later the lip and the alveolar 
process of the upper jaw and intermaxillary bones, while the external portion of 
the nose develops from the frontal process. The intermaxillary bones are de- 
veloped as independent bones, but unite very early with each other and with the 
upper jaw. 
(d) Faulty Closure of the Abdominal and Thoracic Cavities, and the 
Accompanying Malformations. 
§ 136. Arrests of development of the ventral body-wall may take 
place at different points and exhibit different 
grades of severity. They occur most frequently 
in the region of the umbilicus, where the closure 
of the abdominal cavity takes place latest. In 
the event of imperfect development of the ab- 
dominal wall at this point, so that this area is 
closed only by peritoneum and the sheath of 
the umbilical cord, and if these are pushed for- 
ward by the abdominal organs (Fig. 362), 
there is produced the condition known as om- 
phalocele, or umbilical hernia. The umbilical 
cord is attached to the sum- 
mit or at one side of the 
hernial sac, and is more or 
less shortened. 
If the anterior abdominal 
walls wholly or in part fail 
to unite, there arise those 
conditions which are desig- 
nated fissura abdominalis, 
or gastroschisis completa 
and thoracogastroschisis. 
These are characterized by 
the undeveloped abdominal 
coverings not having been 
separated from the amnion, 
but passing into it. The 
greater part of the ab- 
dominal organs lies in a sac 
formed by the amnion and 
peritoneum (eventration). The peritoneum, however, may be wanting, 
likewise the umbilical cord, and the umbilical vessels may pursue their 
course to the placenta independently. 
A cleft confined to the thorax is called thoracoschisis. Should the 
heart, covered only with pericardium or free, protrude, the condition is 
designated ectopia cordis. 
When the failure to close is confined to the region of the sternum, 
the condition is designated fissura sterni. This defect may involve the 
whole or a part of the sternum, at times affecting the bones, at other 
times only the skin. 
The protrusion of the urinary bladder through a cleft in the abdominal 
wall is known as ectopia vesicae urinariae. 
Fig. 362.—Hernia funiculi umbilicalis. Reduced to 
one-third. 406 
DISTURBANCES OF DEVELOPMENT. 
Clefts of the abdominal wall are not infrequently associated with 
clefts of the parts lying behind the wall, not only large clefts (total), but 
smaller ones (partial). When a cleft of the lower portion of the ab- 
dominal wall is associated with a cleft of the urinary bladder, so that the 
posterior wall of the latter prorrudes through the abdominal fissure, the 
condition is known as fissura, or exstrophia, or inversio vesicas urinariae. 
Occasionally the pelvic girdle and the urethra are cleft, the latter being 
represented by a groove open anteriorly. The exstrophy is then said to 
be complicated by fissura genitalis and epispadias. 
When an abdominal fissure or an abdominal and vesical fissure is 
combined with a fissure of the intestines, there is produced fissura ab- 
dominalis intestinalis or vesicointestinalis. The intestinal fissure is sit- 
uated in the caecum or beginning of the colon, and the mucous membrane 
of the cleft intestine protrudes through the opening in the same manner 
as the posterior wall of the bladder; the condition is called exstrophia or 
inversio intestini. 
If the omphalomesenteric duct does not undergo normal involution, 
there remains at the lower end of the small intestine an appendix of intes- 
tine called Meckel’s diverticulum, which arises perpendicularly from the 
outer margin of the intestine. It has the appearance of a glove-finger, and 
either swings free or is attached to the umbilical ring, sometimes being di- 
lated at its end. In case of adhesion to the umbilical ring the intestinal 
mucosa may appear at the navel in the form of a tumor (ectopia intestini, 
adenoma umhilicale). In rare cases a cyst lined with mucous membrane 
may be formed in the abdominal wall (omphalomesenteric cyst). 
Congenital fistulse of the urachus, that is, fistulae lying in the umbilicus 
and connecting with the bladder by a tract, depend on incomplete oblitera- 
tion of the urachus or of the stalk of the allantois. They may be associated 
with an open or a closed urethra. 
The development of the body-form from the flat embryonic primordium begins 
by snaring-off of the individual germ-layers from the outer embryonal area, and 
their folding to form two tubes, the body-wall and the alimentary canal. 
The infolding of these layers takes place at the cephalic and caudal ends, as 
well as at the lateral portions of the embryonal primordium, and as the summits 
of the folds gradually grow together from all directions, those which form the 
body-wall produce a tube whose cavity finally communicates only at the parietal 
umbilicus, by means of a peduncle-like prolongation, with the cavity of the extra- 
embryonic portion of the blastoderm known at this time as the vitelline membrane. 
While the lateral and ventral walls of the embryo are being formed, in the body 
the intestinal furrow also closes to form a tube, which is in communication at only 
one point lying within the parietal umbilicus, known as the visceral umbilicus, with 
the cavity of the umbilical vesicle, by means of a channel known as the omphalo- 
mesenteric duct. 
Umbilical hernia and clefts of the upper portion of the abdominal wall are 
frequently combined with craniorachischisis, while exstrophy of the bladder and 
intestine is often associated with myelocystocele. According to von Recklinghausen, 
the two malformations are to be regarded as coordinated with each other. Further, 
large abdominal clefts are often associated with lordotic and scoliotic curvatures of 
the spinal column. 
(e) Malformations of the External Genitalia and Anus, due to Arrested 
Development. 
§ 137. Malformations of the external genitals may be associated with 
malformations of the abdominal wall, bladder, and the internal genital 
organs, or may occur independently of these. Complete absence of the 
external genitalia occurs most frequently in connection with other mal- DEFECTS OF GENITALS. 
407 
formations of this region, particularly in the case of sirenomelia, (Fig. 
363). The internal genitals usually are also malformed. 
A stunted condition of the penis is not rare, the organ in consequence 
coming to resemble more or less the clitoris. This condition is usually 
associated with hypospadias — that is, the urethra opens on the under 
side, either beneath the glans, the body or the root of the penis, or even 
behind the scrotum (hypospadias perineoscrotalis). These malformations 
may exist in penises otherwise normally developed, and depend on partial 
failure of the sexual furrow to close. 
Epispadias is that condition in which the urethral opening is 
found on the dorsum of the penis. It 
is more rare than hypospadias, and is de- 
pendent on defective or delayed closure 
of the pelvis, so that the cloaca, before 
the closure, becomes divided into an in- 
testinal (anal) and a genital opening. 
Under certain conditions the penis re- 
mains cleft throughout its length; at the 
same time a fissure of the bladder and ab- 
domen may be present. 
Hypertrophy of the prepuce is not 
rare. If the preputial opening is nar- 
rowed so that the prepuce cannot be 
drawn back over the glans, the condition 
is designated hypertrophic phimosis. 
Total absence of the prepuce is rare; 
abnormal shortness is more frequent. 
Defective development of the scro- 
tum is usually associated with retention 
of the testicles in the abdominal cavity or 
in the inguinal canal, and leads to appear- 
ances whereby the external genital organs 
of the male resemble those of the female, 
especially when the penis is stunted. 
In the female the clitoris as well as 
the labia majora and minora may show 
stunted development. Epispadias and 
hypospadias also occur in the female sex, 
the former coincidently with a fissure of 
the abdominal and bladder walls. In 
hypospadias a portion of the posterior wall of the urethra is lacking, 
and the urethral opening may be found within the vagina. 
Absence of the urethra occurs in both sexes (Fig. 363). In girls 
the bladder may open directly into the vagina. 
Closure (atresia) of the urethra likewise occurs in both sexes, and 
results either from a partial defect of the same or from obliteration of the 
orifice. Accumulation of urine in the bladder may lead to marked dilata- 
tion of the viscus (Fig. 363). 
Abnormal narrowness of the urethra may exist in a portion of its 
course or throughout its length. Further, its lumen may be narrowed as 
the result of hypertrophic development of the colliculus seminalis. 
Fig. 363.—Complete absence of the 
urethra and external genitals, with ex- 
treme distention of the body due to an 
enormous dilatation of the bladder. 
Compression and stunting of the lower 
extremities. (In the posterior wall of 
the bladder rudiments of a female 
genital apparatus in the form of por- 
tions of the tubes and ovaries were 
found.) 408 
DISTURBANCES OF DEVELOPMENT. 
In rare cases multiple orifices of the urethra have been observed. 
Further, in men there may be found in the glans penis a blind tube lying 
beside the urethra. 
Atresia ani simplex is closure of the anus, the intestine being at the 
same time well developed. It may arise from failure of the ectoderm to 
fold in at the anal site, or a cloaca already existing and opening outward 
may again become closed through adhesions. If the rectum does not end 
immediately above the anal membrane but higher up, there exists in addi- 
tion to the atresia ani atresia recti, a malformation which may occur even 
when the anus is well developed. 
When, with absence of the anus, there is also arrested development of 
the vaginal wall, which grows downward, between the sinus urogenitalis 
Fic.. 364.—Amelus. 
Fig. 365.—Micromelus with cretin-like facies. 
and intestine, to unite with the perineum, there remains a cloaca in which 
the sinus urogenitalis and the end of the bowel unite. In other cases there 
are found fistulous communications between the rectum and the blad- 
der or urethra (in boys), or between the rectum and the vagina or 
uterus (atresia ani vesicalis, urethralis, vaginalis, uterina). 
In rare cases the intestine, in anal atresia, may open by external 
fistulae in the perineum, scrotum, or sacrum. External fistulse below the 
anus may occur as remains of the post-anal gut. 
(/) Malformations of the Extremities due to Arrested Development. 
§ 138. Defective development of the extremities is not rare, and is 
to be referred to primary defect of the primordium of an extremity, to 
disturbance in the later development of the limbs or the bones, and to con- 
strictions caused by strands of foetal membranes or by loops of the um- 
bilical cord. Defective development of the extremities may also follow 
malformations of the central nervous system. The following forms may 
be distinguished: MALFORMATIONS OF EXTREMITIES. 
409 
(1) Amelus. The extremities are completely absent; in their place 
are found warty or stump-like rudiments. The trunk is usually well 
formed (Fig. 364). 
(2) Peromelus. Stunting of all the extremities. 
(3) Phocomelus. The hands and feet are alone developed and are 
attached directly to the shoulder and pelvis respectively. 
(4) Micromelus. The extremities are developed, but are abnormally 
small (Fig. 365). 
(5) Abrachius and Apus. Absence of upper extremities with well- 
developed lower ones, or vice versa. 
Fig. 366.—Sympus apus. 
Fig. 367.—Sympus dipus. 
(6) Perobrachius and Peropus. Stunting of the upper or lower ex- 
tremities. 
(7) Monobrachius or Monopus. Absence of one of the upper or lower 
extremities. 
(8) Sympus, Sirenomelia, Symmelia. The lower extremities are fused 
(Figs. 366, 367), and rotated on theib axes so that their external aspects 
are in contact. The pelvis is usually defective, as are also the external 
genitalia, the bladder, urethra, and anus. At the end of the blended ex- 
tremities feet may be entirely wanting (sympus apus) and only a few 
toes may be present; in other cases one (sympus monopus) or both feet 
may be present (sympus dipus). 
(9) Absence of individual bones may occur in any part of the ex- 
tremities. 410 
DISTURBANCES OF DEVELOPMENT. 
(10) Perodactylism — stunting of the fingers of toes — appears in a 
great variety of forms, but in general is seen as defective development 
(brachyphalangism) or absence of individual phalanges, or as mem- 
branous or bony connections between the fingers (syndactylism). 
If only the outer fingers or toes are developed while the middle ones 
are lacking, there arise those formations designated cleft-hand and cleft- 
foot. In more extensive malformations of the fingers there occur defects 
in the region of the tarsal and metatarsal bones or carpal and metacarpal 
bones respectively. These malformations are designated respectively 
peropus and perochirus. Absence of the hand or foot is known as achirus 
or apus. 
§ 139. Among the abnormal positions of the extremities congenital 
luxations (slipping of the articular heads from their sockets) are of 
special interest. They are most common at the hip-joint, rare at the 
elbow-, shoulder- and knee-joints. Congenital luxations are due to local 
arrests of development, but may be the result of mechanical influences. 
In the hip-joint the disturbance of development results in a small and 
imperfect acetabular socket, and the head of the femur is more or less 
imperfectly developed. The small acetabulum lies in the normal position, 
but the head of the femur is displaced, most often backward (luxatio 
iliaca). At birth the ligamentum teres is intact, and the capsule of the 
joint covers both the head of the femur and the acetabulum. After much 
use of the leg the ligamentum teres becomes stretched and may tear, the 
capsule becomes dilated and bag-like, and, at the point where it is pressed 
against the bone, may become perforated. A new joint may then be 
formed through proliferation of the surrounding tissues. 
Abnormal positions of the feet and hands are to be referred partly 
to disturbances of development and partly to mechanical influences exerted 
on the extremities during their growth. The most important is congenital 
club-foot (pes equinovarus). The foot is left in the foetal position, with 
accompanying abnormal development of the bones and their articular sur- 
faces. The inner border of the foot is sharply elevated, and the foot at 
the same time is brought into plantar flexion. The collum tali is elongated 
in an anterior and inferior direction. If children thus afflicted learn to 
walk, they tread on the outer side of the foot, which becomes flattened, 
while the foot becomes still more sharply turned inward. 
Congenital club-foot, though usually to be regarded as a primary dis- 
turbance of development, may also be caused by pressure due to a rela- 
tively small uterus. Under these conditions those pathological positions 
of the foot known as pes calcaneus and pes valgus also develop, and 
are characterized by strong dorsal flexion and by outward twisting of the 
foot. Frequently the evidences of pressure to which the feet have been 
subjected are seen in atrophy of the skin and portions of the bones. 
The position of the hand known as club-hand or talipomanus is 
caused by rudimentary development of the radius, and is usually asso- 
ciated with other malformations. 
2. Abnormal Position of the Internal Organs and of the 
Extremities. 
§ 140. Of the abnormal positions of the internal organs, the most im- 
portant is known as situs inversus viscerum — i.e., lateral transposition 
of the internal organs, so that the thoracic and abdominal organs form a 
mirror-image of the normal position. This condition has been observed EXCESSIVE GROWTH; SUPERNUMERARY PARTS. 
411 
both in double monsters and in single individuals. It is entirely compatible 
with life, and may be restricted to the heart alone, or to the abdominal 
organs, or to a part of the latter (situs irregularis). Abnormal positions 
occur especially often in the abdominal organs. For example, the kidney 
is not infrequently found in an abnormal position (dystopia rents), usually 
low, so that it approaches the sacral promontory or lies in front of it. 
The testis is qot rarely retained in the abdominal cavity (ectopia in- 
terna, or abdominalis testis, or cryptorchismus), or in the inguinal canal 
(ectopia inguinalis), or at the external ring (ectopia pubica), or in the 
fold between the thigh and scrotum (ectopia cruroscrotalis), or in the 
perineal region (ectopia perinealis), or in the fold of the groin (ectopia 
cruralis). Abnormal positions of the intestines, particularly of the colon, 
are not rare. 
3. Malformations due to Excessive Growth or Multiplications 
of Organs or Body-parts. 
§ 141. The malformation known as giantism occurs as the result of 
excessive growth of the entire body, during intra-uterine life or later. 
During extra-uterine life such growth 
may occur that the size of the individual 
far exceeds the maximum normal limits. 
Partial giant growth may take place 
during intra-uterine life or after birth. 
The head and portions of the extremi- 
ties are usually affected. Unilateral 
giant growth is restricted to half of the 
face or to one extremity, although in 
rare cases the hypertrophy may involve 
all the parts of one side: face, trunk, and 
extremities. 
Should other tissues become in- 
creased, as in the extremities, trunk, or 
face, so that malformations resembling 
the skin of the pachyderms are pro- 
duced, the growth is designated elephan- 
tiasis (see § 76, Figs. 109, 110). 
Circumscribed hypertrophies of bones occur in various portions of the 
skeleton, and are sometimes multiple. The bones of the skull as well as 
those of the face may be affected. There are cases in which hypertrophy 
may be so extensive that one or both of these regions show marked dis- 
figuration, the condition being known as leontiasis ossium (Fig. 115. On 
the trunk and extremities local growths of bone may lead to enlargement 
of single bones or to atypical excrescences known as exostoses. 
§ 142. The occurrence of supernumerary organs, or of multiplica- 
tion of parts of the skeleton, and of the muscular system, is relatively 
frequent. 
1. Duplication of the extremities. Duplication of an entire ex- 
tremity without duplication of the pelvic or shoulder bones has not been 
observed in man. Duplication of the hands and feet is rare (Fig. 368). 
The number of fingers may reach nine or ten. Much more frequent 
is multiplication of the fingers or toes (polydactylism) on a 
single hand (or foot respectively), in which condition the super- 
Fig. 368—Polydactylism with fork- 
ing of the hand. (After Lancereaux.) 412 
DISTURBANCES OF DEVELOPMENT. 
numerary fingers (or toes) are attached at the ulnar or radial side 
(or tibial and fibular sides, respectively), or intercalated between the 
others. Often the fingers are duplicated only in part — that is, by 
cleavage of the first or the first and second terminal joints. Those at- 
tached at the margin of the hand may be well developed or rudimentary. 
Occasionally they appear as pedunculated fibrous growths. In the fully 
developed supernumerary fingers or toes the phalanges may articulate 
with the metacarpal or metatarsal bones of a neighboring finger or toe, 
or with their own (supernumerary) carpal or tarsal bones. Poly dactyl- 
ism in certain cases is inherited and is therefore dependent on intrinsic 
causes. 
2. Supernumerary nipples and breasts (hyperthelia, hypermastia) 
are not uncommon in both sexes, and are probably to be regarded as a 
reversion to polymastic racial ancestors. The supernumerary organs are 
usually situated on the thorax, along two lines converging from the axil- 
lary to the inguinal regions, but in rare cases may be found elsewhere — 
in the axilla, on the shoulder, on the abdomen, back or thigh. They are 
usually small, but in the event of pregnancy may take on functional 
activity. The number of nipples may reach as high as ten. 
3. The formation in men of breasts resembling those of women 
(gynecomastia) is rarely seen in well-developed men with normal sexual 
apparatus (see Hermaphrodism, § 143), but it not infrequently happens 
that the male breast undergoes moderate enlargement at the time of 
puberty. 
4. Duplication of the penis is of rare occurrence, and may be asso- 
ciated with the formation of two urethrae having independent openings 
into the bladder, and with two scrota, the two penises being typically de- 
veloped. 
5. Supernumerary bones and muscles are of frequent occurrence. 
Supernumerary vertebree may be found in any part of the spinal column; 
and at its lower end may cause lengthening, resulting in the formation 
of a tail. Three forms of tails may be distinguished: true tails containing 
bones; false or imperfect tails which represent an elongation of the verte- 
bral column, but contain neither cartilage nor bones (so-called pig’s tail) ; 
and tail-like appendages of skin which consist of different forms of tissue, 
and are to be classed with the teratomata. True tails are rare; they are 
more often the result of separation or elongation of the vertebrae than of 
an increase in their number. 
Reduplication of the phalanges of one finger is rare. 
Supernumerary ribs in the neck or lumbar region, as well as forking of 
the ribs, are not rare. 
Supernumerary teeth occur. 
6. Duplication or cleavage of the primordium of the thoracic and 
abdominal organs occurs most frequently in the case of the spleen, pan- 
creas, adrenals, ureters, pelvis of the kidneys, and lungs, more rarely in 
that of the ovary, liver, kidney, testicle, and bladder. 
4. True and False Hermaphrodism. 
§ 143. The fact that the sexual organs of both sexes develop from 
originally similar primordia makes it a priori probable that malforma- 
tions might result through unequal development of the right and left sides, HERMAPHRODISMUS. 
413 
or through simultaneous development of organs peculiar to both sexes, or 
through lack of harmonious development of the external and internal 
genitals. 
Those malformations which are characterized by the fact that the 
sexual apparatus of a single individual contains parts belonging to both 
the male and female, are grouped under the designation hermaphrodis- 
mus. When both sexual glands (testis and ovary) are present the con- 
dition is called hermaphrodismus verus (hermaphrodismus glandularis). 
If the mixing of sexual characteristics consists of a combination of male 
and female genital passages with the external genitalia of the opposite 
sex, the condition is known as pseudohermaphrodismus. The true sex 
is determined by the nature of the sexual glands. 
The build of hermaphrodites frequently shows a curious mixture of 
male and female characteristics. For example, the breasts, neck, and 
shoulders may correspond to the female type, while the beard, face, larynx, 
and voice correspond to the male type. In false hermaphrodites the body 
characteristics do not always correspond to the true nature of the sexual 
glands; a male may resemble a female and vice versa. 
The following types of hermaphrodism may be distinguished: 
1. Hermaphrodismus verus or androgynes.—1. Hermaphrodismus verns bi~ 
lateralis, or double-sided hermaphrodism, is characterized by the presence on both 
sides of both ovary and testis, or the presence on both sides of an organ containing 
ttoth ovarian and testicular tissue. Heppner asserts that in a nine-months-old child, 
having hermaphroditic external genitals, with vagina, uterus, and tubes, both ovary 
and testis were found in the broad ligament; epididymis and vas deferens were 
wanting. 
2. Hermaphrodismus verus unilateralis, or one-sided hermaphrodism, is that 
condition in which on one side there exists but one sexual gland, while on the other 
both testis and ovary are present. Salen has reported a case of a woman of forty- 
three years of age, who had menstruated since her seventeenth year, in whom there 
was found on the right side (castration on account of uterine myoma) a herma- 
phroditic gland, the nature of which was confirmed by microscopic examination. 
The ovarian portion of the gland was typically developed; the epithelium of the 
seminiferous tubules of the testicular portion consisted of follicular cells and 
cells of Sertoli, but lacked spermatogonia and seminal cells. Blacker and Lawrence 
have also described a case of hermaphroditic gland occurring in a child still-born 
at eight and a half months. In the hernial sac of an individual twenty years old 
Garre demonstrated the presence of a tube and both sexual glands with parovarium 
and epididymis (the microscopic examination was made by Simon). 
3. Hermaphrodismus verus lateralis is that condition in which there is an ovary 
on one side and a testis on the other. It has been many times observed in man, 
though in the majority of cases no careful microscopic examination was made, 
and when carried out, ovarian tissue could not with certainty be demonstrated. 
Obolonsky reported a case (a twelve-year-old girl) in which histological examina- 
tion showed-on the right side a testicle, and on the left side an ovary, but it is to 
be noted that ova were not seen in the latter. The right broad ligament contained 
a testis, an epididymis, a vas deferens, a rudimentary tube, a round ligament; the 
left broad ligament contained an ovary, with an ovarian ligament, and a well-devel- 
oped tube. Moveover, a_ uterus, vagina, and also a prostate were present. Accord- 
ing to reported observations, the corresponding sexual passages may be present or 
in part wanting. The external genitals are malformed, and combine structures 
belonging to both sexes. 
II. Hermaphrodismus spurius, or pseudohermaphrodismus, is characterized 
by bisexual development of the sexual passages and external sexual organs in 
association with the unisexual development of the essential sexual gland. The 
most pronounced cases occur in males, who, in addition to their proper sexual 
organs, possess a more or less well-developed vagina, uterus, and tubes. It is much 
more rare to find in females development of a portion of the Wolffian duct. 414 
DISTURBANCES OF DEVELOPMENT. 
In male false hermaphrodites the external genitals are frequently malformed 
and approach the female type, while in female false hermaphrodites the external 
genitals resemble those of the male. 
The resemblance of the male external genitals to those of the female is brought 
about by stunting of the penis and total or partial failure of the sexual furrow in 
the penis to close (hypospadias), so that the two halves of the scrotum are 
separated, leaving a depression beneath the root of the penis, which represents the 
remains of the sinus urogenitalis. The scrotal halves come, therefore, to resemble 
the labia majora, particularly in non-descent of the testicles. The external genitals 
of the female approach in appearance those of the male through development 
of the clitoris into a sort of penis, while the vaginal opening is narrowed or closed 
through union of the labia. The vagina and urethra have a common opening, or 
open separately beneath the penis-like clitoris. 
The atypical development of the external genitals may or may not be associated 
with malformations of the sexual passages, and is, therefore, not dependent on 
malformations in other portions of the sexual apparatus. 
1. Pseudohermaphrodismus masculinus occurs in three varieties: 
First, pseudohermaphrodismus masculinus internus, in which the external 
genitals are of the male type, and the prostate is developed, but is usually pierced 
at the colliculus seminalis by a canal opening into the urethra, the former being 
continued above into a rudimentary or more or less well-developed vagina, often 
into a more or less well-formed uterus, and even tubes. The male organs may 
be well developed or malformed. 
Second, pseudohermaphrodismus masculinus completus, or externus et internus, 
in which the vagina, uterus, and tubes are present in rudimentary or more or 
less complete development, while the external genitals resemble the female type. 
The penis presents the condition of hypospadias and resembles the clitoris; beneath it 
lies a furrow at whose posterior end there is usually an orifice leading into a short 
vestibule which divides at once into a urethra and a vagina. Sometimes the vagina 
and vestibule are separate. In rare cases the external genitals appear normal, but 
the penis contains a double canal, the upper one representing the urethra, the other 
tthe sexual passage. In the case of more marked development of the ducts of 
Muller the vasa deferentia are frequently defective, and the seminal vesicles are 
sometimes wanting. 
Third, pseudohermaphrodismus masculinus externus, in which only the external 
genitals depart from the male type, and resemble the female. Since in these cases 
the bodily habitus often simulates that of the female, the sex of the individual may 
easily be mistaken. 
2. Pseudohermaphrodismus femininus also occurs in three similar varieties, but is 
much more rare. 
In pseudohermaphrodismus femininus internus rudiments of the Wolffian ducts* 
lying in the broad ligament or in the uterovaginal wall, and sometimes extending 
to the clitoris, are found in association with well-developed external genitals. 
Pseudohermaphrodismus femininus externus is characterized by external gen- 
italia resembling those of the male. 
Pseudohermaphrodismus femininus externus et internus, in which the external 
genitals resemble those of the male and there is persistence of parts of the Wolffian 
ducts, is rare. Of the internal male genitalia, there was found in one case a pros- 
tate, and in another case a prostate pierced by the vagina, an ejaculatory duct, and 
a sac resembling a seminal vesicle, which opened into the vagina. 
The internal sexual organs develop from the same undifferentiated primor- 
dium in both males and females. These consist of a sexual gland lying on the 
medial anterior side of the Wolffian body, and a sexual passage known as the duct 
of Muller. The latter develops beside the Wolffian duct, and, like it, empties into 
the lower end of the bladder or into the sinus urogenitalis. 
In the male the duct of Muller disappears, only traces in the form of the uterus 
masculinus or vesicula prostatica remaining; the primitive sexual gland unites with 
a small part of the Wolffian body, which becomes the head of the epididymis, 
another small portion forming the vasa aberrantia testis (organ of Giraldes), the 
remainder disappears, while the Wolffian duct becomes the vas deferens and vesicula 
seminalis. 
In the female the Wolffian body and its duct disappear, leaving only a trace in 
the form of gland-tubules known as the parovarium, but remains of the duct are 
not infrequently found in the uterine wall. From the ducts of Muller, which in 
part coalesce at their lower ends, develop the vagina, uterus, and tubes. The 
extreme upper end of the duct of Muller not infrequently persists in the form of MONSTERS. 
415 
a little pedicled sac attached to the abdominal end of the tube, the hydatid of 
Morgagni. 
The primordia of the sexual glands appear in the fifth week. In mammalia 
(probably also in man) they develop through localized thickening of the peritoneal 
epithelium, which becomes the germinal epithelium, while at the same time the meso- 
derm proliferates. Whether the seminal tubules arise from peritoneal epithelium 
(Bornhaupt Egli), or whether they are derived from an ingrowth of the Wolffian 
body into the testis (IValdeyer), is an undecided question (Kolliker). The ova 
arise from germinal epithelium. The environing cells of the Graafian follicle are 
regarded by IValdeyer as derived from the germinal epithelium; while Kolliker 
believes that they arise from the Wolffian body. 
The significance of the pedunculated and non-pedunculated hydatids, found 
in varying numbers near the globus major of the epididymis, is not yet determined 
{Kolliker). The non-pedunculated cyst known as the hydatid of Morgagni is 
regarded by Waldeyer as a remnant of the duct of Muller. According to Roth, 
it may stand in close relation to the Wolffian body, inasmuch as there is occasionally 
found a vas aberrans of the epididymis communicating with it. 
In the development of the vagina and uterus the ducts of Muller and the 
Wolffian ducts unite at their lower portion to form the genital cord. At the end 
of the second month the duct9 of Muller blend to form a single canal, which then 
develops into the vagina and uterus. This union takes place near the middle of 
the genital cord. The W'olffian ducts play no role, though remains of these are 
found at birth in the broad ligament and in the wall of the uterus. According to 
observations of Riedel, remains of the Wolffin duct are found in about a third of 
adult females, in the form of a tube lined by cylindrical epithelium surrounded by 
muscle, or as a muscle-bundle without epithelium, lying anteriorly and to the side 
of the uterus and vagina. 
The external genitals begin to develop, even before the cloaca has separated 
into the intestinal and genito-urinary orifices, by the formation, in the sixth week, 
of a median genital tubercle in front of the cloaca, and further, of two lateral folds, 
the genital folds. Toward the end of the second month the tubercle becomes more 
prominent, and shows on its lower surface a furrow, the genital furrow. In the 
third month the cloaca becomes divided to form the anal and genito-urinary open- 
ings. In the male embryo the genital tubercle becomes the penis, the glans being 
recognizable as early as the third month. In the fourth month the furrow closes 
to form a tube; at the same time the two genital folds unite to form the scrotum. 
The prepuce is formed in the fourth month. The prostate arises in the third 
month as a thickening of the tissues at the junction of the urethra and the genital 
cord. The glands of the prostate develop in the fourth month from the epithelium 
of the canal and grow into the surrounding connective tissue. 
In the female embryo the closure of the genital furrow and the genital folds 
does not take place, so that the sinus urogenitalis remains short. The genital 
eminence becomes the clitoris, the folds become the labia majora, and the edges of 
the genital furrow the labia minora. 
5. Double Monsters. 
(a) Classification of Double Monsters. 
§ 144. Twin-formations lying in a single chorion may be divided 
into two large groups: twins completely separated from one another, and 
twins united by some portion of their bodies. 
Of the twins completely separated from one another there may be 
distinguished two types; one in which both twins are fully developed, and 
one in which one twin is stunted. 
Twins joined by portions of their bodies may likewise be divided 
into two groups: twins showing uniform development and twins showing 
unequal development. To the latter belongs a group of stunted parasitic 
forms that may be classed as teratomata. 416 
DISTURBANCES OF DEVELOPMENT. 
According to the situation of the duplicated portions of the body, there 
may be distinguished: 
1. Monstra duplicia katadidyma or duplicitas anterior. 
2. Monstra duplicia anadidyma or duplicitas posterior. 
3. Monstra duplicia anakatadidyma or duplicitas parallela. 
These may be divided into three classes: 
1. Twins united chiefly by the epigastrium and thorax. 
2. Twins united chiefly by the heads. 
3. Twins united chiefly by the pelves. 
Ahlfeld divides the double monsters into two groups, those with com- 
plete and those with partial doubling of the axial structures. 
In rare instances triple monsters occur. 
(b) The Chief Forms of Double Monsters. 
§ 145. Twins separated from each other and lying in a single chorion 
are designated homologous twins. They are always of the same sex, 
have usually a common placenta, and resemble each other closely. If one 
of the twins should die after its body has been developed, it may be 
pressed flat by the growth of its fellow, giving rise to the condition known 
at foetus papyraceus. 
Fig. 369. 
Fig. 370. 
Fig. 369.—Pygopagus. (After Marchand.) A, B, The two twins; a, b, separated umbilical 
cords; c, blended umbilical cords; d, common placenta. There is a single coccyx and sacrum 
(from the second vertebra downward), and the lower end of the medullary canal is single. 
The two intestinal canals terminate in one anal opening. Vestibule of vagina single, the remain- 
ing portions of the sexual organs double. 
Fig. 370.—Lchiopagus. (After Levy.) MONSTERS. 
417 
When twins possess a common placenta in which the blood vessels 
have abundant anastomoses, the heart of the stronger foetus may control 
the circulation and thereby cause changes in the direction of the blood- 
stream in the weaker twin. As a result of this the latter sulfers disturb- 
ances of development, and becomes changed into an acardius, a monster 
without a heart, developing no heart at all or a rudimentary one. In the 
majority of such cases the head also fails to develop (acardius acephalus) 
or remains rudimentary (acardius paracephalus), and likewise there is 
usually no development, or only a rudimentary one, of the upper extremi- 
ties, thorax walls, lungs, and liver, while the abdomen, pelvis, and lower 
Fig. 371.—Dicephalus dibrachius dipus. 
Fig. 372.—Diprosopus distomus tetrophthalmus dio- 
tus dibrachius. 
extremities are more or less perfectly formed. According to the develop- 
ment of the extremities the following varieties may be distinguished: 
acardins paracephalus (or acephalus) sympus, monopus, dipus, mono- 
brachius, dibrachius. 
In rarer cases there is no recognizable development of any part of the 
body, and there is formed an acardius amorphus, consisting of a shapeless 
mass covered with skin, usually without any indication of extremities and 
possessing only rudiments of organs. 
Of rare occurrence is the formation known as acardius pseudoacor- 
mus — that is, a monster in which the head only is developed, while the 
other parts of the body are represented by rudiments. 
§ 146. Twins equally developed and united occur in the following 
types: DISTURBANCES OF DEVELOPMENT. 
418 
1. Duplicitas anterior (monstra duplicia katadidyma). Anterior du- 
plication with union of posterior portions of the body. 
Pygopagus (Fig. 369). Union of twins in the region of the coccyx 
or of the sacrum. According as the union is more or less extensive, the 
sacrum, coccyx, lower end of the medullary 
canal, anus, lower end of the bowel, and the 
sexual apparatus are doubled or single. 
Ischiopagus (Fig. 370). Union of twins in 
the pelvis, which forms a wide ring, the two 
sacra being placed opposite each other. The 
anus, lower end of the bowel, and the sexual 
organs may be single or double, and the number 
of the lower extremities two to four. 
Dicephalus (Fig. 371) and diprosopus (Fig. 
372). The duplication is limited to the upper 
part of the trunk and head, or to the neck and 
head, or the head alone, or, finally, to por- 
tions of the head. As the external blend- 
Fig. 373. 
Fig. 374. 
Fig- 373-—Craniopagus parietalis. 
Fig. 374.—Cephalothoracopagus or syncephalus, with janus head. Both anterior and posterior 
faces are rhalformed, and possess but one eye, while the nose is represented by a proboscis-like 
organ situated above the eye. 
ing increases in extent, there occurs blending of the internal organs, 
the intestine, liver, lungs, heart, spinal cord, brain, etc. According 
to the number of the lower and upper extremities there may be distin- MONSTERS. 
419 
guished dicephalus tetrapus, dipus, tetrabrachius, tribrachius, dibrachius 
(Fig. 371). When the heads have blended there may be distinguished 
diprosopus tetrophthalmus, triophthalmus, diophthalmus, tetrotus, triotus, 
diotus, distomus, monostomus, tribrachius and dibrachius (Fig. 372). 
The mildest grades of duplicitas anterior are represented by duplica- 
tion of the jaw, mouth, or nose. 
2. Duplicitas posterior (monstra duplicia anadidyma). Union of the 
twins at the head and thence downward with duplication of the posterior 
parts of the body. 
Craniopagus (Fig. 373). Union of twins in the cranial region. Ac- 
cording to the site of union there may be distinguished craniopagus pari- 
Fig. 375.—Thoracopagus tribrachius tripus. The hand of the third arm, common to both 
halves, possesses two dorsal surfaces, and the laterally distorted fingers possess nails on both 
sides. The common third foot has eight toes. 
etalis, frontalis, occipitalis. When the union is more extensive portions of 
the brain are single. 
Cephalothoracopagus or syncephalus (Fig. 374). Blending of 
twins in the region of the forehead and face, and of the abdomen. In the 
region of the united heads there is an anterior and a posterior face (janus, 
janiceps). The two faces may be equally (janus symmetros) or unequally 
developed (janus asymmetros), one face being well developed, the other 
imperfectly. The internal organs present different degrees of blending 
into single organs. 
Dipygus. The duplication is limited to the lower half of the body 
and the lower extremities, while the upper parts are single or partly cleft. 
The duplication of the spinal cord may begin at different heights. Accord- 
ing to the number of extremities different forms may be distinguished. 420 
DISTURBANCES OF DEVELOPMENT. 
The mildest grades of duplication are confined to the lower end of the 
spinal column, the anus, and the external genitals. 
3. Duplicitas parallela (monstra duplicia anakatadidyma). Duplica- 
tion of the anterior and posterior ends of the body with parallel positions 
of the trunk. 
Thoracopagus (Fig. 375). Union of twins by the thorax. Accord- 
ing to the site and extent of the union, as well as the number of extrem- 
ities present, there may be distinguished different forms, particularly the 
following: xiphopagus (union at the xiphoid process), sternopagus 
Fig. 376.—Polymelos. (After Lancereaux.) 
F!G. 377.—Polymelos. (After Liesching.) 
(union at the sternum), thoracopagus tetrabrachius, tribrachius, dibra- 
chius, tetrapus, tripus, and dipus. When portions of the faces have 
blended there results prosopothoracopagus. Blending of the internal 
organs into single organs varies with the degree of external blending. 
The heart may be double or single, in the latter case malformed. Thora- 
copagus is relatively frequent. 
Rachipagus. Blending of twins in the region of the spinal column 
is rare. 
§ 147. Twins joined but unequally developed may occur in any of 
the double forms described in § 146. If the development of one of the 
twins remains rudimentary and if its heart does not develop, its nourish- 
ment can come only through its well-developed fellow. The better devel- 
oped of the two is then known as the autosite, the other as the parasite. 
If the parasite is of markedly rudimentary development, it may be classed 
with the bigerminal teratomata (cf. §§ 127 and 128). 
At the posterior ends of the body there may occur a rudimentary 
double monstrosity in the form of increase in the number of the extrem- 
ities, polymelos (Figs. 376, 377). In so far as the lower extremities are 
concerned such a malformation may be classed as an ischiopagus or a MONSTERS. 
421 
dipygus. The supernumerary extremities may be one or two in number, 
and more or less well developed. Further, there not infrequently occur 
coccygeal teratomata in which the presence of rudimentary extremities 
Fig. 378.—Bigerminal teratoma of the coccygeal region (pygopagus parasiticus.) a, b, c, 
Extremities lying in a sac formed by the skin of the autosite. 
Fig. 379.—Thoracopagus parasiticus (thoracomelus). Three legs spring from the pelvis; one 
of them has a double foot. Two upper extremities project from the anterior chest-wall. 
Fig. 378. 
Fig. 379. 
Fig. 380.—Thoracopagus parasiticus. (After Schenk von Grafenberg.) Parasite attached to 
ohest of autosite. 
Fig. 381.—Epignathus. (After Lancereaux.) 
Fig. 380. 
Fig. 381. 422 
DISTURBANCES OF DEVELOPMENT. 
(Fig. 378, a, b, c) or of various body elements leaves no doubt that the 
tumor-like formation covered by the skin of the autosite is to be regarded 
as a double monster, a rudimentary pygopagus, or as dipygus parasiticus. 
Such a parasite is designated epipygus. 
Supernumerary extremities (Fig. 379) may also be found on the trunk 
or there may occur a headless trunk with extremities (Fig. 380), or a 
rudimentary thorax without extremities, or, finally, teratomata which may 
be interpreted as thoracopagus parasiticus ( omphalopagus) and as dipygus 
parasiticus. The malformation is also called epigastrius. 
The inclusion of such teratomata beneath the skin of the abdomen or 
thorax, or in the abdominal or thoracic cavities of the autosite, gives rise 
to the condition known as inclusio fcetalis subcutanea, or abdominalis, or 
mediastinalis. 
In the region of the head rudimentary twin-formations appear most 
often in the mouth cavity, forming an amorphous mass, firmly attached 
to the base of the skull, consisting of skin, connective tissue, cartilage, 
bone, brain-tissue, teeth, intestinal elements and muscle, and, rarely, 
developed extremities. Such malformations are included under the desig- 
nation epignathus (Fig. 381). 
On other parts of the head (prosopopagus parasiticus) rudimentary 
twin formations or bigerminal teratomata are rare (cf. §§ 127, 128) ; 
they also occur in the cranial cavity (encranius) and in the neck (hygroma 
colli). CHAPTER X. 
The Pathogenic Fission-Fungi and the Diseases Caused by 
Them. 
I. General Considerations Regarding the Schizomycetes or Fission- 
fungi. 
1. General Morphology and Biology of the Fission-fungi. 
§ 148. The Schizomycetes or fission-fungi, designated collectively as 
bacteria, belong to the protophytcs — that is, to the smallest and simplest 
forms of plant-life. Many of them are so small that they stand on the 
border-line of invisibility even with the use of the highest-power objectives 
and eye-pieces. In animal tissues, it is frequently difficult to distinguish 
them from the products of cell-disintegration; often this can be accom- 
plished only through the employment of specific reagents or staining- 
methods, and occasionally only through culture experiments. 
The Schizomycetes are non-chlorophyllaceons, unicellular organisms, 
but as a result of growth and multiplication they form colonies of cells. 
The form and character of single cells, as well as their manner of 
growth, division, and multiplication, vary greatly, and these differences 
are used as a basis for the classification of bacteria. In the first class are 
placed the Cocci, often designated Micrococci, or that form of bacteria 
which occurs in the form of spherical or oval cells. There may be distin- 
guished six forms of cocci: double-cocci or Diplococci, chain-cocci or 
Streptococci, clustered cocci or Staphylococci, tablet-cocci or Merismo- 
pedia, packet-shaped cocci or Sarcince, and tube-cocci or Ascococci. 
The second class constitutes the Bacilli (rod-shaped bacteria). Long 
thread-like bacteria are called Leptothrix. 
To the third class belong the Spirilla (screw-shaped bacteria). Screw- 
shaped forms with short, wide turns are known as Spirilla, those with 
drawn-out turns as Vibrios, those with a long, closely wound screw as 
Spirochcetes. 
The Schizomycetes are composed of cell-contents and cell-membrane, 
both of which consist of an albuminoid body, which varies with the 
species. Many bacilli contain fat in t'heir cell-bodies, at times so abundantly 
that it may be demonstrated by staining with Sudan III. Some of these 
bacteria (tubercle-bacillus, lepra-bacillus, and actinomyces) show the 
presence of fat both when growing in living tissues and when cultivated 
on artificial media; others (staphylococcus aureus, anthrax-bacillus, 
bacillus of glanders) show the presence of fat only when grown on special 
media. In many forms of bacteria the membrane may appear as a hyaline 
capsule surrounding the cell. 
In all forms of bacteria, with the exception of the cocci, there have 
been observed swarming movements which are brought about by fine 
thread-like flagella attached at the ends or scattered over the entire 
cell. In addition there occur slow oscillatory or gliding and creeping 
423 424 
THE PATHOGENIC FISSION-FUNGI. 
movements which are dependent on the contractile and flexible qualities 
of the plasma. Both forms of motion occur only under certain conditions 
of nutrition and growth, and only in certain species. 
Multiplication of bacteria takes place through transverse division 
of cells which have previously become elongated. In some forms divi- 
sion can take place in two or even three dimensions. After division the 
cells separate immediately or remain for a time attached to each other. 
When the cells remain attached after dividing transversely, threads are 
formed (Streptococcus, Leptothrix) ; after dividing both transversely 
and longitudinally, flat, tablet-like colonies; after dividing in all three 
dimensions, colonies resembling a solid body (Sarcina) are produced. 
Long threads may become segmented into shorter pieces. 
If resting bacterial cells, as the result of constantly progressing repro- 
duction or through the accumulation of neighboring cells, heap themselves 
in masses, there are formed colonies, which are called zoogloea. 
Many of the bacteria form spores. These cells are distinguished by 
the fact that they remain alive under conditions in which ordinary forms 
die; and, when brought into fresh nutrient solutions, are able to produce 
a new generation. Spore-formation is most frequently endogenous — 
that is, the spore arises inside the cells (particularly in bacilli), and is 
developed out of the cell-protoplasm, in which there appears a small 
granule which grows into an oblong or round, highly refractive, sharply- 
contoured body always remaining smaller than the mother-cell. After 
the death of the latter the spore is set free. 
In old cultures bacteria show degeneration-forms, which are distorted, 
and stain poorly and irregularly. 
As non-chlorophyllaceous plants, the schizomycetes are restricted in 
their nutrition to ready-formed organic substances which are soluble 
in water, and which are supplied to them in an abundance of water. In 
addition they need various mineral substances, especially sulphur, phos- 
phorus, potassium or rubidium, or caesium and calcium (or magnesium, 
barium, or strontium). Changes in the conditions of nutrition may 
modify the form and dimension of bacteria and also their vital properties. 
Some of the fission-fungi are restricted for their food-supply to dead 
organisms or to solutions of organic matter, and are, therefore, classed as 
saprophytes; others are able to take their nutrition from living animals 
or plants, and live as parasites. 
Free oxygen is necessary for the development of many bacteria; 
others can dispense with it as long as they are under favorable conditions 
of nutrition in other respects; others develop only in the absence of 
oxygen. The first are designated obligate aerobes, the second facultative 
anaerobes, the third obligate anaerobes. 
The pathogenic bacteria are facultative or obligate anaerobes. 
Carbon dioxide has no influence on the development of many bacteria, 
for example, on the typhoid-bacillus and Friedlander’s pneumobacillus. 
On others, it has an inhibitory action, for example, on Bacillus indicus, 
Proteus vidgaris, Bacillus phosphorescens, the bacilli of anthrax and 
cholera, the pus-cocci, and others. The bacilli of anthrax, Asiatic cholera, 
and of rabbit septicaemia die in a few hours in artificial Seltzer water, 
but anthrax-spores remain alive in it indefinitely. 
Light has an injurious or destructive influence on many forms of 
bacteria, and it is therefore possible to disinfect, by means of strong light, 
water which is infected. The virulence of the bacillus of anthrax may DEVELOPMENT OF BACTERIA. 
425 
be lessened by exposure to sunlight. When exposed to the direct rays of 
the sun anthrax bacilli die in twenty-four to thirty hours, the spores sur- 
vive as long as six to eight weeks. According to Geisler the green, violet, 
and ultra-violet rays are particularly active. According to Rieder bacteria 
may be destroyed by the Roentgen-rays. 
The temperature of the surrounding medium acts on bacteria in such 
a way that when it falls the life-processes of the organisms become weaker 
and slower, and finally cease entirely, whereas with elevation of tempera- 
ture they rise to a certain maximum, and at a slight increase above this 
suddenly cease; higher temperatures kill the fungi. The maximum of 
permissible temperature lies at a different height for different fungi, and 
is dependent also on the character of the nutrient substance. There are 
forms of bacteria which grow well at a temperature of 55° C. or higher. 
A low temperature checks development in all varieties; they fall into 
a state of immobility, but do not die even at great degrees of cold. The 
immobility due to cold occurs at different temperatures with different 
varieties. The most favorable temperature for development lies between 
30° and 40° C. for the anthrax bacillus; at temperatures above 44° and 
below 15° C. its development ceases. Many bacilli form spores only at 
high temperatures. 
Boiling zvatcr and steam at 100° C. kill all bacteria and bacterial 
spores, if allowed to act for some time. In dry air bacteria and their 
spores withstand higher temperatures, so that a temperature of 140° C. 
for three hours is necessary to kill the latter. Many bacteria are killed 
at a temperature of 60° to 70° C., provided it is kept up for a long time. 
Anthrax-spores die in boiling water in two hours, in confined steam 
in ten minutes. The action of steam at 105° C. for ten minutes kills all 
spores. Live steam kills all spores in ten to fifteen minutes, and pene- 
trates well into objects to be disinfected. 
If fission-fungi find themselves in a suitable medium, their multiplica- 
tion can be brought to a standstill, since the fluid may contain substances 
which hinder the growth of bacteria or even kill them. This effect is 
produced by many substances (sublimate, lysol, carbolic acid, iodine, 
formaldehyde, etc.) —even in comparatively great dilution. Other sub- 
stances act injuriously on bacteria only when in stronger concentration. 
The point at which multiplication is hindered is reached at a greater 
dilution than that at which the bacteria are killed. Spores are much 
more resistant than the vegetative forms. 
The growth and multiplication of bacteria also cease with insufficient 
amount of water. The fact that fruits preserved in sugar do not fer- 
ment and that salted and dried meats do not putrefy depends on this fact. 
Food-stuffs can be preserved through the removal of water and by the 
addition of substances which are dissolved in the tissue-fluids and in this 
way increase the proportion of the same in solid contents. The limit at 
which the fission-fungi and yeast-fungi cease to develop is reached at a 
much higher degree of humidity than for the moulds. 
If a nutrient fluid contains other lower fungi besides bacteria there 
often takes place competition between the different micro-organisms; 
and fission-fungi, yeasts, and moulds may crowd one another out. Like- 
wise reciprocal crowding between the bacteria themselves may occur. 
For example, cocci may be crowded out and destroyed by bacilli, or one 
form of bacillus by another. This would appear to happen when the 
composition or the temperature of the nutrient medium is more favorable 426 
THE PATHOGENIC FISSION-FUNGI. 
to one form than to the other; or when one form of bacteria produces 
substances which act injuriously on the other, or when one form grows 
more rapidly than the other, and thereby deprives its competitor of 
necessary food-supply. 
According to investigations by Pasteur, Emmerich, Bouchard, Wood- 
head, Blagovestchensky, and others, the antagonism between many forms 
of bacteria is shown in inoculation experiments on animals. By simulta- 
neous inoculation with different bacteria the development of a pathogenic 
bacterium in the body of a susceptible animal may be hindered. For 
example, the development of anthrax bacilli may be hindered by simulta- 
neous inoculation with erysipelas-cocci (Emmerich) or with the Bacillus 
pyocyaneus (Bouchard). 
The question as to whether the bacterial cell contains a nucleus has been a 
subject of much discussion. A. Fischer denies it, while Biitschli, Schottelius, Zie- 
mann, Zettnow, Nakanishi, and Feinberg are inclined to favor the affirmative 
view. According to Zettnow, the bacterial cell contains chromatin or nuclear sub- 
stance mixed with the entoplasm; while the covering of the cell, or ectoplasm, does 
not contain chromatin. According to the investigations of Ziemann, Zettnow, and 
Feinberg, it is possible through staining with a mixture of methylene-blue and 
eosin. (Romanowski-stain) to demonstrate within the majority of bacteria a 
“nuclear substance” or “chromatin” (Ziemann, Zettnow) or a “nucleus” (Fein- 
berg) —that is, there may be demonstrated within the bacteria structures of varying 
size which stain red like the nuclei of malarial plasmodia (Romanowski) or of 
other protozoa or of tissue-cells, while the cell-plasma takes a blue stain. According 
to Nakanishi, circumscribed nuclei are found in young forms. 
The Romanowski-stain is a mixture of methylene-blue and eosin, whereby a 
red dye contained in methylene-blue (Rosin, Berl. klin. Wochen., 1899; Nocht, Cbl. 
f. Bakt., 1899) is precipitated. Zettnow*s formula is as follows: 50 c.c. of a one- 
per-cent. solution of a Hochst methylene-blue is treated with 3-4 c.c. of a five-per- 
cent. solution of soda. To 2 c.c. of this there is added drop by drop while shaking 
1 c.c. of one-per-cent, solution of Hochst eosin BA. Stain five minutes on cover- 
glass and examine in water. 
According to N'dgeli, Zopf, and others, many fission-fungi possess a membrane 
of cellulose or of a carbohydrate closely related to cellulose. Certain bacteria (red 
sulphur bacteria) combine within their cell-substance coloring-matter; others (Bacil- 
lus amylobacter, Spirillum arnyloferum) give at certain stages of their development 
the starch reaction with iodin. 
Babes and Ernst, by means of special staining methods with Loffler’s 
methylene-blue, hrematoxylin, and Platner’s nuclear black, have demonstrated the 
presence of granules within different forms of bacteria, which according to their 
behavior probably stand in some relation to the processes of division and spore- 
formation. Ernst designated the appearances seen by him as sporogenous granules, 
since he was able in certain bacteria to demonstrate their transition into spores; he 
is inclined to regard them as of the nature of cell-nuclei, a view which Biitschli 
also favors. Bunge regards the granules described by Ernst as cell-granules which 
have nothing to do with spore-formation, and describes other granules, which stain 
with Ldfiler’s methylene-blue, as the forerunners of spores. Marx and Woithe 
regard the Babes-Ernst granules as not being nuclei in the ordinary sense of the 
Avord, but as products of the maximal condensation of the euehromatic substance 
of the cells, which are a sign of the highest intensity of vitality on the part of the 
cell. Wagner, on the contrary, holds that certain bodies, which he has observed in 
typhoid- and colon-bacilli, are nuclei. 
According to Nakanishi, the spores form (in anthrax- and hay-bacilli) by 
concentration of the chromophile substance about the nucleus, while the remaining 
portion of the protoplasm becomes clear; a membrane is then formed about the 
chromatin body, it takes on a fat-like shine, and loses its power to take stains 
(methylene-blue BB). 
The bacteria are able to take the carbon necessary for their growth from most 
of the carbon compounds, which are soluble in water. They can also derive their 
carbon from dilute solutions of substances which, in greater concentration, are 
injurious to them—'for example, from benzoic acid, alcohol, salicylic acid, phenol, 
etc. ACTIVITIES OF BACTERIA. 
427 
Their nitrogen is derived from albuminous matter; further, from those com- 
pounds designated as amins (methyl-, ethyl-, propylamin), amido-acids (asparagin, 
leucin) and amides (oxamide, urea), as well as from the ammonia salts and also 
from nitrates. The albuminates, previous to their assimilation, are changed into 
peptone by means of a ferment given off from the bacteria. Free nitrogen cannot 
be assimilated as such. Nitrogenous and non-nitrogenous compounds are not only 
assimilable as such, but also in combination. The fission-fungi are able to take 
nitrogen from ammonia and nitric acid only in the presence of organic carbon 
compounds. 
Sulphur, according to Ndgeli, is essential to the schizomycetes, and they take 
it from sulphates, sulphites, and hyposulphites. The other mineral substances men- 
tioned above are derived from various salts. If in the case of an abundance of 
nutrient material there is too little water present, all further growth ceases; yet 
many of the fission-fungi are able to dispense with water temporarily. Spores 
suffer little from drying. 
Many bacteria are sensitive to acids, so that even a slight dgree of acidity 
hinders their growth (for example, anthrax bacilli and the Frankel-Weichselbaum 
pneumococcus). Others are able to grow with a moderate amount of acid in the 
nutrient fluid. As a general rule they are especially sensitive to mineral acids, but 
the presence of a large amount of citric, butyric, acetic and lactic acids also hinders 
their multiplication. In this connection belongs the fact that the products of 
decomposition caused by the fermentative action of the fungi are at a certain degree 
of concentration harmful to the development of the fungus, and finally stop its 
growth entirely. Thus, in butyric-acid and lactic-acid fermentation the amount of 
butyric or lactic acid gradually formed finally checks the multiplication of the 
fungus. A similar result occurs in the bacterial putrefaction of albumin, since the 
products of the same, such as phenol, indol, skatol, phenylacetic acid, phenylpro- 
prionic acid, etc., hinder the further development of the bacteria. To alkalies the 
fission-fungi are less sensitive, and many can bear a rather high degree of alkalinity 
in the nutrient fluid, but there also exist forms which do not thrive in alkaline 
fluids (acetic-acid fungus). 
According to the investigations of Pfeffer and Ali-Cohen, many motile bacteria 
show chemotactic properties — that is, they are attracted or repelled by certain 
chemical substances dissolved in water. Bacteria swimming about in fluids collect, 
therefore, at places where there are chemical substances which attract; for example, 
typhoid-bacilli and cholera-spirilla are attracted by potato-juice {Ali-Cohen). Potas- 
sium salts, peptone, and dextrin likewise attract, but the individual forms of bac- 
teria behave differently toward these substances {Pfeffer). Free acids, alkalies, 
and alcohol have a repelling action. 
§ 149. The growth and multiplication of fission-fungi give rise to 
chemical transformations of the nutrient material, brought about 
through ferments produced by the bacteria, and through metabolic 
processes occurring in the cells themselves. 
Among ferments or enzymes are to be mentioned the proteolytic or 
albumin-dissolving enzymes (bacteriotrypsins) which bring about solu- 
tion of the albuminous bodies and cause disintegration of the peptone- 
molecule. Further, bacteria give rise to diastatic ferments which convert 
starch into sugar, also to inverting ferments which transform cane-sugar 
(disaccharid) into grape-sugar (monosaccharid). 
The chemical results of bacterial metabolism, brought about by the 
vital activities of fission-fungi aided by the enzymes produced by them, 
consist of decomposition of complex organic compounds. By many 
authors all these processes are designated fermentations, while others 
(Lehmann) speak of fermentation only when a fission-fungus breaks 
down a given food-material with especial ease, thereby giving rise to one 
or more products in marked quantity, in association with or in place of 
its other metabolic products. Other authors narrow the term fermenta- 
tion to the decomposition of carbohydrates. 
In the decompositions caused by fission-fungi different products are 
formed, according to the composition of the nutrient material and the 428 
THE PATHOGENIC FISSION-FUNGI. 
character of the fission-fungus. For the production of fermentation fer- 
mentable material is necessary. Many fungi are able to cause fermenta- 
tion in the presence as well as in the absence of oxygen, while to some 
of them lack of oxygen is necessary. 
Among the products of bacteria of importance to the physician are 
those which have a poisonous action and cause tissue-changes, particu- 
larly those described as ptomdins, toxins, and endotoxins. 
The ptomains are basic, crystallizable, nitrogenous products of the 
bacterial decomposition of albumin; they are also known as putrefactive 
alkaloids or cadaveric alkaloids. They show poisonous properties. The 
best known are sepsin, putrescin (dimethylethylendiamin), cadaverin 
(pentamethylendiamin), collidin (pyridine derivative), peptotoxin, neu- 
ridin, neurin, cholin, gadinin, and substances resembling muscarin. 
The true toxins are specific bacterial poisons produced by pathogenic 
bacteria and are secreted by the latter, giving rise to the severe symptoms 
in diphtheria, tetanus, and sausage poisoning. The endotoxins are sub- 
stances clinging to the bacterial cells that also have a poisonous action. 
In the bacterial cell there also occur bacterial proteins which give rise 
to local tissue-necrosis and inflammation. The significance of these sub- 
stances in the infectious diseases has already been mentioned in § 11. 
Among other decompositions produced by bacteria the following are worthy 
of note: the formation of lactic, formic, acetic, propionic and butyric acid, alcohol 
and carbonic acid from sugar; the formation of acids (acetic, butyric, propionic, 
valerianic, succinic, formic, and carbonic*) from alcohol and organic acids; the 
formation of indol, skatol, phenol, cresol, pyrocatechin, hydrochinon, hydroparacu- 
maric acid, and paroxyphenylactic acid (von Nencki, Salkowski, Brieger), and 
finally hydrogen sulphide, ammonia, carbonic acid, and water from albumin; the 
formation of ammonium carbonate from urea; the transformation of nitrous and 
nitric acids into free nitrogen; the reduction of nitrates to nitrites and to ammonia, 
etc. Finally, there are bacteria living in the soil—'the nitro-bacteria—which are 
able to form nitrous and nitric acids from ammonia (Winogradsky). 
Along with the nitrification of nitrogen there occurs decomposition of earthy 
alkali carbonates, as shown by the fact that the nitrobacteria are able in the presence 
of organic carbon compounds to derive from the carbonates the carbon necessary 
to the building-up of cells. There takes place, therefore, through the vital activity 
of these organisms, synthesis of organic out of inorganic substances. 
Under the influence of the fission-fungi there are formed bitter, sharp, nauseat- 
ing substances (bitter milk)_. Further, bacteria occasionally produce pigments of 
red, yellow, green, blue, or vTolet color. For example, Bacillus prodigiosus produces 
a blood-red coating on bread (bleeding bread) ; bandages and pus take on a bluish- 
green color as the result of the presence of Bacillus pyocyaneus. In many cultures 
there is formed fluorescent coloring-matter. 
The phosphorescence not infrequently seen on decomposing sea-fish depends 
on bacterial products of decomposition, as has been shown by Pfliiger, and appears 
when there is active multiplication of the bacteria. 
2. General Considerations Concerning the Pathogenic Schizo- 
mycetes and Their Behavior in the Human Organism. 
§ 150. Among the schizomycetes there are numerous species which 
are capable of causing disease-processes in the human organism, and are 
therefore called pathogenic schizomycetes. The bacteria concerned must 
possess properties enabling them to multiply in the tissues of the living 
human body. They must therefore find in the tissues suitable nutrient 
material, and in the body-temperature the warmth necessary to their 
growth. The tissues, moreover, must not contain substances which are a 
hindrance to growth (cf. § 31). ACTIVITIES OF BACTERIA. 
429 
If pathogenic fission-fungi succeed in growing in the tissues of the 
body, if infection takes place (cf. § 11), their action is characterized at 
the point of multiplication, by tissue-degenerations, necrosis, inflammation, 
and new-growths of tissue, while at the same time the toxins produced 
by them cause manifestations of poisoning. 
In individual cases the pathological processes vary greatly, in that the 
distribution of the bacteria, their local action, and the production of 
poisons, differ with different forms of bacteria. 
With many the local action on tissue is the most prominent character- 
istic, with others the general intoxication. Many bacteria confine them- 
selves to the region in which they have gained entrance; others advance 
uninterruptedly 'on the surrounding tissues; still others are carried by the 
blood and lymph streams and lead to the formation of metastatic foci, 
and, finally, others increase in the blood. 
If spread of bacteria takes place through the blood, the bacteria may 
pass from the mother to the foetus during pregnancy, since the placenta 
forms no certain filter against pathogenic bacteria. This has been demon- 
strated, for example, in the case of anthrax-bacilli, bacilli of symptomatic 
anthrax, glanders-bacilli, spirilla of relapsing fever, typhoid-bacilli, the 
pneumococcus, and the spirochete of syphilis. Changes in the placenta, 
such as haemorrhage, loss of epithelium, and alterations of vessel-walls, 
favor the passage of bacteria. 
Bacteria which multiply in the human body die out in many cases in a 
short time; and the disease produced by them proceeds to recovery (cf. 
§31). Nevertheless, it not infrequently happens that they are preserved 
for a long time in the body, and excite continuous disease, or remain in 
a condition of inactivity, so that no pathological processes are recognizable 
until, after a period of latency, active reproduction again takes place and 
manifestations of disease show themselves anew. 
Not infrequently secondary infection associates itself with infection 
already existing. The relation between the two is either that the second 
follows the first accidentally, or that through the first infection the soil is 
prepared for the second (cf. § 11). 
Finally, there not infrequently occur double infections, in that two or 
more forms of bacteria develop coincidently in the tissues, and produce 
their characteristic injurious influence on the latter. 
Each pathogenic fission-fungus has a specific action on the tissues 
of the human organism; but different species may exert a similar action. 
For example, there are various bacteria capable of producing suppuration. 
Only in a certain proportion of cases do the tissue-changes show such 
characteristics that from these the species of the pathogenic fission-fungus 
can be recognized with certainty. 
Further, it has been demonstrated that pathogenic properties of 
bacteria are by no means constant; on the contrary, their virulence 
varies, so that bacteria, which cause severe infections may become 
changed (weakened) through external influences, so that they lose their 
power of causing disease, or cause only mild forms. This peculiarity is 
of great practical importance. It explains to a certain extent why a given 
infection does not always run the same course, and, moreover, why with 
severe attacks light ones also occur. On the other hand, it affords the 
possibility of obtaining material for inoculation from attenuated cultures 
of bacteria, by means of which mild grades of infection or intoxication 430 
THE PATHOGENIC FISSION-FUNGI. 
can be produced, which are able to protect the organism from severe 
infections or to bring about the cure of an infection already acquired 
(cf. § 32). 
Weakening of the pathogenic properties of a fission-fungus can be 
brought about through the action on cultures of high temperatures, oxy- 
gen, light, or antiseptic substances, as well as by cultivation of the fungus 
in the body of a less susceptible animal. In some forms it is only neces- 
sary to cultivate the bacteria for some time on artificial media (diplococcus 
of pneumonia), or to expose the culture to the air (bacillus of chicken- 
cholera), in order to bring about attenuation. If it is desired to pre- 
serve the virulence of the pneumococcus, it is necessary, from time to 
time, to pass the bacteria cultivated on artificial media through rabbits, 
which are very susceptible. The glanders-bacilli, tubercle-bacilli, and the 
cholera-spirilla lose virulence when cultivated uninterruptedly on artificial 
media. The streptococcus of erysipelas becomes so attenuated through 
continued cultivation in bouillon that it is no longer capable of killing 
even mice. 
If the presence of bacteria be suspected in tissue-fluid or in the tissue-paren- 
chyma, their demonstration may first be attempted by means of microscopic 
investigation. Occasionally this is successful by the mere examination of a drop 
of the suspected fluid or of a smear-preparation of the tissue-juice diluted with salt- 
solution or distilled water. In other cases it is necessary to employ staining 
methods, in which case cover-glass smears of the fluid are made and allowed to 
dry. The smear is then fixed by passing through the flame, and after cooling is 
stained. For this purpose methylene-blue is preferably employed, a preparation of 
One-per-cent, methylene-blue solution in l-to-10,000 solution of caustic potash. 
Water solutions of fuchsin and methyl-violet are also used. For many bacteria 
there are employed special staining methods, in which ordinarily the preparations are 
heavily overstained with a solution of gentian-violet or fuchsin in aniline water, 
or with a water solution of methyl-violet, the excess of stain then being removed 
by means of weak acids or by iodine and alcohol (Gram’s method). In this way 
it is often brought about that the bacteria alone remain stained, often certain 
forms of bacteria only. 
When it is desired to demonstrate the presence of bacteria in tissues, small 
portions of tissue are hardened in formalin or in absolute alcohol, and are then cut 
into the thinnest possible sections, which are stained by appropriate methods. Here 
again the methods most frequently employed are those mentioned above: gentian- 
violet, methyl-violet, and fuchsin. Good objectives are necessary for the microscopic 
examination; if possible, oil-immersion lenses and illumination with substage con- 
denser shouM be employed. 
If through any method the presence of bacteria in tissue has been demon- 
strated, the attempt is next made to cultivate them. For this purpose the methods 
developed by Koch are usually employed. These, in principle, consist in obtaining 
first a fluid containing the bacteria, by means of scraping or by rubbing up pieces 
of tissue in sterilized salt-solution. This fluid is then evenly distributed in a solu- 
tion of gelatin or agar which has been liquefied by warming; and the mixture is 
then poured upon horizontal glass plates, solidifying as it. cools. The individual 
bacteria or spores, thus separated from each other, develop in the nutrient medium. 
By proper application of this method there are obtained in the layer of 
gelatin various colonies, which differ in appearance so that they may often be 
differentiated from each other by the naked eye alone. When sufficiently separated 
from one another, the individual colonies may be taken up by means of a fine plati- 
num needle, and transferred either to boiled potato, or to a sterile gelatin plate, or 
streaked on the surface of the solidified nutrient fluid in a test-tube. Very often 
the infected needle is stuck into the solidified transparent medium contained in a 
test-tube. 
If the culture on the gelatin plate is pure, and if the entire procedure is carried 
out with the necessary care and the avoidance of contamination, pure cultures may 
be obtained by this method. In stab-cultures, as well as in smear-cultures on pota- CULTIVATION OF BACTERIA. 
431 
toes or any other nutrient medium, special peculiarities often show themselves which 
make it possible for the experienced observer to recognize the form of bacteria. At 
times, however, it is necessary to make a thorough microscopic examination of 
the colonies. 
An infusion of meat containing peptone and gelatin is commonly employed for 
making plates. It consists of a watery infusion of chopped meat, to which a 
definite amount of peptone and salt is added. This is neutralized with carbonate 
of soda, enough gelatin is added to give a solid consistence at ordinary tem- 
peratures. For streak- and stab-cultures this same gelatin is sometimes used; at 
other times a jelly made of a mixture of a watery extract of meat, peptone, and 
agar-agar; or again blood-serum which has been coagulated by warming. 
For stab-cultures the jelly is allowed to solidify within the test-tube in a per- 
pendicular position; for streak-cultures the test-tube is kept in an oblique position 
until the jelly is set. 
Sterilized bouillon is often used for cultures. The inoculated nutrient media 
are kept either at room-temperature or at higher temperatures in an incubating 
oven (30°-40° C.). The proper nutrient medium to be used in individual cases 
must be determined, by experiment. Experience has shown that individual bacteria 
behave differently in this respect, some growing best on one, others on another 
medium. To the nutrient medium there are often added with advantage such sub- 
stances, as sugar, glycerin, urine, brain-substance, etc. 
It is evident that the processes briefly described above may be modified accord- 
ing to the necessities of the case. For example, in those cases in which it is neces- 
sary to grow bacteria at high temperatures, the use of gelatin should be avoided 
and agar-agar plates should be made instead. Occasionally membranes or exu- 
dates from, mucous surfaces (diphtheria) or small bits of excised tissue are placed 
directly into the culture-medium. In the case of many bacteria, as cholera-spirilla, 
the use of hanging-drop cultures is advised. In this method a drop of sterilized 
bouillon hangs down from the under surface of a cover-glass, and is inoculated 
from a previously cultivated pure culture of the fungus. The cover-glass is then 
placed over the excavation in a hollow ground-glass slide. Evaporation is prevented 
by the exclusion of the outer air from the cavity in the slide, by a rim of oil or 
vaseline placed beneath the edge of the cover-glass. By this method the multiplica- 
tion of bacteria can be observed for a long time. 
When bacteria are sought in water, a definite amount of suspected water is dis- 
tributed in gelatin, and plate cultures are made. Earth is rubbed up with sterilized 
salt-solution; air is made to pass in definite amount through sterilized salt-solution; 
the salt-solutions thus infected are then mixed with gelatin, and from this gelatin 
plates are made. 
The culture of bacteria on and in different media, accompanied by the micro- 
scopic examination of the different stages of development, serves for more exact 
identification, and for the differentiation of species. After its properties have been 
studied in this way, the influence of the bacterium on the animal organism is 
tested. As experimental animals, rabbits, dogs, guinea-pigs, rats, mice, and small 
birds are employed. The bacteria to be tested are introduced, sometimes under the 
skin, sometimes directly into the blood-current, sometimes by inoculation into the 
internal organs, sometimes by inhalation into the lungs, or by administration with 
the food into the intestinal canal. Bacteria can be regarded as pathogenic for a 
given animal when they multiply within the tissues and excite disease. If relatively 
large amounts are inoculated, the animal experimented on may die, even if the 
bacteria do not increase in its body, since the poisonous substances formed in the 
culture and introduced by inoculation often suffice to kill the animal. 
Experience has taught that only some of the bacterial infections which occur in 
man, when inoculated into animals, run the same course as in man, and, indeed, only 
those which also occur in animals. In other cases the pathogenic fission-fungi 
occurring in man or in certain animals are, it is true, pathogenic for the experi- 
mental animal, but the pathological process shows another localization and another 
course. In a third case the experimental animals are in part or wholly immune. 
Inversely, fission-fungi that are often extremely pathogenic for experimental 
animals are harmless for other animals or for man. 432 
THE PATHOGENIC FISSION-FUNGI. 
II. The Different Forms of Bacteria and the Diseases Caused by Them. 
I. The Cocci, or and the Morbid Processes Caused 
by Them. 
(a) General Considerations Regarding the Cocci. 
§ 151. The cocci are bacteria that occur exclusively in the form of 
round or oval or lanceolate cells. In their multiplication by division they 
often form peculiar aggregations of cells, which are designated by special 
names according to the character of the different forms. Since certain 
forms of cocci are likely to develop in definitely shaped aggregations, 
advantage is taken of this fact, to classify them in different species. It 
should be noted, however, that a given species does not always appear in 
the same form, but may vary according to nutrient conditions. 
Many of the cocci multiply by division in one plane only — at right 
angles to the length of the cell. If the spheres resulting from division 
remain together for 
some time in the form 
of double spheres, 
and if this form ap- 
pears with frequency 
Fig. 384. 
Fig. 382. 
Fig. 383. 
Fig. 385. 
Fig. 382.—Streptococcus from a purulent peritoneal exudate of a case of puerperal peritonitis. 
a, Single cocci; b, diplococci; c, streptococci or torula-chains. x 500. 
Fig. 383.—Colonies of micrococci in blood-capillaries of the liver, causing metastatic abscess- 
formation. From a case of pyaemia. Necrosis of liver-cells, x 400. 
Fig. 384.—Cocci grouped in tetrads (merismopedia), from a softening infarct of the lung. 
X 500. 
Fig. 385.—Sarcina ventriculi. x 400. 
in any one species, it is designated diplococcus (Fig. 382, b). If, from 
further division of the cells in one plane, rows of cocci result, these are 
known as streptococci (Fig. 382, c) ; this term is used also as the name 
for a group. If the division of the cells takes place irregularly, and the 
cells remain in small collections or heaps, the bacteria are designated 
micrococci (Fig. 383). The name staphylococcus or grape-coccus is 
commonly used to indicate some of these forms. Larger collections of 
cells, held together by a gelatinous substance derived from the cell- 
membranes, are designated sodgloca masses. If the masses of cocci are 
united into larger collections by means of a gelatinous envelope, they are 
spoken of as ascococci or tube-cocci. 
To those cocci which remain united for a long time in a four-cell 
tablet (Fig. 384), the name of tetracoccus or tablet-coccus is applied. 
Others class such bacteria with the micrococci. The cocci that go by the 
name sarcinae are characterized by division in three directions of space, 
so that compound cubical packets of spherical cells are formed from 
tetrads (Fig. 385). THE COCCI. 
433 
The cocci not infrequently show a tremulous molecular motion in fluids. 
The saprophytic cocci grow on different nutrient substrata and cause 
in suitable media various processes of decomposition. Many form pig- 
ments. Micrococcus urcae causes fermentation in urine by which ammo- 
nium carbonate is formed from urea. Micrococcus viscosus is the cause 
of the slimy fermentation of wine. The cause of the phosphorescence of 
decomposing meat was found by Pfliiger to be a micrococcus that forms 
slimy coatings on the surface of the meat. 
Of the pigment-producers the best known are Micrococcus luteus, Mi- 
crococcus aurantiacus, Sarcina lutea, Micrococcus cyaneus and Micro- 
coccus violaceus, which, when grown on boiled eggs or potatoes, produce 
yellow, blue, and violet pigment, respectively. 
Saprophytic cocci are found in the mouth cavity and intestine, as 
well as on the surface of the skin, and in the lungs. 
Sarcina ventriculi (Fig. 385) occurs not infrequently in the stomach 
of man and animals, especially when abnormal fermentations are going 
Fig. 386.—-Streptococcus tracheitis in scarlet fever (alcohol, carmine, methyl-violet, iodine). 
a, Connective tissue; b, desquamated epithelium; c, membrane composed of cells and streptococci; 
d, fibrin-threads. X 300. 
on. According to Falkenheim the stomach sarcines can he cultivated on 
gelatin, and form round, yellow colonies, which contain colorless mono- 
cocci, diplococci, and tetrads, but never cubical packets. They form these, 
however, in neutralized hay-infusion, and their growth causes souring of 
the infusion. The membrane of the sarcinse is said to consist of cellulose. 
Micrococcus tetragenus is not infrequently found in human sputum, 
and in the mouth and throat; it may be present in tuberculous cavities, or 
in haemorrhagic or gangrenous foci of the lungs. It forms tetrads (Fig. 
384) whose cells are held together by a gelatinous membrane. On gelatin- 
plates it forms round or oval, lemon-yellow colonies. It is pathogenic for 
white mice and guinea-pigs, to a less extent for rabbits, and, when injected 
subcutaneously, excites purulent inflammations in the mouse, often sep- 
ticaemia. Intratracheal injections may give rise to inflammations of the 
respiratory passages and lungs. 
The pathogenic cocci cause acute inflammations which usually heal 
after death of the bacteria; but it not infrequently happens that cocci may 
remain in the body for a long time and give rise to chronic processes. 434 
THE PATHOGENIC FISSION-FUNGI. 
(b) The Pathogenic Cocci. 
§ 152. The Streptococcus pyogenes is a coccus which, in multiplying, 
forms double spheres and chains of spheres (Fig. 382) of different 
lengths, containing from four to twelve or more cells. This chain-forma- 
tion comes to especially full development when the streptococcus is grow- 
ing in fluids — in nutrient bouil- 
lon or fluid exudates — but is 
also seen when growing in 
tissues. 
The cocci stain well by 
Gram’s method, are facultative 
anaerobes, grow best at 37° C., 
and form small whitish colonies 
on gelatin and agar. 
Streptococcus pyogenes 
causes in man inflammations, 
which usually, though not al- 
ways, assume a purulent char- 
acter. Occasionally it is found 
on normal mucous membranes, 
for example, in the upper air-passages, or in the vagina and cervix uteri; 
it may be assumed in such cases that its virulence is slight, or that the 
mucous membranes offer successful resistance to its entrance into the 
tissues. 
Infection with streptococci may occur either in healthy individuals, or 
in those who have received some injury, or as an accompaniment or 
sequel of other infections, particularly scarlet fever, smallpox, diphtheria, 
and pulmonary tuberculosis. 
Fig. 387.—Streptococcus pyogenes from a phleg- 
monous focus of the stomach (alcohol, carmine, 
methyl-violet, iodine), a, Leucocytes; b, leucocytes 
containing streptococci; c, free streptococci. 
X 503. 
If the streptococcus mul- 
tiplies on the surface of 
mucous membranes — for ex- 
ample, of the respiratory 
tract (Fig. 386) — it excites 
inflammation, which may bear 
the character of desquamative 
or purulent catarrh (c), or of 
a croupous exudation (d). If 
it penetrates the connective 
tissues of the submucosa, it 
causes inflammations which 
are phlegmonous in character 
— i.e., a more or less quickly 
sipreading, seropurulent, or 
purulent, or fibrinopurulent, or serofibrinous inflammation, which may lead 
to suppuration and abscess-formation. In the exudate the cocci may be 
found free (Fig. 387, c), or inclosed in cells (b). 
The multiplication of streptococci in the stratum germinativum of the 
skin leads to necrosis of epithelium and the formation of purulent vesi- 
cles or blebs. 
If the streptococcus spreads in the corium, into which it penetrates 
through small wounds of the skin, it Utilizes the lymph-spaces and lymph- 
Fig. 388.—Streptococcus erysipelatis (a) inside a 
lymph-vessel (t), in part composed of thickly crowded 
spheres, in part of tornla-chains (alcohol, gentian- 
violet) ; c, neighborhood of lymph-vessel, with pale, non- 
staining nuclei; d, vein; e, perivenous cellular infiltra- 
tion of tissue; f, accumulation of cells in the lvmph- 
vessel. Section of rabbit’s ear two days after inocula- 
tion with erysipelas-cocci. X 225. STREPTOCOCCI. 
435 
vessels (Figs. 388, a; 389, h, i; 390, c) as pathways and as places for the 
development of colonies, causing more or less severe inflammation, char- 
acterized macroscopically by advancing redness and swelling of the skin 
known as erysipelas. To the external appearance there corresponds more 
or less severe serous and cellular infiltration (Figs. 388, d, e„f; 389, m; 
392,c), and often fibrinocellular exudation (Fig. 389, mx). The infection 
of the lymph-vessels in erysipelas involves at times the superficial layers 
of the cutis (Fig. 389), at other times the deeper layers (Fig. 390, c). 
In the latter case the erysipelatous process becomes phlegmonous. With 
infection of the deeper layers streptococci may spread on the surface of 
the epithelium — that is, beneath the horny layer (Fig. 390, g), and cause 
loosening of the epithelial cells and desquamation of the horny layer (/). 
In severe infection with virulent streptococci the process may go on to 
Fig. 389.—Section of the skin in erysipelas bullosum (alcohol, alum-carmine), a, Epidermis; 
h,_corium; c, vesicle; d, covering of vesicle; e, epithelial cells containing vacuoles; /, swollen cells 
with swollen nuclei; g, gi, cavity caused by the liquefaction of epithelial cells, and containing frag- 
ments of epithelium and pus-corpuscles; h, lymph-vessel, partly filled with streptococci; i, lymph- 
vessel filled full of streptococci; k, colony of streptococci in the tissue; l, h, necrotic tissue; 
m, cellular, mx, fibrinocellular infiltration; n, fibrinocellular exudate in the vesicle, x 60. 
liquefaction of epithelium (Fig. 389, e, f, g, gx), and to the formation of 
vesicles (c, erysipelas bullosum), or to necrosis and gangrene of the 
corium (/, lx, erysipelas gangraenosum), or to suppuration. 
In the subcutaneous tissue the spread and multiplication of the cocci 
(Fig. 391, c) lead to progressive seropurulent (d) and fibrinopurulent 
inflammation, often with subsequent suppuration. Such forms of infec- 
tion are known as phlegmons. 
If the muscles become involved in a phlegmonous process, the strepto- 
cocci increase and spread (Fig. 392, a) in the connective tissue of the peri- 
mysium internum, and may penetrate the sarcolemma-tubes. Here also 
the consequences of infection are more or less severe inflammations lead- 
ing to suppuration. 
Bronchogenous infection of the lungs causes purulent, or croupous, or 
haemorrhagic exudations into the alveoli. 
Should bone become involved from the skin or mucous membrane — 
for example, from the middle ear — the cocci may increase in the marrow 436 
THE PATHOGENIC FISSION-FUNGI. 
(Fig. 393, a, b) and give rise to necrosis, and later to purulent inflam- 
mation of neighboring tissues. 
Streptococcus infection may terminate, sooner or later, in that opposing 
forces restrict the further spread of the bacteria, and destroy them. Not 
infrequently, however, infection progresses up to the time of death. 
If streptococci break into the lymph- and blood-vessels, metastases 
are formed, and distant organs are involved. Infection of the lungs 
leads easily to infection of the pleura. Infection of the female genital 
tract, during delivery or the puerperium, leads often to infection of the 
peritoneum by the lymphatics. Infection of the serous membranes is 
Fig. 390.—Erysipelas of the head in a. child of one month of age (bacterial staining, carmine). 
a, Cutis with hair-follicles; b, subcutis; c, lymph-vessel with streptococci and inflamed surrounding 
area; d, rete Malpighii; e, f, horny layer; g, streptococci lying upon the rete Malpighii. x 45. 
usually associated with seropurulent, or fibrinopurulent exudation, the 
streptococci developing luxuriantly in the exudate, and forming long 
chains. In infection of the blood, the streptococci do not increase in the 
circulating blood, but at points where they come to rest; in the small capil- 
laries of the lungs, heart, liver, kidneys, spleen, bone-marrow, joints, 
etc., or on the valves of the heart. At the point of increase there is 
likewise produced inflammation, which bears the same general character 
as the primary inflammation, but is less severe and more circumscribed. 
Hcematogenous streptococcus-infection of the lung leads to the forma- 
tion of inflammatory foci (Fig. 394, a), which for the greater part show 
central suppuration. Collections of streptococci on the surface of the 
endocardium of the valves or of the heart wall (Fig. 395, a) lead to 
superficial necrosis and to the formation of coagula (&), collections of 
leucocytes (&,) and proliferations of granulation tissue (c, d). Deeper 
infection with streptococci causes extensive necrosis accompanied by in- STREPTOCOCCI. 
437 
flammation of the surrounding tissues. If streptococci are carried by the 
blood-stream into the coronary arteries, there are produced in the heart- 
muscle inflammatory foci, usually purulent in character. 
If the cocci pass to a blood-vessel of the skin or subcutaneous tissue, 
they may increase to such an extent that they form casts of the capillaries 
(Fig. 396, c). As the result of surrounding hypersemia there are produced 
in the skin red spots and swellings, and eventually purulent foci. In the 
kidneys, in whose vessels there often occurs an extraordinary multiplica- 
tion of streptococci (Fig. 397, a, b), there arise grayish-yellow circum- 
Fig. 391.—Beginning streptococcus phlegmon on the trunk, after phlegmon of the arm 
(formalin, carmine, methyl-violet), a, b, Skin; c, streptococci in the subcutaneous connective 
tissue; d, beginning collection of leucocytes, x 15. 
scribed areas of discoloration, which are dependent on collection of bac- 
teria, local anaemia, necrosis, and often serofibrinous exudation (d). 
Later, yellow discolorations and softening of tissue appear, corresponding 
to foci of suppuration. Similar changes may be demonstrated in other 
organs. 
The danger of streptococcus infection depends on progressive local 
changes and the formation of metastases, and on the accompanying' in- 
toxication, which finds expression in fever and severe general symptoms. 
If the symptoms of intoxication are prominent the condition is designated 
septicaemia. Metastatic suppuration leads to the form of disease desig- 
nated pyaemia. A combination of both conditions is known as septico- 
pyaemia. 438 
THE PATHOGENIC FISSION-FUNGI. 
The course of streptococcus infection, as well as the mode of entrance 
of the cocci into the body, can usually be recognized, since the infection 
ordinarily starts in injured skin or from penetrating wounds, from the 
mucosa of the digestive and respiratory tracts, or from the genital appa- 
ratus as the result of childbirth. Cryptogenic infection is, however, not 
rare; in such cases the first symptoms recognizable clinically are those 
dependent on disease of an internal organ, so that it appears as if the 
infection were primary in this organ. 
The individual foci in streptococcus infection may present different 
degrees of inflammation; this is dependent on the virulence of the bac- 
teria, on individual differences of the infected persons, on the seat of 
the infection, and on the influence of preceding or accompanying condi- 
Fig. 392.—Streptococcus phlegmon in muscle. (Alcohol, Weigert’s stain.) a, Masses of 
streptococci; b, leucocyte infiltration; c, transverse section of muscle-fibres. X 100. 
tions. In respect of this last factor it may be noted that many infectious 
diseases (diphtheria, scarlatina, smallpox, tuberculosis, typhoid fever, in- 
fluenza) which lower resistance increase the predisposition to strepto- 
coccus infection. In the growth of streptococci on the surface of the 
endocardium, the inflammation often bears a pronounced proliferative 
character (Fig. 395, d, c). In hsematogenous streptococcus-dermatitis 
(Fig. 396) the process may cease with the formation of red spots. 
Phlegmons, although they usually pursue a rapid course and lead in a 
short time to necrosis and suppuration, may also have a chronic course, 
particularly in the neck, and are characterized by progressive swelling and 
induration of the affected area, so that the affection is familiarly designated 
“ wooden phlegmon.” Fever may be absent. The process consists of 
progressive proliferation of granulation tissue and new-formation of con- 
nective tissue due to streptococci (or staphylococci), while suppuration 
is absent or confined to circumscribed areas. STREPTOCOCCI. 
439 
The biological characteristics of Streptococcus pyogenes are variable; this is 
well shown both in its behavior as a disease-producing agent and in cultures of 
streptococci taken from different cases. Consequently an effort has been made to 
divide streptococci into different species, in particular has the streptococcus which 
causes erysipelas been regarded as a distinct form — the Streptococcus erysipelatis. 
Further, according 'to the place in which the streptococcus was found, it was for- 
merly customary to speak of Streptococcus puerperalis, Str. articulorum, Str. scarla- 
tinosus; or, according to the manner of growth, of Str. longus and Str. brevis, 
etc. These characteristics are, however, not sufficient to form a basis for the separa- 
tion of streptococci into different species; and it appears more correct, or at least 
more expedient, to consider all the chain-forming streptococci as one species, which 
appears in many varieties. According to Howard and Perkins {Jour, of Med. Re- 
search, 1901) there is a small group of pathogenic capsulated streptococci char- 
acterized by the viscidity of their growth and by the formation of gelatinous exuda- 
tions in animals. For this group they propose the name of Streptococcus mucosus. 
Fig. 393.—Streptococcus infection of the petrous portion of the temporal bone, from a child 
of eight months of age (formalin, nitric-acid decalcification, carmine, methyl-violet), a, Medullary 
spaces completely filled with streptococci; b, beginning invasion by streptococci; c, bone marrow; 
a, trabeculae of bone, x 300. 
In diphtheria and scarlet fever, streptococcus infections of the throat and air- 
passages are extremely common, particularly in the first-named, so that many 
authors are inclined to assign to the streptococcus a co-ordinate position with the 
diphtheria-bacillus in the causation of diphtheria—'the diphtheria-bacilli predomin- 
ating in the lighter forms of infection, the streptococci in the more severe. Pure 
streptococcus infections may present the same picture as that produced by Loeffler’s 
bacillus. If both forms of bacteria are present, their effects may be combined; per- 
haps the presence of streptococci increases the virulence of diphtheria-bacilli. 
The Streptococcus pyogenes is especially pathogenic for mice and rabbits (les9 
so for dogs and rats) ; but its virulence varies greatly, and rapidly decreases in 
cultures grown on ordinary media. Its virulence is retained for a relatively long 
time (Marmorek) in cultures of the cocci in human- or in horse-serum (serum two 
parts, bouillon one part), or in a mixture of bouillon and ascitic fluid. 
The nature of the poisons produced by streptococci is not known. It has 
been definitely determined that filtered cultures sterilized at 65*70° C. contain 
poisons; but it is not yet known whether this poison, like the toxin of the diphtheria- 
bacillus, produces an antitoxin. 440 
THE PATHOGENIC FISSION-FUNGI. 
According to Simon there can be distinguished an intracellular weakly virulent 
poison and a toxin excreted by the streptococcus. The latter, however, is produced 
only under certain conditions, for example, under the influence of the bactericidal 
juices of the animal body. Under certain conditions the streptococcus can also 
produce haemolysin. 
Numerous investigators (Neufeld, Rimpau, Tavel, Menser, Aronson, Marmorek, 
Moser, and others) have attempted to immunize animals against streptococci and 
to produce an antistreptococcus serum, and the sera thus obtained have been used 
in the treatment of streptococcus affections in man. At present it is not possible to 
judge as to the therapeutic value of these procedures. 
Fig. 394.—Metastatic hematogenous streptococcus pneumonia, after angina (alcohol, alum- 
carmine, methyl-violet, iodine), a, Pneumonic focus with (blue) streptococci; b, slightly inflamed 
lung tissue about the focus, x 80. 
§ 153. The Diplococcus pneumoniae, Streptococcus lanceolatus, or 
Diplococcus lanceolatus, familiarly known as the Pneumococcus, is of 
frequent occurrence. It forms spherical, oval, and lanceolate cocci (Fig. 
398, a), which in the human body are usually surrounded by a capsule, 
and are grouped in pairs (b, d), or more rarely in chains of such pairs 
(c), or in large colonies (d). 
The pneumococcus stains well with fuchsin and with gentian violet, 
and by these stains the capsule may be demonstrated in smear-prepara- 
tions. The cocci are also stained by Gram’s method. 
The cocci are facultative anaerobes. They will not grow on gelatin at 
ordinary room-temperature, but do so on slightly alkaline blood-serum- 
gelatin, on agar and in bouillon, at a temperature above 22° C., and best 
at the temperature of the body. They form on the surface of the 
medium a delicate, translucent, glistening culture, which suggests the 
dew-like deposit of moisture on glass (Frankel) ; and consists of diplococci 
and chain-cocci without capsules. The growth is, however, scanty; and 
easily dies out. Upon potatoes cultures do not thrive. PNEUMOCOCCUS. 
441 
The Diplococcus pneumoniae is in a great number of cases (according 
to Weichselbaum in seventy-one per cent.) the cause of croupous pneu- 
monia, in which the lung is the seat of an acute inflammation ushered in 
by congestive hyperaemia (Fig. 399, a). In the course of the disease the 
alveoli over large areas become filled with coagulated exudate consisting 
of desquamated epithelium, leucocytes, red blood-cells, serous fluid and 
fibrin (Fig. 176). In favorable cases the exudate becomes liquefied and 
absorbed. As has been shown by numerous observations, the Diplococcus 
Fig. 395.—Endocarditis of the wall of the left auricle, due to streptococci (alcohol, methyl- 
violet, carmine), a, Masses of cocci; b, bt, leucocytes and coagula; c, area of proliferation; d, 
inflamed endocardium. X ioo. 
pneumoniae may also cause other inflammatory processes bearing- the 
character of a catarrhal or bronchopneumonia. During the course of the 
disease the cocci are found in the inflamed areas, in greatest numbers at 
the beginning of the inflammation; they lie free in the alveoli (b) and 
clinging to cells (d). They are also found in parts of the lung bordering 
on the inflamed area, in the pleura, and under certain conditions in the 
pericardium, peritoneum, meninges, accessory nasal cavities, cellular tis- 
sue of the neck, in the mediastinum, submucosa of the soft palate and 
pharynx, in the conjunctiva, and skin. In all these places they may give 
rise to inflammatory changes. At times they may be demonstrated in the 
spleen, and in the blood, and in pregnant women may pass into the foetus 
(Viti). Under certain circumstances they may be widely distributed 
through the body; and may cause, in the meninges, pleurse, pericardium, 
and peritoneum, fibrinous, serofibrinous, and at times seropurulent and 
fibrinopurulent inflammations, without giving rise to pneumonia. Fur- 
ther, they may cause inflammations of the conjunctiva, middle ear, endo- 
cardium, joints; these inflammations may lead to suppuration. In many 
cases the mouth and nasopharynx appear to be the avenue of entrance 
— in these regions the cocci are not infrequently found in healthy in- 442 
THE PATHOGENIC FISSION-FUNGI. 
dividuals. Correspondingly, in cerebral and cerebrospinal meningitis the 
maxillary cavities, tympanic cavity, and the ethmoid labyrinth often con- 
tain exudates with diplococci. They are found in the exudates in all the 
forms above mentioned; the gelatinous capsule may present a variable 
thickness. 
When inoculated into rabbits, guinea-pigs, and mice, the Diplococcus pneu- 
moniae increases in the form of encapsulated cocci, particularly in the blood and 
serous cavities, and may cause pneumonia with bloody serous exudate. When in- 
jected beneath the skin of the rabbit’s ear (Neufeld) they produce erysipelatous 
inflammations. Rabbits are especially susceptible; they die with symptoms of 
septicaemia in from thirty-six to forty-eight hours after subcutaneous inoculation. 
Fig. 396.—Erythema multiforme, due to streptococcus infection, arising in the middle ear 
(Fig. 393), from a child eight months old. Section through a red spot in the skin of the back 
of the foot (alcohol, .methyl-violet, carmine), a, Corium; b, subcutaneous tissue; c, capillaries 
filled with streptococci, x 46. 
The injection of pure cultures into the pleural cavity of rabbits gives rise to pleur- 
itis as well as splenization of the lung, in which the parenchyma of the organ is 
filled with a haemorrhagic serous exudate. 
According to A. Frank el the cocci easily lose their virulence, particularly when 
cultivated on milk; and if it is desired to retain their virulence they must, from 
time to time, be passed through susceptible animals. Cultivation of the cocci at 
42° C. for one or two days destroys their virulence. 
It may be regarded as demonstrated that theDiplococcus pneumoniae can cause 
meningitis; there also exists a coccus, the Diplococcus intracellularis meningitidis 
{Weichselbaum), which is different from the pneumococcus and is to be regarded 
as the cause of epidemic cerebrospinal meningitis. Albrecht, Ghon, and Weichsel- 
baum point out its great similarity to the gonococcus. It is found in the nasal 
secretions of epidemic meningitis and also in that of individuals coming in contact 
with such cases. In the cerebrospinal exudate it is found particularly in the polv- 
nuclear leucocytes. The essential pathological lesions are inflammatory changes in 
the membranes of the cord and brain, and in the tissue of the brain, cord, and 
nerves.. Flexner and Jobling (Jour. Amer. Med. Assoc., July, 1908) report en- 
couraging results in the treatment of epidemic meningitis with a serum prepared 
in the horse by inoculation of Diplococcus intracellularis. PNEUMOCOCCUS. 
443 
Pneumotoxin is formed by pneumococci most abundantly in the human and 
animal organism, but only sparsely in nutritive media (Isaeff). It is doubtful 
whether bactericidal antibodies or antitoxins arise during the course of the disease. 
It is therefore probable that the pneumotoxin does not belong to the true toxins. 
Animals may be immunised in various ways against pneumococci, and the serum 
of an immunized animal may be used as a healing serum. The results of treat- 
ment in man are still doubtful. Difficulties arise through the fact that pneumonia 
can be caused by other bacteria (pneumo-bacilli, pus cocci, influenza-bacilli, etc.). 
Literature. 
(.Pneumococcus and Meningococcus.) 
Albrecht u. Ghon: Meningococcus intracellularis. Cbl. f. Bakt., Orig., xxxiii., 
1903. 
Councilman, Mallory, and Wright: Epidemic Cerebrospinal Meningitis, Boston, 
1898. 
Flexner: Antimeningitis serum. Jour, of Exper. Med., 1908. 
Herrick: Pneumococcic Arthritis. Amer. Jour, of Med. Sc., 1902. 
Weichselbaum: Aetiologie der acuten Lungen- und Rippenfellentziindungen. 
Med. Jahrb., Wien, 1886; Histor. Bericht iib. die Aetiologie der acuten Lungen- 
und Rippenfellentzundungen. Cbl. f. Bakt., i., 1887; Aetiologie d. acuten 
Fig. 397.—Extreme streptococcus infection of the kidney (grayish areas), arising after 
streptococcus angina (alcohol, Weigert’s stain), a, Cocci in the intertubular; b, in the glomerular 
capillaries; c, urinary tubules; d, fibrin in the urinary tubules, x 280. 
Meningitis cerebrospinalis. Fortschr. d. Med., v., 1887; Aetiologie u. path. Ana- 
tomie der Endocarditis. Beitr. v. Ziegler, iv., 1888: Seltenere Localisation 
des pneumonischen Virus. Wien. klin. Woch., 1888; Der Diplocoocus pneu- 
moniae als Ursache der primaren acuten Peritonitis. Cbl. f. Bakt., v. 1889; 
Diplococcus pneum. u. Meningokokken. Handb. d. path. Mikroorg., iii.. 1903. 444 
THE PATHOGENIC FISSION-FUNGI. 
§ 154. The Staphylococcus pyogenes aureus or Micrococcus pyo- 
genes consists of spherical cells occurring singly or in pairs, by multipli- 
cation forming grape-like clusters. The cocci are easily stained by various 
aniline dyes, and by Gram’s method. They are 
facultative anaerobes, but grow better when sup- 
plied with oxygen. 
The staphylococcus thrives on all culture-media, 
even at room-temperatures, though better at 37° C. 
It forms colonies which produce pigment in those 
parts exposed to the air and become orange-yel- 
low. The pigment-formation is most marked on 
agar and potatoes. Gelatin is slowly liquefied. 
In the presence of grape-sugar it forms lactic, 
acetic, and valerianic acid. In bouillon-cultures 
there are produced poisons of violent action. The 
Staphylococcus pyogenes is one of the most fre- 
quently occurring pathogenic bacteria, and is, with Streptococcus pyo- 
genes, the most common cause of suppuration. Both forms are therefore 
designated pus-cocci. It is widely distributed through the external 
world, and has been demonstrated in milk, wash-water, and waste-water, 
Fig. 398.— Diplococcus 
pneumoniae. (Weichsel- 
baum.) a, Cocci without 
capsule; b, single and 
double cocci with a gela- 
tinous capsule; c, chain of 
encapsulated cocci; d, col- 
ony of cocci, x 500. 
Fig. 399.—Diplococcus pneumonia in early stage (formalin, fuchsin). a. Hypersemic vessels; 
b, diplococci; c, cellular exudate; d, swollen epithelial cells covered with cocci. X 500. 
as well as in the air of operating-rooms and sick-chambers. Increasing in 
the tissues of the human body (Figs. 400-402) it causes tissue-degenera- 
tions and necroses followed by inflammation (Figs. 400, d, e; 401, b, c; 
402, c, d) which is usually purulent in character, but not infrequently 
it does not lead to suppuration. STAPHYLOCOCCI. 
445 
The suppurations produced by staphylococci are usually circumscribed 
(Figs. 400, 401), and show less tendency to involve surrounding tissue 
than the suppurations caused by streptococci. In the skin they give rise 
to furuncle, and cutaneous and subcutaneous abscesses. In the osseous 
system they are the most frequent cause of suppurative osteomyelitis 
Fig. 402) and periostitis. They not infrequently cause purulent inflam- 
mations of the liver, lungs, pleura, peritoneum, brain, meninges, muscle, 
myocardium, spleen, kidneys, joints, etc.; and are often the cause of 
inflammations of the endocardium. Since the virulence of staphylococci 
varies, they may produce, in the regions named, transitory inflammations 
which heal with or without scar-formation. 
The portal of entrance of staphylococci is often easily recognizable 
(especially wounds), and the same is true of the path of metastasis to 
internal organs, whereby inflammations of the lymph-vessels (lymphango- 
Fig. 400.—Multiple abscesses of the skin due to staphylococci (alcohol, carmine, Gran.’s 
method). Child of three weeks, a, Epithelium; b, corium; c, hair-follicle; d, e, purulent foci 
with cocci, x 40. 
it is) and of the blood-vessels (phlebitis, arteritis) make their appearance. 
Cryptogenic infections are, however, not infrequent, so that the first 
recognizable localization of the infection appears in the endocardium, 
myocardium, or bone-marrow. The spread of staphylococci through the 
blood leads to multiple localizations with abscess formation ; this condition 
is designated pyaemia. The complication of staphylococcus infection with 
severe symptoms of intoxication is known as septicaemia; and the com- 
bination of staphylococcus-pysemia with septicaemia is known as septi- 
copyaemia (cf. § 11). 
Staphylococcus pyogenes aureus is also pathogenic for animals: horse, 
dog, cattle, goat, sheep, rabbit, guinea-pig, and mouse, particularly for 
the first-named, less so for the last. In these animals, it causes suppu- 
ration. The staphylococcus loses its virulence easily in cultures. The 
inoculation of cultures of high virulence into susceptible animals causes 
gelatinous oedema. 446 
THE PATHOGENIC FISSION-FUNGI. 
Related to the Staphylococcus pyogenes aureus are the Staphy- 
lococcus pyogenes albus and the Staphylococcus pyogenes citreus. 
The albus forms whitish, the citreus lemon-yellow colonies. The former 
is the cause of the so-called “ stitch-abscesses ” in surgical wounds, but 
is otherwise of negligible significance. 
Staphylococcus pyogenes aureus usually occurs alone in pus-foci, but 
may be associated with other pus-cocci or even bacilli, for example, the 
Bacterium coli commune, or the typhoid-bacillus. 
The staphylococcus forms a haemolysin and a leukocidin (Van der Velde, 
Neisser, and Wechsberg) which destroys the leucocytes of rabbits, and also poisons 
which have a degenerative action on the tissues. The bodies of dead staphylococci 
cause inflammation when injected into tissues. Staphylolysin and haemolysin and 
leukocidin form in the organism antistaphylolysin and antileukocidin and therefore 
belong to the toxins. 
A serum produced by pathogenic staphylococci will agglutinate both the homol- 
ogous strain as well as the majority of other pathogenic strains (Kloppstock and 
Bockenheimer). 
Fig. 401.—Miliary purulent nephritis, caused by staphylococci, primary focus in skin 
(furunculosis) (alcohol, methyl-violet, carmine), a, Normal kidney tissue; b, collections of cocci; 
c, purulent focus, x 43. 
§ 155. The Micrococcus Gonorrhoeae or Gonococcus (Fig. 403) was 
described by Neisser in 1879. It is constantly present in the discharges 
of the purulent catarrh, known as gonorrhoea, of the male and female 
urethra, and the female genital canal (especially of the cervix), as well 
as in the secretions of gonorrhoeal ophthalmia. It is universally regarded 
as the cause of gonorrhoea. Besides the specific cocci, other cocci may be 
present in gonorrhoeal secretions, some of them closely resembling the 
gonococcus; pus-cocci may also be present. 
The gonococcus may be cultivated on coagulated human blood-serum, 
blood-serum gelatin, on human blood-serum-agar, on urine-agar; and 
forms on the surface of the nutrient medium a thin grayish-yellow layer 
having a smooth surface. It dies easily, and grows only at higher tem- 
peratures. GONOCOCCUS. 
447 
The gonococcus contains a poison (Wassermann) which, when 
injected into the tissues, excites inflammation. 
Animals are immune against inoculations with the gonococcus with 
the exception of the higher apes. Efforts to inoculate human beings with 
artificially cultivated gonococci have been successful in producing purulent 
catarrh of the inoculated mucous membrane. 
In the purulent secretion of the mucous membrane infected with gon- 
orrhoea the coccus usually forms clumps, and appears in the form of 
diplococci, the opposing surfaces of which are flattened (Fig. 403) ; but 
occurs also free (a), and inclosed within cells (&). It stains easily with 
aniline dyes, but is decolorized by Gram’s method. 
The gonococcus penetrates into the epithelial layer of the affected 
Fig. 402.—Staphylococcus osteomyelitis of calcaneus. (Alcohol, methyl violet, carmine.) 
a, Trabeculse of bone; b, fatty marrow; c, purulent area; d, cocci, x 100. 
mucous membrane, and lies between and in the epithelial cells, and in 
leucocytes. Only the uppermost layers of the connective tissue are 
infiltrated. The infiltration is most marked in the case of cylindrical 
epithelium, while in regions covered by squamous epithelium (fossa 
navicularis, vagina) the cocci lie more superficially. They cause inflam- 
mations which bear the character of purulent catarrhs, and are associated 
with cellular infiltration of the tissue of the mucosa (Fig. 404, b, c, d) and 
with epithelial desquamation. The male and female urethra and the 
adjoining parts of the genital glands and ducts and the urinary passages 
form the chief seats of localization. According to Scholz there occurs, 
after three-weeks’ duration of the disease in the male urethra, meta- 
plasia of cylindrical into stratified squamous cells, and the secretion 
decreases after this time. To what extent the deeper inflammations so 448 
THE PATHOGENIC FISSION-FUNGI. 
frequently accompanying or following gonorrhoea (peri-urethral abscesses, 
prostatitis, epididymitis, vesiculitis, cystitis, inflammation of the ducts 
of Bartholin’s glands, salpingitis, ovaritis, pelvic peritonitis, arthritis, etc.) 
are to be referred to the spread of the gonococcus or to what extent to 
secondary infections by pus-cocci is a question. There can be no doubt 
that the gonococcus may become widely spread over the surface of 
mucous membranes. It has been demon- 
strated in the blood, in the inflamed epidi- 
dymis, tubes, ovaries, joints, cardiac valves, 
tendon-sheaths, bursae, in peri- and para- 
metritic foci of inflammation, and in peri- 
urethral abscesses. In these cases it is 
usually regarded as the cause of the inflam- 
mation, yet the processes which lead to sup- 
puration, and even the metastases in dis- 
tant organs, appear to be more frequently 
dependent on the presence of pus-cocci. 
Gonorrhoeal infection is at the beginning 
an acute process, but may become chronic, 
and is cured with great difficulty, since 
gonococci maintain themselves in the 
urethra, tubes, etc., for vears, and continue to cause inflammation. 
Fig. 403.—Gonococci in the urethral 
secretion from a fresh case of gonor- 
rhoea (methylene-blue, eosin). a, 
Mucus with single cocci and diplo- 
cocci; b, pus-cells with, c, pus-cells 
without diplococci. X 700. 
Irons {Jour. Infect. Dis., 1908) found that the injection of dead gonococci into 
individuals suffering from chronic gonococcus infections gave a “gonococcus-re- 
action ” which may be of assistance in diagnosis. 
Fig. 404.—Urethritis gonorrhoica. Cross-section through the mucous membrane which had 
been thrown into folds (Muller’s fluid, haematoxylin, eosin). a, Normal connective tissue; b, c, 
inflammatory, infiltrated, proliferating connective tissue of the mucosa; d, infiltrated and 
desquamating epithelium; e, desquamated epithelial cells and pus-corpuscles, x 100. BACILLI. 
449 
2. The Bacilli and the Polymorphous Bacteria, and the Patho- 
logical Processes Produced by Them. 
(a) General Considerations Regarding Bacilli and the Polymorphous 
Bacteria. 
§ 157. Under the designation bacilli may be classed all those bacteria 
which occur in the form of straight rods or rods which are slightly bent 
in one plane. 
I he bacilli multiply by division. The rods grow in length, and divide 
into approximately equal parts through the formation of a transverse 
partition-wall. If the division of one of the elongating bacilli is delayed, 
or if the separation of the individual rods from one another is not dis- 
tinctly recognizable, there arise long, unbranched rods or threads 
(Fig. 406, b). If the divided rods remain attached to each other, there 
Fig. 405. 
Fig. 406. 
Fig. 405.—Bacillus subtilis in various stages of development (Prazmowski). a, Single rods; 
b, rods with flagella; c, chain of rods; d, single cells with spores; e, chain of rods with spores; 
f 1—5, germination of a spore, x 800. 
Fig. 406.—Clostridium butyricum (Prazmowski). a, Short rods; b, long rods; c, chain of 
rods; d, cells with spores; e 1—7, germination of a spore, x 800. 
are formed chains of rods (Figs. 405, c ; 406, c). In many forms of 
bacilli the ends of the individual rods are blunt, in others rounded or 
pointed. 
In many bacilli, resting as well as swarming stages are observed. 
Flagella serve as the organs of motion (Fig. 405, b) ; they are situated 
sometimes at the ends, sometimes on the sides, of the rods, and may occur 
in large numbers. In many bacilli endogenous spore-formation is 
observed (Figs. 405, d, e; 406, d), the spores lying sometimes in the 
middle, sometimes at one end, of the cell. Not infrequently the spores 
appear within jointed threads. The germination of spores results in the 
formation of new rods (Figs. 405, f, 1-5 ; 406, e, 1-7). 
During spore-formation the rods usually do not change their shape 
to any marked extent. In other cases they assume a spindle-, club-, or 
pear-shape (Fig. 406, d). 
The polymorphous bacteria are distinguished from bacilli by the 
fact that they form, besides rods, long threads, with false or true branch- 
ing; in individual cases a basal non-proliferating end and an apical pro- 
liferating end may be distinguished. In this category may be placed the 
fungi designated Streptothrix, Cladothrix, Beggiatoa, and Crenothrix. 
They are placed with the bacilli, because their botanical position is not 450 
THE PATHOGENIC FISSION-FUNGJ. 
definitely determined, while, in so far as they are pathogenic, they con- 
form closely to the bacilli in their biological properties (cf. diphtheria- 
bacilli, tubercle-bacilli and actinomyces). 
The saprophytic bacilli produce various forms of fermentation by 
their growth in nutrient fluids; many form pigments. A sharp line cannot 
be drawn between saprophytic bacilli and pathogenic forms, since some 
saphrophytes (proteus vulgaris, Bacillus pyocyaneus, B. tetani, B. 
cedematis maligni) occasionally develop in the human organism. Some 
also form toxins (B. botulinus, B. pyocyaneus) which when taken into 
the organism produce intoxication. 
Bacillus botulinus (Van Ermengem) is an obligate anaerobic bacillus 
which develops occasionally in sausage, particularly in blood and liver 
sausages, in smoked meat, canned meats, game pies, salted fish, and in 
preserved fruits and vegetables. The bacillus is 4—6 //, long, 0.9—1.2 n 
broad and possesses 4—8 peripherally arranged flagella. It stains accord- 
ing to Gram. In ordinary nutritive media it grows best under anaerobic 
conditions at a temperature of 18°-25° C., and forms endogenous spores. 
Acids inhibit its growth. 
When growing in the foods mentioned, it produces a toxin which is 
poisonous for experimental animals, and causes the formation of an 
antitoxin. The poison is rendered inactive by heating to 80° C., but is 
not changed by the digestive juices. The consumption of food in which 
the bacillus has already formed its toxins leads, therefore, to intoxication. 
On the other hand, the bacillus does not develop in the human organism, 
its growth being hindered by the high body temperature. The bacillus 
should be classed as a toxicogenic saprophyte. 
The intoxication known as botulismus comes on about twenty-four to 
thirty-six hours after the taking of poisoned food, and is characterized 
by nervous disturbances of central origin (paralysis of accommodation, 
mydriasis, ptosis, and double vision), dryness and redness of the mucous 
membrane of mouth and pharynx, aphonia, dysphagia, etc. Constipation 
and retention of urine frequently take place, or there may be diarrhoea 
and vomiting. Death often results after a short time through bulbar 
paralysis. 
It has been shown that the designation botulism, or sausage poisoning, 
is inappropriate to this form of bacterial intoxication, at least as it occurs 
in the United States. Canned string beans, asparagus, corn, apricots, ripe 
olives and cheese have at various times and places been implicated. The 
majority of outbreaks recorded in this country have been due to house- 
hold canned foods, but the bacillus may also find its way into canning 
factories. In either event, the spores of the causative micro-organism 
may survive relatively high temperatures and subsequently germinate to 
produce a potent toxin, the ingestion of which gives rise to symptoms of 
poisoning. There seems to be no doubt that the early statements of 
Van Ermengem relative to the low heat resistance of this organism are 
incorrect as applied to all strains. For example, most of the American 
strains have been found to withstand much higher temperatures, some 
even resisting the temperature of boiling water for a considerable period. 
Outbreaks of botulism have been recorded in Belgium, France and Ger- 
many. Thus far, Great Britain appears to have been exempt. In the 
United States, the majority of cases have been reported from California, 
Idaho, Colorado, Indiana, Massachusetts, Michigan, New York, Kentucky 
and Illinois, so that the disease occurs in widely separated parts of the BACILLI. 
451 
country. Several recent outbreaks have been traced to canned ripe olives. 
(Journal of the American Medical Association, December 13 and 20, 
1919.) 
As Proteus vulgaris, Hauser has described a bacillus which is fre- 
quently present in decomposing animal substances and in human cadavers, 
and in gangrenous ulcers. It forms rods of varying length, and produces 
substances poisonous for animals. It is not infrequently found in human 
tissues, in association with streptococci, pneumococci, and diphtheria- 
bacilli ; and by its presence aggravates infection and causes putrid decom- 
position of pus and necrotic tissue. In rare cases it may alone cause 
inflammation, particularly of the urinary bladder (cystitis). Cases of 
hcemorrhagic enteritis have been described, in which a form of proteus 
was regarded as the causal agent. 
The pathogenic bacilli and polymorphous bacteria cause both acute 
and chronic affections, the former terminating in death or in healing 
after destruction of the bacteria. In acute diseases the bacteria may 
remain in the body for a long time after the disappearance of symptoms. 
The chronic affections are characterized by persistence and multiplication 
of the bacteria in the body, so that the disease assumes a progressive 
character, and sometimes slowly, sometimes rapidly, new regions are 
invaded and suffer changes. 
Bacillus subtilis is a fission-fungus whose spores are widely distributed in the 
ground, in hay (hay-bacillus), and in the air. When cultivated on potato or on the 
dung of herbivorous animals, it forms whitish-yellow colonies; on liquids it forms 
pellicles. It requires oxygen for development. 
The fully developed rods (Fig. 405, a) are 6 M long. The snake-like motions 
occurring at times are produced by lateral and terminal flagella. Through the 
growth of the rods undivided threads are formed which after division form chains 
of rods. The separate cells may develop in their interior glistening, sharply con- 
toured spores (d, e), which lie either in the middle or nearer to one end of the 
cell. Later the cells in which the spores have been formed die. During germination 
the spores become pale (Fig. 405, f, 1*5), lose their glistening appearance and sharp 
contour. A shadow then appears at each pole, while the spore begins a tremulous 
motion. After a time the contents of the spore project from the membrane of 
the spore in the form of a germinal utricle, which later becomes elongated, divides 
and produces swarming rods. 
Bacillus prodigiosus grows on potatoes and bread, as well as on agar-agar, 
and on gelatin, liquefying the latter. It forms a red coloring matter which is 
soluble in alcohol. The pigment is formed only in the presence of oxygen; in the 
growth in milk the coloring-matter is contained in the fat-droplets. The bacilli 
themselves are colorless. 
Bacillus pyocyaneus occurs occasionally in bandages on suppurating wounds 
and causes a greenish-blue discoloration of the same. The coloring-matter called 
pyocyanin is soluble in chloroform and crystallizes from the solution in long blue 
needles. In addition, it forms a coloring matter soluble in water that produces a 
greenish fluorescence of gelatin. 
(b) The Pathogenic Bacilli and Polymorphous Bacteria. 
§ 158. The Bacillus anthracis (Bacteridie du charbon) is the cause 
of anthrax, a disease occurring chiefly in cattle and sheep, occasionally 
transmitted to man. It is a fission-fungus which, when inoculated into a 
susceptible animal, increases locally in the tissues and later enters the 
blood. 
Anthrax-bacilli (Fig. 407) are 3 to 10 n long and 1 to 1.5 /x broad. 
In the blood of animals affected with anthrax they occur either singly or 
in thread-like jointed bands of two to ten rods, whose ends are sharply 452 
THE PATHOGENIC FISSION-FUNGI. 
cut across (Figs. 407, 408), more rarely concave or slightly convex. 
They possess a gelatinous capsule which is best brought out by staining 
dried preparations by the method of His or Welch. They can be culti- 
vated on blood-serum-gelatin, in bouillon, on slices of potatoes or turnips, 
and on plain agar, in the presence of oxygen, and grow most rapidly at a 
temperature of from 30° .to 40° C. At temperatures below 15° and 
above 43° C. development is impossible. 
Under suitable conditions of growth the rods increase in length, and 
within a few hours form non-encapsulated threads of considerable length. 
These consist of short segments whose outlines may be made visible by 
treatment with iodine or by stains (Fig. 408). Ten hours later the clear 
contents of the threads become 
granular, and at regular inter- 
vals there become apparent 
bodies which, after a few hours, 
Fig. 408.—Spore-containing 
anthrax-bacilli and free 
spores. Cover-glass prepara- 
tion from a culture of the 
bacilli grown in the incubator 
upon a potato, and stained 
with fuchsin and methylene- 
blue. X 800. 
Fig. 407.—Section from a liver whose capil- 
laries contain numerous anthrax-bacilli and 
scattered leucocytes (alcohol, gentian-violet, 
vesuvin). x 300. 
enlarge into strongly refractive spores (Fig. 408). Later the threads 
disintegrate and the spores become free. 
If the bacilli or spores gain entrance to the blood, they increase and 
form rods as described, that stain with aniline dyes, and by Gram’s 
method. Sections of hardened tissue show that they are present in large 
numbers in the capillaries (Fig. 407), particularly in the spleen, liver, 
lungs, and kidneys. The neighboring parenchyma appears unchanged; 
still local proliferation of the bacilli can cause tissue-degeneration, 
necrosis, and haemorrhagic inflammation. If infection of the blood takes 
place during pregnancy the infection may pass to the foetus. 
Anthrax-bacilli or their spores may gain entrance into the skin of 
man through small wounds, an event which is particularly likely to 
happen in individuals who butcher, or shear, or prepare the skins of 
animals infected with anthrax; occasionally infection may be transmitted 
by means of the sting of a fly which has taken up blood from an animal 
infected with anthrax. Infection not uncommonly is due to the use of 
shaving brushes made of infested hairs or to the wearing of contami- 
nated furs. There develops at the place of infection a pustule (Fig. 409) 
from 6 mm. to several centimetres in diameter, having an arched or flat- 
tened surface, and a red or yellowish color. This is after a time covered 
with vesicles, or after the loss of epithelium becomes moist, so that 
through drying of the exudate, a scab is formed (Fig. 409, g). ANTHRAX. 
453 
The centre may become depressed through the formation of an area 
of softening, so that the edges form a wall about the latter. The neigh-, 
borhood of the pustule is sometimes but slightly changed, at other times 
reddened and swollen, and may be set with minute yellow or bluish-red 
vesicles. If the process remains local, the gangrenous pustule may be 
thrown off. Infection of the blood is fatal. In rare cases the infection 
from the beginning may show itself as an extensive, intense, cedematous 
swelling of the tissue without the formation of a circumscribed elevation 
(malignant anthrax oedema). 
In the region of a fully developed anthrax-pustule (Fig. 409), the 
corium (d, dx) and the papillary body (c) are infiltrated with serocel- 
lular exudate as well as by bacilli. The bacilli lie particularly in the outer 
portions of the corium (dx) and in the papillary body (c), but may pene- 
Fig. 409.—Section from an anthrax-pustule ten days old, taken from the arm of a man 
(alcohol, Gram’s method, vesuvin). a, Epidermis; b, corium; c, papillary body oedematously 
swollen and infiltrated with exudate and bacilli; d, outer layer of corium, infiltrated with cells; 
di, the same containing also bacilli; e, deep layers of the corium infiltrated by cords of cells; 
f, dermal tissue infiltrated with bacilli and cells; g, bloody exudate containing bacilli, lying upon 
the surface; h, hair-follicle; i, sweat-gland, x 33. 
trate the deeper layers of the corium (/). In the neighborhood of the 
papillary body (c) the exudate is sanguineous. Vesicles filled with 
bloody fluid result, if the exudate extends to the epithelial covering, and 
if the deeper portions of the latter become liquefied, permitting lifting of 
the superficial layers by the exuded fluid. If the upper layers of the skin 
are lost, the bloody fluid containing bacilli (g) appears on the surface. 
The cellular infiltration has its seat chiefly in the corium (d, dlf e), 
and the impression is gained that massing of cells forms a protection 
against the spread of the bacilli. The cells which collect belong for the 
greater part to the polynuclear leucocytes (Fig. 410). The bacilli lie 
sometimes in, sometimes between the cells. 454 
ANTHRAX. 
If infection with anthrax-spores takes place in the intestinal canal, 
an event which occurs most frequently in the small intestine, less often 
in the stomaCch and large intestine, there develop dark-red or brownish- 
red haemorrhagic foci, the size of a lentil or bean or larger, with a grayish- 
yellow or greenish-yellow slough in the centre. In other cases the crests 
of the folds of the mucosa are swollen and haemorrhagic, and show evi- 
dences of sloughing. 'I he mucosa and submucosa are infiltrated with 
blood in the region of the foci; the surrounding tissues are oedematous 
and hyperaemic. Bacilli are found in the tissues in and about the foci, 
particularly in the blood- and lymph-vessels, and may be demonstrated 
in neighboring lymph-nodes. 
Primary lung infection may occur in man as the result of inhalation 
of anthrax-spores, proving fatal in from two to seven days. Individuals 
who handle the hair of animals that have died of anthrax are especially 
exposed to infection; the rag-sorter’s disease, 
which occurs in men and women employed in 
the sorting of rags in paper-factories, is an 
anthrax infection. The spores taken into the 
lungs in respired air develop in the bronchi 
and alveoli, in the lymph-spaces of the lungs 
and pleura and in the bronchial nodes, and 
penetrate into vessels. Their growth causes 
inflammatory haemorrhagic processes in the 
lungs, as well as haemorrhagic exudations into 
the pleural cavity and mediastinal tissue, and 
swellings of the lymph-nodes. It may also 
lead to necrotic foci in the lungs and in the 
bronchial and tracheal mucosa. 
Mice, rabbits, sheep, horses, and sparrows are susceptible to anthrax; 
white rats, dogs, and Algerian sheep are less susceptible or immune. 
Cattle are easily infected through taking in of spores from the alimentary 
canal, but are less susceptible to inoculation. Formation of spores does 
not take place in the tissues and blood. 
Fig. 410.—Portion of an- 
thrax pustule from the arm 
(Fig. 409), containing bacilli. 
X 3SO. 
Among certain animals, geographically as well as zoologically, anthrax is the 
most widespread of all acute infective diseases. In occasional instances it is trans- 
mitted to man, usually through abrasions of the skin that have been in contact with 
infested hides, furs, shaving brushes made of contaminated hairs, and the like, 
but sometimes by swallowing or breathing. In recent years the occurrence of 
anthrax in human beings has undergone increase and is now regarded by students 
of ihdustrial conditions as an occupational disease of moment. Moreover, in view 
of the fact that hides, furs and other products of anthrax-infested districts are 
seldom, if ever, subjected to disinfection before shipping, it is to be expected that 
anthrax will undergo still further increase as our trade with the cattle countries 
enlarges. In this climate anthrax is most often encountered among handlers of 
hides imported from the Argentine and Far East. Sometimes the disease appears 
in epidemic form among longshoremen engaged in unloading the same cargo. 
Malignant anthrax oedema of the face and neck is practically always fatal. 
In the same way the so-called wool-sorters’ disease, which is an anthrax septicemia 
with intense pulmonary and cerebral symptoms, and anthrax of the intestinal tract, 
are likewise deadly. The malignant pustule, on the other hand, not infrequently 
heals and the patient recovers. In malignant pustule of the face, however, the 
mortality is five times greater than that of an extremity, in which only a small 
percentage of cases terminates fatally. In the past four years 20 cases of malig- 
nant pustule have been treated at Bellevue Hospital. Of these, 13 recovered. This 
variety of anthrax is, at the beginning, a purely local lesion. The malignant pustule 
is a characteristic and easily recognized lesion. At the site of inoculation a small 
papule appears and within a few hours is surrounded by extensive oedema. The ANTHRAX. 
455 
papule rapidly undergoes enlargement and central necrosis attended by the forma- 
tion of a series of silvery vesicles scattered over the scab or immediately circum- 
ferential to the necrotic zone. The patient’s mentality is usually preserved through- 
out. The swelling of the tissues in the immediate vicinity of the pustule may be 
extreme and depends on infiltration by so-called anthraco-mucin, which is a pro- 
tective substance. In it anthrax bacilli do not thrive. Incision of the oedematous 
area, therefore, is contraindicated. 
In recent years the serum treatment of anthrax has received a great deal of 
attention. The serum is injected intravenously in large doses at frequent inter- 
vals. Local injection of serum at multiple points in the immediate vicinity of the 
anthrax pustule is an exceedingly important part of the specific treatment and should 
Fig. 41 i.—(Bellevue Hospital.) Anthrax pustule of left side of neck showing the wide- 
spread swelling of the surrounding tissues due to infiltration by anthraco-mucin. 
never be neglected. There are those who advocate at the same time excision or 
cauterization of the pustule, while others depend entirely on the local injection of 
serum to control the infection. After the bacillus invades the blood stream, of 
course, the outlook is hopeless, serum or no serum. 
The bacilli of anthrax are killed by high temperatures, drying, and through 
decomposition of the nutrient fluid. The spores, on the other hand, are resistant, 
and are usually the medium of spread of the disease. 
The colonies on gelatin show a wavy, irregularly shaped margin, and consist of 
interlacing strands or threads, which grow out of the culture in all directions. 
The gelatin is liquefied immediately about the culture. On potato the bacillus forms 
grayish-white, slightly granular colonies having a sharply outlined border. On 
blood-serum it forms a white coating. 
Stab-cultures in gelatin are white and during the process of growth radiate at 
right angles from the line of inoculation into the gelatin, particularly near the sur- 
face. After liquefaction of the gelatin they sink to the bottom. 
Marked attenuation of anthrax-bacilli may be produced by keeping the bacilli 
for ten minutes at a temperature of 55° C. (Toussaint) or for fifteen minutes at 456 
THE PATHOGENIC FISSION-FUNGI. 
52° G, or for twenty minutes at 50° C. (Chauveau), or through the influence of 
oxygen under high pressure {Chauveau). The bacilli attenuated by exposure to 
high temperatures quickly regain their virulence; those attenuated at lower tem- 
peratures remain weakened for many generations. 
The addition of carbolic acid to the nutrient fluid in a proportion of 1 :600 
permits the development of anthrax-bacilli, but destroys their virulence within 
twenty-nine days {Chamberland, Roux). Likewise, attenuation may be produced 
by the addition of potassium bichromate (1:2,000-1:5,000). The addition of car- 
bolic acid up to 1:800 hinders the formation of spores. 
Through cultivation of the bacilli at 42-43° C. {Toussaint, Pasteur, Koch) their 
virulence may be so weakened that they no longer kill first sheep, then rabbits and 
guinea-pigs, and finally mice. If the temperature is kept in the neighborhood of 
43° C. this result may be obtained in six days; at 42° C. it may require about thirty 
days to decrease the virulence to this extent {Koch). By first inoculating with 
bacilli which kill mice but are harmless for guinea-pigs, and afterward with bacilli 
which kill guinea-pigs but not strong rabbits, immunity against anthrax may be 
obtained in sheep and cattle but not in mice, guinea-pigs, and rabbits. Such pro- 
tective inoculations are, however, not of practical value, since, in order to protect 
against natural infection with spores from the intestinal canal, such virulent inocu- 
Fig. 412. 
Fig. 413. 
Fig. 412.—Typhoid-bacilli from a pure culture. Streak-preparation (methylene-blue) 
x 1,000. 
Fig. 413.—Typhoid-bacilli with flagella. (After Bunge.) x 1,200. 
lation-material must be used that a large per cent, of sheep (ten to fifteen per cent.) 
die from the inoculations. Further, the protection afforded by the inoculation is of 
short duration, and the inoculation must be repeated within a year’s time. 
According to observations by Roux and Chamberland anthrax bacilli which are 
cultivated in bouillon to which a small amount of potassium bichromate (1:2,000) 
or carbolic acid (1 to 2:1,000) has been added, permanently lose their power of 
spore-formation while retaining their virulence. 
True toxins or endotoxins have not yet been demonstrated in anthrax bacilli. 
§ 159. The Bacillus typhi abdominalis (Fig. 412) is a fission fugus 
which occurs in the form of rods 2 to 3 n long, having rounded ends, in 
cultures growing in pseudo-threads. It is regarded as the cause of 
typhoid fever, a disease which was once widely prevalent, but is now 
rarely encountered. In cultures the typhoid bacillus shows lively move- 
ments which are accomplished by flagella (Fig. 413) attached to the sides 
of the bacilli and to their ends. The flagella may be demonstrated by 
staining-methods. 
The bacilli gain entrance to the body through drinking-water and food. 
They develop in the solitary and agminated follicles of the small and large 
intestines, as well as in the mesenteric lymph-nodes, and in the spleen. 
In the intestine they cause hyperplasia of the lymphoid tissues, which 
project above the surface as flattened or rounded elevations, and later 
undergo necrosis and sloughing with the formation of ulcers. In the TYPHOID BACILLUS. 
457 
process of ulceration blood vessels may be opened with the production of 
haemorrhages of greater or less degree, or perforation of the gut may 
occur with the escape of intestinal contents into the cavity of the peri- 
toneum and secondary peritonitis. 
T lie swelling of the lymph-nodes, in the mesentery and vicinity, ends 
either in healing through absorption of the hyperplastic lymphoid cells, 
or may lead to necrosis. Rupture of necrotic lymph-nodes into the peri- 
toneum sometimes occurs, and results in the escape of typhoid bacilli and 
peritonitis. 
The bacilli are usually distributed through other parts of the body, 
and it is probable that inflammatory exudations in the lungs occurring 
during the course of typhoid fever are due to increase of the bacilli in 
the lungs. It should always be borne in mind that aspiration-pneumonias 
are of frequent occurrence in typhoid patients, and that secondary infec- 
tions may take place from the intestinal ulcers and give rise to metastatic 
inflammations. The swellings of the mucosa and. submucosa and of the 
perichondrial tissue, which occur in the palate, throat, and larynx, are in 
part the result of the specific infection, and in part of secondary disease. 
Typhoid-bacilli have been demonstrated in the blood, liver, gall-bladder, 
in the rose-spots of the skin, in the kidneys, central nervous system, 
testicles, in pleuritic and peritoneal fluids, in the periosteum, bone-mar- 
row, etc. The bacilli circulate in the blood for about two or three weeks 
and cultivation from this source is often employed as a diagnostic method. 
When typhoid fever occurs during pregnancy the bacilli may pass to the 
foetus. 
In the course of typhoid fever there appear in the blood certain sub- 
stances which cause degeneration of typhoid-bacilli (cf. § 31). This may 
be demonstrated by the fact that (Widal-Gruber reaction), through the 
addition of serum from an individual ill or convalescent from typhoid 
fever, to a bouillon-culture of freely motile typhoid-bacilli, the latter 
become motionless, clump (agglutination), and die. This reaction may 
be used as a means of diagnosis, but is not infallible, since agglutination 
may be produced by the serum of individuals who have not had typhoid 
fever, and may be absent in typhoid. The agglutinating power can last 
for years, or may vanish after a month. 
Individuals who have had typhoid fever may harbor the bacilli in their bodies 
for years after the attack, without showing any symptoms of infection (“typhoid 
carriers”). By giving off bacilli through urine or faeces typhoid carriers become 
an element of danger to the community in which they live. (“Typhoid Bacilli 
Carriers.” Park, J. Amer. Med. Assoc., 1908.) 
The typhoid-bacillus stains well in cover-glass preparations, with gentian- 
violet, alkaline methylene-blue, and Bismarck brown. It is decolorized by Gram’s 
method. It is difficult to demonstrate it in sections of hardened tissues. 
The bacillus may be cultivated on gelatin, agar-agar, and blood-serum, in milk, 
and on potato. On the last named it forms a coating which can be scarcely recog- 
nized by the naked eye; but when touched with a platinum wire it becomes apparent 
that it is covered with a pellicle. 
On gelatin and agar-agar the bacilli form gravish-white, irregularly shaped, 
flat growths. Gelatin is not liquefied. Milk in which the bacilli are grown is not 
changed externally. 
The cultures thrive at room as well as body temperature. Potato-cultures 
made in the usual manner, when kept between 30° and 42° C., produce rods which 
have glistening bodies in their poles. Gaffky regarded these as spores, and the 
majority of authors formerly accepted this view. According to Buchner and Pfuhl, 
however, these granules are degeneration phenomena, which occur particularly when 
acid is present in the culture medium. The polar granules represent condensed 458 
THE PATHOGENIC FISSION-FUNGI. 
protoplasm, and therefore stain in fresh preparations more quickly with aniline 
dyes than the other parts of the cell. The clear, colorless spots which are seen at 
the ends of the rods in dried and stained bacilli have been held to be identical 
with the polar granules and therefore regarded as spores, but are due, according to 
Buchner, to hollow spaces formed at the ends of the rods as the result of retraction 
of the protoplasmic tube following death and drying of the bacilli. Spore-formation 
has, therefore, not been demonstrated. 
Cultures of typhoid-bacillus show few characteristic appearances and are with 
difficulty distinguished from those of other bacteria widely scattered in the outer 
world. Their properties are similar to those of Bacillus coli communis (§ 160). 
Certain points of difference are as follows: The typhoid-bacilli produce no indol, 
while similar bacteria, such as Bacillus coli, produce it, so that bouillon cultures 
become red through the addition of potassium nitrite and sulphuric acid. The 
typhoid-bacillus produces no gas in a two-per-cent, grape-sugar bouillon, while 
Bacillus coli produces gas. Finally typhoid-bacilli in milk cause weak acidity but no 
coagulation, while the Bacillus coli will cause at 37° C., even in twenty-four to forty- 
eight hours, strong acidity and coagulation of the milk. When typhoid bacilli are 
grown on agar colored blue with litmus, the color remains unchanged, while Bacillus 
coli decolorizes the blue. 
In moist earth, in pure and impure water, typhoid-bacilli may remain alive for 
weeks. In artificial Seltzer water they do not die out for a longer period. In 
privy vaults and faecal masses, or in earth saturated with faecal matter they may 
live for weeks and months. 
Inoculations of the bacilli in animals ordinarily used for experiment do not 
produce a disease corresponding to typhoid fever in man. Experimental investiga- 
tions show, however, that the typhoid-bacilli produce active toxins (endotoxins?) 
which in large doses kill the animals, causing hyperaemia and swelling of the 
intestinal follicles, mesenteric nodes, and spleen. Cultures injected into the tissues 
cause local inflammation of greater or less intensity. 
The value of the agglutination test is limited, since it is hard to decide whether 
the agglutinating effect of the serum is brought out by the same kind of bacillus 
or by a related variety. In general the serum of a patient agglutinates the 
species causing the disease in a greater dilution than in the case of a related organ- 
ism, but there occur exceptions to this rule. According to Lubowski and Steinberg 
the agglutinatibility of typhoid-bacilli can be increased in guinea-pigs and rabbits 
through proteus or staphylococcus infection. Much more positive as a diagnostic 
method is the demonstration of typhoid-bacilli in the blood by means of cultures. 
Paratyphoid fever is a disease similar to typhoid fever, but is caused by a 
form of bacillus of which a type A and a type B have been described. Clini- 
cally the disease runs a lighter course than typhoid fever and is rarely fatal. The 
anatomical findings are similar to those of typhoid fever, but the intestinal changes 
are less marked and ordinarily are confined to the colon. It is possible to make a 
differential diagnosis by means of the Widal reaction; yet it should be noted that 
paratyphoid serum may agglutinate typhoid-bacilli. 
The paratyphoid bacteria stand, as far as their cultural characteristics are con- 
cerned, between the typhoid-bacillus and the Bacillus coli communis. The round, 
smooth-edged gelatin colonies of freshly cultivated strains do not show the super- 
ficial vein-like furrowing. In type A they are almost colorless, while in type B 
they are whitish. Both consist of short rods and are motile; they ferment sugar 
without coagulating milk; cause fluorescence in neutral-red media; grow as blue 
colonies on Drigalski-C onradi plates and do not produce indol in bouillon cultures. 
Type A forms more delicate pellicles than B, and grows on potatoes in a manner 
similar to the bacillus of typhoid fever. Milk is not changed by type A, while it is 
cleared (alkaline) after several weeks by type B. 
§ 160. The Bacillus coli communis or Bacterium coli commune is a 
fission-fungus which is constantly present in the intestinal tract of man as 
well as of other mammalia. The bacilli are 2-3 g long and 0.3-0.4 g 
thick. They are motile and may possess as many as twenty flagella on 
one rod. The bacilli grow at room-temperature as well as at the tem- 
perature of the body. They form in gelatin small, round, white colonies; 
on its surface pellicle-like coatings. Upon potatoes they form moist 
coatings of the yellow color of maize or pease. They do not form spores; 
and are not stained by Gram’s method. DYSENTERY BACILLUS. 
459 
Bacillus coli is similar to'the typhoid bacillus, but may be differen- 
tiated by cultivation and by the employment of suitable reactions 
(cf. § 159). It was formerly regarded as a harmless saprophyte; but 
it cannot be doubted that it possesses pathogenic properties. Under suit- 
able conditions (perforation or incarceration of the intestine, or impac- 
tion of faeces) it may pass into the peritoneal cavity and excite purulent 
inflammation, or at least take part with other bacteria in the production 
of inflammation. It not infrequently gains access to the bile-passages and 
gall-bladder, as well as to the descending urinary passages and the kid- 
neys, giving rise to inflammations of varying intensity. 
§ 161. Under the designation Bacillus enteritidis (Gartner) there is 
a group of bacilli found in animals suffering from inflammations of the 
intestine, lungs, uterus, or udder, and with septicaemia. Gaining entrance 
into the human alimentary tract these bacilli excite more or less severe 
inflammations of the intestine characterized by swellings of the follicles. 
Man is infected by eating meat from animals slaughtered while in a 
diseased condition; such infection takes place most often through the 
meat of calves. Other sources of infection (drinking-water, milk, fish 
that have eaten diseased meat, oysters, etc.) are not excluded. The 
affection belongs to the group of meat-poisonings (see Bac. botulinus, 
§ 157) occurring in the form of local epidemics. v 
The bacilli are short, often ovoid, at times motile, and possess four to 
twelve flagella. They are not stained by Gram’s method. They form 
poisons that are resistant to high temperatures; and are pathogenic for 
mice, guinea-pigs, rabbits, calves, and apes. Injected into the tissue they 
cause local inflammation and give rise to haematogenous and lymph- 
ogenous metastases in different organs. Their entrance into the 
alimentary tract causes gastro-enteritis. 
The Bacillus enteritidis was first studied by Gartner in 1888 and recognized 
as the cause of the gastro-intestinal form of meat-poisoning. His findings were 
confirmed by the investigations of Van Ermengem, Fischer, Durham, Thomassen, 
Petri, and others. The bacillus is distinguished from other bacilli such as the Bac. 
typhi, Bac. coli, etc., by its cultural characteristics and by the agglutinating action 
of the serum of infected individuals or of previously immunized experimental ani- 
mals. Surface colonies on gelatin are similar to those of the colon-bacillus. They 
form no indol, do not coagulate milk, but cause it to take on a yellow color; they 
ferment sugar with the production of gas. The infection is caused most often 
through the consumption of the flesh or organs of calves and cattle that have suf- 
fered from the various diseases designated as septicaemia of calves, dysentery, 
enteritis, pneumo-enteritis; and infectious inflammation of the intestine. 
Intoxications caused by the consumption of meat undergoing ordinary 
putrid decomposition (Proteus, Bac. coli) are rare and are not severe. Game 
and cheese are often eaten in a condition of decomposition without exciting gastro- 
intestinal disturbances or other symptoms of intoxication. 
§ 162. The Bacillus dysenteriae is probably the cause of catarrhal, 
diphtheritic, haemorrhagic, and purulent inflammations of the colon that 
are classed with epidemic dysentery. Besides this form of bacillary 
dysentery there occur affections classed as dysentery that clinically and 
anatomically are similar to it, but are due to other parasites, amcebce in 
particular, or to chemically active substances (sublimate, septic poisons), 
or are induced by faecal retention. 
The dysentery bacillus is a plump, short rod, with rounded ends, often 
tapering. They have no flagella and are non-motile. They are easily 
stained by aniline dyes (methylene-blue, carbol fuchsin) and often show 460 
TETANUS BACILLUS. 
polar staining. Ihey are decolorized by Gram’s method. On ordinary 
nutrient media the bacillus grows best at a temperature of 37° C., either 
under aerobic or anaerobic conditions. 
According to American investigators, bacillary dysentery is due to a number 
of types of bacilli, differing in their fermentative action, bacteriolytic and agglutina- 
tion tests. In the treatment of the disease Shiga recommends a polyvalent serum 
active against all types. 
§ 163. The Bacillus pyocyaneus was first demonstrated in the pus of 
wounds in which it had produced a bluish-green discoloration. It is 
widely distributed throughout the outer world, being found particularly 
in liquid manure and dung-heaps, in water, and in the intestinal contents 
of animals (swine) and of man. 
Bacillus pyocyaneus forms rods of varying size (0.6-1—6 /x). They 
possess a terminal flagellum. It is decolorized by Gram’s method. 
Spores are not formed. It is easily cultivated on ordinary media and pro- 
duces ferments that liquefy gelatin, coagulate milk, and break tin alhnmin 
It produces in the presence of oxygen, bluish-green 
pyocyanin, which is soluble in chloroform, and a greenish 
fluorescent pigment soluble in water but not in chloroform 
and which in gelatin cultures causes greenish fluorescence 
of the gelatin. For the majority of experimental animals 
it is pathogenic, particularly for guinea-pigs and goats, and 
causes inflammation at the seat of inoculation, but later 
may spread through the blood. In bouillon cultures it 
forms both a true toxin and an endotoxin. 
§ 164. The Bacillus tetani is (Fig. 414) widely dis- 
tributed through the superficial layers of the earth, and 
is the cause of tetanus. According to observations made by Nicolaier in 
1885, it is possible to produce in mice, guinea-pigs, and rabbits, by sub- 
cutaneous inoculation of surface-earth, typical tetanus with fatal 
termination. 
Fig. 414.—Teta- 
nus-bacilli with 
terminal spores. 
X 1,000. 
It was demonstrated by Rosenbach in 1886 that this bacillus is present 
at the seat of injury in tetanus in man following trauma or freezing; and 
that when inoculated into guinea-pigs and mice it again produces tetanus. 
This discovery has been corroborated. 
The tetanus-bacillus is anaerobic and thrives in an atmosphere of 
hydrogen, but not in carbonic-acid gas. It grows on peptone-agar that is 
slightly alkaline, on blood-serum, and in nutrient gelatin. The latter is 
liquefied with evolution of gas. The addition of from 1.5 to 2 per cent, 
grape-sugar to agar accelerates the growth; a temperature of 36°—38° C. 
is most favorable for its development. The bacillus forms long, thin, 
bristle-shaped rods which develop spores (Fig. 414) giving rise to a 
spherical swelling at the end of the rod (knobbed bacilli). In cultures it 
may form long pseudothreads. Cultures give off an offensive odor; gelatin 
is slowly liquefied. The bacilli stain by Gram’s method. They are motile 
except during the time of spore-formation, and possess peritrichous 
flagella. Pure cultures inoculated into horses, asses, guinea-pigs, mice, 
rats, and rabbits cause tetanus, but in rabbits larger amounts must be 
injected. The tetanic contractures begin in the neighborhood of the 
point of inoculation. Suppuration does not occur at the point of inocu- 
lation. The bacilli cannot be demonstrated after the death of the animal 
except at the seat of inoculation. BACILLUS OF MALIGNANT CEDEMA. 
461 
The specific action of the tetanus-bacillus is to be referred to a toxin 
(tetanus toxin) which, through its haptophore group, is bound to the 
cells of the nervous system, and after a certain period excites tetanic 
convulsions. An antitoxin is produced in the body of man and experi- 
mental animals and by it animals may be made immune against tetanus 
(see § 32). 
The infection — intoxication — of man usually takes place through 
small wounds; idiopathic tetanus, which does not start from demonstrable 
wounds, may arise through infection from the mouth-cavity and respira- 
tory tract. When taken into the alimentary tract the poison becomes 
inactive as the result of changes produced by the digestive juices 
(see §29). 
The tetanus-bacillus is not isolated either in the earth or in infected wounds, 
and inoculations, therefore, consist of a mixture of bacteria. Attempts to isolate 
the bacillus by means of cultures were unsuccessful until the year 1889, when 
Kitasato succeeded by heating for a half-hour to one hour, on the water-bath, at 
80° C. mixed cultures that had been kept for several days in the incubator, and 
then plating the cultures in an atmosphere of hydrogen. Through heat bacteria 
growing with the tetanus-bacilli were killed, while the latter survived. Tetanus 
toxin (Kitasato) is destroyed by heating (65° C. and over) for a few minutes and 
by direct sunlight (fifteen to eighteen hours), and also loses its virulence in a few 
weeks under the influence of diffuse daylight. 
Literature. 
(Bacillus Tetani.) 
Moschcowitz: Tetanus, a Study, etc. (Lit.). Studies from Dept, of Path, of 
Columbia University, 1899-1901. 
§ 165. The Bacillus of malignant oedema (Vibrion septique of 
Pasteur) is an anaerobic bacillus present in various putrefying substances, 
and its spores are almost never absent from earth fertilized by decom- 
posing fluids or liquid manure. The bacilli are 3-3.5 n long, and 1—1.1 fx 
broad; they often form long pseudothreads. They resemble anthrax- 
bacilli, though somewhat more slender, and are rounded at the ends, not 
sharply cut across. In spore-formation a swelling of the rod takes place, 
as in the case of Bacillus butyricus, so that spindle- and tadpole-shaped 
forms arise. 
The bacillus is motile, and possesses flagella on the ends as well as 
on the sides. It is not stained by Gram’s method. 
It grows in nutrient gelatin as well as in agar and coagulated blood- 
serum, but must be introduced deeply into the medium and protected 
from the air. Nutrient gelatin to which one to two per cent, of grape- 
sugar has been added is an especially favorable medium. Nutrient 
gelatin and blood-serum are liquefied, the latter with evolution of gas. 
The bacillus can be obtained by sewing garden-earth under the skin 
of a guinea-pig, care being taken to prevent the access of air at the point 
of inoculation. The ensuing multiplication of the bacillus excites 
oedematous swelling of the subcutaneous tissue. At a later stage the 
bacilli spread over the serous membranes, and involve the spleen and 
other organs. 
Mice, guinea-pigs, horses, donkeys, sheep, swine, cattle, and pigeons 
are susceptible to the bacilli; rabbits and fowls are less susceptible, while 
rats, dogs, and cats are still less so. 462 
THE PATHOGENIC FISSION-FUNGI. 
The bacilli of malignant oedema occasionally develop in the human 
body, particularly when the tissues are poorly nourished and the bacilli 
through accident — puncture of a hypodermic syringe — get into the 
deeper tissues. They excite gangrenous processes associated with haemor- 
rhagic oedema and gas-production. 
As the Bacillus phlegmones emphysematosae R. Fraenkel in 1892 
described an anaerobic bacillus staining with Gram’s method, that, in 
many cases, is to be regarded as the cause of phlegmonous inflammation 
associated with gas-formation. According to Fraenkel the bacillus is non- 
motile and only exceptionally forms spores. In cultures it forms gas. 
It occurs in the external world (by Fraenkel it was demonstrated on a 
splinter of wood with which a man dying of gas- 
phlegmon had been wounded) ; and when injected 
subcutaneously into guinea-pigs or sparrows pro- 
duces a progressive gangrenous process with disin- 
tegration of the subcutaneous tissues and muscle, as 
well as free collections of fluid and gas. Intra- 
venous injection into rabbits and guinea-pigs is fol- 
lowed by the formation of gas in the internal organs. 
Gas-phlegmon in man occurs most frequently 
after severe injuries, for example, compound frac- 
tures, but may also proceed from small wounds. The 
bacillus is found at times in company with other bac- 
teria, pus-cocci, colon-bacilli; at other times alone and may be present in 
great numbers. In pure infections there occurs production of gas asso- 
ciated with liquefaction of tissue, particularly of muscles and of reticular 
connective tissue. 
It is probable that this bacillus is identical with one described by 
Welch and Nuttall as Bacillus aero genes capsulatus. 
Besides Fraenkel’s gas-bacillus other bacteria cause changes cor- 
responding to those of gas-phlegmon and foamy organs, especially as the 
result of localization in an already infected tissue (lactic-acid-bacilli, 
proteus vulgaris, and colon-bacilli). 
Fig. 415.—Bacillus pneu- 
moniae (Friedlander). a, 
Oval cells and rows of 
cells with gelatinous cap- 
sule; b, rod with gela- 
tinous capsule, x 800. 
Literature. 
(.Bacillus CEdematis Maligni. Bacillus Phlegmones Emphysematosce.) 
Davids: Malignes Oedem. Ergebn. d. a. P. vi., 1901 (Lit.). 
Frankel: Ueber die Gasphlegmone, Hamburg, 1893. Gasplegmone und Schaum- 
organe. Z. f. Hyg., 40 Bd., 1902; Gasphlegmone, Gascysten, Schaumorgane. 
Ergebn. d. allg. Path., viii., 1, 1904 (Lit.). 
Harris, Welch: Morbid Conditions caused by Bacillus Aerogenes Capsulatus. 
Bull, of Johns Hopkins Hosp., 1900. 
Howard: A Contribution to the Knowledge of Bacillus Aerogenes Capsulatus. 
Welch Festschrift, 1900; The Origin of Gas and Gas Cysts in the Central Ner- 
vous System. Jour, of Med. Res., 1901. 
Norris: Infection with Bacillus Aerogenes Capsulatus. Amer. Jour, of Med. 
Sciences, 1899. 
Pasteur: Vibrion septique. Bull, de l’Acad. de med., 1877, 1881. 
Simonds: Monographs of the Rockefeller Institute, 1915. 
Welch and Nuttall: Johns Hopkins Hospital Bull., 1892. 
§ 166. The Bacillus pneumoniae (Friedlander) or Bacillus Mucosus 
Capsulatus, is plump, non-motile, without flagella, about 0.5—1.25 ju, broad 
and 0.6-6.0 n long. It forms no spores (Fig. 415). It belongs to the INFLUENZA BACILLUS. 
463 
group of capsulated bacilli. It is easily stained with aniline dyes, but is 
decolorized by Gram’s method. It grows easily on the usual nutrient 
media, under both aerobic and anaerobic conditions, and does not liquefy 
gelatin. Stab cultures in gelatin show the so-called nail-culture, in that 
the bacteria growing over the stab-canal form a white mass of bacilli 
similar to a nail-head. 
White mice and guinea-pigs are especially susceptible to the bacillus. 
The first named die within sixteen to forty-eight hours after subcutaneous 
inoculation. The point of inoculation and the regional lymph-nodes are 
inflamed and contain encapsulated bacilli, the latter are also found in the 
blood. Rabbits are almost immune to inoculation. 
Friedlander and Frobenius, who first described the bacillus (1882), 
believed that it was the most frequent cause of 
croupous pneumonia, a view that may be ex- 
plained by its confusion with the, at that time un- 
known, Diplococcus pneumonia;. It is now recog- 
nized that it is rarely the cause of this disease 
(according to Weichselbaum, in about six per 
cent, of cases, according to Honl, in eight to ten 
per cent.) ; but it may cause focal pneumonia, 
pleuritis, pericarditis, pharyngitis, rhinitis, otitis 
media, and meningitis. In severe infections it 
can pass into the blood and set up metastases. In 
inflammatory exudates the bacilli are found in the 
form of rods and short oval cells surrounded by capsules, often forming 
chains (Fig. 415). 
Capsule-bacilli similar to the pneumonia-bacillus are often found in 
the chronic inflammation of the nasal mucosa known as oza;na, which is 
characterized by a foul-smelling secretion and the formation of scabs; 
they have been demonstrated in rhinoscleroma (see below), and it has 
been assumed that thev stand in causal relation to these diseases. 
Fig. 416.—Influenza-bacilli 
and pus-corpuscles, from 
sputum (fuchsin). x 1,000. 
According to Fricke the bacterium of Friedlander is representative of a group 
of bacteria which are classed under the name Bacillus mucosus capsulatus, and rep- 
resent varieties of a single species. The fission-fungus described as the ozena-bacil- 
lus is identical with the pneumonia-bacillus, probably also the bacillus from the 
milk-faeces of nurslings described as Bacterium, lactis a'crogenes (Escherich). It 
is possible that a greater etiological significance may be attached to it so far as the 
origin of many diarrhoeas is concerned. 
§ 167. The influenza-bacillus (Fig. 416) was described by R. Pfeiffer, 
in 1892; it is regarded as the cause of influenza. In influenza it is found 
in the catarrhal respiratory passages, occasionally in the lungs; the small 
bronchi may contain enormous numbers in pure culture. It is assumed 
that their multiplication in the respiratory tract gives rise to inflammation, 
and that the bacilli produce poisons, which, when absorbed, cause the 
symptoms of influenza. 
Influenza-bacilli are small, thin rods with rounded ends (Fig. 416), 
separate or joined in twos. They stain with ordinary aniline dyes, but 
not by Gram’s method. They may be cultivated at body-temperature on 
blood-agar on which they form small, dew-like colonies. The nutrient 
medium must contain hemoglobin. Spore-formation has not been 
observed. In apes catarrhal inflammation of the respiratory tract may be 
produced by intratracheal injections of pure cultures. 464 
THE PATHOGENIC FISSION-FUNGI. 
In 1918 a disease popularly known as influenza swept around the world, 
killing hundreds of thousands. It was characterized by a variety of pneumonia of 
abrupt onset and amazingly rapid course. Death not infrequently occurred in 
24 or 36 hours, or within a week at the latest. The pneumonic lesions were 
bilateral in distribution, involved the bases of the lungs most frequently, and were 
lobular in type, confluence of the solidified lobules, giving rise to extensive areas 
of consolidation. The exudate was composed largely of red cells and exuded blood 
serum, together with polynuclear leucocytes. Interstitial, parenchymatous and 
pleural haemorrhages were almost constant. The pleura, in the majority of cases, 
was not involved by the inflammatory process. Areas of acute vesicular emphysema 
were common and rupture was sometimes followed by extensive subcutaneous 
infiltration of air. The naked eye and histological appearances of the lungs bore 
a striking resemblance to those of bubonic plague. Bacteriologically, the findings 
varied greatly, and the cause of the disease is still in doubt. Influenza bacilli, 
haemolytic streptococci, pneumococci and other micro-organisms were to be found 
in the lungs in pure culture or in various combinations. The kidneys, in most 
cases, presented marked evidences of acute parenchymatous 
degeneration. In some instances, the rectus muscles were 
the seat of Zenker’s degeneration associated with haemor- 
rhagic extravasation, occasionally ending in secondary in- 
fection and abscess formation. 
About a year later the same variety of disease recurred 
in various parts of the world, but in milder form. Pneu- 
monia was relatively rare and its course was more pro- 
longed. The anatomical changes in the lungs were ex- 
tremely variable, but conformed in a general way to the 
confluent lobular htemorrhagic and exudative pneumonia of 
the pandemic year. Pulmonary and subpleural abscesses 
were frequent. The pleura was involved in the majority 
of cases and empyemata were common. The interlobar 
and interlobular pleural extensions were often richly in- 
filtrated by inflammatory exudate. Recovery from the 
pneumonia was commonly followed by sequelae in the form 
of persistence of pulmonary abscesses, empyemata, and 
organization of the pleura and its intrapulmonary prolongations. (Blanton and 
Irons, Jour. Amer. Med. Assn., 1918; Symmers, New York Med. Jour., 1918; Jour. 
Amer. Med. Assn., 1918.) 
According to Czaplewski and Plensel and Koplik (Centralbl. f. Bakt., 1897), 
there is found in the respiratory tract in whooping-cough a small, non-motile 
bacillus similar to the influenza-bacillus, that is thought to be the cause of 
whooping-cough. Later investigations have shown that bacilli of the same type 
are to be found in the respiratory mucous membra«es in a variety of conditions. 
Their significance is highly doubtful. 
Fig. 417.—Diphtheria- 
bacilli from a pure cul- 
ture. Streak preparation 
(methylene-blue). X 
1,000. 
§ 168. Tlie Bacillus diphtherias (Fig. 417) is found in the croupous 
membrane in diphtheria, and is the cause of this disease. 
The bacilli are 1.5-3 long, and are often somewhat swollen at the 
ends. In cultures they form rods of varying length (Fig. —), the ends 
of which are often clubbed. When stained the bacilli appear spotted or 
granular. They stain best in a solution of 30 c.c. of concentrated alcoholic 
methylene-blue in 100 c.c. of 0.0001 per cent, potassium hydroxide, after 
which the sections are treated for a few seconds in 0.5 per cent, acetic 
acid and then with alcohol. In stained preparations the bacilli often 
appear segmented. They also stain by Gram’s method, provided treat- 
ment with Lugol’s solution and alcohol is brief. 
Diphtheria-bacilli grow best in the presence of oxygen on a mixture 
of three parts of calf’s or sheep’s serum, and one part of neutralized 
veal-bouillon, to which one per cent, of peptone, one per cent, of grape- 
sugar, and 0.5 per cent, of common salt are added; or on blood-serum 
and agar with an addition of ten per cent, glycerin or of sugar-containing 
bouillon. They form grayish-white colonies. For development they need DIPHTHERIA. 
465 
a temperature above 20° C.; they grow best at 33°-370 C. They are 
resistant to drying; but may be quickly killed by moist heat. Spore- 
formation has not been observed. 
Guinea-pigs inoculated subcutaneously with cultures of diphtheria- 
bacilli die in two to three days. Haemorrhagic oedema is found at the 
point of inoculation. The inoculation-area contains bacilli, the internal 
organs, on the contrary, are free, although the adrenals are intensely 
injected or even haemorrhagic. The introduction of cultures into the 
trachea of rabbits, chickens, and pigeons, as well as inoculation of the 
conjunctiva of rabbits and the vagina of guinea-pigs is followed by 
inflammation with the formation of a pseudomembrane. Sheep, horses, 
cats, dogs, cows, rabbits, and pigeons are susceptible to subcutaneous 
inoculation. Rats and white mice are nearly immune. 
Roux, Yersin, Loffler, Spronck, and others observed paralysis in 
pigeons and guinea-pigs surviving inoculation. Rotlx and Yersin assert 
that the intravenous injection of filtered bouillon-cultures free from 
bacteria will cause in guinea-pigs and rabbits after two to three days 
paralysis and death. 
The virulence of cultures varies greatly. Diphtheria bacilli produce in 
the human body and in cultures toxins, which may be precipitated by 
alcohol as a whitish powder. 
Water-solutions of the poison injected subcutaneously into animals 
cause local necrosis, haemorrhagic oedema, and inflammation; when taken 
into the body-juices they give rise to pleural effusions, nephritis, fatty 
degeneration of the liver, and paralysis. 
Diphtheria in man is characterized by inflammation involving the 
mucous membrane of the pharynx, palate, arch of the palate, and upper 
respiratory passages, sometimes localized areas of skin. It appears as a 
febrile disease associated with symptoms of intoxication and gives rise to 
localized croupous exudations, and to sloughing (cf. § 91, Figs. —, —). 
The croupous membranes constitute the most striking feature of the 
disease; they are found in the throat and nose in the form of patches; or 
they may form a continuous layer lining the larynx and trachea, or even 
the bronchi. Beneath the croupous membrane the epithelium is lost; and 
the connective tissue is hyperaemic, infiltrated, and swollen (Fig. -—). 
In severe cases the superficial layers of the connective tissue are necrotic. 
Of the deeper tissues the regional lymph-nodes often reveal, microscop- 
ically, foci of necrosis. Of the internal organs the kidneys may show 
changes, in the form of fatty degeneration of the epithelium and of the 
cells of the capillary walls; not infrequently they also present focal areas 
of small-cell infiltration. In the spleen there are frequently found 
necroses of the lymphoid follicles. Degenerative changes and areas of 
inflammation not infrequently occur in the heart-muscle. Paralyses are 
caused by degeneration and necrosis (Katz) of the ganglion-cells of the 
medulla oblongata and of the spinal cord and of the corresponding nerves. 
The lungs are not demonstrably changed by the diphtheria poison 
itself, but pneumonia, due to aspiration of irritating bronchial contents 
or to extension of inflammation to the pulmonary parenchyma, is of fre- 
quent occurrence. 
Local inflammations of mucous membranes as well as symptoms of 
intoxication may be caused by diphtheria bacilli and their toxins; but it 
must be noted that streptococci are almost regularly present in the 
diseased area, and that a pure streptococcus infection may present the 466 
THE PATHOGENIC FISSION-FUNGI. 
clinical and anatomical picture of “ diphtheriaWhen both micro- 
organisms are present the injurious effect of one may be supplemented by 
that of the other; the presence of streptococci appears to increase the 
virulence of diphtheria bacilli. In severe forms of diphtheria streptococci 
are usually present in numbers; nevertheless streptococcus infection does 
not warrant a bad prognosis, since the virulence of the cocci varies 
greatly. 
In the course of infection with diphtheria bacilli there arise anti- 
toxins, which nullify the action of the toxins, and aid recovery. The 
formation of antitoxins follows inoculation of animals with attenuated 
bacilli, and on this rests the possibility of obtaining from animals (sheep, 
horses), that have been repeatedly inoculated with bacilli of increasing 
virulence, a serum which contains antitoxin of therapeutic value 
(cf. §32). 
There are frequently present in the mouth and throat bacilli, which are 
designated pseudo-diphtheria bacilli. Since diphtheria-bacilli may lose their 
virulence, it is not impossible that both forms represent varieties of the same 
species. 
§ 169. The bacillus of bubonic plague (Bacillus pestis) was dis- 
covered in 1894 by Kitasato and Yersin, of the Japanese and French 
commission, while investigating an epi- 
demic in Hong-Kong. The pest-bacillus 
is a small rod with rounded ends (re- 
sembling the bacillus of chicken-cholera). 
It stains with aniline dyes, especially well 
with methylene-blue, and shows exquisite 
polar staining (Fig. 418). It is decolor- 
ized by Gram’s method. It is found in 
all cases of plague, in abundance in the 
swollen lymph-nodes, but also in the spleen 
and blood. It may be cultivated on vari- 
ous media, and forms bluish-gray colonies. 
It multiplies abundantly in bouillon con- 
taining sugar, and forms toxins. Inde- 
pendent movements have not been observed. Spores are not formed. The 
bacilli are easily killed by warming, but are able to withstand drying. 
Bubonic plague, which destroyed great numbers of the inhabitants of 
Europe, at the close of the seventeenth and beginning of the eighteenth 
centuries (“Black Death”), has disappeared from Europe. In Asia 
(Yunnan in China, Arabia, Mesopotamia), and in the interior of Africa 
the disease seems to be endemic, and spreads from time to time in the 
same manner as cholera. 
Man is infected usually through the skin, more rarely from the 
mucous membrane of the mouth, nose, throat, and conjunctiva, still more 
rarely from the deeper parts of the respiratory tract, although cases of 
primary pest-bronchitis and pest-pneumonia occur. Small wounds usually 
form the avenue of entrance in the skin, but it appears (Albrecht and 
Ghon) that rubbing of the skin with infected fingers or clothing may be 
sufficient to bring about infection. 
The bacilli are taken up by the lymph-vessels and deposited in the 
regional lymph-nodes, where they cause marked swelling of the infected 
node or group — the primary bubo. Through infection of lymph-nodes 
Fig. 418.—Plague bacilli (fuchsin). 
x 580. BUBONIC PLAGUE. 
46 7 
situated farther along the lymph-system there arise primary buboes of the 
second class, and by metastasis through the blood-stream secondary 
buboes are formed. The plague is thus characterized by an acute 
polyadenitis. Since the poisons which are in association with the bodies 
of the pest-bacilli exert a degenerative and necrotic effect on the ves'sel- 
walls, numerous hcemorrhages are caused; these are absent only in rare 
cases. To these changes there are also added circumscribed foci in the 
spleen, liver, kidneys, lungs, skin, etc. With the exception, therefore, of 
those rare cases in which pest-infection is confined to the primary bubo, 
the disease is to be regarded as a general infection which arises from the 
taking-up of bacteria from a primary focus of infection, and runs its 
course with the clinical picture of polyadenitis and hcemorrhagic septi- 
caemia. 
The individual foci are characterized by areas of coagulation-necrosis, 
inflammation, and haemorrhage, and are caused by the presence of extraor- 
dinarily large numbers of bacilli. The lymph-nodes of the primary bubo 
are hiemorrhagic, swollen and of medullary consistence. After a few 
days they also show yellow necrotic areas which later undergo liquefac- 
tion. When the disease has lasted longer than six days, the liquefaction 
of lymph-nodes may take on the character of suppuration. 
The tissues in the neighborhood of the lymph-nodes are oedematous 
and infiltrated with blood; haemorrhages are also found in the walls of 
the neighboring large veins. 
The secondary inflammations of the lymph-nodes and of the lymph- 
adenoid tissue of the mouth and throat do not usually cause such a 
marked degree of swelling as do the primary; they resemble the medullary 
swelling in typhoid fever. The surrounding tissues are also less changed, 
but if the process be prolonged the picture comes to resemble that of the 
primary buboes. 
The spleen of plague-patients is somewhat swollen, dark red, finely 
granular, shagreened, and often contains small necrotic foci, which are 
caused by the development of bacilli in great numbers. 
In the glandular organs and skin, there occur, besides haemorrhages, 
necrotic areas and exudative inflammations, all due to the presence of 
bacilli. In the lungs there may occur, in addition to the primary pest- 
pneumonia, secondary metastatic focal inflammations and aspiration- 
bronchopneumonias. 
The majority of individuals infected with pest die within the first 
eight days, but others may live several weeks and then die of marasmus. 
Not infrequently secondary infections, particularly by streptococci and 
diplococci, are associated with the pest-infection. They arise chiefly in 
the tonsils and follicular glands of the tongue following changes catised 
by the pest-bacilli. 
Among animals, rats, mice, apes, and cats are especially susceptible to 
pest; in rats, spontaneous infections occur, so that these rodents aid in 
the spread of epidemics. Swine and dogs are less susceptible, birds still 
less so. 
The changes in infected animals agree in general with those observed 
in man. The infection may remain local or become general. After 
lymphadenitis and multiple haemorrhages there arise miliary, tubercle-like 
foci in the spleen, liver, and lungs. The course is usually acute, rarely 
chronic. In the latter case the larger necrotic foci may be encapsulated 
by connective tissue. The animals are easily infected from the skin, as 468 
THE PATHOGENIC FISSION-FUNGI. 
well as from the mucous membranes of the intestinal and respiratory 
tracts; infection may take place from an uninjured mucous membrane. 
The inoculation of one mouse confined in a cage with other mice may 
give rise to a cage-epidemic (Schottelius). 
Attempts to immunise animals and man against pest by means of dead and 
attenuated pest-bacilli have been many times carried out, especially by Yersin, 
Haffkin, and Lustig; and have been successful in so far that rodents, horses, and 
apes have been rendered immune against inoculations otherwise fatal. According 
to the reports of such attempts in man, a smaller per cent, of inoculated individuals 
acquire the disease than of those not inoculated; but doubt is thrown upon the 
results of these inoculations by other authors (Bitter). Further, attempts at 
immunisation and healing have been made in man, with the serum of animals which 
have been rendered immune, particularly of horses (Yersin, Lustig) ; and different 
authors ascribe to such serum a favorable influence. 
Sticker differentiates the following forms of pest according to the first localiza- 
tion of the bacilli: (1) Bubonic plague (the most common form) ; (2) the cutaneous 
form (formation of vesicles and ulcers or furuncle-like inflammations) ; (3) the 
pulmonary form; (4) the intestinal form. 
Through the investigations of Ducrey, Krefting, and Petersen (cf. Petersen, 
“ Ulcus Molle.” Arch. f. Derm., xxix., 1894; xxx., 1895, and Babes, “ Handbuch d. 
pathog. Mikroorg., iii., 1903) it is probable that ulcus molle or soft chancre is caused 
by a bacillus. Tomasczewski (“Der Erreger des Ulcus,” Z. f. Hyg., 42 Bd., 1903) 
has demonstrated through self-inoculation that typical ulcus molle can be produced 
with cultures grown on blood-agar or blood. The bacillus is non-motile, does not 
stain with Gram’s method, and often forms chains. (See also “Observations on 
the Distribution and Culture of the Chancroid Bacillus,” by Davis, Jour, of Med. 
Res., 1902). 
Literature 
{Plague.) 
Albrecht u. Ghon: Ueber die Beulenpest in Bombay im J. 1897, Wien, 1898, 
1900. 
Crowell: The Pathology of Plague. Philippine Jour, of Science, 1912. 
Dieudonne: Pest. Handb. d. path. Mikroorg., ii., Jena, 1903 (Lit.). 
Flexner: The Pathology of Bubonic Plague. Univ. of Penn. Med. Bull., 1901. 
Herzog: The Plague. Rep. of Gov. Laboratories, Manila, 1904, 1905. 
Kitasato: Preliminary Note on the Bacillus of Bubonic Plague, Hong-Kong, 
1894. 
Metschnikoff: La peste bubonique. Ann. de l’lnst. Pasteur, 1897. 
Netter: Le microbe de la peste. Arch, de med. exp., 1900 (Lit.). 
§ 170. The Bacillus tuberculosis is the cause of the infectious disease 
occurring so frequently in man and the domestic animals which is known 
as tuberculosis, sometimes called pearl disease in animals. 
The tubercle-bacillus was discovered and thoroughly studied by Koch 
in 1882. It is a slender rod (Fig. 419), of 1.5-4 /x in length, and is usually 
slightly curved. It may he stained by aniline-dyes (fuchsin, gentian- 
violet) to an aqueous solution of which an alkali, or carbolic acid, or 
aniline oil is added. The bacilli when once stained retain the stain, even 
when the preparation is decolorized in dilute sulphuric acid, or nitric acid, 
or hydrochloric acid and alcohol. 
The stained bacilli not infrequently show in their interior clear, shin- 
ing, unstained areas, or are composed of little stained spherules. Koch 
regarded these clear spots as spores, and this view was accepted for a 
long time. Nevertheless, germination of these structures could not be 
demonstrated, and they are no longer regarded as spores. Consequently, TUBERCULOSIS. 
469 
tubercle-bacilli are not specially resistant forms, although they are more 
resistant to external influences, for example, drying, than are many other 
bacteria. 
Tubercle-bacilli may be cultivated at the body temperature and in the 
presence of oxygen on coagulated blood-serum, blood-serum-gelatin, agar 
to which rabbits’ blood has been added, and in glycerin bouillon. The 
special medium devised by Petroff is excellent. They increase, however, 
very slowly, so that only on the seventh to tenth day or even later, do the 
cultures become visible in the form of dull-white flakes resembling little 
scales. Larger cultures form, on the surface of coagulated blood-serum, 
whitish, irregularly shaped, lustreless deposits. According to Nocard, 
Roux, and Bischoff growth of the bacilli is aided by the addition of 
glycerin (four to eight per cent.). In cultures tubercle-bacilli form 
threads, which in part show branching. 
At temperatures below 28° C. and above 42° C. the growth of the 
bacilli ceases. Sunlight kills the bacilli in a short time. 
If bacilli from pure cultures are inoculated into certain experimental 
animals, tuberculosis is produced; in- 
fection may be produced by inocula- 
tion under the skin, into the peri- 
toneal cavity, or the anterior chamber 
of the eye, by inhalation of an atom- 
ized suspension, by feeding, and by 
injection into veins. In experimental 
feeding success is often attained only 
after long administration of the 
bacilli, since not every bacillus gain- 
ing entrance into the intestinal tract 
leads to infection. It is also true that 
bacilli lodging on the mucous mem- 
brane of the respiratory tract do not 
always succeed in growing in the 
tissue. Guinea-pigs, rabbits, cats, and 
gray field mice are especially susceptible ; dogs, rats, and white mice less so. 
Infection of man and of animals occurs from the taking up of tubercle- 
bacilli from the lungs, respiratory passages, and the intestinal tract, or 
from wounds and tissue-ulcerations. In the alimentary tract, the lymph- 
adenoid apparatus, tonsils, and the intestinal lymph-follicles form the most 
frequent avenue of entrance. Nurslings are particularly susceptible to 
intestinal infection. 
Fig. 419.—Tubercle-bacilli. Sputum 
from a man suffering with pulmonary 
tuberculosis. Smear-preparation on 
cover-glass, stained with fuchsin and 
methylene-blue, x 400. 
The opinion seems to be held by certain surgeons that primary or so-called 
surgical tuberculosis of the intestine is a not uncommon occurrence, and, based on 
this opinion, extensive resections have actually been carried out. Anatomically, 
there are two well recognized varieties of intestinal tuberculosis. One of them 
invites surgical interference. This lesion is a chronic productive tuberculous 
inflammation, usually located in the region of the caecum and often involving a large 
portion of the ileum. It produces massive thickening of the intestinal wall and 
obstruction or even occlusion of the lumen. Three such cases were encountered 
among approximately 30,000 surgical specimens examined at Bellevue Hospital. The 
second variety of surgical intestinal tuberculosis consists in solitary or multiple, 
discrete or confluent, tuberculous ulcers corresponding, as a rule, to the distribu- 
tion of the lympoid tissues of the gut. Among 6,000 consecutive autopsies at 
Bellevue Hospital, Palinsky (Proceedings New York Path. Soc., 1919) found 285 
cases of tuberculous enteritis (46 per cent.). Of this number, however, only 3 
(1 per cent.) were unaccompanied by tuberculous lesions in other portions of the 470 
THE PATHOGENIC FISSION-FUNGI. 
body. In 37 per cent, of all cases of intestinal tuberculosis, more than one part 
of the gut was found to be involved. Not infrequently the ulcerative lesions occu- 
pied both the colon and the small intestine. It is apparent, therefore, that primary 
intestinal tuberculosis is an extremely rare condition and that operative removal of 
any portion of the gut for tuberculosis should be approached with caution. 
Direct transmission of the bacilli from mother to foetus in utero may 
occur, but is rare. The production of tuberculosis occurs usually at the 
points of entrance of the bacilli, but may occur at distant points after 
transportation of bacilli through the blood or lymph, so that hsemato- 
genous or lymphogenous disease of the internal organs, for example, of 
the lymph-nodes, bones, 
brain, and tubes, may oc- 
cur as the primary local- 
ization. 
The bacilli are spread 
through the external 
world chiefly by sputa, 
under certain conditions 
by the faeces and urine, 
from tuberculous ulcers, 
or from tuberculous or- 
gans taken from living or 
dead persons. Since the 
bacilli are rather resis- 
tant, they may be pre- 
served outside the animal 
body for a long time un- 
der certain conditions, 
and may become mixed 
with the respired air, as 
well as with food and 
drink. The milk of 
tuberculous cows con- 
tains the bacilli, espec- 
ially when the udder is diseased; but bacilli may also pass into the milk 
when no disease of the udder can be demonstrated (Hirschberg, Ernst, 
Leuch). 
If tubercle bacilli succeed in developing in any tissue of the human 
body, they lead by a series of changes to the formation of nodular masses 
of fibroblastic tissue or tubercles, which are devoid of blood-vessels, and 
after reaching a certain stage of development undergo retrogressive 
changes. The formation of the nodule may be accompanied by more or 
less extensive inflammatory exudation. 
The first effect of the development of the bacilli in tissue is degenera- 
tion, in which the tissue-cells as well as the connective-tissue ground-sub- 
stance over a larger or smaller area are destroyed. To the degenerative 
processes there is added inflammatory exudation — emigration of leuco- 
cytes and lymphocytes — and proliferation of the tissue-cells that remain 
preserved in the affected area (Fig. 420, a). The degree of the exudative 
processes in the region of the nodule varies and is dependent on the 
number and virulence of the bacilli present and on the mode of infection. 
When a large number of bacilli are introduced into the lung through the 
Fig. 420.—Tubercle from a fungous granulation of bone 
(Miiller’s fluid, Bismarck brown), a, Giant-cell; b, epitheli- 
oid cens; c, iymphoid ceils, x 400. TUBERCULOSIS. 
respiratory tract the exudative inflammation is pronounced. It is less 
marked in the introduction of bacilli into the liver through the portal vein. 
The cells of the exudate are chiefly polynuclear leucocytes, but later 
mononuclear lymphocytes and leucocytes predominate. The appearances 
of proliferation may be shown by the second day. 
The cellular nodule which, after a few days represents the tubercle at 
Fig. 421.—Giant-cell containing bacilli, and showing necrotic centre, from a tubercle. Stained 
with gentian-violet and vesuvin, mounted in Canada balsam, x 350. 
the height of its development, usually shows three types of cells — large 
epithelioid cells, with clear nuclei (Fig. 420, h), multinuclear giant-cells 
(a), and lymphocytes (c). The first two are found particularly in the 
central part of the tubercle, the latter at the periphery. The number of 
the individual cell-forms varies, and under certain conditions the lympho- 
Fig. 422.—Tuberculosis of the pleura (alcohol, Van Gieson’s). a. Thickened and proliferating 
pleura; b, tubercle with giant-cells; c, deposit of fibrin. X 200. 
cytes may be so numerous as to overshadow the larger cell-forms. At 
other times epithelioid cells with lightly staining nuclei predominate. 
These cells are in part changed lymphocytes arising from the blood; in 
part fibroblasts arising through proliferation of connective-tissue cells 
in loco. 472 
THE PATHOGENIC FISSION-FUNGI. 
The giant-cells belong usually to the syncytial type and arise through 
confluence of cells, it is also possible that they arise through the multi- 
plication of the nucleus in a single cell. The nuclei lie usually in the peri- 
Fig. 423.—Large-cell tubercle containing fibrin, from a tuberculous lung (alcohol, fibrin-stain) 
a, Fibrin; b, giant-cell; c, large-cell tissue. X 300. 
pheral portion of the protoplasmic mass (Figs. 420, a and 421) ; some- 
times collected at one pole, sometimes at both poles; sometimes arranged 
in a wreath or crescent. They often contain bacilli (Figs. 421 and 424, c). 
The non-nucleated portion of the protoplasm may often be recognized 
as degenerate or necrotic because of its re- 
action toward stains (Fig. 421). 
Through proliferation of cells the con- 
nective-tissue stroma of the original tissue 
is pushed farther and farther apart, so 
that the individual cells are finally sepa- 
rated from one another only by scanty 
fibres, whose general arrangement in the 
form of a network is consequently called 
the reticulum of the tubercle. 
New vessels are not formed in the 
tubercle; and old vessels are closed 
through proliferation of the vessel-walls. 
Usually the nezv-formation of connective 
tissue stops with the production of fibro- 
blasts. 
The neighborhood of the tubercle may 
show no essential change, but usually 
presents small-cell infiltration or proliferation (Fig. 422, a). 
Serous exudation is usually, associated with the cellular emigration, 
and fibrin may be formed both in the tubercle itself (Fig. 423, a) and in 
its neighborhood (Fig. 422, c). 
Fig. 424.—Caseous necrosis of tuber- 
culous granulation tissue (alcohol, 
fuchsin, aniline blue), a, Granular, ai, 
lumpy caseous masses; b, fibrocellular 
tissue; c, giant-cell with bacilli; d, 
bacilli in cellular tissue; e, bacilli in 
necrotic tissue; f, bacilli enclosed in 
cells, x 200. CASEATION OF TUBERCLES. 
473 
At the height of development the tubercle forms a small, gray, trans- 
lucent cellular nodule} which may reach the size of a millet-seed, and 
encloses in its tissue tubercle-bacilli in larger or smaller numbers. When 
it has reached a certain size retrogressive changes usually appear in its 
centre, the tubercle becoming cloudy, opaque, and of a white or grayish- 
white or yellowish-white color — these changes are designated caseation. 
Caseation of the tubercle is dependent on necrobiosis of cells, and 
on the deposit of coagulated substances between the cells. The celh 
necrosis is characterized by loss of nuclei and transformation of the cells 
into lumpy masses which disintegrate and become granular (Fig. 424, 
ar, a). The deposit between the cells consists of a network of fibrin 
(Fig. 423, a) or of a granular or hyaline reticulated fibrinoid substance 
Fig. 425.—Section of miliary tubercle of the omentum (alcohol, hrematoxylin, eosin). 
a, Caseous centre containing remains of fat-cells; b, fibrocellular periphery; c, giant-cells; d, 
fat tissue, x ioo. 
but which does not take Weigert’s fibrin stain and is stained yellow by 
Van Gieson’s method. In the further course of the process of caseation 
the fibrin and fibrinoid substance disintegrate into a granular mass which 
fuses with the cell-detritus (Figs. 424, a; 426, a). 
Caseation affects first the central portion of the tubercle, and is usually 
confined to this, while connective tissue is formed at the periphery, so 
that the tubercle comes to consist of a caseous centre (Fig. 425, a) and a 
fibrocellular periphery (b) which usually contains giant-cells. Under 
certain conditions caseation may involve the entire tubercle. If caseation 
does not affect the periphery, the fibrocellular tissue of the peripheral 
zone, sooner or later, becomes transformed into pure fibrous tissue, a 
fibrocaseous tubercle (Fig. 426, a, b) is formed, the connective tissue 
of which is coarsely fibrillar or hyaline and poor in cells (b), and in the 
course of time usually becomes sharply defined from the caseous centre 
(a), so that the latter appears to be encapsulated. If the disease runs a 
favorable course the centre instead of caseating may undergo connective- 
tissue replacement, and (Fig. 427, b, c, d), the tubercle becomes changed 
into a fibrous nodule. 474 
THE PATHOGENIC FISSION-FUNGI. 
The infectious nature of tuberculosis was determined by experimental trans- 
mission of tuberculosis to animals (Villemin, Lebert, PVyss, Cohnheim, Klebs, Lang- 
hans, and others), before the discovery of the tubercle-bacillus. Nevertheless, it 
was a long time before the view that tuberculosis is an infectious disease received 
general acceptance, and opposition to this view has even to-day not wholly dis- 
appeared. 
The peculiar behavior of the tubercle-bacillus toward stains — that is, its prop- 
erty of retaining the stain after treatment of the preparation with acids and alcohol, 
the so-called acid- and alcohol-resistance — makes it possible to demonstrate 
tubercle-bacilli in the sputum or in tissues, and to differentiate it from other 
bacteria. It should be noted, however, that other bacteria show these properties; 
the bacillus of leprosy, the smegma-bacillus (a bacillus frequently found on the 
corona glandis, between the scrotum and thigh and in the folds between the labia 
majora and minora), two bacilli found in butter (one described by L. Rabinowitsch 
and Petri, the other by Korn), and finally different bacilli cultivated by Moeller 
from grasses (timothy-grass) and from cow-dung. All these acid-resisting bacilli 
Fig. 426.—Fibrocaseous tubercle of the lung (alcohol, Van Gieson’s). a, Caseous centre; 
b, thick, homogeneous connective tissue poor in nuclei; c, connective tissue rich in cells; d, lung 
tissue. X 80. 
may under certain conditions lead to errors of diagnosis; for example, the smegma- 
bacillus in the examination of urine, the butter-bacilli in the examination of butter, 
the latter particularly, since the bacillus described by Rabinowitsch, when injected 
into the peritoneal cavity of guinea-pigs, causes a disease of the abdomen similar 
to true inoculation-tuberculosis, while the bacillus described by Korn causes pseudo- 
tuberculosis in white mice (these animals showing but slight suceptibility to true 
tuberculosis). Acid-fast bacilli, which probably represent a variety of the Rabi- 
nowitsch butter bacillus, have been found in gangrenous foci in the lung 
(Rabinowitsch) as well as in the sputum of pulmonary gangrene (Folli, Mayer, 
Ophuls, Birt and Leishman). Moeller has found acid-fast bacilli in nasal and 
pharyngeal mucus. 
Since the tubercle-bacillus in cultures forms simple and branching threads 
(Klein, Fischel, Coppen-Jones, Nocard, Maffucci, and others) and bud- and club- 
like swellings, many authors are inclined to group it with the thread-fungi. Leh- 
mann and Newmann designate it as Mycobacterium tuberculosis, Coppen-J ones 
as Tuberculomyces. 
Since the tubercle-bacillus in caseous pulmonary foci (Coppen-Jones), and 
after direct injection into the parenchyma of the brain, kidneys, mammary glands, 
and testicles, as well as after the intra-arterial injection of large numbers of bacilli 
(Babes, Levaditi, Schulze, Lubarsch, Friedrich, and Nosske) forms, in addition to 
the ordinary colonies of bacilli, fungus-masses resembling those of actinomyces, on TUBERCULOSIS. 
475 
the outer surface of which ray-like clubs radiate into the surrounding tissue, 
Lubarsch and others, on the assumption that the consist of branch- 
ing threads, have classed the tubercle bacillus with the actinomyces or ray-fungi. 
Lubarsch regards the ray-fungi as a sub-class of the Streptothrices, an intermediate 
group between the Schisomycetes and the Hyphomycetes, and characterized by the 
formation of clubs; and to this class he assigns the butter- and dung-fungi men- 
tioned above. According to Friedrich and Nbsske the fungus-masses regarded as 
resembling those of actinomyces consist only of rods. 
According to the investigations of Hammerschlag, Ruppel, Sata, and others, 
tubercle-bacilli contain an abundance of fat, which under proper conditions may 
be demonstrated by staining with sudan (Sata). According to Hammerschlag 
tubercle-bacilli contain twenty-seven per cent, of substances soluble in alcohol and 
ether (fats, lecithin, poisonous substances), while other bacteria contain only 1.7—10 
per cent, of the same. The remaining substance insoluble in alcohol contains 
albumin and cellulose. Apparently the acid resistance of the bacilli is dependent on 
the rich fat content; young bacilli which lack the fat covering are not acid-fast 
(M armor ek). 
Fig. 427.—Fibrous tubercle in the thickened synovial membrane of the knee-joint (alcohol, haema- 
toxylin, picric acid, fuchsin). o. Connective tissue; b, c, d, fibrous tubercle, x 75. 
According to the investigations of Prudden, Hodenpyl, Kostenitsch, Vissmann, 
Masur, Kickel, and others, dead tubercle-bacilli, when introduced into the tissues 
of an animal by inoculation, or into the blood-stream, or through introduction into 
the respiratory passages, excite, at the point of deposit, inflammation and tissue- 
proliferation similar to that caused by living bacilli, and in the case of a large inocu- 
lation may lead to suppuration. These changes differ, however, from those pro- 
duced by living bacilli, in that the bacilli are destroyed after a few weeks and the 
nodules heal through transformation into fibrous tissue; and by the fact that the 
severity of the local tissue-proliferation is dependent wholly on the amount of dead 
bacilli introduced, and that there is no spread of the process throughout the body. 
The dead bacilli must therefore contain substances (proteins) which cause inflam- 
mation and later tissue-proliferation. 
The active substance of the bodies of the bacilli — tuberculin — was first pro- 
duced by Koch (1890) from six- to eight-weeks-old cultures in a weak alkaline 
veal-infusion, to which one per cent, of peptone and four to five per cent, of 
glycerin were added, by evaporation on a water-bath to one-tenth of the original 
volume and filtering through a filter of earthenware and silicipus marl. Later 
(1897) he dried highly virulent cultures of tubercle-bacilli in a vacuum-exsiccator, 
then triturated the dry substance, mixed it with distilled water and centrifugated 
it. The active principle is in the muddy precipitate thus obtained, which is again 
dried and triturated and dissolved in water to which twenty per cent, of glycerin 476 
THE PATHOGENIC FISSION-FUNGI. 
is added for the purpose of preservation. This tuberculin (designated by Koch 
as T. R.) is said to contain 10 mgm. of solid substance in 1 c.c. 
Whether tubercle-bacilli produce a true toxin is a question that has not yet 
been decided, but this is probably not the case; in favor of this is the fact that 
localized tuberculosis clinically shows no symptoms of intoxication. The tuberculins 
obtained by various methods contain a mixture of different substances which, like 
the substances derived from other bacteria, excite inflammation. Perhaps they con- 
tain also specific albumin bodies which, in the organism, cause the production of 
specific bactericidal protective forces, either through the formation of bacteriolysins 
or of agglutinins and precipitins that act on bacteria. (See § 33.) 
Through the investigations of Arloing and Courmont we know that an emul- 
sion of tubercle-bacilli grown on potatoes is agglutinated by the serum of tuber- 
culous men and animals. Through a special method Koch has prepared a fluid 
containing bacilli in which clouding and a flocculent precipitate is produced by an 
Fig. 428.—Lupus of the skin with atypical growth of epithelium, from the region of the 
knee (alcohol, hematoxylin, fuchsin, picric acid), a, Corium converted into granulation tissue 
in which there are scattered tubercles; b, epidermis; c, epithelial plugs growing into the deeper 
tissues; d, tubercle, x 50. 
agglutinating serum. The serum of healthy animals (rabbits, dogs, cow, and 
donkey) shows no agglutinating action when the test fluid is added to the serum 
in the proportion of 1:25; yet there are exceptions to this, and horse serum 
usually shows an agglutinative power. According to Koch and Romberg the serum 
of children possesses no agglutinative power. After the fourteenth year it is 
frequently present, probably as the result of latent tuberculosis. Through treat- 
ment of an animal with dead or living cultures of tubercle-bacilli it is possible to 
produce a serum capable of agglutination {Koch) or to increase that already pres- 
ent, particularly easily in goats and donkeys. 
Animals possessing the power of agglutination show a more or less high degree 
of immunity against artificial infection with tubercle-bacilli, and the agglutinative 
power may therefore be regarded as an indication of the existence of protective 
substances. 
In men suffering from tuberculosis the power to agglutinate is not usually 
shown in dilutions of 1:25. In advanced tuberculosis the agglutination power is 
usually wanting, since in the course of malignant tuberculosis the protective sub- 
stances are either not formed at all or at least only in small amounts. A mixture 
of pulverized tubercle-bacilli in 100 parts of water plus 100 parts of glycerin when TUBERCULOSIS. 
477 
injected in increasing doses (0.8 per cent, salt solution, the first dose contains 
0.0025 mg. of the cell substance of the bacilli) has, in the hands of Koch, increased 
the agglutination power of numerous consumptives (from 1:25 to 1 TOO and 1 :300), 
so that it may be assumed that it is also possible to produce in consumptives a 
certain amount of protective substance. 
As to the value of the old and new tuberculin of Koch writers differ. Its 
worth as a diagnostic aid is not questioned, particularly the old tuberculin, since 
small doses excite fever in tuberculous animals but not in healthy ones, yet there 
are exceptions to this. The old tuberculin finds use in the recognition and removal 
of tuberculous domestic animals. As a curative method (it is used in small doses 
in tuberculosis) it is praised by some, but at present its use is not extensive. 
Much clinical interest has been excited over the diagnostic use of tuberculin 
in the cutaneous reaction (" Pirquet’s reaction") and the conjunctival reaction 
(“Calmette’s reaction”). 
Von Behring has succeeded in rendering cattle immune against virulent bovine 
tubercle-bacilli. He uses first cultures of human tubercle-bacilli which are less 
virulent for cattle, and begins with an intravenous injection of 1 mgm. of a serum- 
culture of a definite strength of infection. In younger animals the immunization 
is more easily produced than in older ones. Von Behring regards it as possible to 
feed nurslings with milk of cows made immune against tuberculosis and thus to 
convey to them antibodies which may serve to protect them from infection. 
Literature. 
(Tubercle-bacilli and Formation of Tubercles.) 
Arloing et Courmont: De l’agglutination du bacille de Koch. Z. f. Tub., i., 
1900, u. D. med. Woch., 1900. 
Baumgarten: Tuberkelbakterien. C'bl. f. d. med. Wiss., 1882, 1883; Tuberkel 
u. Tuberkulose. Zeitschr. f. klin. Med., xi., 1885; Verhaltniss von Perlsucht 
und Tuberkulose. Berk klin. Woch., 1901; Wirksamkeit d. Tuberkelbacillen. 
Ib., 1901. 
v. Behring: Phthisiogenese u. Tuberkulosebekampfung. D. med. Woch., 1904, 
u. S.-A., Berlin, 1904. 
v. Behring, Romer, Ruppel: Tuberkulose, Marburg, 1902. 
Koch: Die Aetiologie der Tuberkulose. Berk klin. Woch., 1882, No. 16; 1883, 
No. 10. Verh. d. Congresses f. inn. Med., Wiesbaden, 1882; Mittheil. a. d. 
Kais. Gesundheitsamte, ii., Berlin, 1884; Mittheil. iib. ein Heilmittel geg. 
d. Tuberkulose. Deut. med. Woch., 1890; Mittheil. iiber das Tuberkulin. 
Ib., 1891; Neue Tuberkulinpraparate. Ib., 1897; Ueber die Agglutination 
der Tuberkelbacillen. D. med. Woch., 1901. 
Petroff: Johns. H. Hosp. Bulk, Aug., 1915. 
Prudden: A Study of Experimental Pneumonitis in the Rabbit Induced by the 
Infection of Dead Tubercle Bacilli. New York Med. Journ., 1891. 
Prudden and Hodenpyl: Action of Dead Bacteria in Living Body. New York 
Med. Jour., 1891. 
Ziegler: Ueber die Herkunft der Tuberkelelemente, Wurzburg, 1875; Ueber 
patholog. Bindegewebs1- u. Gefassneubildung, Wurzburg, 1876; Tuberkulose. 
Eulenburg’s Realencyklop., xxiv., 1900 (Lit.), u. Eulenb. Jahrb., ii., 1904. 
See also § 171. 
§ 171. Tuberculosis is at the beginning a local disease, which occurs 
most frequently in the lungs, intestinal tract, and skin; that is, in places 
accessible from without. Cases of cryptogenic infection are by no means 
rare; in these the first demonstrable changes appear in tissues concealed in 
the deeper portions of the body-parenchyma— for example, in the lymph- 
nodes, adrenals, bones, joints, brain, tubes — and it is to be assumed that 
under certain conditions the bacilli enter the body without causing de- 
tectable changes at the point of entrance, and develop in some distant 
organ to which they are carried by the blood or lymph, and through multi- 
plication give rise to tissue-degeneration, emigration of white blood-cells, 
and proliferation of tissue. 478 
THE PATHOGENIC FISSION-FUNGI. 
The local disease usually begins with the formation of miliary tu- 
bercles— that is, cellular nodules of the kind described above—which 
arise in the tissue singly or (in case of multiple infection) in great num- 
bers simultaneously, or one after another (secondary dissemination of the 
multiplying bacteria). The tissue in the neighborhood of the individual 
tubercles, as well as that between the tubercles, shows more or less pro- 
nounced inflammatory exudation and proliferation of a cellular type; 
through these processes there are 
frequently formed large granula- 
tion-areas in the infected connective 
tissue. 
In surface colonisation of the 
bacilli, such as is possible in the 
alveoli of the lung and in the smallest 
bronchioles, exudative catarrhal in- 
flammation may be the first sign of 
the infection, while proliferative 
processes in the connective-tissue 
stroma and in the pulmonary ves- 
sels appear at a later period. 
In mucous membranes and in the 
skin (Fig. 428) large areas of 
mucosa and submucosa, or corium 
respectively, may undergo, through 
the formation of such granulations, 
nodular or diffuse flattened thicken- 
ing. In serous membranes there 
may develop large, flattened nodules 
in whose neighborhood the serosa is 
thickened and covered with fibrinous 
exudate. In the synovial membrane 
of joints and bursae there often 
arise soft, spongy proliferations, the 
so-called fungous granulations (Fig. 
429); in the periosteum and bone- 
marrow round, grayish-red, or gray 
granulation-areas of varying size ap- 
pear. All these areas have one 
feature in common — namely, in 
their neighborhood are found in- 
flammatory infiltrations and proli- 
ferations of tissue, which bear the 
character of granulation tissue 
(Figs. 428, a; 429, b) inclosing char- 
acteristic non-vascular, cellular nodules — tubercles (Figs. 428, d; 429, 
c)—'which often contain giant-cells. In grayish-red tissues rich in blood 
the tubercles may often be recognized by the naked eye as gray, or, when 
undergoing caseation, as white or yellowish-white nodules. 
The area of tuberculous granulation tissue becomes larger by opposi- 
tional grozvth, by means of which the same processes, as just described, 
consummate themselves at the periphery. There may arise in this way, 
either in an infected organ, or on its surface, nodules of large size, solitary 
tubercles (Fig. 430, r) for example, in the pia, brain, and on the dura 
fromGIhe42s%IS^ 
(M4ller’? fluid- Bismarck brown), a Con- 
nective tissue; b, granulation tissue; c, tubercle. 
x 8o. TUBERCULOSIS. 
479 
mater, that not infrequently resemble tumors. Further, the tissue trans- 
formed by the tuberculous process or the newly formed tissue respectively, 
may suffer various fates; there may be distinguished three chief forms of 
termination, which may, 
however, be combined in 
various ways. 
In one group of cases 
the production of connective 
tissue results in induration 
(Fig. 431) with the de- 
velopment of dense, fibrous 
tissue (a). If the process 
does not come to a standstill, 
there may be found in asso- 
ciation with the fibrous tis- 
sue proliferations of granu- 
lation tissue (b), and often 
a larger or smaller number 
of typical tubercles (c). If 
the process comes to a 
standstill and to cure of the 
infection, the entire area 
may be converted into dense 
fibrous tissue (Fig. 432, 
a, b) which in part shows a nodular arrangement (a), and in part is 
hyaline and homogeneous in character. In the lungs such connective- 
tissue nodules contain more or less carbon-pigment (Fig. 432). 
Fig. 430.—Large solitary tubercle of the pia mater of 
the cerebellum in vertical section, a, Cerebellum; b, dura 
mater adherent to the tubercle; c, laminated tubercle; 
d, gray peripheral zone adherent to the dura mater and 
beset with yellowish-white, nodular deposits. .Natural 
size. 
Fig. 431.—Tuberculous induration of the lung (alcobol, hematoxylin, and eosin). a, Dense, 
fibrous tissue; b, cellular granulation tissue; c, giant-cells. X 40. 
A. second form of termination is a combination of caseation and 
fibrous induration comprising dense fibrous tissue (Fig. 433, b, d) and 
caseous foci (a) of varying size. 480 
THE PATHOGENIC FISSION-FUNGI. 
The third termination consists essentially in caseation, the tuberculous 
granulation tissue dying and producing no connective tissue at all, or 
only in such slight amount that it is completely overshadowed by the 
caseous masses (Fig. 434, c). 
Both the fibrocaseous and the purely caseous areas may become healed, 
through encapsulation by the surrounding connective tissue (Figs. 433, b; 
434, c, e). Such healing can be regarded as complete only when in the 
connective-tissue capsule (Fig. 434, c,e), and its neighborhood (a) neither 
fresh granulation-tissue nor tubercles are present. Occasionally calcifi- 
cation of the encapsulated caseous mass may occur as a further sign of 
termination of the process. 
The caseous masses of tuberculous foci are sometimes firm, some- 
times soft, and in the latter case often suffer disintegration and lique- 
Fig. 432.—Tuberculous induration of the lung (alcohol, hsematoxvlin, eosin). a. Homogenous 
fibrous nodules poor in cells and in part pigmented; b, diffuse induration of the lung, x 24. 
faction leading to the formation of milk-white, crumbling, and pultaceous 
or thin fluid masses, so that the tuberculous area presents the picture of 
an abscess (cold abscess). Rupture and emptying of the abscess ex- 
ternally leads to the formation of cavities and fistulous passages and to 
ulcers. 
Disintegration and cavity-formation occur particularly in the lung, 
and may lead to cavities as large as a man’s fist or larger. They also occur 
not infrequently in caseating lymph-nodes, and in caseous foci in the 
kidneys, brain, muscles, skin, and bones (Fig. 435). The cavities (h) 
contain in the beginning the liquefied tuberculous tissue, in which remains 
of the original tissue may not infrequently be recognized in the form of 
sequestra (/). After evacuation of the contents the wall may furnish 
sufficient material to fill the cavity again, through secretion of pus or the 
breaking-off of necrotic tissue. Hccmorrhagcs commonly arise through 
erosion of blood-vessels. TUBERCULOSIS. 
481 
The walls of the caverns and abscesses are lined by caseating granu- 
lation tissue containing tubercles (Fig. 435, e) ; the surrounding tissue be- 
comes indurated, and the seat of caseating foci. 
Ulcers occur most frequently in mucous membranes (Fig. 436, h) and 
in the skin, since the softening caseous masses in these regions most 
frequently break through to the surface. The edges and base of the 
ulcers are surrounded by a zone of infiltrated granulation tissue, often 
containing tubercles. 
If a tuberculous focus does not become healed through induration, 
sequestration or encapsulation of the dead tissue, or through the removal 
or death of the bacilli, there exists the danger of metastasis. 
This takes place oftenest by the lymph-channels; and a part of the 
Fig. 433.—Encapsulated area of caseation of the lung with induration and eruption of 
tubercles in the neighborhood (formalin, alcohol, haematoxylin, eosin). a, Caseous area; b, 
fibrous capsule; c, tubercle; d, indurated lung tissue; e, area of granulation tissue, x 40. 
picture of progressive tuberculosis is the development of tubercles in the 
lymph-spaces and in the walls of the lymph-vessels (Figs. 436, i, iL; 437, 
e, f, g, h, i) in the neighborhood of the primary focus. 
Lymphogenous miliary tuberculosis is in some cases limited to the 
immediate neighborhood of the primary focus (Fig. 437), at other times 
it involves larger areas and may, for example, extend from a caseating 
tubercle in the lung over a large part of the pulmonary lymphatic system. 
These lymphangoitic tubercles present the appearance of gray nodules, 
often surrounded by a red zone, and consist essentially of the same 
structure as the primary focus. 
The lymph-nodes may be affected early and tubercles develop in them, 
leading through successive crops to more or less enlargement and finally 
to caseation of the nodes, or to induration, or to a combination of these 482 
THE PATHOGENIC FISSION-FUNGI. 
processes. The thoracic duct may become infected from caseating and 
disintegrating lymph-nodes, and through this channel infection of the 
blood may take place. 
Often the formation of metastases takes place through the blood- 
stream; in the first place, by the entrance of bacilli through the lymph 
from the thoracic duct as mentioned above, but also as the result ot 
direct entrance into the circulating blood. In tuberculous tissue bacilli 
may pass directly into small veins, though obstruction to the circulation 
due to closure of the vessels usually prevents further dissemination. Often 
enough the bacilli gain entrance into larger veins — for example, through 
adhesion of caseating lymph-nodes at the hilum of the lungs with 
neighboring veins, the tuberculous process thus involving the vein- 
Fig. 434.—Encapsulated area of tuberculous caseation in the lung, a, Normal lung tissue; 
b, pleura; c, area of caseation; d, remains of elastic fibres in the area of caseation; e, small 
encapsulated caseous nodules; f, thickened pleura, x 15. 
walls by direct extension. Moreover, infection of veins may occur 
in the neighborhood of a tuberculous focus, so that the small veins of 
an entire vascular system may present well-marked tuberculous disease 
— that is, inflammatory proliferation of the vessel-walls with the forma- 
tion of tubercles and subsequent caseation (Fig. 440, b), and, if thrombosis 
does not occur, large numbers of bacilli may enter the blood-stream from 
the diseased walls. In rare cases the arteries, particularly the pulmonary 
arteries, become tuberculous through infection from surrounding tissues, 
and may give off bacilli to the blood-stream. 
The transportation of bacilli through the blood-stream gives rise to 
haematogenous miliary tuberculosis — that is, to an eruption of miliary 
tubercles (Fig. 441, a) at those places where the bacilli become lodged 
and multiply. Just where these places will be, and how numerous the 
tubercles, depend on the location of the point of rupture and on the 
number of bacilli entering the blood. The entrance of many bacilli may 
lead to cenc»'rl tuberculosis. TUBERCULOSIS. 
483 
If bacilli enter the blood-stream in small numbers and are deposited in 
only one organ, and if death does not ensue, there arises in this organ 
progressive local tuberculosis. 
The exudative inflammation accompanying lymphogenous and 
haematogenous eruption of tubercles is sometimes more, sometimes less 
pronounced, and is usually most severe in the meninges and in the lungs. 
Should a tuberculous focus in the lung break into a bronchus, as the 
result of softening of a caseous area, or if a caseating focus in the kidney 
should invade the kidney-pelvis, there will result dissemination of tuber- 
cle-bacilli over the surface of the mucous membranes. From the 
bronchi the bacilli spread into the trachea, larynx, mouth-cavity, and 
Fig. 435.—Tuberculous, cavern in the tibia (alcohol, picric acid, haematoxylin, carmine). 
Transverse section, a, Periosteum; b, rarefied cortex; c, periosteal deposit of bone; d, fibrous 
tissue on the inner surface of the cortex; e, granulation tissue containing tubercles; /, sequestrum 
with bony trabeculae, infiltrated with granulation tissue; g, union of the granulation tissue with 
the sequestrum; h, cavity that had been filled with pus and caseous masses, x 3)4. 
thence into the alimentary canal; through aspiration they may be carried 
into other portions of the lungs. From the kidneys the bacilli may spread 
through the descending urinary passages. 
Secondary infection may result from this spreading of the bacilli, 
although only a small percentage thus distributed give rise to infection; 
experience has taught us that only certain portions of the mucous mem- 
branes are susceptible to infection — notably the tonsils and the lymphade- 
noid tissue of the intestines, while the oesophagus and stomach are almost 
immune; in the descending urinary passages, the kidney-pelvis, the ureters, 
and bladder are usually infected, while the urethra almost always escapes. 
If bacilli enter the great body-cavities they may spread over the 
surfaces of the serous membranes, infect the latter, excite diffuse inflam- 
mation and the formation of nodules (Fig. 442). New-formations of 
connective tissue may follow later 484 
THE PATHOGENIC FISSION-FUNGI. 
Should tubercle-bacilli be present in the circulating blood of a woman 
during pregnancy, infection of the placenta and foetus may follow, so 
that the child will be born infected. In so far as data concerning this 
point exist, this event is not of frequent occurrence; it is more usual for 
children of tuberculous parents to become infected after birth. Concep- 
tional infection of the embryo through infected semen has not been 
demonstrated, and is unlikely. 
Secondary infections are not infrequently associated with that caused 
by tubercle-bacilli; this occurs particularly when tuberculous cavities or 
ulcers are accessible from without. Secondary infections of tuberculous 
lungs are of frequent occurrence, and are due particularly to streptococci 
and staphylococci, pneumococci, influenza-bacilli, micrococcus tetragenus, 
and baterium coli. Many authors are inclined to refer all severe inflam- 
Fig. 436.—Tuberculous ulcer of the intestine with eruption of tubercles in the neighborhood 
(alcohol, Bismarck brown). a, Mucosa; b, submucosa; c, muscularis interna; d, muscularis 
externa; e, serosa; /, solitary follicle; g, mucosa infiltrated with cells; h, ulcer; hi, area of 
softening; i, recent, ii, caseous tubercle, x 30. 
matory exudations accompanying pulmonary tuberculosis to secondary 
infections; but this is not correct in that the formation of tubercles by 
tubercle-bacilli may be accompanied by inflammatory exudations of such 
severity that serous or serofibrinous, or pure fibrinous, or fibrinopurulent 
exudates may collect in large quantities in the tissues (in the pulmonary 
alveoli, on the pleura, and in the subarachnoid space, etc.). High (septic) 
fever, rapid destruction of tissues with a tendency to suppuration, 
and unusually severe inflammation, in part of haemorrhagic character, 
point to secondary infection. Nevertheless, it is often impossible to de- 
termine, without special investigation directed to this point, whether 
pure tuberculosis or mixed infection is present. 
For the treatment of tuberculosis with bacterial extracts and curative 
serum see § 32. 
The question as to how often tuberculosis is transmitted by the passage of 
bacilli from the mother to the child is an open one. It has, however, been 
shown by Schmorl, Birch-Hirschfeld, and Landouzy that in cases of miliary tuber- TUBERCULOSIS. 
485 
culosis in pregnant women, tubercle-bacilli are present both in the intervillous 
spaces and in the blood of the chorionic vessels, and that the liver of the foetus 
may contain bacilli. Further, cases of tuberculosis of the placenta occur (Schmorl, 
Kockel, Lungwitz, Warthin and Cowie), which may be regarded as stages on the 
way of the tubercle-bacillus from the mother to the fcetus. 
Cases of tuberculosis occurring at an early period of life reported by Demme, 
Baunigarten, Rilliet, Charrin, and others, as well as the statements of Armanni, 
Landouzy, and Martin, that the inoculation of portions of the organs of human 
foetuses obtained from tuberculous mothers produced tuberculosis in guinea-pigs, 
speak in favor of passage of tubercle-bacilli from the mother to the foetus. Still 
more important are the experimental investigations of de Renzi and Gartner, who 
succeeded through the inoculation of pregnant guinea-pigs, white mice, and rabbits 
in producing tuberculosis in a part of the young born of these animals. Gartner 
Fig. 437.—Beginning tuberculosis of the lung without catarrh (alcohol, orcein), a, Caseous 
area with remains of elastic tissue; b, normal lung tissue; c, pleura with tubercles; d, e, 
tubercles in the neighborhood of the caseous area; f, tubercle in the pleura; g, periarterial, h, 
peribronchial, i, perivenous tubercles of the lymph-vessels; k, new-formation of fibrous tissue 
beneath the limiting elastic layer of the pleura, x 16. 
is consequently of the opinion that under certain conditions tubercle-bacilli may 
pass from the mother to the foetus in the case of both animals and man. Finally, 
Maffucci and Baunigarten succeeded in effecting transfer of tubercle-bacilli to im- 
pregnated hen’s eggs, and discovered that the infection did not disturb the develop- 
ment of the chick, but, on the contrary, the bacilli that were taken up by the 
embryo remained in the tissue of the latter without multiplying to any extent, later 
to cause tuberculosis in the body of the hatched-out chick. According to the evi- 
dence of anatomical investigations placental transmission of tuberculosis to the 
child cannot be doubted. On the other hand, conceptional transmission of tuber- 
culosis from the father to the embryo has not been proved. Moreover, according 
to the investigations made up to the present time it may be emphasized that tuber- 
culosis is to be referred usually to extrauterine infection and that children of tuber- 
culous parents suffer from tuberculosis so frequently because they are more ex- 
posed to infection than are the children of healthy parents. Special predisposition 
to tuberculosis in the children of tuberculous parents has not been demonstrated 
In animals transmission of tuberculosis to the foetus seems occasionally to occur, 
according to the reports of Zippelius, lessen, Piitz, Grothans, Malvoz, Lydtin, 
Brouvier, Adams, and others. Johne was not only able to demonstrate in a foetal 
calf the presence of miliary nodes and larger nodules in the lungs, liver, and various 
lymph-nodes, but to show the presence of characteristic bacilli in the lesions. 486 
THE PATHOGENIC FISSION-FUNGI. 
By clinicians so-called scrofula is often regarded as a special pathological 
condition of the organism of the child, predisposing it to tuberculosis. As scro- 
fulous are regarded those chil- 
dren who frequently suffer 
from inflammations of the 
mucous membranes (nose and 
its accessory cavities, con- 
junctiva, middle ear), as well 
as of the skin, from swelling 
of the lymph-nodes, leading 
occasionally to necrosis and 
suppuration, finally from 
chronic inflammations of the 
bones and joints, and who 
present a flabby, pale, often 
bloated appearance. In many 
cases these symptoms are due 
to tuberculosis; in other cases 
they are caused by infection 
with streptococci or staphylo- 
cocci, or are the results of 
syphilis. Scrofula is not a 
disease-entity, but a special 
symptom-complex belonging to 
different diseases. Whether 
the affected children possess 
special predisposition to all 
these infections which may be 
designated scrofula is difficult 
of proof. The organism of the 
child is in general easily in- 
fected by these agents, and the 
frequent illness of certain chil- 
dren due to these infections 
may be referred to lack of cleanliness, or to conditions of environment, or to in- 
juries, etc., as well as to predisposition of the child itself. According to the elder 
Gross, many so-called scroful- 
ous children are born with the 
stigmata of status lymphaticus 
and are hence more susceptible 
to infections, particularly those 
that enter through the lym- 
phoid tissues. 
Von Behring upheld the 
view that tuberculosis is al- 
most always the result of 
bacilli entering through the in- 
testine in infancy, and that 
later infections play a sub- 
ordinate role. This theory is 
correct in so far as the long- 
known fact is concerned, that 
the intestine of infants takes 
up bacilli more easily than the 
adult intestine, and that in- 
fection is not always manifest 
at the point through which the 
bacillus enters, but develops in 
those organs, the lymph-nodes, 
lungs, brain, bones, etc., to 
which it has been carried by 
the blood or lymph. Infection 
with tubercle-bacilli may oc- 
cur at any age. The primary 
intestinal infection is not the 
dominating one, but the infec- 
Fig. 438.—(Bellevue Hospital.) Tuberculosis of 
lymph-nodes of neck. 
Fig. 439.—Eruption of tubercles in a lymph-gland (alco- 
hol, haematoxylin). a, Tubercle; at, caseous tubercle; b, 
tissue of the lymph-gland; c, giant-cell in the centre of a 
tubercle; ci, giant-cell at the edge of a caseous focus; d, 
large-cell tissue between the tubercles; e, blood-vessel, 
x iso. TUBERCULOSIS. 
487 
tion of the respiratory tract is. The latter usually results from direct entrance 
of the bacilli into the respiratory parenchyma. Primary infection of the nose, 
larynx, trachea, and bronchi also occurs, but is relatively less frequent than primary 
lung-infection. 
Calmette’s view of the intestinal origin of anthracosis has also been turned as 
an argument favoring the ingestion-theory of tuberculosis. Much has been written 
on this subject during the last several years, and while the opinion of the majority 
of pathologists favors the aerogenous nature of tuberculous infection in late 
childhood and adult life, the etiological importance of infection through the intes- 
tine in infancy cannot be disregarded. 
Tuberculosis of mammals is observed most frequently in cattle, and pre- 
sents a course similar to that of the disease in man, though the granulation- 
areas develop more frequently into tumor-like nodules, particularly in cattle, 
and the tendency to generalization of the disease is less. The tuberculosis of 
serous membranes which is often designated pearl disease begins with the 
Fig. 440.—Tuberculosis of the veins in the neighborhood of a tuberculous retroperitoneal 
lymph-gland (formalin, hoematoxylin, eosin). a, Tuberculous lymph-gland with giant-cells and 
caseous foci; large blood-vessels at the periphery; b, veins whose walls are thickened by tuber- 
culous granulation tissue, the inner layers of which show caseation; c, fat tissue, x 28. 
formation of small nodules, leading then to more marked proliferation of con- 
nective tissue, giving rise to the formation in the thickened serosa of nodules the 
size of a pea or bean or even as large as a hen’s egg or man’s fist, which in the 
beginning are soft and sarcoma-like, but later become firm and dense and often 
enclose calcified areas. The form of the proliferation is sometimes villous-like and 
warty, at other times mulberry- or grape-like, cauliflower-like or polypoid. 
Next to cattle the hog is most frequently affected with tuberculosis, more rarely 
the horse, goat, sheep and cat, and still more rarely the dog. 
Of wild animals in captivity, the ape, lion, tiger, bear, jackal, panther, jaguar, 
giraffe, and dromedary easily acquire tuberculosis. Of the small animals used for 
experiment the guinea-pig is the most susceptible. After subcutaneous inoculations 
there results progressive tuberculosis which kills the animal in from about four to 
eleven weeks. In rabbits inoculation tuberculosis may heal. Field mice and white 
mice are infected with difficulty. 
Tuberculosis is of frequent occurrence in birds (chickens, pigeons, pheas- 
ants, and parrots), and is usually localized in the abdominal organs. 488 
THE PATHOGENIC FISSION-FUNGI. 
The cultures of tubercle-bacilli from man are dry, warty, or scaly and lustre- 
less ; those of avian tuberculosis moist, wrinkled, and soft, and grow best at 43° C. 
Dogs are immune to avian tuber- 
culosis, but not to human tuberculosis. 
The intra-peritoneal inoculation of 
mammalian tuberculosis (Leray) 
causes in rabbits numerous caseous 
foci in the liver and spleen with few 
giant-cells and scanty bacilli, and in 
the lungs caseous nodules containing 
numerous bacilli. Inoculations into 
these animals of chicken-tuberculosis, 
on the other hand, cause scanty pro- 
duction of non-caseating cellular pro- 
liferations containing giant-cells and 
great numbers of bacilli. 
According to Mciffucci, Martin, 
Gartner, and others, the inoculation of 
human tuberculosis into chickens does 
not produce tuberculosis, although the 
bacilli remain alive for weeks in the 
body of the chicken. Pigeons (An- 
clair) die after intra-peritoneal inocu- 
lation, but no tubercles are found in 
the tissues; the liver and lungs may 
contain living bacilli fourteen days 
after inoculation. In guinea-pigs 
(Straus) the bacilli of human tuber- 
culosis cause more severe changes 
than do the bacilli of chicken-tuberculosis. In mice infected with avian tuber- 
culosis (Weber and Bofinger) there occurs moderate increase of the bacilli with- 
out intoxication and without 
marked reaction on the part 
of the tissue. When kept in 
the mammalian body (guinea- 
pigs and mice) for one or two 
years the virulence of avian 
bacilli for guinea-pigs is not 
changed. Whether man is sus- 
ceptible to avian tuberculosis 
is still an open question. 
The question whether 
tuberculosis of animals, par- 
ticularly of domestic an:mals, 
is identical with that of man 
has been the subject of lively 
discussion. The majority of 
writers believe in their iden- 
tity. Koch and von Baum- 
garten deny it. In favor of 
the latter view may be taken 
the fact that the bacilli of 
different sources show differ- 
ences in cultures, cultures of 
avian tuberculosis in particular 
showing essential differences 
from those of human tuber- 
culosis. Further, inoculations 
of human tubercle-bacilli into 
domestic animals, for example, 
cattle, are either negative or 
cause a milder disease than 
that resulting from the in- 
oculation of bacilli obtained from sick cattle. In spite of these facts it 
cannot be doubted that we have to deal, not with different forms of disease, but 
that the tuberculosis of man and that of the domestic animals are identical 
Fig. 441.—Hxmatogenous miliary tuberculosis 
of the liver (alcohol, carmine). a, Developed 
tubercle in the connective tissue about the portal 
vein; b, collection of leucocytes, x 150. 
Fig. 442.-—Tuberculosis omenti (Miiller’s fluid, carmine). 
a, Centre of tubercle; b, cells of epitheloid character; c, 
lymphatic elements; d, proliferating epithelium (endo- 
thelium) in the neighborhood, x 200. TUBERCULOSIS. 
489 
diseases produced by varieties of the same species of bacillus. When the 
bacilli increase for a long time in the same species of animal they acquire properties 
that make them less virulent for other species and they are with difficulty made to 
grow in the latter. Human tuberculosis is nevertheless still directly transmissible 
into other mammals, and man may be infected with the bacilli of mammalian tuber- 
culosis. Uncooked cow’s milk and meat containing tubercle-bacilli can convey 
bovine tuberculosis into man, and the attendants of cattle can be infected from sick 
animals through wounds or the respiratory tract. The avian strain of tubercle- 
bacilli is the farthest removed in its properties from the human strain. In parrots 
there occurs tuberculosis the bacilli of which are identical in their properties with 
those of human tuberculosis. 
Tuberculosis occurs also in cold-blooded animals, fish, blind worms, frogs, 
snakes, lizards, tortoises, etc., and is likewise caused by an acid-fast bacillus, that 
possesses an optimum of growth at 15° C., and grows at temperatures of 10o-31° C. 
It has been assumed (Bataillon, Ferre, and others) that this bacillus is a variety of 
the bacillus of mammalian tuberculosis. Friedman attempted to immunize guinea- 
pigs against tuberculosis by inoculating them with less virulent bacilli of the tuber- 
culosis of cold-blooded animals. 
As pseudotuberculosis may be classed those affections characterized by the 
formation of cellular and fibrous nodules, in part undergoing necrosis, and which 
are similar to tubercles, but which are not caused by Koch’s bacillus. According 
to etiology the following forms may be distinguished: 
1. Pseudotuhercidosis due to dead foreign bodies. This may be caused by the 
experimental injection of lycopodium-spores, olive-oil, and mercury into the blood- 
vessels, the inhalation of irritating material irjto the lungs, the injection of large 
quantities of milk into the peritoneal cavity, etc. The presence in the tissue of 
caterpillar hairs, pieces of wadding, silk threads, cholesterin tablets from ruptured 
ovarian cysts, etc., may lead to the formation of fibrocellr.lar nodules. 
2. Pseudotuberculosis caused by monomorphous and polymorphous bacteria. 
Eppinger, Bucholz, and Flexner have described forms of Cladothrix and Strcpto- 
tlirix obtained from apparently tuberculous lungs and bronchial glands which they 
are inclined to regard as the cause of the disease. Courmont found in an appar- 
ently tuberculous elbow-joint a bacillus which was not identical with Koch’s bacillus. 
An affection of the peritoneum resembling tuberculosis may be produced in guinea- 
pigs by injection of the butter-bacillus of Rabinountsch (which probably comes from 
cow-dung) as well as by the grass-bacillus of Moeller; and in white mice by inocula- 
tion of the butter-bacillus of Korn. 
In rodents a disease resembling tuberculosis is not infrequently produced by a 
plump, thick bacillus with rounded ends (Pfeiffer, Prcisz, Zagari, Nocard, Bonome, 
Delbanco, and others). Other forms of bacillary pseudotuberculosis have been 
observed in rabbits (Ebertli), in birds (Muir), in the cow (Courmont), etc. 
3. Pseudotuberculosis due to hyphomycetes occurs in the lungs and may be pro- 
duced artificially by the injection of different forms of aspergillus and mucor; but 
the affections so produced show peculiarities which permit differentiation from true 
tuberculosis. 
4. Pseudotuberculosis caused by animal parasites occurs in the sheep, hog, goat, 
cat, hare, roe, stag, and chamois, and is caused by different forms of Strongylus 
and by Pseudalius capillaris (Muller) ; it is a vermian pseudotuberculosis. 
Literature. 
{Pathology of Tuberculosis.) 
d’Arrigo: Uebertragung der Tuberk. durch die Placenta. Cbl. f. Bakt., xxvii., 
1900. 
Baumgarten: Samml. klin. Vortrage v. Volkmann, No. 218. Berliner klin. 
Woch., 1883; Experimentelle congen. Tuberkulose. Arb. a. d. path. Inst, 
zu Tubingen, i., 1892. 
Benda: Acute Miliartuiberkulose. Berk klin. Woch., 1899. 
Ortner: Die Lungentuberkulose als Mischinfection, Leipzig, 1893. 
Pasquale: Die Streptokokken bei der Tuberkelinfection. Cbl. f. Bakt., xiv., 
1894. 490 
THE PATHOGENIC FISSION-FUNGI. 
Pertik: Pathologie d. Tuberkulose. Ergebn. d. a. P., viii., 2 Wiesb., 1904 (Lit.). 
Ponfick: Skrofulose u. Tuberkulose. Jahrb. f. Kinderheilk., 1901. 
Ribbert: Ueber die Ausbreitung der Tuberkulose im Korper, Marburg, 1900. 
Romberg: Die Serumdiagnose beit Tuberkulose. D. med. Woch., 1901. 
§ 172. Syphilis, like tuberculosis, is an infectious disease, which, from 
a local infection, spreads throughout the body by the blood- and lymph- 
channels, and leads to the formation of localized inflammations and pro- 
liferations of granulation tissue, which, however, do not present so char- 
acteristic a structure as the tubercle. 
In 1905 Schaudinn and Hoffman announced the discovery of the constant occur- 
rence in syphilitic lesions of a characteristic organism. Control examinations of 
non-syphilitic lesions failed to reveal it. To the newly discovered parasite the 
name of Spirochaete pallida was given. Corroboration of the finding of Schaudinn 
and Hoffman was soon forthcoming from investigators in all parts of the world. 
It was found to be constantly present in the primary lesions, in all forms of 
secondary and tertiary lesions, in the blood, lymph, and cerebrospinal fluid of 
syphilitics, in the lesions of congenital syphilis and in the blood, lymph, cerebro- 
spinal fluid and organs of cases of congenital syphilis, and in the placenta of such 
cases. It has also been demonstrated in the experimental syphilis of apes (Met- 
schnikoff and Roux, Ann. de l’inst. Pasteur, 1903, 1904, 1905). The spirochaete of 
syphilis has recently been cultivated on artificial media and its etiological signifi- 
cance is now established beyond all doubt (Schereschewsky, Miihlens, Nogouchi, 
Zinsser and Hopkins). 
The Spirochaete pallida is a delicate, non-refractile spiral organism, varying in 
length from 2~20 g, the average length being about 4-14 The spirals are tight 
and corkscrewlike, fading out at the pointed ends. They vary in number from 
three to twenty-five or more. The large number of spirals in proportion to the 
length of the entire organism is characteristic. The whole organism is usually 
somewhat curved. Delicate terminal flagella have been observed. The spiral form 
is retained when the organism is at rest. It has the power of rotation on its long 
axis, of moving forward and backward, and of making whip-like undulations. A 
nucleus has not been demonstrated. It does not bear spores and no evidence of 
transverse division has been observed. Schaudinn believed that it possesses an 
undulating membrane. At the present time it is not definitely decided whether to 
regard the organism as a protozoon or as a spirillum. Schaudinn favored the 
former view. In accordance with this belief the names Spironema and Treponema 
pallidum have been proposed for it. 
The Spirochcete pallida stains poorly, but can be demonstrated in smears from 
primary lesions by Wright’s stain, the Romanowsky or Giemsa stain. It is import- 
ant that the smears be stained as soon as made; it often cannot be found in smears 
that are not perfectly fresh. From the Spirochaete ref ring ens it is distinguished 
by its delicacy, pale staining, and the number of its spirals and their tight, cork- 
screw arrangement. The refringens is larger, thicker, more refractile, stains easily, 
and has broad, wavy spirals, and its ends are usually blunt. Levaditi’s method may 
be used for staining the pallida in sections. The micro-organism in the living state 
may be demonstrated by appropriate methods (hanging-drop preparation and dark- 
field illumination) and is an easy and extremely valuable means of early diagnosis. 
The infective agent through whose inoculation syphilis is produced 
occurs only in the human organism, where it is reproduced, and com- 
municated by direct or indirect transfer. Metschnikoff, Roux, Lassar, 
and Neisser succeeded in conveying syphilis to anthrapoid apes (the 
chimpanzee) through the inoculation of syphilitic tissue. When im- 
planted the infective agent excites inflammatory processes of varied in- 
tensity and extent — from local transitory hypersemia to the production 
of large tumor-like granulations, or extensive hyperplasias of connective 
tissue. The child of a mother infected with syphilis may receive infection 
through the placenta. SYPHILIS. 
491 
In acquired syphilis the first focus of inflammation develops at the 
point of infection, which is usually located in the skin or mucous mem- 
branes (mouth, throat, mucosa of genital apparatus). There is first 
formed a papule which spreads towards the surface, and within eight 
Fig. 443.—Initial sclerosis (alcohol, hsematoxylin, eosin). a, Corinm, slightly inflamed; b, 
initial sclerosis; connective tissue infiltrated with cells; c, rupture of the cells into the epithelium; 
d, e, lymph-vessels filled with round cells, x 35. 
to ten days forms scales, or ulcerates and secretes a small amount of serous 
fluid which dries to a scab; at the same time its base becomes hardened 
and forms a thick disc-like or a thin parchment-like deposit. Occasionally 
a vesicle is formed, this becomes an erosion, and then an ulcer with scanty 
secretion and indurated base. In 
still other cases an ulcer is first 
formed, and the base becomes in- 
durated subsequently. 
The induration is called the 
initial sclerosis (Fig. 443, b) ; the 
ulcer is known as a hard chancre. 
(Hunterian chancre). The former is 
caused by a collection of small 
round cells (Figs. 443, b; 444, a) in 
the spaces of the connective tissue. 
Occasionally epithelioid cells (Fig. 
444, b) and isolated giant-cells are 
formed (c). With these changes the 
height of the process is reached; the 
tissue disintegrates and ulcerates, 
or is absorbed after disintegration. 
A part of the cells is utilized in the formation of scar tissue. 
Within the area of initial sclerosis and in its immediate neighborhood 
the lvmph-vessels (Fig. 443, d, e) are dilated and filled with round cells. 
After the lapse of a certain length of time the lymph-nodes, skin, and 
mucous membranes become involved in inflammatory processes (symp- 
Fig. 444.—Section from a syphilitic initial 
sclerosis (alcohol, alum carmine), a, Round- 
cell infiltration; b, large mononuclear formative 
cells; c, multinuclear giant cells, x 350. 492 
THE PATHOGENIC FISSION-FUNGI. 
toms of the secondary stage). Still later, there follow syphilitic inflam- 
mations of the internal organs and the bones (tertiary stage). These, 
in many respects, resemble non-syphilitic inflammations, but special 
forms of granulation tissue are sometimes produced. The syphilitic 
affections of the skin, which are grouped under the term syphilides, 
sometimes form red spots, sometimes larger or smaller papillary 
elevations which may be associated with vesicles and pustules as well 
Fig. 445.—(Bellevue Hospital.) Ulcerative annular syphilide of back. 
as with scales. Accordingly, the cutaneous syphilides are called by 
different names, as follow: Roseola syphilitica, and papular, macular, 
papulo-macular, vesicular, pustular, and ulcerative syphilides as well as 
psoriasis syphilitica. A common element in these affections is inflamma- 
tion, characterized by infiltration and in part by proliferation. Thus, in 
the large papular syphilide or condyloma latum there is a teat-like eleva- 
tion of the skin caused by infiltration of the papillary body (Fig. 446, i), 
the corium (k), and the epithelium (e, f, g, h) with cells and fluid exudate 
which coagulates, causing induration of the part. If the horny layer of 
the epidermis becomes macerated, quantities of exudate appear on the 
surface, and give rise to a moist condition of the condyloma. In pustular SYPHILIS. 
493 
syphilides inflammation leads to liquefaction of epithelium, and in the 
ulcerating forms to softening and disappearance of the papillary body and 
corium. 
Inflammatory and degenerative changes appear in the secondary stage 
of syphilis, in the mucous membranes of the mouth, throat, and respira- 
tory passages, particularly in the form of localized, whitish plaques known 
as mucous patches. 
Syphilitic lesions of the tertiary stage in internal organs, glands, bones, 
muscles, subcutaneous and submucosal tissues, in the meninges of the 
Fig. 446.—Condyloma latum ani (alcohol, Bismarck-brown), a, Horny layer; b, mucous 
layer of the epidermis; c, corium; d, loosened horny layer infiltrated with small cells; e, swollen, 
f, swollen and infiltrated mucous layer; g, epithelial cells containing round cells; h, granular 
masses of coagula; i, swollen papillary body infiltrated with cells and fluid; k, corium, swollen, 
and infiltrated with cells, fluid and coagulated albumin; l, dilated lymph-vessels filled with clots; 
m, sweat-glands, x 150. 
brain, etc., consist of degenerative and inflammatory processes or hyper- 
plasias of connective tissue without characteristic features, and are desig- 
nated gummata or syphilomata. In its early stages the gumma 
represents a localized inflammatory process; it is usually rich in cells and 
undergoes central caseous necrosis (Fig. 447, d.,), while at the periphery, 
granulation tissue (d) and later connective tissue (dx) are developed. 
The gumma occurs in the periosteum (Fig. 448) and membranes of the 
brain (Fig. 447), as well as in the parenchymatous organs, especially in 
the liver (Fig. 449, a, b), lymph-nodes and lungs. 
In the meninges of the brain and spinal cord syphilitic inflammations 
lead to cicatricial thickenings and to the formation of gummata. Peri- 494 
THE PATHOGENIC FISSION-FUNGI. 
osteal syphilis occurs most frequently in the flat bones of the skull-cap, 
(Fig. 448), in the facial bones and the great long bones (tibia), but 
may extend over the greater part of the skeleton, and exhibits the char- 
acter of a granulomatous inflammation which leads to scar-tissue and new 
bone, so that osteophytes or hyperostosis result. The severe forms, rep- 
resented by gummata, lead to caries and necrosis. The fresh inflamma- 
tory focus appears as a translucent, yellow or grayish-white area sur- 
rounded by hypersemic tissue that may extend to the marrow. The 
yellowish foci consisting of masses of small cells (Fig. 448, c) may die, 
the cells losing their nuclei (d) ; in such places necrosis of bone may 
Fig. 447.—Meningoencephalitis syphilitica gummosa (Muller’s fluid, alcohol, haematoxylin). 
a, Brain cortex; b, inner meninges; c, vein surrounded by cellular exudate, d, frdsh cellular 
granulation tisrue; di, fibrocellular granulation tissue; di, caseated granulation tissue; e, artery 
with markedly thickened intima and adventitia infiltrated with cells; f, cellular infiltration of the 
pia-sheaths of the cortical vessels; ft, perivascular cellular infiltration of the cortical substance; 
g, diffusely spreading cellular infiltration invading the brain-substance, x 14. 
result. In living periosteal and endosteal tissue there occurs new-forma- 
tion of connective tissue (e, /), which, with the formation of multi- 
nucleated osteoclasts (g) and of Howship’s lacunae, leads to destruction 
of the bony trabeculae. In the process of healing this connective tissue 
may be changed into bone. 
In the liver syphilitic lesions lead to the formation of radiating scars 
(Fig. 449, b, c, d), which often enclose cheesy remnants of the original 
inflammatory focus (a), that is, a gumma. The process is similar in other 
organs, for example, in the testicles and spleen. 
The disintegration of syphilitic foci of the skin and subcutaneous 
tissue, and of the mucosa and submucosa, leads to the formation of ulcers, 
which, in mucous membranes, occur most frequently in the region of the 
mouth, throat, and upper respiratory tract. In the neighborhood of the 
ulcers in mucous membranes there are not infrequently papillary pro- 
liferations. HEREDITARY SYPHILIS. 
495 
The cause of the disintegration and necrosis occurring in syphilitic 
inflammations lies in the peculiar character of the infective agent. A 
second factor is the extensive participation of blood-vessels, particularly 
arteries, in the inflammation. When syphilitic inflammation leads to the 
formation of granulation tissue or to connective-tissue hyperplasia, the 
vessel-walls become thickened, particularly the intima (Fig. 447, e) and 
the lumen is narrowed and not infrequently closed. Occasionally the 
syphilitic process is localized in the vessels. 
Besides the foci of inflammation which point to localization of the 
spirochaete of syphilis, there not infrequently occurs in syphilitic indi- 
viduals specific degenerations of the central nervous system (tabes, pro- 
Fig. 448.—Syphilis of the skull-cap. a, Periosteum; b, bony trabeculs; C, small-cell infiltra- 
tion of the marrow; d, necrotic infiltrated marrow-tissue; e, periosteum proliferating into the 
bone; i, fibrous endosteum; g, osteoclasts and Howship’s lacunae, x 40. 
gressive paralysis), associated with proliferation of neuroglia. Although 
these affections now regarded as sequela of syphilis, present no histo- 
logical peculiarities characteristic of syphilis, they are universally accepted 
as due to infection by spirochaeta pallida. Spirochaetes-have been demon- 
strated in the brains of subjects dead of general paralysis of the insane, 
or paresis. (Nogouchi and Moore.) 
Hereditary syphilis is characterized by tissue-changes which differ 
from the manifestations of acquired syphilis, although changes occur 
which correspond to the latter. In the skin hereditary syphilis causes 
macular, papular, and pustular syphilides which may lead to ulceration. 
The liver, kidneys, adrenals, and bones may show circumscribed necrotic 
foci or cellular infiltrations. The spleen is usually more or less enlarged, 496 
THE PATHOGENIC FISSION-FUNGI. 
and may attain many times its normal volume. In the liver there occur 
collections of round cells in closely packed foci associated with new- 
formation of connective tissue in the perilobular spaces and with hyper- 
plasia of connective tissue throughout the liver (Fig. 452, a, b), giving 
to the organ a firm consistence and a peculiar yellowish-brown color 
(pericellular cirrhosis). The lungs may present, throughout or in part, a 
dense gray or grayish-white structure resembling that of sarcoma. This 
appearance is due to the formation of cellular connective tissue (Fig. 
453, a, b) which contains imperfectly developed alveoli (e, et) and 
bronchi (d, dfi) or none at all. In cases of slight severity there is thicken- 
ing of the peribronchial and perivascular tissue and interalveolar septa, 
Fig. 449.—Gumma hepatis (alcohol, alum carmine), a, Caseous nodule; b, homogeneous 
connective tissue; c, connective tissue with remains of liver tissue; d, connective-tissue bands 
radiating into the liver tissue; e, cellular focus at the edge of the caseous nodule; f, cellular 
focus within the connective-tissue rays; g, liver tissue, x 12. 
associated with accumulation of desquamated epithelium in the alveoli. 
Interstitial gummata may be present in the more advanced cases. The 
lesion is known as pneumonia alba (Virchow). In the kidneys and testi- 
cles the supporting connective tissue may be increased in places, and 
abnormally rich in cells. Congenital syphilis often causes in glandular 
organs development of connective-tissue elements and collections of round 
cells, while epithelial tissues are retarded. This is well shown in con- 
genital syphilitic pancreatitis, which is characterized by diffuse overgrowth 
of connective tissue and diminution in the glandular elements. Finally, 
there not infrequently occur in bones disturbances of endochondral ossi- 
fication, characterized by irregularity in the formation of the medullary 
cavity and by the deposit of lime-salts in the cartilage, leading to disturb- 
ances in the structure of the subchondral spongy bone-substance. Through 
the formation of granulation-tissue which undergoes caseous necrosis, 
larger defects may arise in the bone substance. LEPROSY. 
497 
§ 173. The Bacillus leprae (described by Armauer Hansen in 1879) 
is a slender bacillus, from 4 to 6 /x long. It is regarded as the cause of 
leprosy. It is found constantly in great numbers in the diseased tissues 
(Figs. 454, 455, 456) and in the excretions from leprous sores. 
Foci of leprosy are characterized by proliferation (Fig. 454) of cells 
of different sizes and a fibrous ground tissue. The bacilli lie between (e), 
and in the cells (c, d), in the latter in such numbers that the cells 
become swollen (d) and changed into mono- and multinuclear giant-cells 
(Fig. 455). The latter occasionally enclose large vacuoles which con- 
tain great numbers of bacilli. The nuclei remain preserved for a long 
time, and are pressed to the periphery by the vacuoles containing the 
Fig. 450.—(Bellevue Hospital.) Gumma of cheek. 
bacilli. Later the nuclei are destroyed, and the cell becomes changed 
into a vacuole containing bacilli (Fig. 455). 
The bacilli react to stains in much the same manner as tubercle-bacilli. 
The same methods may be used for the former as for the latter, with 
certain slight modifications, since the bacillus of leprosy stains more 
easily and is decolorized more readily than the tubercle bacillus. In 
tissues, the leprosy bacillus is easily to be detected by proper methods of 
staining, while the tubercle bacillus is evasive. The leprosy bacillus is 
less apt to display a beaded appearance and is rather less slender than 
the tubercle bacillus. 
Attempts to cultivate lepra bacilli have led to no conclusive results. 
In the transplantation of leprous tissues into animals the bacilli do not 
multiply and leprosy is not reproduced. 
The infection of man takes place by direst transfer from individual 
to individual. The nasal secretion is especially infectious when leprous 
lesions are present in the nose. In leprous affections of the respiratory 498 
THE PATHOGENIC FISSION-FUNGI. 
tract the sputum contains bacilli; the excretions from ulcers in the skin 
contain them in vast numbers. Contagion seems to result most frequently 
from the nose; in favor of this view is the fact that the anterior nasal 
region is usually involved early. The bacilli are spread through the 
body by the lymphatic system; they may also invade the blood-stream. 
The peripheral nerves are often concerned in the disease; the bacilli 
may also multiply in the testicles, liver, ganglia, and spleen, giving rise 
to foci of disease in these organs. 
At the place of colonization the bacilli excite inflammation. Granu- 
lation tissue is formed; this for a 
long time is characterized by great 
richness in cells, and forms nodules 
and tumors in the skin and nose and 
spindle-shaped thickenings of the 
nerves. The tissue-proliferations 
often group themselves in the skin 
about the hair-follicles (Fig. 456, d), 
the ducts (/), and the coil (g) of 
the sweat-glands, although such a re- 
lationship is not always to be seen 
(h). Moreover, the bacilli may 
penetrate the hair-follicles, and 
sweat-glands, and thence the surface 
of the skin. Infection of the arterial 
walls causes arteritis, by which the 
walls become thickened and the 
lumina narrowed. In the nervous 
system the bacilli are found in the 
connective tissue and ganglion cells. 
The cells occupied by them undergo 
degeneration, with the formation of 
vacuoles. 
Leprosy of the skin occurs 
oftenest on the face, on the extensor 
surface of the knees and elbows, and 
on the back of the hands and feet. 
It begins with the formation of red 
spots which vanish, leaving pig- 
mented spots behind, or become 
elevated into nodules of a brownish- 
red color. In the region of the red 
spots the tissue contains large num- 
bers of bacilli and even at this stage proliferation of cells can be demon- 
strated. According to Muller, the vesicular eruptions which occur in 
leprosy, and which were formerly regarded as sequeke of leprous disease 
of the nerves, are caused by the presence of bacilli. 
The nodules may remain unchanged for months, or increase in size 
and become confluent, so that large protuberances are formed, which, 
because of the distortion of the face that they occasion, have given rise 
to the designation facies leontina. 
Through external influences ulcers may be produced which show no 
tendency to heal. New nodules occasionally appear following erysipelas. 
Fig. 451.—(Bellevue Hospital.) Syph- 
ilitic sclerosis of testicle. LEPROSY. 
499 
Leprosy of the nerves (lepra nervorum sive anccsthetica) leads first to 
hyperaesthesia and pain, later to anaesthesia, more rarely to motor paraly- 
ses. Further consequences of disease of the nerves are disturbances which 
Fig. 452.—Induration of the liver in congenital syphilis (Muller’s fluid, hsematoxylin, eosin). 
a, Hypertrophic periportal connective tissue; b, indurated gland tissue infiltrated with con- 
nective tissue; c, collection of cells, xioo. 
express themselves in the skin by the formation of white and brown spots 
(lepra maculosa, maculo-anccsthetica, morphcea nigra et alba), and, in the 
bones and muscles, by atrophy. Since those suffering from the disease 
are likely to injure themselves after the appearance of anaesthesia, ulcers 
Fig. 453.—Changes in the lung in congenital syphilis (Muller’s fluid, haematoxylin, eosin). 
a, Proliferating stroma rich in cells; b, cellular granulation-foci; c, artery with thickened 
adventitia; d, di, gland-like bronchi, which in part (di) contain desquamated epithelium and 
round cells; e, e\, alveoli, which in part (ei) contain desquamated epithelium and round cells. 
X 52. 
are often formed which cause deep erosions and may lead to the loss of 
entire phalanges (lepra mutilans). 
Leprosy of the skin and of the nerves are usually combined; more 
rarely do they occur alone. Besides the nose, skin, and nerves, the 500 
THE PATHOGENIC FISSION-FUNGI. 
central nervous system, mucous membranes, cornea, the cartilages, liver, 
lungs, spleen, lymph-nodes, and testicles, become diseased. 
in Europe leprosy is confined mainly to Norway, Sweden, Finland, 
the Baltic Sea provinces of Russia, and the coasts of the Mediterranean; 
Fig. 454. 
Fic. 455. 
Fig. 454.—Tissue from a leprous nodule (alcohol, fuchsin, methylene-blue), a, Fibrocellular 
tissue; b, round-cells; c, medium-sized cells; d, very large cells filled with bacilli; e, free bacilli. 
X 200. 
Fig. 455.—Giant-cells with vacuoles containing bacilli, from leprous proliferations of the 
nasal mucosa (alcohol, Gabbet’s stain), x 400. 
but occurs sporadically in other regions. It occurs frequently in Hindu- 
stan, China, Sumatra, Borneo, Java, and Mexico, on the northern and 
eastern coasts of South America, in Upper and Lower Guinea, in Cape 
Colony, and on the northern coast of Africa. 
Fig. 456.—Section through a leprous nodule of the skin (alcohol, Gabbet’s method), a, 
Epidermis; b, corium; c, hair-follicle; d, leprous focus in the neighborhood of the hair-follicle; 
e, duct of sweat-gland; f, leprous nodule about duct of sweat-gland; g, leprous foci in the 
neighborhood of sweat gland; h, leprous focus having no especial relation with any of the 
specific skin structures; i, foci of bacilli. X 32. LEPROSY. 
501 
Leprosy is prevalent in Mexico, the West Indies, and in the Philippines, and 
cases are found in New Brunswick and other parts of Canada and scattered 
throughout the United States, the most important centres being in Louisana, Cali- 
fornia, and Minnesota. According to a Senate report of 1902, there were at that 
time 278 known cases of leprosy within the borders of the United States. 
Fig. 457.—(Bellevue Hospital.) Leprosy in a Filipino, showing the lion-like facies, the 
macular eruption on the arms and legs, a nodule in the left groin and another on the left fore- 
arm. In this patient, leprosy bacilli occurred in the nasal secretions in great profusion. 502 
THE PATHOGENIC FISSION-FUNGI. 
§ 174. The Bacillus mallei was discovered by Loffler, Schutz, and 
Israel in glanders foci, and later confirmed and studied by Weichselbaum, 
Kitt, and others. It is the cause of glanders (malleus, maliasmus) and of 
farcy (skin glanders, malleus farciminosus), a contagious disease of 
horses, which occurs in man chiefly through transmission from horses. 
The glanders bacilli are small, slender rods, which occur in the 
diseased foci, sometimes scattered, sometimes lying in small clumps. 
Alkaline methylene-blue or gentian-violet is employed for their staining. 
The bacilli at times appear in the blood (Loffler, Kitt). 
The bacilli grow at a temperature of 30°-40° C., on coagulated blood- 
serum, potato, and agar. On blood-serum they form small yellowish 
transparent drops which later become milky white. On agar the colonies 
Fig. 458.—Glanders of a cat’s testicle (Muller’s fluid, haematoxvlin). a, Seminiferous tubules; 
b, c, tubules filled with leucocytes; d, foci of leucocytes in the cennective tissue, x 90. 
are grayish-white. In cultures club-shaped forms and threads are not 
infrequently seen. Spore-formation has not been demonstrated. 
Horses, asses, sheep, young dogs, goats, cats, guinea-pigs, and field- 
mice are suitable for inoculation. In cats, after inoculation, there develop 
in the testicles cellular foci consisting of leucocytes (Fig. 458), which 
lie in the canaliculi (b, c) and around them (d). The injection of the 
pus of glanders into the peritoneal cavity of male guinea-pigs causes the 
testicles to swell rapidly (Straus). This reaction is of great diagnostic 
value. After subcutaneous inoculation ulcers develop at the seat of 
inoculation, followed by swelling of the neighboring lymph-nodes. Later, 
nodules may develop in the internal organs, and ulcers may be formed 
in the nose. Typical glanders may be produced in horses and asses. 
Cattle, white mice, and house-mice are immune. 
The usual atrium of infection in horses is the mucous membrane of 
the nose; following this is involvement of the submaxillary glands, and GLANDERS, RHINOSCLEROMA. 
503 
metastasis in various organs. In the nasal mucosa there arise diffuse 
cellular infiltration or subepithelial nodules the size of a millet-seed or 
pea. In chronic farcy larger nodules are developed which join in rows, 
forming worm-like cords. 
The nodules in the mucous membrane break down easily. The cells 
of which they are composed are for the greater part pus-corpuscles. 
Through disintegration, softening, and suppuration ulcers with yellowish, 
infiltrated bases are formed. These enlarge through progressive infiltra- 
tion and subsequent disintegration of the edges of the ulcer, as well as 
through confluence of neighboring ulcers. Horses dying of glanders 
often present in the mucosa of the nasal septum extensive, irregularly 
shaped, sinuate ulcers, with eroded edges and floors covered with gray and 
yellowish material. In addition to these there are numerous small, lenticu- 
lar ulcerations and gray or yellowish nodular foci which are on the point 
of breaking down. Healing is characterized by the formation of radiating 
scars. 
The cervical lymph-nodes are constantly swollen and inflamed. Of the 
internal organs the lungs especially are involved. They contain nodules 
having a caseated centre and a grayish periphery, or foci of lobular pneu- 
monia, which present a gray or haemorrhagic appearance, or through 
fatty and cheesy metamorphosis become opaque and yellowish-white. 
Occasionally the mucosa of the alimentary tract contains nodules of 
varying size, in part clear gray and consisting of cellular tissue, or opaque 
yellowish-white, undergoing caseation or approaching suppuration. The 
spleen, liver, kidneys, and bone-marrow may also contain nodules. 
In farcy, which runs a more chronic course than glanders, there are 
formed in the skin and muscles nodules consisting of small-cell tissue 
which later undergoes retrogressive metamorphoses, caseates and disin- 
tegrates. 
In man infection with glanders usually takes place through small 
wounds of the skin, but may occur primarily in mucous membranes ad- 
jacent to the skin. In the skin and subcutaneous tissue it gives rise to 
roseolar spots, haemorrhages, and papular, nodular, and pustular exan- 
themata, carbuncular and phlegmonous inflammations which may result 
in suppuration, and to purulent inflammations of the lymph-vessels and 
lymph-nodes. In the mucosa of the respiratory tract catarrhs are pro- 
duced and suppurating nodules and nodes are formed, leaving ulcers 
behind. In the internal organs metastatic nodules are formed, showing 
a tendency to suppuration; also abscesses and purulent infiltrations, 
especially in the muscles. In chronic farcy, which may last for years, 
large nodules are occasionally formed in the skin and muscles that, 
through disintegration, give rise to ulcers which heal with difficulty. For 
diagnosis of the condition bacteriological examination and inoculation 
experiments are necessary. 
According to the investigations of Kalning, Preusse, and others, an active 
poison, mallein, may be extracted from cultures of glanders bacilli, that, when 
injected in small doses into horses sick of glanders, causes a febrile rise of tempera- 
ture, and may be used as a diagnostic aid. 
§ 175. The Bacillus of rhinoscleroma is constantly present in the 
disease known as rhinoscleroma or scleroma respiratorium, and is re- 
garded as the cause. It stains best with methyl-violet, the sections being 
left in the stain for twenty-four to forty-eight hours. After staining, the 504 
THE PATHOGENIC FISSION-FUNGI. 
sections are treated with iodine water, or left in absolute alcohol for one to 
three days. I he bacilli possess a capsule and belong in the Friedlander 
group. 
Rhinoscleroma occurs chiefly in eastern Austria and southwestern 
Russia; isolated cases have been observed in Silesia, Italy, Egypt, Belgium, 
Sweden, Switzerland, and Central America. It is a chronic disease 
beginning in the nose, more rarely in the pharynx, larynx, or palate, and 
extending thence to neighboring parts — the external nose, lips, lachrymal 
duct, trachea, etc. In the nose the disease is characterized by thickening 
of the nasal wall which is sometimes dififuse, sometimes elevated or 
nodular. T he external skin takes on a red or brownish-red color, be- 
comes stiff and fissured and covered with scales. In the throat and 
respiratory tract dense, cartilage-like infiltrations are sometimes present, 
at other times contracting cicatricial tissue is formed. The infiltrations 
appear in the form of nodes and nodules or as elevations and flattened 
areas of thickening, or may spread out more diffusely. By transformation 
into scar tissue marked deformities are produced. Deep destruction of 
Fig. 459. 
Fic. 460. 
Fig. 459.—Section of rhinoscleromatous tissue, with numerous degenerated and vacuolated 
cells containing bacilli (osmic acid, haematoxylin). Preparation by Stepanow. x 340. 
Fig. 460.—Cells in condition of hyaline degeneration, and hyaline spherules, from rhino- 
scleromatous tissue of the vocal cord and of the nose. Preparation by Stepanow. a, b, c, d, 
Hyaline-degenerated cells containing small bacilli; e, hyaline cells with encapsulated bacilli; 
f, g, cells with hyaline spherules; h, free hyaline spherules, a, b, c, d, Stained with Loffler's 
solution; e, with haematoxylin; f, g, h, with fuchsin. x 425. 
tissue is absent; superficial ulcerations may, however, occur. On section 
the infiltrated tissue appears yellowish, or shows a gray or grayish-red 
color. The afifected areas consist partly of granulation tissue, partly 
of fibrous connective tissue. If the former extends to the epithelial cov- 
ering there appear proliferation of and degenerative processes in the 
epithelial cells, the latter being characterized by the formation of vacuoles. 
The vacuoles often contain bacilli. 
The granulation tissue itself shows in many places no peculiarities. 
In other places, there are found large connective-tissue cells containing 
one vacuole or showing total vacuolar degeneration or a reticulated 
structure, in the meshes of which bacilli may be demonstrated (Fig. 459), 
some possessing capsules. 
There also occur cells of various shapes which have undergone 
hyaline change (Fig. 460, a, b, c, d, e). These contain bacilli with and 
without capsules, and coccus-like forms. Through loss of nuclei these 
cells may become converted into homogeneous lumps (d). Finally, there 
are cells which enclose hyaline spherules (/, g) ; free spherules are also 
found lying in the tissues (h). In places not yet afifected by cicatricial 
retrogression the hyaline formations may be present in large numbers. ACTINOMYCOSIS. 
505 
According to Paltauf, von Eiselsberg, Dittrich, Wolkowitsch, and others, the 
bacilli of rhinoscleroma may be cultivated on blood-serum, gelatin, agar-agar, and 
potatoes, and form capsules in the cultures. When grown in bouillon they show on 
the contrary no capsules (Dittrich). Stab-cultures in gelatin resemble the nail- 
cultures of the Friedlander pneumonia-bacillus, but are translucent grayish-white 
and not dead-white. The bacilli stain more easily than the pneumonia bacilli, and 
are Gram-negative. Stepanow observed, 
in inoculations into the eyes of guinea- 
pigs, progressive inflammation and pro- 
liferating granulations containing bacilli 
and hyaline cells. 
Fig. 461.—Actinomyces hominis. Teased preparation, x 700. 
Fig. 462.—Actinomycosis of the tongue (alcohol, alum carmine.) a, Actinomyces; b, c, cellular 
nodules; d, transverse section of muscle; e, f, connective tissue with blood-vessels. x 175. 
Fig. 461. 
Fig. 462. 
§ 176. The Actinomyces or ray-fungus is a fission-fungus which 
appears in different forms of growth in the human and animal organism 
Fig. 463.—Actinomyces, surrounded by epitheloid and pus-corpuscles (alcohol, hsematoxylin, 
eosin.) a, Fungus; b, mononuclear and multinuclear epithelioid cells; c, pus-corpuscles; 
d, phagocyte, enclosing a pus-corpuscle; e, granulation tissue, x 500. 
and in cultures. It is the cause of actinomycosis, a disease occurring in 
man and in cattle, swine, and horses, more rarely in sheep, dogs, and 506 
THE PATHOGENIC FISSION-FUNGI. 
cats, and characterized by progressive inflammation that produces granu- 
lation and connective tissue, and pus. The botanical position of the 
fungus is unsettled. By many it is classed with the thread-fungi, others 
group it with the polymorphous bacteria. Bostrom places it in the group 
cladothrix; Kruse, among the streptothrix. 
According to the investigations of Bostrom actinomyces differs from 
bacilli in that in cultures on beef s-blood serum or agar it forms branching 
threads. The threads are straight or wavy, at times twisted spirally. 
Fig. 464.—Actinomycosis of the lung (alcohol, carmine, Gram’s), a, Fungus; b, small-cell 
nodule; c, fibrous tissue; d, alveoli filled with large and small cells; e, bronchiole with wall 
infiltrated with cells; f, small-cell focus in the neighborhood of the bronchus (e) ; g, alveoli filled 
with vascularized connective tissue; h, connective tissue growing into the alveoli; i, blood-vessels 
of the lung tissue; k, blood-vessels of the inflamed area, x 42. 
They break up by transverse division into short rods and coccus-like 
forms, which under suitable conditions again grow into threads. 
Within the human and animal organism the fungus appears in the 
form of granules scarcely recognizable by the naked eye, or in spherules 
up to 2 mm. in diameter. These are sometimes colorless and transparent, 
at other times white and opaque, sometimes yellow, or brown, or green 
and yellowish-green. Many of the smaller ones consist of a feltwork of 
fine, partly branched threads, which are straight, wavy, or twisted. 
The majority of the granules contain peculiar club-shaped structures 
(Fig. 461), which form the ends of the threads, and if present in large 
numbers have a radial arrangement (Figs. 462, a; 463, a), and give to 
the fungus a ray-like appearance. Occasionally hand-shaped or fan-like 
forms develop on the ends of the threads. According to Bostrom, these 
peculiar structures are due to swelling of the membrane of the threads, 
and are retrogressive changes. ACTINOMYCOSIS. 
507 
The actinomyces is usually taken into the body with the food or 
respired air, and often first develops in the tissues of the mouth, gums, 
tongue, etc. Not uncommonly club-shaped forms are to be found in the 
crypts of the tonsils in individuals in whom there is no indication of 
actinomycosis. The fungus has not been demonstrated outside the human 
and animal organism. It must be remarked that often bits of higher 
plants have been found in the pus of actinomycotic foci, and that the 
swallowing of portions of plants or the contamination of wounds with 
vegetable material, have preceded the development of actinomycosis. It 
is, therefore, probable that the fungus is present on the higher plants 
or on wood. Johne demonstrated it as early as 1882 on beards of wheat 
found in the tonsils of swine. 
If the ray-fungus lodges in a tissue it excites inflammation in the 
neighborhood. While the fungus which has penetrated into the tissue 
develops a mycelium and a fungus-granule (Figs. 462, a; 463, a; 464, a) 
there is formed in its neighborhood a nodular focus of inflammation, 
which at first consists of leucocytes (Figs. 462, b, c; 464, b), and later 
(Fig. 463, f) contains epithelioid and giant-cells (b, d). 
The fungus-granules may increase in the nodule and lead to its 
enlargement; it often happens that cellular nodules contain a large num- 
ber of fungus-foci, which are usually situated at the periphery. New 
fungus-foci, and consequently new cellular foci, appear in the neighbor- 
hood. The further spread of infection takes place by means of small 
rods and threads, which are broken off from the larger masses, and may 
be seen in the tissues free and enclosed in cells. 
Larger nodules often undergo purulent liquefaction of their central 
portions, with the formation of small abscesses, which become confluent 
to form pus-cavities, or rupture and lead to sinuses. In the neighborhood 
of the purulent areas (Fig. 464) there is active proliferation of tissue, the 
formation of vessels (k) and young granulation tissue, which later 
becomes transformed into cicatricial tissue (c, g, h). If connective- 
tissue proliferation attains considerable proportions, it leads to induration 
(Fig. 464), often to enlargement of the part. The connective-tissue may 
extend into the small-cell areas, and replace them, the fungi probably 
being destroyed in this way. 
Predominance of tissue-necrosis and suppuration over tissue-produc- 
tion gives rise to sinuous cavities and fistulous tracts communicating with 
one another or with the exterior. The walls consist of granulation- 
tissue and hyperplastic connective tissue, and here and there contain 
fungus-foci. The masses of fungi may become partly calcified. 
In cattle the disease affects chiefly the lower jaw, but may involve 
the upper jaw, the tongue, throat, laynx, oesophagus, stomach, intestinal 
wall, skin, lungs, and subcutaneous and intermuscular tissues; in swine it 
is found in the udder and different bones of the skeleton, while in horses 
it occurs chiefly in the vas deferens following castration. In cattle it 
leads to more or less extensive fibrous tumors containing purulent foci, 
and was formerly given various names, such as osteosarcoma, bone-cancer, 
bone tuberculosis, lumpy jaw, wooden tongue, tuberculosis of the tongue, 
lymphoma, fibroma, worm-nodules, etc. 
In man infection takes place through the mouth, fauces, oesophagus, 
stomach, intestine, and lung, or by external injury. In the mouth infec- 
tion may take its start from carious teeth, or from injury to the soft 
parts of the jaw or cheek. Thence it spreads and may finally involve the 508 
THE PATHOGENIC FISSION-FUNGI. 
face and the hairy portions of the head, as well as the throat, neck, back, 
and breast. 
With the advent of actinomycosis there arise swellings which soften 
and give fluctuation. When the latter is the case, pus is formed which is 
at times thin and watery, at other times more viscid, and contains the 
characteristic granules. If the abscesses break externally there may be 
formed fistulous tracts, which either close again, or continue to secrete 
pus. 
Besides the purulent foci, which sometimes are small, at other times 
extensive, granulation tissue arises and may be abundant. As a result 
of fatty degeneration and disintegration of its elements the granulation 
tissue often becomes whitish or yellowish or reddish-white in color, and 
permeates the diseased tissue in an irregular manner. In other places it 
develops into connective tissue, particularly in those places where the 
process is not spreading. 
Through development of connective tissue local healing resulting in 
cicatricial induration may take place, but in other parts the process makes 
further progress and may lead to extensive destruction. If the disease 
encroaches on the bones of the spinal column or of the thorax these may 
be gradually destroyed, and become eroded and carious. In rare cases 
the jaw-bone may be attacked from within through the alveolar process, 
and so undergo destruction. From the base of the skull infection may 
extend into the interior and lead to actinomycotic meningitis and 
encephalitis. 
In primary infection of the respiratory apparatus the process takes 
the form of bronchopneumonia characterized by the formation of nodular 
foci (Fig. 464, b) the central portions of which at an early stage assume 
a yellowish-white color. Through disintegration of the inflammatory 
foci cavities may be formed which contain fluid, pus-corpuscles, fatty 
detritus, spherules of fatty granules, disintegrated red cells, and masses 
of actmomyces. The tissue lying between the mycotic foci suffers more 
or less extensive, often marked, inflammatory thickening (Fig. 464, c), and 
may thus be transformed into a slate-gray or gray and white mass, devoid 
of air, later undergoing cicatricial contraction. In this manner a large 
portion of the lung may be replaced by scar tissue. 
From the lung the process sooner or later extends to the visceral 
pleura, from this to the costal pleura or pericardium, giving rise to inflam- 
matory exudations and proliferations of tissue, which lead to adhesions 
between the opposite layers. From the costal pleura cellular infiltration, 
pus formation, and fatty degeneration and disintegration of the granu- 
lation tissue may extend between the ribs and spread in the connective 
tissue and muscles, and finally break through the skin. From the lungs 
rupture may take place into the mediastinum or pericardial sac, and 
finally into the heart, or through the diaphragm into the abdominal 
cavity, or from the posterior mediastinum into the retroperitoneal con- 
nective tissue. 
The secondary areas of destruction lying outside the lung often reach 
an extremely large size, while in the lung the primary process advances 
but little and may even undergo cicatrization. At one time softening 
predominates, at another time the formation of granulation tissue and 
induration. 
Primary actinomycosis of the intestinal tract begins with the forma- 
tion of plaque-shaped whitish patches or of nodular mucosal and sub- ACTINOMYCOSIS. 
509 
mucosal foci, which contain the specific fungus, and lead to ulceration. 
From the intestine the process spreads over the peritoneum and through 
the retroperitoneal connective tissue, as well as to' adjacent organs — for 
example, the liver; and may finally break through the abdominal wall. 
Metastasis may be associated with local progression of the disease, 
but is rare. It usually results from direct rupture into a blood-vessel. 
The metastases arising from a primary focus in the intestine are found 
especially in the liver; those arising from a primary focus in the lungs 
are found in the skin, muscles, bones, brain, intestine, and kidneys. The 
metastatic nodules behave like the primary foci. In rare cases there 
occur primary foci of actinomycosis in the internal organs—for 
example, in the brain and liver. The portal of entrance in these cases 
may not be demonstrable. 
Johne, Ponfick, Bostrom, Wolff, and Israel attempted inoculation 
experiments in animals, and according to their reports obtained positive 
results (Johne, Ponfick, Wolff, and Israel). Wolff and Israel, by inocu- 
lation of rabbits and guinea-pigs, reproduced a characteristic disease 
with the formation of inflammatory foci containing the fungus-masses. 
They were also able to cultivate the fungus from these foci. 
Levy, as well as Kruse, assumes that there are two forms of actinomyces, an 
aerobic cultivated by Bostrom and an anaerobic cultivated by Wolff, Israel, Aschoff, 
and himself, the two forms being closely related. Mertens announces that he 
succeeded in changing the Wolff-Israel form into the Bostrom. Levy regards the 
actinomyces as well as the fine-threaded fungus known as streptothrix as belonging 
to a group, the Hyphomycetes, characterized by the formation of branching, prob- 
ably unicellular mycelia and which multiplies through acrogenic snaring-off of 
conidia-chains or through fragments of threads resembling bacilli. Since the ray- 
fungi do not correspond to any one of the known hyphomycetes-groups, he places 
them in a separate group, the Actinomycetes. In this group he also places the 
tubercle-bacillus, the lepra-bacillus, the diphtheria-bacillus, and the bacillus of 
glanders. Lubarsch regards the streptothrices, with which he classes the ray-fungi 
(to which the tubercle-bacillus also belongs), as a transition form between the 
bacilli and the moulds. 
Berestnew distinguishes different forms of actinomyces (cultivated by him 
from hay, straw, etc.), and, in addition to actinomycosis, recognizes a variety of 
pseudo-actinomycosis, which runs a similar course to that of the former, but is 
caused by fungi which do not belong to the ray-fungi. Krause and Gilbert likewise 
regard the etiological factor of actinomycosis as being of varied nature and not 
representing a definite entity. Schiirmayer emphasizes the variability of actino- 
myces according to the conditions of growth. Wright believes that human and 
bovine actinomycosis are identical, and holds that there is but one species of micro- 
organism (Actinomyces bovis) concerned in the production of actinomycosis. The 
lesions produced by other forms of branching organisms he would class under the 
head of nocardiosis, reserving the term actinomycosis for those conditions in which 
characteristic “ drusen ” are formed. 
Petruschky unites Actinomyces, Streptothrix, Cladothrix, and Leptothrix into 
one family, which he calls Hair fungi or Trichomycetes. These he groups with 
the hyphomycetes, of which he distinguishes two great classes, the mould fungi and 
the hair fungi. 
Actinomyces is characterized by radiating forms; streptothrix by true branch- 
ing, late fragmentation of the wavy threads and the formation of conidia; clado- 
thrix by false branching of the threads (lateral direction of the membrane with 
continuation of the longitudinal growth in the other direction) and rapid frag- 
mentation of the threads; while leptothrix is characterized by stiff threads without 
branching. 
There occur numerous observations in which organisms apart from the actino- 
myces described above and belonging to the trichomycetes, particularly to the 
streptothrices, gave rise to local-tissue changes, particularly purulent and granu- 510 
THE PATHOGENIC FISSION-FUNGI. 
lating inflammations, and also to tubercle-like changes, but in many cases the authors 
are not agreed as to what species the fungus concerned belonged. 
As early as 1855 fungus masses were observed by von Graefe in the inflamed 
lachrymal duct. These were at first regarded as favus, but later Cohn (1874) re- 
garded them as streptothrix and gave them the name Streptothrix foersteri. Like- 
wise Axenfeld, who has many times cultivated the fungus, regarded it as a variety 
of streptothrix. 
Under the term Cladothrix asteroides, Eppinger described a polymorphous 
fission fungus or hair fungus found in the pus of an old cerebral abscess causing 
death through meningitis. Since in the affected individual changes similar to 
tuberculosis were found in the lungs and bronchial glands and since inoculation of 
guinea-pigs and rabbits gave rise to a disease resembling tuberculosis, he designated 
the disease produced by the fungus as Pseudotuberculosis cladothrichica. Mac- 
Callum regards Eppinger’s fungus, which he obtained from a purulent peritoneal 
exudate, as belonging to the Actinomyces group and calls it Actinomyces asteroides. 
Schabad regards a fungus characterized by branching threads which he found in 
a subpectoral abscess, and according to its behavior in cultures apparently identical 
with the Eppinger fungus, as belonging to the actinomyces group, and designates it 
atypical actinomyces, which differs from the typical form in that it produces no 
clubs and is acid-fast. In animals it causes pseudotuberculosis. 
Buchholtz found a variety of streptothrix in a pneumonic lung containing large 
cavities with ragged walls. Longer found a streptothrix pathogenic for guinea- 
pigs in the sputum of a thirteen-year-old-boy that probably arose from an oeso- 
phageal diverticulum. 
According to investigations by Kanthack, Boyce, and Vincent it is probable 
that the disease occurring in India known as Madura-foot or Mycetoma, char- 
acterized by gradual swellings in the extremity, with nodular deposits becoming 
changed into abscesses and fistulous tracts through suppuration, and on pressure 
discharging purulent gray, or brown to black, fish-roe or truffle-like granules is 
caused by a polymorphous fungus related to Actinomyces and designated by Vincent 
as Streptothrix maduroc. Kanthack regards the fungus which is enclosed in the 
granules as identical with Actinomyces, but the investigations of Vincent and 
Boyce do not agree with this assumption. According to Boyce, the Streptothrix 
maduroc occurs in two varieties, one white or yellow, with fine dichotomous branch- 
ing threads, and one black, with branched pigmented threads. Unna and Delbanco 
also distinguish different fungi which they class with the Actinomyces. According 
to Oppenheimer mycetoma is a granuloma with abscess formation caused by two 
kinds of fungi; the yellow form is an actinomyces, while the fungus of the black 
form cannot at present be classified, but probably belongs to the o’idia or moulds. 
The parasite of the madura disease has been known since the year 1874 (Carter, 
Lewis, and Cunningham), and was formerly called Chionyphe Carteri. 
Literature. 
(Actinomycosis.) 
Bollinger: Eine neue Pilzkrankheit beim Rinde. Cbl. f. d. med. Wiss., 1877; 
Dent. Zeitschr. f. Thiermed., iii., 1877; Munch, med. Woch., 1887. 
Bostrom: Unters. fiber die Aktinomykose des Menschen. Beitr. v. Ziegler, ix., 
1890. 
Chiari: Darmaktinomykose. Prag. med. Woch., 1884. 
Howard: Actinomycosis of Central Nervous System (Lit.). Jour, of Med. Res., 
1903. 
Johne: Deut. Zeitschr. f. Thiermed., vii., 1881; Cbl. f. d. med. Wiss., 1882; Ak- 
tinomykose im Samenstrang kastrirter Pferde. Fortschr. d. Med., iii., 1885. 
Israel, J.: Mykose des Menschen. Virch. Arch., 74, 78 Bd., and Cbl. f. d. med. 
Wiss., 1883; Klin. Beitr. z. Kenntniss d. Aktinomykose des Menschen, 
* Berlin, 1885. 
Israel: O.; Kultivirbarkeit d. Aktinomyces. Virch. Arch., 95 Bd.; Cbl. f. d. 
med. Wiss., 1886. 
Wright: Madura Foot. Jour, of Exp. Med., 1898; Actinomycosis. Ref. Hand'b. 
of Med. Sc., 2d ed., 1900. Biology of the Microorganism of Actinomy- 
cosis. Jour, of Med. Res., 1905. CHOLERA. 
511 
Literature. 
(Streptothrix, Cladothrix, and Leptothrix.) 
Carter: Mycetoma or the Fungus Disease of India, London, 1874. 
Foulerton and Jones: Pathogen. Act. of the Genus Streptothrix. Trans, of the 
Path. Soc. of London, liii., 1901. 
Kanthack: Madura Disease and Actinomyces. J. of Path., 1892. 
Lewis and Cunningham: The Fungus Disease of India, Calcutta, 1875. 
MacCallum: On the Life-history of Actinomyces Asteroides. C. f. Bakt., Orig., 
xxxi., 1902. 
3. The Spirilla and the Diseases Caused by Them. 
(a) General Remarks on the Spirilla. 
§ 178. The Spirilla, or Spirillaceae, or Spirobacteria are divided 
into two genera, one of them called Spirillum, the other Spirochcete. 
Many writers recognize still another genus, Vibrio. 
The genus Spirillum is characterized by the formation of short, stiff, 
shallow spirals, which possess flagella and show active swarming move- 
ment. The wavy rods are called vibriones by many writers. 
The genus Spirochaete is characterized by long, flexible, or closely 
turned spirals. 
(b) The Pathogenic Spirilla. 
§ 179. The Spirillum Cholerae asiaticae, Vibrio choleras, or comma- 
bacillus, was discovered by R. Koch in 1884, and is the cause of Asiatic 
cholera. The spirilla (Fig. 465) form small comma- 
like, curved rods, from 0.8-2 /x long. 
Cultures of cholera-spirilla may be obtained on a 
great variety of media of slightly alkaline reaction. The 
temperatures most favorable for their development lie 
between 25° and 30° C.; between 16° and 8° C. they 
are still capable of feeble development. 
In fluid media in the presence of oxygen they show 
lively movements that may be easily observed in the 
hanging drop. The movements are produced by means 
of a terminal flagellum. 
Cholera, spirilla are often destroyed by the gastric juice, but escaping 
this and gaining entrance to the intestinal tract of man they develop both 
in the small and large intestines, and multiplication is followed by trans- 
udation from the intestinal mucosa, so that the intestine becomes filled 
with a fluid resembling meal-soup or rice-water due to flakes of 
desquamated epithelium. 
The spirilla are always present in great numbers in the intestinal con- 
tents, and are found in the lumina of the intestinal glands, whence they 
may penetrate between and beneath the epithelial cells. 
In recent cases the spirilla may be demonstrated in cover-glass 
preparations stained with methylene-blue or fuchsin. Fresh dejecta, as 
well as soiled linen, are suitable for the examination, since, according to 
observations made by Koch, the spirilla may multiply actively for some 
Fig. 465.—Cholera- 
spirilla from a pure 
culture. Cover-glass 
preparation stained 
with fuchsin. x 400. 512 
THE PATHOGENIC FISSION-FUNGI. 
time on moist linen and moist earth. In old cases the demonstration of 
spirilla is more difficult, and is attainable most surely by plate-cultures. 
The presence of cholera-spirilla in the intestine excites inflammation, 
which finds expression in redness, swelling, marked transudation, mucoid 
degeneration of epithelium, and desquamation; later, by haemorrhages, 
sloughs, and ulceration. It is characterized constantly by more or less 
marked cellular infiltration of the tissues. The solitary follicles and 
Peyer’s patches are swollen, even in fresh cases. Death may take place 
after a few hours or after one to three days. If the disease lasts a longer 
time, the intestinal contents become more consistent and the intestinal 
mucosa shows ulcerative changes. 
According to our present knowledge, the spirilla produce substances 
which cause local damage to the mucosa of the intestinal canal, and when 
absorbed give rise to symptoms of intoxication and paralysis of vessels. 
Small foci are often present in the liver and kidneys, in which the gland- 
cells show cloudy, fatty, or hyaline degeneration, or are necrotic. More- 
over, the kidneys frequently show cloudiness caused by degeneration of 
the epithelium. Ecchymoses in the epicardium are frequent; in the later 
stages patches of necrosis may occur in the mucous membrane of the 
vagina. Finally, the spirilla may be crowded out by putrefactive bacteria 
m the intestine, and through absorption of products of decomposition 
intoxication may arise, which is not dependent on the original spirilla. 
Cholera-spirilla may also be found in the vomitus, and in the ductus 
choledochus and gall-bladder. The spirilla do not usually enter the blood, 
but in cases of severe infection may spread throughout the body. 
Koch demonstrated the presence of spirilla in a tank in India which 
furnished the inhabitants of the region with water for drinking and other 
purposes, at a time when part of the inhabitants were sick and dying of 
cholera. Since then, spirilla have often been demonstrated in water- 
supplies during cholera epidemics. 
Asiatic cholera is endemic in Lower Bengal. Thence it spreads at 
times throughout India. Since the spirilla are easily killed outside the 
body transportation must be effected mainly by individuals suffering from 
the disease. The infection probably occurs exclusively through the ali- 
mentary tract, as the result of the introduction of infected beverages, 
food, or other substance into the mouth; but not every introduction of 
cholera-spirilla into the digestive canal is followed by infection due, most 
likely, to the destructive action of the. gastric juice. 
Moreover, it not infrequently happens that the spirilla increase in the 
intestine, but excite only slight changes, so that the infected individual 
suffers no marked symptoms, and the diagnosis can be made only through 
the demonstration of spirilla in the stools. 
If cholera-spirilla get into the water-supply and increase, cholera may 
develop in the region with great rapidity. If, on the contrary, infection 
takes place by contagion from man to man, the spread is slow, in that the 
disease is confined to those who come in contact with the sick, or with 
contaminated articles. The incubation period is from one to two days. 
In the intestines of convalescents the spirilla may live for a long time 
and multiply without giving rise to any symptoms betraying their 
presence. Kolle was able to demonstrate them in a number of cases after 
five to eighteen days, and even as long as twenty to forty-eight days. 
One attack of cholera makes the individual immune for a certain 
time. The immunity depends on the presence of bactericidal anti-bodies. CHOLERA. 
513 
On gelatin-plates cholera-spirilla form round, flat, yellowish discs which 
liquefy the gelatin slowly. At low magnification the colonies are irregular in out- 
line, and of a granular or furrowed and rough surface, as if strewn with small 
particles of glass {Koch). Through liquefaction of the gelatin there is formed 
in its immediate neighborhood a funnel-shaped cavity, to the bottom of which the 
colony sinks. 
Stab-cultures in gelatin form on the second diay a whitish cord corresponding 
to the stab, in the immediate neighborhood of which the gelatin is liquefied. 
The canal thus formed widens above into a funnel part which is filled in its 
lower portion with liquefied gelatin and in its upper part with air. The widening 
of the funnel takes place slowly, so that its edge reaches the wall of the tube only 
after five to six days. 
On potatoes at from 30°~35° C. the spirilla form light-brown cultures, on agar- 
agar grayish-yellow slimy cultures. They grow also in bouillon, blood-serum, and 
milk. 
They do not increase in pure water {Bolton), but do so in water contaminated 
with substances furnishing nutrient material. 
The cholera-spirilla are aerobic, but are also able to grow under anaerobic con- 
ditions. According to investigations by Hneppe, cultivation with a deficient supply 
of oxygen increases the virulence of the culture; but the resisting power against 
injurious agents — for example, against acids — is lowered; with free access of 
oxygen the reverse takes place. Pfeiffer, however, found that young cultures grown 
in the presence of oxygen also contained poison. The spirilla present in fresh dejec- 
tions {Hueppe) are easily killed, and have but little infecting power; whereas growth 
of the spirilla outside the body increases their resistance (for example, against the 
gastric juice) and makes them more capable of causing infection in new individuals. 
They are easily destroyed by desiccation in free air {Guyon), by high temperatures, 
and by boiling for a short time. They are easily supplanted by saprophytic bac- 
teria when the nutrient material and the temperature are not suitable. In the 
contents of privy-vaults they soon die out {Koch). They are easily killed by acids, 
mercuric chloride, and carbolic acid. According to Koch, they may live in well 
water for thirty days, in sewage for seven days, and on damp linen for three to 
four days. Nicati and Reitsch found them alive after eighty-one days in water 
taken from the harbor of Marseilles. 
In cultures they sometimes form short rods, more or less curved (Fig. 465) 
and often joined in pairs; at other times they form long spirals. With these there 
also occur straight rods, and occasionally the majority form rods which show the 
curve only imperfectly or not at all. 
At a certain degree of exhaustion of the food-material there frequently appear 
involution forms, in which the rods are sometimes shrunken, sometimes swollen, 
thus creating a variety of forms. Globular swelling, as well as the formation of 
spots which do not take the stain in stained preparations, occurs as the result of 
degeneration, and have been erroneously interpreted as phenomena of fructifica- 
tion. Spore formation has not been demonstrated. The addition of hydrochloric 
or sulphuric acid to cultures of cholera-spirilla in peptone-containing media (pep- 
tone-meat-infusion or an alkaline, one-per-cent solution of peptone containing one 
per cent of salt) causes the culture to assume a rose-red or Burgundy-red color, 
due to the formation of coloring-matter, cholera-red. According to Salkowski, this 
is a nitrosoindol reaction. 
In order to facilitate the separation of cholera-spirilla from other intestinal 
bacteria, Schottelius recommends mixing the dejecta with double the amount of a 
slightly alkaline meat-infusion, and allowing the mixture to remain uncovered for 
twelve hours at a temperature of from 30°~40° C. The spirilla requiring oxygen 
will develop on the surface, and may be transferred thence to plate-cultures. 
Koch recommends for this purpose a solution of peptone with common salt. 
According to Nicati, Rietsch, von Ermengem, and Koch, symptoms resembling 
cholera may be produced in experimental animals through the introduction of 
cholera-spirilla into the intestinal canal. This experiment succeeds when cultures 
are introduced directly into the duodenum or small intestine {Nicati and Rietsch) ; 
as well as when the gastric juice of the animals (guinea-pigs) is neutralized with 
a five-per-cent solution of soda, the bowels being quieted by an injection of 1 c.c. 
of tincture of opium to every 200 gm. of the body-weight, and one or more drops 
of a pure culture of the spirilla then introduced into the stomach {Koch). 
The animals thus inoculated die with symptoms of collapse. The small intes- 
tine is found to be filled with a watery, flocculent, colorless fluid containing spirilla 
in great numbers; the intestinal mucosa is reddened and swollen. 514 
THE PATHOGENIC FISSION-FUNGI. 
The poison which is produced by the cholera-bacillus and which causes the 
clinical symptoms of infection is not known. Gamaleia believes that it is a nucleo- 
albumin; Scholl, that it is a peptone (choleratoxopepton). Pfeiffer is of the opinion 
that it is an element of the cell-body. According to Metschnikoff and others, it is 
secreted by the cells. According to Oppenheimer, it is probably an endotoxin which 
is labile and easily passes over to a secondary poisonous mixture rich in toxoids. 
Further, the spirilla contain a protein which is not specific and which excites in- 
flammation. 
The virulence of cholera-cultures differs greatly, according to the place of origin 
and the age. Virulence decreases with age. Guinea-pigs, which are susceptible 
to intraperitoneal inoculations of cholera, may be protected against infection by 
the intraperitoneal injection of attenuated cultures; but no absolute immunity can 
be produced in this way. The blood-serum of human individuals that have re- 
covered from an attack of cholera shows protective properties for guinea-pigs for 
several weeks after the attack. 
The nitroso-indol reaction in cultures of the cholera-spirilla is due to the fact 
that the cholera-spirillum in pepton solutions not only forms indol but also nitrites. 
The addition of hydrochloric or sulphuric acid sets free nitrous acid which forms 
a red color with indoh With the Spirillum of Finkler, the Spirillum of Metsch- 
nikoff, and the Spirillum of Deneke, which also produce indol, the red color of the 
cultures occurs only when potassium nitrite is added with sulphuric acid, or when 
nitrous acid alone is added. 
Spirilla Resembling the Cholera-Spirillum. 
(1) The Spirillum of Finkier and Prior, was found by these observers in the 
dejecta of persons suffering from cholera-nostras, after the discharges had stood 
for some time in a vessel. The spirilla are similar to the cholera-spirilla, only some- 
what longer and thicker. In plate-cultures they are distinguished from the latter 
only in the fact that the small colonies are not distinctly granular and have a sharp 
contour. Gelatin is quickly liquefied; and in stab-cultures after twenty-four hours 
a sac-like tube filled with cloudy fluid is formed, which soon reaches the walls of 
the tube. 
On potatoes (Fliigge), even at room temperatures, they form within forty-eight 
hours a grayish-yellow, slimy coating, sharply marked off from the substance of 
the potato by a whitish border; while cholera-spirilla do not grow at room-temper- 
ature, and at higher temperatures form brown coatings. 
Further, they cause foul-smelling decomposition; and are rather resistant to 
drying. When introduced into the intestine of guinea-pigs by the method given 
above, they produce effects similar to those caused by cholera-spirilla, but less 
intense. 
It is doubtful whether the Spirillum of Finkler and Prior possesses a patho- 
genic significance for cholera-nostras, since the dejecta from which these investigators 
obtained their cultures were not fresh; and other authors have failed to find the 
spirilla in corresponding cases (Kartulis, “ Zur Aetiologie der Cholera nostras,” 
Zeitschr.. f. Hyg., vi., 1889). Knisl (Miinchener drstliches Intelligenzblatt, 1885), 
on the other hand, found them in the csecal contents of a suicide. 
(2) Spirillum tyrogenum, found in cheese by Deneke (Deut. med. Wochenschr., 
1885), is also much like the cholera-spirillum, but somewhat smaller, and the long 
spiral threads are more closely wound. Cultures on gelatin-plates form sharply 
contoured discs that by low magnification appear dark, and liquefy the gelatin more 
rapidly than the spirillum of Koch. In stab-cultures they behave like the Finkler- 
Prior spirillum, but do not grow on potato. 
(3) Vibrio of Metschnikoff (Gamaleia, “Vibrio Metschnikovi et ses rapports 
avec le microbe du cholera asiatique,” Annal. d. I’Inst. Past., ii., 1888; iii., 1889; 
Pfeiffer, “Ueber den Vibrio Metschnikovi und sein Verhiiltniss zur Cholera asiat- 
ica,” Zeitschr. f. Hyg., 1889) is a fission-fungus isolated by Gamaleia in an epidemic 
disease occurring in chickens in Odessa, characterized by diarrhea and enteritis. 
When cultivated it shows a great resemblance to the cholera-spirillum of Koch. 
The spirillum is most easily obtained pure by inoculating pigeons with the blood 
of diseased chickens. The pigeons die in from twelve to twenty hours and show 
the spirilla in the blood and in the intestinal tract. 
Ziegler has transferred Relapsing Fever to the protozoan diseases, following 
Schaudinns view that the spirochetes are protozoa. If this opinion be correct, 
Syphilis should likewise be classed, with the protqzoan infections. As mentioned 
below, the correctness of such a view is doubted by other writers (Novy), who 
believe that the spirochetes are bacterial and are to be classed with the spirilla. CHAPTER XI. 
The Yeasts and Moulds, and the Diseases Caused by Them. 
§ 180. The yeasts (Blastomycetes) and the moulds (Hyphomy- 
cetes) belong, as do the schizomycetes, to the non-chlorophyllaceous 
thallophytes. With the schizomycetes they have no phylogenetic relation- 
ship ; on the other hand, they are closely related to one another, and both 
belong to the branching fungi or the eumycetes. 
ihe moulds and yeasts, like the schizomycetes, derive their nourish- 
ment from organic substances containing carbon. The majority find 
their food in dead organic substances, and belong therefore to the sapro- 
phytes; some are able to obtain nourishment from living tissues, and are 
to be classed, at least at times, with the parasites. In human beings both 
forms occur. 
Outside the organism the moulds are generally known as producers 
of the different mouldy films which so frequently develop on organic 
substances. They belong to different groups of fungi. 
The yeast-fungi are the cause of alcoholic fermenta- 
tion, and form the scum on the top of alcoholic beverages. 
§ 181. Yeasts occur in man in the form of naked or 
encapsulated, oval or round cells of varying size. They 
are found chiefly as harmless saprophytes, most fre- 
quently in the upper part of the intestinal canal — in 
the stomach —• where they are almost constantly present; 
when beverages in the process of alcoholic fermentation 
are taken they occur in large numbers, and may multiply. 
In the bladder they may likewise multiply if the urine contains sugar; 
and may cause fermentation of the urine with evolution of carbonic- 
acid gas. 
As parasites no importance was attached to them until recently, but 
the investigations of Busse, Buschke, Sanfelice, Curtis, and others have 
established the fact that there are species of Saccharomycetes of patho- 
genic importance. According to these observations the pathogenic yeasts 
multiply in different tissues, in the skin, periosteum, lungs, and glandular 
organs, and excite purulent inflammations, or proliferations of granu- 
lation tissue, which run a course similar to that of infection with actino- 
mycosis or tuberculosis. In inflammatory foci the yeast cells are for the 
chief part provided with a capsule. 
In solutions containing sugar the blastomycetes form oval cells (Fig. 
466). Reproduction takes place through budding and constriction; on 
any portion of the parent cell there may develop on excrescence, which is 
constricted off after it reaches the size of the mother cell. The cells may 
grow out into threads or hyphae, but in these threads no subsequent seg- 
mentation occurs; jointed threads arise through budding. A dilute 
culture-medium favors the formation of threads. 
Mould-fungi are found in man in the form of simple or branched, 
unjointed or jointed threads of varying thickness; and as oblong or 
Fig. 466—Saccha- 
r o m y c e s ellipsoi- 
deus. x 400. 516 
THE PATHOGENIC YEASTS AND MOULDS. 
spherical cells. The threads are designated hyphae (Figs. 467, 468), 
and the mass which they form as mycelium; the spherical or long oval or 
short cylindrical cells, which are frequently arranged in the form of a 
rosary, as spores, or better as conidia-spores (Figs. 467, 468). Only 
rarely has there been observed in the body fructification on special organs. 
The moulds are partly saprophytes and partly parasites; and are 
found almost exclusively in regions accessible from without, as the skin, 
intestinal canal, respiratory tract, external ear, vagina, etc. Only excep- 
tionally do they reach the internal organs, for example, the brain. On 
the whole, the living tissues of the human organism do not afford a suit- 
able nutrient medium for the mould-fungi, and the life-activities of the 
tissue-cells do not permit their development and multiplication. The need 
for oxygen prevents the growth of moulds in many tissues; and for 
many the temperature of the body is too high. 
Moulds growing as saprophytes occur in man most frequently in 
the alimentary canal, particularly in the mouth, pharynx, and oesophagus. 
They develop in these regions par- 
ticularly when the ingesta or 
desquamated cells lie undisturbed 
in one position for a long time, and 
when the function of the organ con- 
cerned is lowered. They are recog- 
nized through the formation of 
hyphse and conidia. 
Fig. 467.—Fresh favus-mass con- 
sisting of hypce, conidia, and epi- 
thelial cells. (After Neumann.) 
Fig. 468.—'From a growth of 
thrush on the tongue of a man 
dying of typhoid fever. x 275. 
In the external auditory canal moulds may grow in masses which fill 
the passage and consist of cerumen, or of inflammatory exudates and 
desquamated cells, and of substances introduced from without. 
In the lungs moulds are occasionally found on the necrotic walls of 
cavities, particularly those due to tuberculosis, in necrotic and gangrenous 
infarcts, etc. In the air-passages they are observed most frequently in 
bronchiectases. 
In the alimentary tract, and in the ear and lungs, the moulds form a 
whitish deposit on or in the tissues. In the event of fructification on 
special fruit-bearers they take on a brown, gray, or even black appear- 
ance. In the intestinal canal the food and drink may give them various 
colors. 
At first the moulds grow in dead material, but may penetrate thence 
into living tissue; cases have been observed in which they entered the 
circulation and were carried to distant organs. THRUSH. 
517 
The fungous growth called thrush, which appears chiefly on the 
mucous membrane of the mouth, pharynx, and oesophagus, more rarely on 
that of the stomach, intestine, and vagina, and on the nipples of nursing 
women, cannot be regarded as a pure saprophytic, but as a parasitic 
growth, which penetrates living epithelium (Fig. 469, c), and even the 
underlying connective tissue. It is true that thrush occurs chiefly in 
infants and in debilitated invalids who are no longer able to cleanse the 
mouth, throat, and oesophagus, so that some local predisposition appears to 
be necessary for its development; thus it is probable that primary coloni- 
zation of the fungus takes place in dead material. Nevertheless, penetra- 
tion into living tissue occurs — first, into the epithelium (c, d), but often 
into connective tissue (a, /), and blood-vessels, and from these portals of 
invasion metastases may develop in the internal organs. Thus, Zenker 
observed hyphse and conidia in an abscess of the brain; and Paltauf 
Fig. 469.—Section through a thrush-covered oesophagus of a small child (alcohol, carmine, 
Gram’s). a, Connective tissue; b, normal epithelium; c, swollen and desquamated epithelium 
infiltrated with fungus-threads; d, epithelium infiltrated with cells; e. cocci and bacilli; f, cellular 
focus in the connective tissue, x 95. 
reported a case in which a mould-fungus was conveyed from an intestinal 
ulcer to the brain and lung. Schmorl and Heubner have described thrush- 
metastases in the kidneys. 
Moreover, growths of moulds in the lungs are not always confined 
to dead material or to the cavity of the bronchus, but it occasionally 
happens that they penetrate the living respiratory parenchyma, forming 
small white or yellowish, nodular masses, in which the lung tissue is 
necrotic, while in the neighborhood there is inflammatory infiltration. In 
the injured cornea they may likewise penetrate and cause necrosis and 
inflammation. 
Local colonizations of moulds cause more or less marked irritation of 
the surrounding tissues, and give rise to degeneration (Fig. 469, c) and 
inflammation. Such changes may be observed in mycosis of the lung, and 
of the intestine (c, d, f) and ear. Invading the lungs they form hyphse 
which resemble the granules of actinomycosis, and are surrounded by 
collections of cells. Their action, however, is limited; they produce no 
substances which are injurious to the organism as a whole, or which 
cause symptoms of poisoning. The finding of moulds in abscesses of the 
subcutaneous tissues and internal organs is probably due to the fact that, 518 
THE PATHOGENIC YEASTS AND MOULDS. 
with the bacteria of suppuration, moulds get into the tissues, as well as 
into the circulation. Generalization of mould-fungi does not occur in 
these cases; the development of the mould is confined to the place of 
metastasis. 
The moulds which are saprophytic, or, to a limited extent, parasitic 
in man, belong to the Mucor, 
Aspergillus, and Eurotium 
genera. From the ear various 
species have been obtained: 
Aspergillus famigatus, As- 
pergillus flavus or flavescens, 
Aspergillus niger or nigri- 
cans, Aspergillus nidulans, 
Eurotium malignum, Mucor 
corymbifer, and Trichothe- 
cium roseum; so far as 
known, these are the same 
species which occasionally 
occur in the respiratory 
tract. 
In the mucors there ap- 
pear special fruit-bearers 
(Fig. 470, c), which accord- 
ing to the species are single 
or branched, and on the ends 
of which are knob-like swell- 
ings from which the sporangia (d)—that is, spherical vesicles filled with 
conidia-spores — grow. 
Mucor corymbifer, for example, forms branched fruit-bearers (Fig. 
470, c). The sporangia (d) on the ends possess a smooth membrane and 
enclose at the time of ripening yellowish conidia-spores. 
The aspergilli form conidia- 
bearers, which swell spherically 
above, and then produce numer- 
ous sterigmata — that is, cone- 
like outgrowths, radially arranged, 
thickly crowded, and sprouting 
from the upper half of the sphere. 
From each sterigma a chain of 
conidia is later constricted off 
(Fig. 471, a, b). 
The botanical position of the 
fungus of thrush is still unsettled. 
Formerly it was called Oidium 
albicans, and classed with the 
genus Oidium, which occurs in 
different species in the form of 
filmy coatings on organic sub- 
stances. When cultivated from conidia is produces hyphse which be- 
come joined and develop conidia through transverse division of the 
threads, but form no peculiar fruit-bearers. 
According to Rees, Grawitz, Kehrer, the thrush-fungus grows by 
budding and by the production of mycelia and conidia, which in turn 
Fig. 470.-—Mucor corymbifer in fructification (culture 
upon glass-slide). a, Aerial hyph.e; b, mycelia lying 
within the nutrient gelatin; c, branching fruit-bearers; 
d, sporangia, x 100. 
Fig. 471.—Hyphae with conidia-bearers_ of Asper- 
gillus fumigatus. a, Fruit-head in optical cross- 
section; b, fruit-head seen from above. X 275. EFFECTS OF PATHOGENIC YEASTS. 
519 
produce at their ends, by a process of constriction, new conidia, in a 
manner similar to that which takes place in the forms of mycoderma 
belonging to the yeast-fungi. Consequently this fungus should be desig- 
nated Mycoderma albicans. Linossier and Roux are, however, of the 
opinion that the thrush-fungus does not belong to,the saccharomycetes. 
Cao, who has investigated numerous varieties of oidium, regards the 
oidia as a well-defined class of fungi standing between the blastomycetes 
and the hyphomycetes, which they approach through the production of 
mycelia. 
According, to Plaut the thrush-fungus is identical with a mould, 
Monika Candida, which occurs frequently in nature. Kehrer suspects 
that it is one of the higher moulds that has become degenerate through 
parasitism. 
According to Nenmayer all varieties of yeasts are resistant to the digestive 
juices, and may pass through the human intestinal tract without being killed. 
They exert an influence on the intestinal canal only when fermentable substances 
are introduced, whereby at the high temperature of the body abnormal products of 
fermentation are produced having an irritating action on the intestinal tract. 
Busse found (1894) great numbers of yeast-cells developing in the diseased 
areas present in a woman, thirty-one years of age, who died from multiple inflam- 
mations of the bones, skin, lungs, kidneys, and spleen, partly tumor-like and partly 
abscess-forming. According to his findings it may be regarded as certain that the 
yeast was the cause of the disease. The yeast could be easily cultivated on suit- 
able media. Mice were particularly susceptible to inoculation, dying in from four 
to eighty-three days after the injection. At death the yeast-cells were found to 
have increased both at the point of inoculation, and in the internal organs. Pro- 
liferation of tissue occurred only after long duration of the infection. 
Buschke found yeasts in multiple ulcers of head and neck, arising from acne- 
like lesions. Gilchrist and Stokes found yeasts in a lupus-like affection of the skin. 
Lozuenbach and Oppenheim found a yeast in the skin of the nose showing nodules 
and scar-tissue. 
In 1896 Gilchrist described a progressive affection of the skin characterized by 
epithelial hyperplasia, miliary abscesses, and infiltration of the cutis. In the 
abscesses doubly-contoured, refractive, round and oval bodies were found. They 
varied in size from 10-20 and presented buds of varying size. To this organism 
the name of Blastomyces dermatitidis was given, and the skin condition was called 
blastomycetic dermatitis. Many cases of this kind have since been reported, the 
majority of them by Chicago observers. In some of the cases a fatal generalized 
infection has been seen. The organisms cultivated from the cases fall into three 
groups: 1, blastomycetoid; 2, oidium-like; and 3. a hyphomycetoid group. Accord- 
ing to Ricketts they may be included in a common genus, Oidium, and he has pro- 
posed the term oidiomycosis for the various lesions produced by these organisms. 
At the present time the exact botanical classification of the latter is not possible. 
Under the designation of coccidioidal granuloma there has been described a 
condition closely resembling oidiomycosis, but apparently differing from it in certain 
clinical characteristics and in the nature of the organisms found in the lesions. 
It runs a more severe and progressive course than the latter condition, and gener- 
alized infection is the rule. The organism multiplies by endogenous sporulation 
instead of by budding. Ophuls would class it with the oidia under the name of 
Oidium coccidioides. The lesions produced by it resemble tubercles closely in the 
majority of cases, and clinically the disease has been mistaken for tuberculosis. 
Of 35 cases collated by Hektoen and by Brown up to 1907, 34 originated in Cali- 
fornia, many of them in the San Joaquin Valley, chiefly in men engaged in railway 
construction. The disease occurs (a) as a primary pulmonary affection with or 
without cutaneous lesions, (b) as a primary lesion of the skin, and (c) as a gener- 
alized process following either primary cutaneous or pulmonary infection. Clini- 
cally, the cutaneous lesions may resemble those of glanders. Moreover, injection 
of the pus into male guinea-pigs may be followed bv changes in the scrotum and 
testicles resembling those produced by glanders bacilli. 520 
THE PATHOGENIC YEASTS AND MOULDS. 
Sanfelice experimented with yeasts from fruit-juices, and found among these 
one pathogenic for guinea-pigs (Saccharomyces neof ormans) and one pathogenic 
for chickens and dogs (Saccharomyces lithogenes). Curtis found, in multiple pro- 
liferations of the skin resembling myxosarcoma, yeast-cells which were pathogenic 
for mice, rats, and dogs. Cohn, who experimented with the yeast described by 
Klein, found that its inoculation into the peritoneal cavity of mice caused death 
through the formation of great yeast-tumors. The intravenous injection of larger 
animals led to severe disturbances of brain and spinal cord, associated with in- 
flammation of the mucous membranes, particularly of the conjunctiva. 
Sanfelice, Corselli, Frisco, Rancali, Binaghi, Leopold, and others believe that 
blastomycetes may be the cause of true tumors, sarcoma and carcinoma; but true 
tumors have never yet been produced experimentally by inoculations of yeast-cells 
or by injections of the same into the blood. Only suppurations and inflammatory 
tissue-proliferations have been produced by such experiments; and the finding of 
yeast-like structures in true tumors, even if part of these were true yeast-cells, 
does not permit the conclusion that tumors are caused by yeasts. 
According to investigations by Koch, Loffler, Lichtheim, Hiickel, and Lindt, 
the conidia of Aspergillus fumigatus, A. flavesccns, A. nidulans, Eurotium malig- 
num, Mucor rhizopodiformis, M. corymbifer, M. pusillus, and M. ramosus, grow 
at the body-temperature, and, when introduced into the blood-current of animals, 
grow into the tissues and form hyphse, although there is no new-formation of 
conidia, and consequently no progressive infection of the animal extending beyond 
the area within which the spores have been introduced. Conidia of Mucor rhizo- 
podiformis and M. corymbifer grow, when introduced into the blood-stream 
of rabbits, chiefly in the kidneys and the lympathic apparatus of the intestines, 
where they cause haemorrhagic inflammation. According to Cad, there are different 
species of oidia which, when injected into rabbits, cause inflammations, abscesses, 
or proliferations of granulation tissue; many produce also a toxic action on the 
organism. 
According to Ceni, Aspergillus fumigatus which grows at summer temperature 
produces poisons in its conidia. One of these can be extracted with alcohol and 
causes tetanic convulsions in experimental animals. It is possible that the asper- 
gillus growing on corn plays a role in the etiology of pellagra. 
Aspergillus mycoses of the respiratory tract are not rare in animals, espe- 
cially in birds, and the proliferating mycelia cause tissue-necrosis and inflammation. 
According to Chantemesse, Aspergillus fumigatus causes in pigeons diseased condi- 
tions of the mouth, lungs, liver, and kidney, that of the first two organs resembling 
diphtheria, that of the latter two closely resembling tuberculosis. It may, there- 
fore, be designated pseudotuberculosis aspergillina. According to Potain, the in- 
fection may be transmitted to man and give rise to ulcerative diseases of the lung. 
Eurotium and Aspergillus, according to Siebenmann, are two different families, 
having, however, a close resemblance to each other, in that the mycelia and conidia 
are similarly formed. The essential differences between the two lie in the fact that 
Eurotium produces perithecia in the form of shining, light-yellow or sulphur-yellow, 
translucent bodies the size of a grain of sand, delicate and easily crushed, and 
which ultimately develop into spores capable of germination; while the true Asper- 
gillus forms hard, woody sclerotia usually embedded in a thick, white matted mass 
of mycelia. The development of these takes place in two periods. The second 
part of the development occurs only when the sclerotium finds lodgment upon a 
moist substratum. 
Aspergillus, flavus of Brcfeld (Eurotium Aspergillus flavus of de Bary) forms 
golden yellow, green, and brown growths; round, yellow, olive-green, or brown 
fruit-heads; round, rarely oval, sulphur yellow to brown conidia with minute warts 
on the surface; diameter 5-7 M. Aspergillus fumigatus of Fresen (Aspergillus 
nigrescens of Robin) forms green, bluish, or gray growths; the fruit-heads are 
long, in shape resembling an inverted cone; conidia, round, rarely oval, smooth, 
mostly clear and colorless; diameter 2.5-3 M. Aspergillus niger of Van Tieghen 
(Eurotium Aspergillus niger of de Bary) forms dark chocolate-brown growths; 
conidia are round, brownish-black, or grayish-brown when ripe; surface smooth or 
warty; diameter 3.6-5 M. 
Aspergillus can develop upon the injured cornea and give rise to purulent in- 
flammation. Leber (Graefe’s Arch., xxv.) cultivated it upon the cornea and in the 
anterior chamber of the eye of the rabbit. Finally, Aspergillus also appears in the 
pelves of the kidneys. Babes (Biol. Centralbl., ii.) found the conidia and hyphse 
of a mould in ulcers of the skin which were covered by scabs, and gave to it the 
name of Oidium subtile cutis. FAVUS, 
521 
Literature. 
(Pathogenic Blastomycetes.) 
Brown: Coccidioidal Granuloma. Jour. Am. Med. Assoc., 1907. 
Evans: Blastomycosis of Skin from Accidental Inoculation. Jour, of Amer. 
Med. Assn., 1903. 
Foulerton: Pathogenic Action of Blastomycetes. Jour, of Path., vi., 1899. 
Frothingham: Tumor-like Lesion in the Lung of a Horse Caused by a Blas- 
tomyces (Torula). Jour, of Med. Res., 1902. 
Gilchrist and Stokes: Pseudolupus Caused by a Blastomyces. Jour, of Exp. 
Med., iii., 1898. 
Hyde: Blastomycetic Dermatitis. Jour, of Amer. Med. Assn., 1902. 
Nichols: The Relation of Blastomycetes to Cancer. Jour, of Med. Res., 1902. 
Ophiils: Coccidioidal Granuloma. Jour, of Amer. Med. Assn., 1905. 
Ormsby and Miller: Systemic Blastomycosis. Jour. Cut. Dis., March, 1903. 
Ricketts: Oidiomycosis (Blastomycosis) of the Skin and its Fungi. Jour, of 
Med Res., 1901. 
Weis: Four Pathogenic Torulae (Blastomycetes). Jour, of Med. Res., 1902. 
Wolbach: The Life Cycle of the Organism of “ Dermatitis Coccidioides.” Jour, 
of Med. Res., 1904. 
(The Moulds and the Mould-Mycoses.) 
Boyce: Remarks upon a Case of Aspergillus Pneumonomycosis. Jour, of Path., 
i„ 1892. 
Hochheim: Pneumonomykosis aspergillina. V. A., 169 Bd., 1902. 
Pearson: Pneumonomycosis due to the Aspergillus fumigatus. Proc. of the 
Path. Soc. of Philadelphia, 1900. 
Rothwell: Experimental Aspergillus. Jour, of Path., vii., 1900. 
Schenck: Subcutaneous Abscess Caused by a Fungus. J. Hopkins Hosp. Bull., 
1898. 
§ 182. Thread-fungi are to be regarded as the exciting cause of 
certain affections of the skin, as favus, herpes tonsurans, pityriasis versi- 
color, erythrasma. In all of these diseases the epithelial parts of the skin 
contain colonies of hyphse and conidia. 
The fungus of favus (Fig. 467) is usually called Achorion Schonleini 
(discovered by Schonlein in 1839). 
Favus (tinea favosa, scald-head) affects the hairy portions of the 
head, more rarely other regions, for example, the substance of the nails. 
It is characterized by the formation of discs (favus scutula), varying in 
size from a lentil to that of a five-cent piece, of surphur-yellow color, and 
indented or pierced by a hair. In an abortive course it may merely form 
scales similar to those of herpes. 
According to Kaposi, the favus scutulum originates as a small, puncti- 
form, yellow focus lying under the epidermis and penetrated by a hair. 
This grows in a few weeks to the size of a lentil and then forms a 
sulphur-yellow, indented disc showing through the upper layers of the 
skin. The scutulum consists of hyphse and conidia spores, and lies in a 
cup-shaped depression of the skin, beneath the horny layer, which is 
drawn away above it. If the mass be removed during life, the cavity 
shows a red moist surface. The favus itself forms a white, crumbling 
mass which is easily disintegrated in water. 
If the scutula are not removed, they join to form larger masses. 
When the epidermis is desquamated the favus-mass becomes exposed and 
dries into a yellowish-white, mortar-like material. The hairs appear 522 
THE PATHOGENIC YEASTS AND MOULDS. 
lustreless, as if covered with dust, and are easily pulled out, since the 
mycelia and conidia of the fungus penetrate into the hair-shaft and hair- 
bulb, as well as into the sheath of the hair-root. 
Through the growth of the fungus-masses the hairs may not only be 
shed, but the papillae become atrophic. At the same time there is pro- 
duced in the neighborhood of the hair-follicle more or less intense inflam- 
mation which may take on an eczematous character. 
The development of achorion in the nails (onychomycosis favosa) 
gives rise to sulphur-yellow deposits or uniform thickenings of the 
parenchyma of the nails with simultaneous loosening and cheesy 
disintegration. 
Trichophyton tonsurans, the fungus of herpes tonsurans (“ barber's 
itch” “ringworm”), consists of long narrow threads, branching but 
little, and with few conidia. It forms no scutulous masses, but penetrates 
easily into the hair-shaft, and 
makes the hairs brittle. It shows 
certain differences of growth, ac- 
cording to whether the herpes de- 
velops on hairy surfaces or on 
areas devoid of hairs. 
Herpes or Trichophytosis ton- 
surans capillitii forms bare discs 
varying in size from a five-cent 
tpiece to that of a dollar. Those 
spots in which the hairs are broken 
off short resemble places in which 
the hair has been badly shaven. 
The surface is smooth or covered 
with scales, and somewhat red- 
dened at the border of the disc. If 
the fungus-threads penetrate the 
hair-follicles, pustules and scabs 
are formed. Such discs may ap- 
pear in many places, and may in- 
crease in size until healing finally 
takes place. 
On places devoid of hairs the 
herpes forms vesicles (Herpes ton- 
surans vesiculosus), and red scaly spots, discs, and circles (Herpes ton- 
surans squamosus). At times red spots appear in numerous places; these 
quickly spread, and as rapidly heal. The fungus is found between the 
uppermost layers of the epidermis, beneath the stratum corneum 
(Kaposi). 
If trichophyton develops in the nail, the nail becomes cloudy, scales 
off, and is easily broken — a condition designated onychomycosis tricho- 
phytina. 
Sycosis parasitaria arises through development of the fungus accom- 
panied by severe inflammation of the hairy parts of the skin, leading to 
infiltration and suppuration — that is, to the formation of pustules, 
abscesses, and papillary proliferations. According to Kaposi and others 
eczema marginatum is also caused by trichophyton tonsurans. The 
condition occurs in those regions where two surfaces of skin come into 
Fig. 472.—Culture of Trichophyton tonsurans, 
a. Branching threads with long joints which have 
delicate walls; b, threads with thick-walled, short 
segments, some of them being spherical, x 270. THREAD-FUNGI. 
523 
contact with each other and are macerated by sweat; and is characterized 
by the formation of vesicles, pustules, and scabs, which are situated at the 
periphery of a pigmented surface. 
Microsporon furfur, the fungus of pityriasis or mycosis versicolor 
or dermatomycosis furfuracea, likewise occurs in the form of hyphse 
and conidia, which are somewhat smaller than those of other skin-fungi. 
The pathological changes produced by this fungus are characterized by 
the formation of pale yellow or yellowish-brown to dark-brown and 
brownish-red spots, varying in size from a lentil to that of the hand, 
sometimes smooth and shining, at other times dull and exfoliating, and of 
irregular shape. They may be spread uniformly over large areas of 
skin; and are found chiefly on the trunk, neck, and flexor surfaces of the 
extremities, but never on the hands, feet, or face. 
Microsporon minutissium is the name given to a thread-fungus, 
which is found in the skin affection known as erythrasma. The disease 
is characterized by the formation, on the inner side of the thigh, of brown 
or reddish-brown patches, which are only slightly scaly, and may be as 
large as the palm of the hand. The fungus is found in the epidermis, 
and is smaller than that of pityriasis. 
The thread-fungi occurring in the diseased areas of the skin may be 
cultivated on proper media (agar-agar, agar-glycerin, gelatin, potatoes, 
blood-serum, etc.), and on such the conidia develop into single and 
branching threads, which become jointed (Fig. 472, a), and form chains of 
short cells (&). Club-like formations which frequently appear on the 
ends of the threads in cultures, are regarded by Quincke and Elsenberg 
as imperfect sporangia. The botanical position of these fungi is not yet 
determined; and nothing is known with certainty concerning their distri- 
bution outside the human and animal body. 
According to Quincke, three forms of fungi occur in favus-masses, two of these 
being varieties of one species of fungus. Elsenberg found only two, which he 
regards as varieties of the same species. Pick, Plant, and Biro believe in the 
eitological unity of favus. 
Saboitraud advances the view that the fungi causing trichophytosis represent 
different species, all of which belong to the genus Botrytis. Krosing distinguishes 
three groups of trichophyton-fungi according to the different appearances of the 
cultures on potato, and emphasizes, moreover, the differences in their organs of 
generation and fructification. Roscnbach, who has studied the moulds occurring in 
deep suppurating inflammations of the skin, differentiates several trichophyton-fungi 
as the cause of these affections. 
According to Spietschka, the Microsporon furfur may be cultivated from the 
scales of the skin, and in cultures can be well differentiated from other pathogenic 
thread-fungi. Through inoculation of the fungus typical mycosis may be produced 
in man. 
From the great number of recent investigations by various writers it is im- 
possible to deduce anything definite concerning the number of kinds of favus- and 
trichophyton-fungi. It is, however, evident from these investigations that the 
nature of the nutrient medium influences the character of the growth (Saboaraud, 
Waelsch), and the difference in findings is to be referred in great measure to dif- 
ferences in the nutrient media on which the moulds were grown. 
Inoculations with fungi grown in cultures into the skin of human beings, rab- 
bits, mice, etc., which were made by Grawitz, Boer, Miinnich, and others, gave 
partly negative, partly positive results. According to Plaut, the inoculations never 
give positive results when spore-formation has taken place in the cultures. 
Von Hebra has described (Wiener med, Blatter, 1881: “Die krankh. Verand. 
d. Haut,” Braunschweig, 1881) as dermatomycosis diffusa flexorum, a peculiar 
itching dermatosis, which occurs on the elbow and bend of the knee and is thought 
to be caused by fungi, which are like those of pityriasis versicolor. 524 
THE PATHOGENIC YEASTS AND MOULDS. 
According to the investigations by Wehmer, the cause of the skin eruption 
known as tokelau which occurs in various South Sea Islands (Fiji, Samoa, and 
Solomon) and which is characterized by the formation of scaly rings, is an 
Aspergillus. 
Favus and herpes tonsurans occur in domestic animals, as well as in mice and 
rats (cf. Friedeberger and Frohner, “Lehr. d. spec. Pathologie der Hausthiere ”). 
Waelsch inoculated human individuals with favus fungi, which he had cultivated 
from mice affected with favus, and obtained typical favus scutularis. 
Intravenous injections of favus-fungi into rabbits (Bukovsky) produced in the 
lungs of these animals a form of pseudotuberculosis; and cellular nodules are found 
in which fungus threads have developed in a manner suggesting the lesions of 
actinomycosis. After a time the fungi die. 
In Invertebrate animals there not infrequently occur diseases produced by 
mycelium-fungi. Thus Botrytis Bassiani causes the so-called muscardine in silk- 
worms; Cordyceps militaris destroys the injurious pine-spider Gastropachia pini; 
Tarichium megaspermum, a black-colored fungus, kills the destructive earth-cater- 
pillar Agrotis segetum. Fungi belonging to the genus Empusa attack the caterpil- 
lars of the cabbage-butterfly (Empusa radicans), and the house-fly (Empusa mus- 
coe), their mycelia growing through the caterpillar and finally killing it. Achyla 
prolifera, according to Harz (Jahresber. d. Munchener Thierarzneischule, 1882-83), 
grows through the musculature of crayfish, and is the cause of the crayfish pest. CHAPTER XII. 
The Animal Parasites and the Diseases Produced by Them. 
I. Protozoa. 
§ 183. Of the Protozoa occurring as parasites in man, only a small 
number was known up to a few years ago; and even the known forms 
possessed but slight significance, since there could be ascribed to them 
no marked influence on the tissues. Through the investigations of the 
last few years, however, different forms have 
been recognized as the cause of morbid proc- 
esses; and it is quite possible that there are 
still other protozoa capable of exciting patho- 
logical changes in the human body. The 
forms already recognized are representatives 
of all four classes of protozoa. 
Of the Rhizopoda there occur in the in- 
testine three amoebae, known as Amoeba coli 
vulgaris, Amoeba coli mitis, and Amceba 
dysenterice. The Amoeba dysenterise is dis- 
tinguishable from the other two, while the Amoeba coli vulgaris and the 
Amoeba coli mitis resemble each other closely, and may be identical. 
The Amoeba coli vulgaris is a harmless parasite which is not infre- 
quently present in the intestine (Roos, Kruse. Pasquale). The Amoeba 
coli mitis was observed by Roos and Quincke in cases of chronic enteritis 
in patients who had always 
lived in North Germany. 
The Amoeba coli mitis con- 
sists, according to Roos, of a 
protoplasmic cell-body, from 
28-30 yu. in diameter, (in the 
spherical condition). It ex- 
hibits slow movements, and 
frequently encloses foreign 
bodies, for example, bacteria 
and food remains (Fig. 473, 
a). Besides the motile form, 
there occur, according to Roos, 
encysted spherical forms which 
are surrounded by a double-contoured membrane, and enclose clear, round 
vesicles in their interior (b). When fed to animals (cats) no pathogenic 
properties are disclosed. 
The Amceba dysenteriae (identical with the Amoeba coli described by 
Loesch) has a diameter, according to Roos, of from 15-25 /x, but accord- 
ing to Kruse and Pasquale, from 10-50 /a. In the cell-body there may 
be recognized a homogeneous ectoplasm and a granular entoplasm, the 
arrangement of which varies according to the form of the animal (Fig. 
Fig. 473.—Amoeba colt mitts. 
(After Roos.) a, Free motile amoe- 
bae; b, encysted amoebae, x 590. 
Fig. 474.—Amoeba dysertteriae sive Amoeba coli 
felts. (After Roos.) a, Amoebae without inclusions; 
b, amoebae containing blood; c, amoebae with large 
vacuoles in their protoplasm; d, young forms; e, en- 
cysted forms, x 665. 526 
THE ANIMAL PARASITES. 
474, a). By staining, a nucleus becomes visible in the cell. The cells are 
capable of active movement, and thereby assume varied shapes (d). 
They often contain foreign bodies, particularly red blood-cells or remains 
of such (b), or are studded with clear vacuoles (c). According to Roos, 
they may also become encysted (e). 
According to Koch, Kartulis, Kruse, and Pasquale, they are invariably 
present in the dysentery prevailing in Egypt, and are usually demonstrable 
in the dejecta. They have also been observed in dysentery in Russia, in 
America, in Germany, and in Austria. According to investigations by 
Kartulis, Councilman, Lafleur, Kovaes, Roos, Kruse, Pasquale, and 
others, it cannot be doubted that they are of significance in the origin of 
certain forms of dysentery. It is only questionable whether they alone, 
or with the aid of changes produced by bacteria, are able to bring about 
pathological alterations. In support of the latter theory is the fact that, 
when present in the tisues, they are always accompanied by bacteria. 
Amoebic dysentery is characterized by the occurrence of a haemor- 
rhagic catarrh, and by the formation of circumscribed ulcers with under- 
mined edges. The amoebae increase not only in the intestinal mucosa, 
but penetrate into the mucosa and submucosa, and form large colonies, in 
the region of which the tissue undergoes necrosis without the formation 
of any large amount of exudate. By rupture of the submucosal foci 
through the mucosa there are formed ulcers with undermined edges, 
which, gradually increasing in size, may attain large dimensions. 
If abscesses of the liver arise during the course of amoebic dysentery, 
these may contain the amoebae in addition to bacteria; it may be assumed 
that the former also take part in destruction of the liver tissue. 
The amoebee of dysentery are pathogenic for cats, and, when fed to 
them or when introduced into the rectum of the animal, cause a rapidly 
progressive, often fatal dysentery, which is similar in all respects to 
amoebic dysentery in man. The amoebae also penetrate into the mucosa 
and submucosa of these animals. 
Von Leyden and Schaudinn (“Leydenia gemmipara,” Sitzber. d. K. Akad. d. 
Wiss., Berlin, 1896), found, in the fluid of two cases of ascites occurring in malig- 
nant disease of the abdomen, an amoeba which consisted of colorless gelatinous 
cells, which put out ps'eudopodia, and showed a hyaline entoplasm and a granular 
ectoplasm. They were found chiefly in groups. 
Literature. 
(Amoeba?.) 
v. Baumgarten: Jahresbericht, xvii., Leipzig, 1903. 
Behla: Die Amoben, Berlin, 1898 (Lit.). 
Celli u. Fiocca: Beitr. z. Amobenforschung. Obi. f. Bakt., xvi., 1894. 
Councilman and Lafleur: Amoebic Dysentery. Johns Hopkins Hosp. Rep., ii., 
Baltimore, 1891. 
Gilchrist: Protozoan Infection. Johns Hopkins Hosp. Rep., 1896. 
Harris: Amoebic Dysentery. Am. Journ. of the Med. Sc.,. 1898. 
Kartulis: Zur Aetiologie der Leberalbscesse. Cbl. f. Bakt., ii., 1887; Pathogenese 
der Dysenterieamoben. Ib., ix., 1891; Pathogene Protozoen. Zeitschr. f. 
Hyg., xiii., 1893. 
Kruse u. Pasquale: Unters. iib. Dysenterie u. Leberabscess. Zeitschr. f. Hyg., 
xvi., 1894. 
Losch: Massenbafte Entwickelung von Amoben im Dickdarm. Virch. Arch., 
65 Bd„ 1875. 
Walker: The Parasitic Amoebse of the Intestinal Tract of Man and Other Ani- 
mals. Jour, of Med. Res., 1908. FLAGELLATES. 
527 
§ 184. A large number of species of the Flagellates (sub-class of the 
Mastigophora) occur in man, mammals, and birds, most frequently as 
parasites of the body-passages accessible from without, but occurring also 
in the blood. 
Cercomonas, a small flagellate (Fig. 475) with a flagellum on the 
anterior end and a long-drawn-out posterior extremity, was observed by 
Kannenberg and Streng in gangrenous foci of the lung. 
Fig. 475.—Cercomonas in- 
iestmalis. (After Davaine.) 
Fig. 476.—Trichomonas hom- 
inis, after Grassi (from Doflein). 
Fig. 477.—Trichomonas 
vaginalis (from Doflein). 
Trichomonas (Cercomonas intestinalis, Lambl; Trichomonas intes- 
tinalis, Leuckart; Monocercomonas hominis, Grassi) is a pear-shaped 
flagellate, 4-10 /x long, with three flagella on the anterior end (Fig. 476), 
Trichomonas hominis occurs in the small intestine of man. It 
appears to be a harmless inhabitant of alkaline intestinal contents. 
Trichomonas vaginalis is a flagellate similar to Trichomonas hominis 
(Fig. 477), and is often found in the human vagina. According to Miura, 
Marchand, and Dock, it may occur in the human urinary bladder. 
Lamblia intestinalis (Megastoma entericum, 
Grassi; Megastoma intestinalis, Blanchard; Cerco- 
monas intestinalis, Lambl; Hexamitus duodenalis, 
Davaine) is a turnip-shaped animal, having an in- 
dentation on the ventral surface (Fig. 478, A, B). 
It is about 10-16 n long, and is found especially in 
the upper part of the small intestine, and has been 
observed in man, mice, dogs, cats, sheep, and rab- 
bits. The parasite clings tightly to the epithelium 
of the intestine, but no pathological changes can be 
demonstrated in the underlying tissue. 
§ 185. Of the Flagellates that occur as blood- 
parasites of man the form known as Spirochaete 
obermeieri has been known for some time, but for- 
merly was classed with the spiral varieties of bac- 
teria (spirilla). The investigations of Schaudinn, 
however, make it probable that the spirochastes are 
to be added to the protozoa. 
Fig. 478.—Lamblia in- 
testinalis (after Grassi 
and Schewiakoff). A, 
View from ventral sur- 
face; B, view from the 
left side. 
Schaudinn’s conclusions are not universally accepted. According to Novy, 
Spirillum obermeieri belongs to the bacteria and not to the protozoa, and he 
believes that the majority, if not all, of the spirochsetes will be returned to their 
former place among the bacteria. Sp. duttoni and Sp. gallinarum have both been 
shown to be non-pi\.tozoal in nature. 528 
THE ANIMAL PARASITES. 
The Spirochaete obermeieri (Fig. 479) is found constantly in the 
blood of patients suffering from relapsing fever during the attacks of 
fever, and the multiplication of these organisms in the body is the cause 
of the disease. 
The spirochsete is 16—40 long, and possesses numerous spiral turns. 
In a fresh drop of blood it shows active motion. The subcutaneous inocu- 
lation into apes of blood containing the 
spirochsete is followed after several days by 
an attack of fever, and the spirochaete is found 
in the blood during the febrile stage. The life 
history of the Spirochaete obermeieri is not 
known, but it may be similar to that of the 
spirochaetes occurring in the blood of birds as 
studied by Schaudinn (see below). Accord- 
ing to autopsy-findings in man, the spleen is 
swollen and contains numerous yellow foci of 
degeneration, and anaemic infarcts. 
According to investigations by Nikiforoff, 
the histological examination of the spleen 
shows extensive cell-necrosis and cell-degeneration (Fig. 480, c), as 
well as deposits of fibrin in the veins of the pulp, and proliferative proc- 
esses in the pulp-cells. Further, numerous large pulp-cells (/) enclose 
red and white blood-cells or the remains of such. Finally, numerous 
spirilla are found, especially in regions which are not wholly necrosed 
but contain degenerate and necrotic cells, free (a), and enclosed in 
Fig. 479.—Spirochaete Ober- 
meieri from the blood of an indi- 
vidual ill with relapsing fever. 
After a dried preparation stained 
with methylene blue, x 473. 
Fig. 480.—Portion of tissue and isolated cells from a splenic follicle with partial necrosis, 
in relapsing fever. (After Nikiforoff.) (Potassium bichromate and sublimate, methylene-blue.) 
a, Free spirilla; b, lymphocytes with spirilla; c, non-nucleated lymphocytes; d, large, e, small 
mononuclear pulp-cells; f, phagocytes enclosing leucocytes and red blood cells and their remains; 
g, free red blod-cells. x about 600. 
leucocytes (b), partly well-preserved, and partly beginning to show 
disintegration. 
According to Karlinski and Schaudinn, the infection* is probably 
transmitted by bed-bugs. 
Spirochaetes have been observed also in birds, owls (Schaudinn), geese 
(Sacharoff, Gabri'tschewsky), and fowls (Marchaux, Salimbeni, 
Levaditi), and may cause epidemics in which great numbers of animals 
perish. SPIROCH/ETES. 
529 
The life-history of the Spirochaetes classed with the bacteria was not known 
until recently. Through the investigations of Laveran and Schaudinn it was first 
determined that in their life-cycle there occurs an alternation of generation and of 
host. Schaudinn carried out his studies on the spirochaetes found in the small owl 
(Athene noctua), which he named Spirochceta ziemanhi (called by Laveran the 
Hcemamccba siemanni). As a result of his investigations he believed that he had 
demonstrated the transmission of this spirochaete from the owl to the mosquito, 
Culex pipiens, in the intestine of which it passed certain stages of development, as 
described in the following paragraphs. 
Within the owl there develop male and female individuals, the microgameto- 
cytes and the macrogametes. Copulation takes place in the intestine of the mos- 
quito. From the fertilized macrogamete there develops an ookinete which pro- 
duces in the intestine of the mosquito an enormous number of trypanosome-like 
offspring. These become transformed into true spirochaetes, spread through the 
body of the mosquito, increase by logitudinal division, and wander into the oeso- 
phagus, whence, in the act of biting, they again pass inio the blood of the owl. 
After an asexual period of multiplication in the form of spirochaetes they again 
form gametes or sexual individuals in the blood of the owl. As a result of their 
distribution through the body of the mosquito the spirochaetes pass into the ovaries 
of the latter and are transmitted to the next generation. 
The fertilization in the intestine of ihe mosquito follows ripening of the 
macrogametes (female cells) and the formation of microgametes (spermatozoa) from 
the microgametocytes. The ookinete resulting from the fertilization of a macro- 
gamete is a worm-like body rolled up into a complicated skein. Through grouping 
of the protoplasmic masses around the individual nuclei there are formed small 
trypanosome-like individuals having a characteristic flagellum-apparatus. Further, 
there may be developed both male and female individuals. The female forms 
are larger than the indifferent forms, their plasma is dark, the nucleus and ble- 
pharoplast relatively small, and the margin of the undulating membrane is not 
continued to form a flagellum. The males are small and scarcely recognizable. 
Through continued division the indifferent spirochaetes in the intestine of the 
mosquito also become very small, so that single individuals can barely be made out. 
Within the blood of the owl the spirochaetes become parasites of the haemo- 
globin-containing erythroblasts, in that they attach themselves to these by their 
posterior extremities. This is seen particularly in the bone-marrow and also in the 
spleen. After a certain time they form in the blood macrogametes and micro- 
gametes, which, on gaining entrance into the mosquito, again form new generations 
in the manner described. The macrogametes can also produce new generations in 
the blood without fertilization (parthenogenesis) and thereby cause relapses. 
The above-given life-cycle of the spirochsetes according to Schaudinn falls 
to the ground in the light of Novy’s studies. The latter has shown that the 
Spirochcete ziemanni is not a spirochaete, but a trypanosome, and has no connection 
with the intracellular parasites of the owl’s blood. Further, Novy regards Sp. 
obermeieri as belonging to the bacteria, basing his view on his inability to demon- 
strate in the organism a nucleus, blepharoplast, undulating membrane, or 
flagellum of the protozoan type. On the other hand the spirilla of relapsing fever 
possess whips having all the characteristics of those of bacteria, divide transversely, 
multiply rapidly, resist changes in osmotic tension, show a greater resistance to heat 
than do the trypanosomes, excite the production of immune and germicidal bodies, 
and do not exhibit the aerotropism shown by trypanosomes. 
In relapsing fever we have most probably to deal with a group of closely re- 
lated organisms (Novy), which, while they may in one sense be regarded as dis- 
tinct species, are derived from one stem. Five distinct strains of spirilla causing 
relapsing fever have been discovered : Spir. obermeieri, Spir. novyi, Spir. kochi, Spir. 
duttoni, and Spir. carteri. These differ from each other in the duration and severity 
of the initial attack, the frequency and intensity of relapses, and in the mortality 
following injection of a uniform dose of 0.25 c.c of spirillar blood. The relapse 
is probably due to the survival of a few individuals that are more or less immune, 
so that a serum-fast strain develops. This in turn calls out a new anti-body. If 
this is less active or more unstable, or more readily eliminated, the relapses con- 
tinue 
If Schaudinn’s views on the protozoan nature of the organism found in syphilis 
(Spir. pallida, Treponema pallidum) are correct, that organism should then be 
classed with the protozoa. At the present time this question cannot be regarded as 
settled, but it is most probable that the organism is of bacterial nature and should 
be classed, along with the spirochsetes of relapsing fever, with the spiral forms of 
bacteria (spirilla). (See Syphilis.) 530 
THE ANIMAL PARASITES. 
Literature. 
(Spirochcctes.) 
Cantacuzina: Spirilloses des oies. Ann. dc l’lnst. Pasteur, 1899. 
Gabritschewsky: Zur Pathol, d. Spirochaeteninfection. Cbl. f. Bakt., xxvi., 
1899, u. xxvii., 1900. 
Honl: Febris recurrens. Ergebn. d. allg. Path., iii., 1897. 
Karlinski: Aetiol. des Gefliigeltyphus. Cbl. f. Bakt., Orig., xxxi., 1902. 
Levaditi: Spirillose des poules. Ann. de l'lnst. Pasteur, 1904. 
Marchoux et Salimbeni: Spirillose des poules. Ann. de l’lnst. Pasteur, 1903. 
Metschnikoff: Ueb. den Phagocytenkampf bei Riickfalltyphus. Virch. Arch., 
109 Bd., 1887. 
Nikiforoff: Zur path. Anat. u. Histol. d. Milz bei Recurrens. Beitr. v. Ziegler, 
xii., 1892. 
Novy: Studies on Spirillum Obermeieri and Related Organisms. Jour, of In- 
fect. Dis., 190b. 
Obermeier: Cbl. f. d. med. Wiss., 1873; Berl. klin. Woch., 1873, No. 33. 
Puschkareff: Zur pathol. Anatomie der Febris recurrens. Virch. Arch., 118 
Bd., 1888. 
Schaudinn: Generations- u. Wirtswechsel bei Trypanosomen u. Spirochiiten, 
Berlin, 1904. 
Sudakewitsch: Rech. sur la fievre recurrente. Ann. de l’lnst. Pasteur, v. 1891. 
Wladimiroff: Riickfallfieber. Handb. d. pathog. Mikboorg., iii., Jena, 1903 
(Lit.). 
§ 186. The genus Trypanosoma forms a second class of blood-para- 
sites belonging to the Flagellata, found in man, mammals, and birds, and 
also in cold-blooded animals. Most authors place all the parasites of this 
class in the genus trypanosoma and distinguish different species. Doflein 
Fig. 481.—Trypanosoma (herpetosoma) lewisi in the blood of the rat. (From Doflein after 
Rabinowitsch and Kempner.) Er, Erythrocytes. 
divides them according to the character of the flagella into three sub- 
genera: Trypanosoma, Trypanomonas, and Hcrpetosoma. Van Wasie- 
lewski classes only the blood-parasites of the frogs and fish with the 
trypanosomes, and would apply the name Herpetomonas, given by Kent, 
to the trypanosomes found in mammals. TRYPANOSOMES. 
531 
Trypanosoma lewisi (Herpetomonas, Trypanomonas, Trichomonas, 
Hcematomonas) is a common parasite of rats. It is 8—3G /t long and 
3-8 ix broad (Fig. 481), consists of a nucleated granular entoplasm and 
a delicate hyaline ectoplasm or periplastem, the latter forming an undulat- 
ing membrance (Fig. 482, c) and a flagellum (d) which arises in the 
beak-like posterior end from a rod-like body and extends anteriorly along 
the edge of the undulating membrane. 
The rod-shaped body (b) is designated micronucleus, or nucleolus, or 
centrosome, or blepharoplast. It has the significance of a nucleus and 
arises from the chief nucleus. 
The trypanosome infection occurs extensively among rats of many 
regions. In other animals these trypanosomes do not appear to develop. 
The infected rats are apparently healthy, yet epidemics occur in which 
great numbers of them die. Intraperitoneal inoculations of rats are 
followed by multiplication of the trypanosomes, in the abdominal cavity 
and in the blood. According to Rabinowitsch and Kempner reproduction 
Fig. 482.—Trypanosoma (herpetomonas) lewisi, in different stages of development. (After 
A. von Wasielewski.) A, Fully developed parasite with nucleus (a), rod-shaped body (f>), 
undulating membrane (c), and flagellum (d) ; B, parasite with two nuclei and one rod-shaped 
body; C, parasite with one nucleus and two rod-shaped bodies; D, division into two parasites; 
E, parasite with four nuclei and four flagella; F, daughter-individuals still united into a colony, 
x 1,500. 
takes place by longitudinal and transverse division of flagellated indi- 
viduals, and through the segmentation of large non-flagellated forms in 
which cell-division is initiated by division of the nucleus, designated 
as the chromatin framework, while new nucleoli are snared off from 
the chromatin mass. According to von Wasielewski the chief nucleus 
(B) sometimes first divides, at another time the rod-shaped root of the 
flagellum or the blepharoplast (C) ; the cells sometimes divide with two 
nuclei (D), and sometimes after the formation of several nuclei and 
flagellum-roots (E, F), so that the resulting dividing flagellates remain 
for some time united in colonies. The infection of rats occurs probably 
through the medium of fleas and lice. 
Trypanosoma brucei, Plimmer and Bradford, is similar to Tr. 
lewisi, only the body is somewhat broader and the posterior end somewhat 
blunter. It is the cause of Nagana or the tsetse-fly disease of cattle, 
horses, antelopes, buffalo, donkeys, dogs, sheep, and goats, occurring in 
Southern and Southeastern Africa, which is transmitted through the 
tsetse-fly (Glossina morsitans). The number of parasites in the blood 
may be great; infected animals suffer from fever and become ansemic- 532 
THE ANIMAL PARASITES. 
cedema develops in different parts of their bodies; there is conjunctivitis 
and the spleen is swollen. The period of incubation is not more than nine 
days. The infected animals die after one and one-half to eight months. 
It is probable that the disease known as Surra, occurring endemically 
in horses, mules, camels, buffalo, cattle, and elephants in Dutch India, 
Indochina, and the Philippines, and which is transmitted by gad-flies, is 
due to this trypanosome. It is likewise regarded as the cause of the 
trypanosome disease ofjaorses and donkeys known as the coitus-disease 
or dourine occurring in Algiers, Southern France, Sumatra, Novarra, and 
the Pyrenees, and which is spread by coitus, and is inoculable into rab- 
bits, rats, and dogs. Many authors regard the parasites found in these 
diseases as representing different species, giving to the first the name of 
Trypanosoma evansi and to the latter that of Tr. equiperdum. A variety 
of trypanosome found in Central South America and which causes the 
disease of horses known as mal de caderas is designated Tr. equinnm. It 
is assumed that Stomoxys calcitrans acts as the agent of transmission of 
the parasite. 
A variety of trypanosome known as Tr. theilcri is found in cattle in 
South Africa and is inoculable only into cattle. 
The occurrence of trypanosomes in man was first observed by Nep- 
veu (1898). The investigations of Dutton, Todd, Boyce, Ross, Sherring- 
ton, Bruce, Castellani, Manson, Daniels, Laveran, etc., have shown that 
trypanosome diseases also occur in man. The sleeping-sickness of the 
negro is now known to be due to trypanosome infection. Castellani 
found the parasite in the cerebrospinal fluid of sleeping-sickness, and his 
findings have been confirmed by different observers. The disease occurs 
throughout tropical West Africa, and in recent years has spread through 
Central and Eastern Africa. Negroes are chiefly affected, but cases 
have also been observed in Europeans. The infection is transmitted by a 
biting-fly (Glossina palpalis). The parasites develop in the blood, and 
during this period symptoms may be wanting, or there may be attacks of 
fever. When the parasites gain access to the cerebrospinal fluid and 
increase, cerebral symptoms, particularly coma, are produced as the result 
of meningitis. The disease runs a chronic course and is invariably fatal. 
Trypanosomes are also found in the disease known as Gamba-fever 
which occurs in Senegambia and the Congo, both in the natives and 
Europeans. According to Laveran, it is due to the same species of try- 
panosomes observed by Castellani in Uganda. Further, trypanosomes 
are believed to be the cause of tropical splenomegaly, which occurs in 
India, China, Arabia, Egypt, and Tunis, and is characterized by intermit- 
tent or remittent attacks of fever associated with marked swelling of the 
spleen, leading after many months’ duration to progressive anaemia and 
cachexia having a fatal termination. It is probable that the disease known 
as Kdla-azar (black fever), which is widely distributed through the valley 
of Assam watered by the Brahmaputra, is related to tropical splenomegaly. 
The life-history of the trypanosomes is similar to that of the spirochaetes. 
According to investigations by Schaudinn the Halterida (Hcemoproteus noctuce 
of Celli and San Felice) of the little owl are the sexual stages of a trypanosome 
which multiplies in the common mosquito, Culex pipiens, so that after a compli- 
cated wandering through the body of the mosquito, through its bite again reaches 
the blood of the owl, in which after a period of asexual increase it changes into 
the familiar male and female Halteridia. The parasite must, therefore, be called 
the Trypanosoma noctuce. (Whether other members of the genus Halteridium or 
Hsemoproteus are to be classed with trypanosomes remains to be settled.) Accord- TRYPANOSOMES. 
533 
ing to Novy {Jour, of Infect. Dis., 1905) the observations of Schaudinn are open 
to an entirely different interpretation. He believes that the Trypanosoma noctuce 
and the Spirochceta siemanni of Schaudinn probably represent trypanosomes that 
have multiplied in the mosquito and are not to be considered as stages in the life- 
history of cytozoa. According to Novy’s investigations trypanosome infection of 
birds is widespread. With the trypanosomes there may be associated intracellular 
parasites, but no constancy can be shown to exist between a given trypanosome and 
a given cytozoon. 
It has not been decided whether human trypanosomiasis is due to more 
than one variety of trypanosome. The different clinical course of the affections 
makes this probable. In the forms known as tropical splenomegaly or cachectic 
fever and kala-asar, there are found (Leishman, Marchand) in the spleen, liver, 
bone-marrow, lymph-nodes, and in intestinal ulcers, great numbers of small bodies, 
partly free and partly intracellular, consisting of an intensely staining ring-shaped 
chromatin body surrounded by a circular or oval, clear area staining lightly with 
eosin. Besides the chromatin-body there is often found (Marchand, Ledingham) a 
small, intensely staining round or elongated granule, which is often connected with 
the chromatin-ring by a delicate stalk. These bodies (“ Leishman-Donovan bodies’’) 
were first found by Leishman and Donovan in smears from the spleen, and were 
later studied by Marchand, Ledingham, Manson and Low, Bentley, Rogers, and 
others, the general opinion being that they represented degeneration forms of 
trypanosomes. Rogers has succeeded in growing them outside the body and in 
demonstrating their transformation into elongated flagellated organisms resembling 
trypanosomes. On account of the absence of an undulating membrane Rogers 
believes the organism to be a herpetomonas. Ross regards it as a new genus and 
has called it Leishmani donovani. Nothing is absolutely determined concerning the 
transmission of this fatal infection. Rogers believes that it is transmitted by 
bed-bugs or mosquitoes. Nicolle {Arch, de I’lnst. Pasteur, Tunis, 1908) has suc- 
ceeded in cultivating the Leishman-Donovan bodies from cases of infantile 
splenomegaly in Tunis. He regards the protozoon obtained as a new species. 
Leishmania infantum. The protozoa found in a case of tropical sore by Wright 
{Jour, of Med. Res., 1903) and called by him Helcosoma tropicum, are regarded as 
Leishman-Donovan bodies, and designated by Nicolle as Leishmania zvrighti. They 
are regarded as the infective agent of “ Delhi boil.” 
According to the majority of writers trypanosome or Gambian fever is but the 
early stage of sleeping-sickness, both conditions being due to infection with the 
same parasite, the Trypanosoma gambiense. The first stage is of variable duration, 
lasting from three months to three years or longer. During this stage there is 
polyadenitis and the trypanosomes may be demonstrated in the blood and lymph- 
nodes. As a diagnostic method the examination of a drop of fluid removed from 
an enlarged cervical node by means of a hypodermic needle is advised, since the 
parasites can be found in this way immediately if they are present in the body. 
Literature. 
( Trypanosomes.) 
Baker: Trypanosoma in Man. Brit. Med. Journ., i., 1903. 
Bradford and Plimmer: The Trypanosoma Brucei. Quart. Jour, of Micr. Sc., 
xlv., 1901. 
Bruce: Rep. on the Tsetse Fly Disease. UbomJbo, 1895 and 1896; Trypanoso- 
miasis. Brit. Med. Journ., ii., 1904. 
Bruce, Nabano, and Greig: The Etiol. of Sleeping Sickness. Brit. Med. Journ., 
ii., 1903. 
Castellani: Aetiologie der Schlafkrankheit. Centralblatt fiir Bakteriol., Orig., 
xxxv., 1903. 
Donovan: The Etiology of One of the Heterogeneous Fevers of India. Brit. 
Med. Journ., ii., 1903. 
Dutton: Trypanosoma Occurr. in the Blood of Man. Thompson-Yates Lab. 
Rep., iv., 1902. 
Dutton and Todd: Rep. to the Trypanosomiasis Exped. to Senegambia. Thomp- 
son-Yates Lab. Rep., v., 1903. 
Gunther: Trypanosomen bei Menschen. Munch, med. Woch., 1904. 534 
THE ANIMAL PARASITES. 
Laveran: Des trypanosomes parasites du sang. A. de med. exp., iv., 1892; 
Trypanosomiase humame. Compt. rend, de l’Ac. d. Sc., cxxxviii., 1904. 
Laveran et Mesnil: Maladie de la mouche tsetse. Ann. de l’inst. Pasteur, 1902; 
Trypanosomes et Trypanosomiases. Paris, 1904. 
Leishman: On the Possibility of the Occurrence of Trypanosomiases in India. 
Brit. Med. Journ., i., 1903, p. 1252; Discussion on the Leishman-Donovan 
Body. Ib., ii., 1904, p. 642. 
MacNeal: The Life-history of Tr. Lewisi and Tr. Brucei. Journ of Infectious 
Dis., 1904. 
Manson and Daniels: A Case of Trypanosomiasis. British Medical Journal, 
i., 1903. 
Marchand u. Ledingham: Ueber Infektion mit Leishmanchen Korperchen. 
Z. f. Hyg., 47 Bd., 1904 (Lit.). 
Marchoux: La fievre jaune. Ann. de l’lnst. Pasteur, 1903. 
Novy: The Trypanosomes of Tsetse Flies. Journ. of Infect. Dis., 1906. 
Novy and MacNeal: Cultivat. of Trypanosoma Brucei. Journ. of Infect. Dis., 
i., Chicago, 1902, u. Biol. Obi., xxiv., 1904; On the Trypanosomes of Birds. 
Journ. of Infect. Dis., 1905. 
Novy, MacNeal, and Torrey: The Trypanosomes of Mosquitoes. Journ. of 
Infect. Dis., 1907. 
Salmon and Stiles: Rep. on Surra: XVIII. Ann. Rep. of the Bureau of Animal 
Industry, Washington, 1902. 
Schaudinn: Generations- u. Wirtswechsel bei Trypanosomen u. Spirochiiten. 
Arb. a. d. K. Gesundheitsamte, xx., 1904. 
§ 187. Of the Sporozoa occurring as parasites in man and other 
mammals, the coccidia are to be mentioned first. In their young state 
they exist as non-encapsulated inhabitants of epithelial cells, particularly 
in those of the intestinal canal and its adnexa, the liver especially, and 
more rarely in the organs of excretion. Some of the mature forms sur- 
Fig. 483.—Section through the wall of a dilated bile-duct, filled with coccidia and lined 
with papillary proliferations. From a rabbit’s liver that was studded with coccidia nodules 
(Muller’s fluid, haematoxylin, eosin). a, Connective tissue; b, branching papillary proliferations 
covered with epithelium; c, coccidia. x 23. 
round themselves with a capsule and become changed into round or oval 
permanent cysts or oocysts (Schaudinn), which leave their resting-place 
and usually also their host, and under certain conditions form sickle- 
shaped sporozoites through repeated division of their cell body 
(sporogony). Through the taking-up of sporozoite-containing oocysts 
into a new host there is produced an infection of the latter, in that the 
sporozoites are set free and seek out epithelial cells for their further 
development. COCCIDIA. 
535 
Besides this form of multiplication there occurs in the infected organ 
reproduction by schizogony — that is, there are developed from mature 
but non-encysted individuals, by means of segmentation, a large number 
of new sickle-shaped individuals, the so-called merosoites, which seek out 
epithelial cells, and develop in them. 
Coccidium oviforme (Fig. 484) is a parasite of the intestine and 
biliary passages, occurring especially in rab- 
bits. Podwyssozki claims to have observed 
them in the human liver. 
In the liver of rabbits the invasion of 
coccidia leads to the formation of white 
nodules which may reach the size of a hazel- 
nut. These nodules contain a soft, white, or 
yellowish-white mass, and consist of dilated 
bile-passages, the inner surface of which is 
more or less richly furnished with papillary 
growths (Fig. 483), and whose lumen con- 
tains numbers of coccidia. 
The coccidia occur in the bile-passages 
partly in the form of non-encapsulated proto- 
plasmic structures, and partly in the form of 
encapsulated bodies. The smallest coccidia, 
which are regarded as the younger forms, ex- 
hibit a coarsely granular protoplasmic structure (Fig. 484, a, b), 
within which a nucleus (a) may occasionally be demonstrated. The 
larger forms exhibit on their outer surfaces regularly arranged granules 
(c, d), which stain intensely with haematoxylin. The encapsulated forms 
occur as oval, doubly contoured, clear bodies (e, f, g, h) within which 
lies a variously shaped mass exhibiting various forms of granulation, but 
never entirely filling the space within the capsule. 
To the coccidia belong those parasites which occur in the epidermis 
Fig. 484.—Coccidia from the 
biliary duct of the rabbit’s liver 
(Fig. 483), showing different 
stages of development (Miiller’s 
fluid, hxmatoxylin). a, b, Small, 
coarsely granular young forms; 
c, d, large forms with darkly stain- 
ing peripheral granules; e, /, g, 
h, oval, encapsulated forms, the 
protoplasm of which — partly 
coarsely granular and partly fine 
— fills up only a portion of the 
capsule, x 400. 
Fig. 485.—Epithelioma contagiosum. Section through greatest diameter (Muller’s_ fluid, 
hsmatoxylin). a, Epidermis; b, connective tissue; C, sebaceous gland; d, gland-like epithelial 
proliferations; e, parasites; f, horny cells mingled with parasites; g, duct filled with horny 
epithelium and parasites, x 13. 
of man and form peculiar growths known as epithelioma contagiosum 
(Fig. 485). In its fully developed condition the growth consists of a 
nodule, the size of a pea or larger, which is elevated above the surface of 
the skin, shows a small groove in its centre, and possesses a waxy lustre. 
On section there may be seen a lobulated epithelial growth (Fig. 485, d), 536 
THE ANIMAL PARASITES. 
with a central cavity opening externally (g), thus resembling a 
gland; it has many times been mistaken for a hypertrophic sebaceous 
gland. It represents an independent new-formation of epithelium due to 
a parasite. The parasites develop inside the epithelial cells of the growth 
(e), but are pressed by the 
growth of adjacent epithelium 
toward the central cavity (/), and 
lie in a meshwork of desquamated 
and horny epithelial cells. 
The earliest stages of develop- 
ment of the parasites occur in the 
epithelial cells as small proto- 
plasmic bodies (Fig. 486, a, b), 
which can be distinguished from 
the cell-protoplasm only with diffi- 
culty; occasionally they contain 
in their interior small, distinct 
granules, and are therefore more 
evident. Later they increase in 
size, and finally fill the cell (c, d, 
e), pressing the nucleus to one 
side. At the same time the gran- 
ules in the cell (c) increase, and 
grow to larger bodies, so that the 
parasite finally becomes divided into a greater or less number of well- 
defined structures (d, e, /) lying in a finely granular network. The 
nucleus of the epithelial cell is destroyed during this time. 
Fig. 486.—Parasites of Epithelioma contagiosum 
in various stages of development, lying inside epi- 
thelial cells (Muller’s fluid, haematoxylin). a, b, 
Epithelial cells, enclosing a protoplasmic body in- 
side of which lie single large granules; c, epithelial 
cell almost completely filled with parasites; d, 
e, f, parasites completely filling the epithelial cells, 
and divided into numerous separate bodies lying in 
a granular network; the cell-nucleus has been de- 
stroyed in f. x about 500. 
Fig. 487.—Miescher’s sacs, from swine-muscle, a, b, Muscle cut longitudinally and transversely, 
X 100. c, Longitudinal section. X 580. 
The epithelial cells which enclose parasites develop early a distinct 
membrane, which becomes more and more clearly defined, and surrounds 
the parasite. The parasites which are expelled from the cells form oval 
bodies enclosed in a capsule and present a homogeneous appearance. 
They stain deeply with hsematoxylin. 
The contagious epitheliomata may appear in great numbers in one and MIESCHER’S SACS. 
537 
the same individual, and several persons living together may be simul- 
taneously or successively attacked. 
By many writers the molluscum bodies are not believed to be parasites, but are 
regarded as hyaline or horny products of cell-degeneration. 
Our knowledge of the significance of the so-called Miescher’s sacs 
is still incomplete. They are tube-shaped structures which are not infre- 
quently found in the muscles of the hog (Fig. 487, a, b), cattle, sheep 
(especially in the oesophagus), and mice. They vary in size, and lie in 
the muscle-fibres. In mature parasites the contents of the tubes are dif- 
ferentiated into single segments defined by a membrane (Fig. 487), which 
enclose spherical (c), kidney-shaped, or sickle-shaped bodies. The 
Fig. 488.—Cycle of development of Coccidium Schubergi. (After Schaudinn and Ltihe). 
1, Sporozoite (or merozoite) penetrating into an epithelial cell; 2, mononuclear schizont in an 
epithelial cell; 3, multinuclear schizont; 4, division of the schizont (schizogony) into numerous 
merozoites; 5, macrogamete (female cell) arising from a merozoite; 6, fully developed marco- 
gamete surrounded by extruded chromatin granules; 5a, microgametocyte (male cell) arising from 
a merozoite; 6a, microgametocyte surrounded by loosened microgametes (spermatozoa); 7, fer- 
tilization of the macrogametes by microgametes; 8, young oocysts; 9, oocysts with sporoblasts; 
10, oocysts with sporocysts, each containing two sporozoites; 11, sporozoite. 
parasite is classed with the Sarcosporidia. The separate segments are 
designated sporocysts or sporoblasts, since within these the round or 
sickle-shaped spores (Rainey’s bodies) arise. From the latter, new 
Miescher’s sacs may develop under favorable conditions (Pfeiffer). 
Ingestion of meat containing sarcosporidia is not dangerous to man, 
although sarcocysts have been observed in man in the muscles, heart, 
intestine, and liver. 
As early as 1870 Eimer published observations on the development of coccidia, 
but their life-history has been accurately determined only in recent years through 
the investigations of R. Pfeiffer, Simond, Leger, Schaudinn, Schuberg, Siedlecki, 
Schneider, von Wasielewski, Labbe, and others. 538 
THE ANIMAL PARASITES. 
The reproduction of coccidia occurs (Liihe) partly through sporogonv, partly 
through schizogony. The first method serves for the spreading of infection and the 
preservation of the species,. the second increases the extent of the infection in the 
infected host. Sporogony is closely connected with a previously occurring copula- 
tion which in its course suggests the fertilization of the egg of the metazoa. Alter- 
nation of generations also takes place. 
The development and reproduction take place in the following manner: In 
schizogony the sickle-shaped germ (Fig. 488, 1) arising as a sporozoite or merozoite 
develops within an epithelial cell into a schizont (2) in which there soon takes place 
multiplication of the nucleus (3). There then results (on the second day after 
the over-feeding of sporocysts) formation of merozoites (4) corresponding in 
number to the nuclei, and a residual body which is left behind after the seg- 
mentation. 
The merozoites again seek epithelial cells, and the same development begins 
anew. If the affected organ, as the result of these processes, becomes overcrowded 
with parasites, there are then formed sexual individuals (Schaudinn). Some of the 
merozoites grow into large cells, the macrogametes (5, 6) or female cells, which, 
when mature throw off a portion of their chromatin-substance (6), and either 
remain naked or surround themselves with a capsule, which is provided with a 
micropyle. At the same time other merozoites develop into the male sexual cells 
or microgametocytes (5a, 6a), the nuclei of which divide into many daughter- 
nuclei. The latter approach the surface of the cell, and, surrounded by a certain 
amount of protoplasm, are constricted off, (6a) and then represent the micro- 
gametes (corresponding to the spermatozoa of the higher animals). The copulation 
of the microgametes with the macrogametes takes place in a manner similar to 
that of the fertilization of the metazoan egg, in that the microgamete penetrates 
the encapsulated form of macrogamete through the micropyle and the naked 
form through a certain point which pushes itself outward to form a prominence 
(7), the conceptional protuberance. Sporogony follows the fertilization—that is, 
the oocyst (8) is formed, in which, through division of the nucleus and proto- 
plasm, there arise four sporohlasts (9), each of which later produces two sickle- 
shaped sporozoites (10). 
Numerous authors hold the view that local pathological conditions of the 
tissues in man other than those described above may be referred to sporozoa, par- 
ticularly carcinoma, Darier’s disease, Paget’s disease, peculiar diseases of the urin- 
ary passages, etc. It may, however, be remarked that this assumption in part is 
based on error, and has not been proved by investigations made up to the present 
time. 
So far as carcinoma is concerned, in spite of the great number of works on 
the subject, so numerous indeed that they can scarcely be perused (cf. § 121), no 
proof has been given that protozoa, coccidia in particular, are present in the 
epithelial proliferation and are to be regarded as the cause of the same. All the 
appearances described as occurring as carcinoma cells, even the sickle-shaped forma- 
tions which have been thought to be convincing and those provided with a sort 
of capsule, may be otherwise interpreted, and may be explained as changed nuclei, 
as altered protoplasm of the cancer-cells, as cell excretions, and finally as a product 
of cell-fusion or of the taking up of leucocytes by the cancer cells. 
The disease described by Darier as psorospermose folliculaire vegetante, and re- 
ferred by him to the presence of sporozoa, is probably an inflammatory affection of 
the skin characterized by pathological cornification (keratosis follicularis of von 
Withe), in which horny plugs and pegs are developed successively in the epithe- 
lium of certain parts of the body, while the cutis shows slight inflammatory changes. 
According to Buzzi, Miethke, Rieck, Krosing, Petersen, and others, the “corps 
ronds,” described by Darier as parasites, contain kerotohyalin and eleidin, sub- 
stances which are present in cornified cells but not in gregarinae. 
Paget’s disease is an affection spreading from the nipple, beginning with an 
eczema-like inflammation, and leading to superficial ulceration, and ending in carci- 
nomatous infiltration of the skin. It has been referred by Darier, Wieckham, 
Malassez, and others to the presence of a parasitic sporozoon in the epithelial 
cells; but is, however, either eczema arising from other causes, and leading to 
cancer, or a primary cancer accompanied by inflammatory processes (Ehrhardt), 
in which peculiar changes take place in the epidermis, particularly swelling of the 
protoplasm and nuclei, with formation of vacuoles, and proliferative changes, the 
peculiar appearances of which might be mistaken for parasites. According to 
Jacobaeus these appearances are brought about through penetration of the carcinoma 
into the superficial epithelium. THE MALARIAL PARASITE. 
539 
In variola and vaccinia there occur constantly in the epithelium that has 
undergone recent changes small lightly staining bodies surrounded by a clear zone, 
often in great numbers. Their constant occurrence in repeated inoculations and 
their characteristics make it very probable that they represent parasites belonging 
to the protozoa, and this view is favored by numerous authors (Guarnieri, E. 
Pfeiffer, L. Pfeiffer, Bose, Funk, Councilman, von Wasielewski, and others). 
Pliickel and Borrel have attempted to interpret these structures in another way. 
Negri (“Etiologie der Tollwut,” Z. f. Hyg., 43 und 44 Bd., 1903) describes 
small bodies found in the nervous system of dogs inoculated suibdurally with 
the virus of rabies that he regards as protozoa and considers to be the cause 
of rabies. Investigations by Volpino (“Struttura dei corpi descr. da Negri nella 
Rabbia.” A. per le Sc. Med., xxviii., 1904), and by Luzzani (“La dimonstraz. 
del Parass. specif, in un caso di rabbia nel l’uomo.” Ibid.) support the view of 
Negri, but offer no further information as to the nature of the parasite. Accord- 
ing to A. W. Williams, the Negri bodies possess a definite chromidium and are, 
therefore, to be classed with the rhizopods (Journ. of Infect. Dis., 1906). 
Mallory (“Scarlet Fever.” Jour, of Med. Res., x., 1904) found a protozoon- 
like body in four cases of scarlet fever. Field (Journ. of Ex per. Med., 1905) 
believes that these bodies are products of degenerating tissue-cells and leucocytes. 
Gotschlich (“ Protozoenbefunde im Blute von Flecktyphuskranken.” D. med. 
Wochenschr., 1903) found pear-shaped bodies in six cases of typhus fever that 
resembled the parasites of Texas fever, and in four cases he also found flagellated 
bodies. 
According to Hess and Guillebeau, coccidia may occasion in young cattle dis- 
eases of the intestine resembling dysentery. According to Olt and Voisin, the 
shotty eruption of swine characterized by the formation of little cysts in the skin 
is caused by coccidia (C. fuscum), but according to Liihe the description of the 
parasites does not correspond to coccidia. 
Literature. 
(Coccidia; Parasite of Epithelioma Contagiosum; Miescher’s Sacs.) 
Barrat: The Nature of Psorospermosis. Journ. of Path., iv., 1896. 
Councilman: A Preliminary Communication on the Etiology of Variola. Journ, 
of Med. Res., 1903. 
Delepine and Cooper: A Few Facts Concerning Psorospermosis. British Med 
Journ., ii., 1893. 
Gilchrist: Protozoa, etc. Johns Hopkins Hosp. Rep., i., 1896. 
Johnson: A New Sporozoan Parasite of Anopheles. Journ. of Med. Res., 1902. 
Kartulis: Pathogene Protozoen. Zietschr. f. Hyg., xiii., 1893. 
Nocard: Coccidial Tumor from the Small Intestine of the Sheep. Journ. of 
Path., i., 1893. 
Rixford and Gilchrist: Protozoan Infection. Johns Hopkins Hosp. Rep., i., 
1896. 
Thomas: Bone Tumor Surrounding Encysted Coccidia. Report of the Boston 
City Hosp., 1899. 
Tyzzer: Coccidium Infection of the Rabbit’s Liver. Journ. of Med. Res., 1902. 
White and Robey: Molluscum contagiosum. Journ. of Med. Res., 1902. 
§ 188. Under the designation Plasmodium malariae (Marchiafava 
and Celli) or the haemosporidia of malaria are grouped those parasites 
which are regarded as the cause of human malaria. The parasites are 
found in the blood of malarial patients in different forms, usually enclosed 
in cells; and, according to the observations of Golgi, Celli, Marchiafava, 
and others, a definite relation can be demonstrated between the number 
and the stage of the development of the parasite and the attacks of fever, 
The parasites pass through different stages of development in the interval 
between the attacks of fever, these stages, according to the authors 
mentioned, differing in febris quart ana, febris tertiana, and febris 
quotidiana. At the same time the parasites of the different forms of 
fever exhibit certain differences in their physiological characteristics. 540 
THE ANIMAL PARASITES. 
Supported by these facts, there may therefore be distinguished in man 
different species of the malarial plasmodium. In its narrower sense the 
designation Plasmodium malarias is used only with reference to the para- 
sites of quartan fever. The parasite of vernal tertian on account of its 
active movements is known as Plasmodium vivax (Grassi and Feletti) ; 
and the parasite of tropical malaria, which in Italy appears in the autumn, 
is designated Plasmodium prcecox. 
Schaudinn’s classification of the malarial parasites is accepted by most writers. 
He recognizes three varieties: Plasmodium vivax (tertian), Plasmodium malarice 
(quartan), and Plasmodium immaculatum (aestivo-autumnal parasite). 
The development and increase of the plasmodia take place within 
the red blood-corpuscles, in which, first of all, small, colorless amoeboid 
Fig. 489.—Plasmodium malariae of quartan fever, in different stages of development. 
(After Golgi.) a, Red blood-cell with a small non-pigmented plasmodium; b, c, d, e, pigmented 
plasmodia of varying size inside the red blood-cells; f, plasmodium in beginning segmentation, 
with centrally placed pigment; g, segmented plasmodium; h, plasmodium divided into separate 
spherules; i, free gamete (sexual individual). 
bodies (Fig. 489, a) appear. In quartan fever the further development 
of the parasite proceeds by enlargement of the small amoeboid forms 
(Fig. 489, a, b, c, d, e), so that the red cell becomes more and more 
filled by the parasite. At the same time pigment-granules appear within 
the bodies of the plasmodia. When the plasmodia have attained a cer- 
tain size, the pigment-granules move toward the centre, while at the 
same time a radiating cleavage sets in, and daisy-like figures {“rosettes”) 
(/, g) are formed, which consist of a pigmented centre and non-pig- 
mented, radiating club-shaped petals. Later the clubs become detached 
from the central mass of pigment and take on a.circular form (h). 
According to Golgi, the development and division of the plasmodia of 
quartan fever require three days for completion, and the attacks of 
fever coincide with the division of the plasmodia. The red cells occupied 
by the parasites are destroyed; the young plasmodia formed by division 
penetrate into blood-corpuscles, and the cycle of development begins 
anew. The pigment-granules formed by the plasmodia are taken out of 
the circulating blood partly free and partly enclosed in cells, and are 
deposited in different organs, particularly in the spleen, liver, and bone- 
marrow. 
In febris tertiana (vernal tertian) the cycle of development is com- 
pleted in two days. The plasmodia developing within the red cells (Fig. 
490, a-d), which are designated Plasmodium vivax, show much livelier 
motion and lead much more quickly to decolorization of the red blood- 
corpuscles than those of quartan fever; the red cells become decolorized 
on the first day after the fever, while the plasmodia are still small. The THE MALARIAL PARASITE. 
541 
protoplasm of the plasmodia of tertian fever is also more delicate and 
less sharply contoured and the pigment-granules are smaller. In its 
division each plasmodium splits up into from fifteen to twenty new cells 
(e), while the parasite of quar- 
tan fever forms only from six 
to twelve. According to Celli 
and Marchiafava, sporulation 
not infrequently occurs prema- 
turely, from five to ten spores 
arising within a red corpuscle. 
The parasite of tropical or 
pernicious malaria, the plas- 
modium prcecox, differs from the 
haemosporidia of the vernal 
fevers, particularly in the fact 
that it is smaller (Fig. 491, a, 
b, c, d) and executes lively 
movements within the red cells. 
It completes its life-cycle in 
twenty-four to forty-eight hours. 
Through the formation of a central vacuole it often appears in the form 
of a ring. During the stage of multiplication the parasite collects in the 
internal organs, so that division-figures (d) must be sought in the spleen, 
liver, bone-marrow, and brain (where they are present in great numbers). 
Some of the infected red cells become crenated and prickly, and of a 
brassy color (Marchiafava, Celli) ; they die prematurely, and blood-cells 
which contain no parasites are 
also destroyed. The attacks of 
fever can in the case of autum- 
nal tertian fever become so pro- 
longed that they pass into one 
another, and the condition 
thereby assumes the character 
of a sub-continuous or con- 
tinuous fever. 
According to Marchiafava 
and Celli, there also occurs a 
quotidian parasite similar to the 
latter, but producing no pig- 
ment at all. 
Nuclear bodies may be 
demonstrated, during certain 
stages of development, in the 
protoplasm of all the endoglobular forms of malarial hsematozoa. Ac- 
cording to Ziemann, in sporulation there first occurs division of the 
chromatin into small clumps, and later division of the cell-body, so that 
every clump of chromatin is surrounded by a zone of protoplasm. 
Besides the forms of development which lead to intracellular increase 
of the plasmodia through schizogony, there occur extraglobular, also 
endoglobular, round and oval, sickle- or crescent-shaped structures (Figs. 
489, i; 491, e, f), as well as round bodies with flagella (Figs. 490, f; 491, g) 
which also contain a nucleus and pigment. The crescent forms occur 
Fig. 490.—Plasmodium vivax of a vernal tertian, 
showing different stages of development. (After 
Golgi.) a, First stages of development; b, c, enlarged 
plasmodia with pseudopodia; d, plasmodia before 
sporulation, the red blood-cell decolorized; e, spor- 
ulation; f, free parasite with flagellum (micro- 
gametocyte). 
Fig. 491.—Plasmodium praecox of tropical malaria, 
showing different stages of development. (After 
Golgi and Sanfelice.) a, First stages of development; 
b, plasmodia with pseudopodia; c, round plasmodium 
with pigment, before segmentation; d, sporulation; 
e, intraglobular sexual individual; f, g, free sexual 
cells. 542 
THE ANIMAL PARASITES. 
particularly in the pernicious fever (Fig. 491, e, /). Celli regards them 
as diagnostic of this form of fever; Ziemann also holds that typical 
crescents are not formed in other varieties of malaria. 
The last-named forms Laveran described as structures belonging to 
Fig. 492. 
Fig. 493. 
Fig. 492.—Anopheles claviger. (After Meigen, loc. cit.) x 4. To the right a wing at higher 
magnification. 
Fig. 493.—Ookinete of human pernicious malaria (Plasmodium praecox) in the intestinal 
wall of a mosquito. (After Grassi.) 
the cycle of development of the plasmodia, while Golgi, Canalis, Celli, 
Marchiafava, Bignami, Bastianelli, Ziemann, and others regarded them 
as sterile vegetation-forms that die without further development. First 
through the investigations of Manson, Bignami, Ross, and MacCallum, to 
which were later added those of Grassi, Bastianelli, Bignami, Celli, 
Laveran, Koch, Schaudinn, and others, it was shown that the crescents, 
the oval bodies, the spherical bodies, as 
well as the flagellated bodies known 
as polymitus, are intended for repro- 
duction by copulation. The flagella- 
producing hyaline spheres arising from 
the crescents are male sexual individ- 
uals or microgametocytes, and the 
flagella developing from them, in 
whose formation the chromatin of 
the cell takes an essential part (Sach- 
aroff), have the significance of seminal 
cells, spermatozoa, or microgametes; 
while the non-flagellated spheres arising 
from the granular crescents have the 
significance of female sexual cells or 
macrogametes. The crescents leading 
to the formation of the sexual cells ap- 
pear only after infection has lasted for 
several days. In the chronic cachexia following malaria the forms lead- 
ing to schizogony are absent, and the crescents alone are present. 
The copulation of the malarial parasites of man takes place normally 
in the stomach of the mosquito, in different species of Anopheles (Fig. 
492), which take up parasites during the sucking of blood from malarial 
patients. 
Fig. 494.—Oocyst of Plasmodium prae- 
cox, filled with sporozoites. (After Grassi.) THE MALARIAL PARASITE. 
543 
The copula arising from the union of the macrogamete and micro- 
gamete is designated ookinete (Schaudinn), a long, motile structure 
which penetrates into the stomach-wall of the mosquito (Fig. 493), where 
through the formation of a capsule it becomes the oocyst. The latter then 
enlarges, and forms numerous daughter-nuclei, and then sporoblasts, 
which break up into the sporozoites (Fig. 494) and the residual body. 
According to Grassi, as many as 10,000 sporozoites may be formed in 
one oocyst. 
The sporozoites, which are formed in enormous numbers, pass into 
the body-cavity after the rupture of the oocyst, and collect principally in 
the salivary glands, and through the bite of the infected mosquito are 
again transmitted to man, in whose blood they multiply within the red 
blood-cells through schizogony. 
The pathogenic significance of the malarial plasmodia rests on the 
destruction of red blood-cells. In the pernicious form this may be so 
extensive that hsemoglobinuria may take place. The melanotic pig- 
ment formed in the parasite is a product of the vital activity of the 
parasites. In addition, as the result of the destruction of haemoglobin, 
there occur deposits of haemosiderin in the bone-marrow, spleen, liver, 
and occasionally in the kidneys. In marked destruction of the red blood- 
cells there may occur excretion of dark red urine, haemoglobinuria {black- 
water fever.) The massing of the parasites of pernicious malaria in the 
cerebral capillaries may cause circulatory disturbances with the occurrence 
of numerous haemorrhages, and severe cerebral symptoms. 
As the result of retention of pigment-containing malarial parasites 
and the deposit of the products of blood-destruction, there occurs marked 
swelling of the spleen associated with hyperaemia, followed by tissue- 
degenerations and by tissue-proliferations. 
After a long duration of the process the spleen may become markedly 
enlarged, pigmented, and greatly changed in structure. Likewise, in the 
liver there may be found degenerations and pigmentations, and also 
indurative proliferations. 
Certain varieties of the plasmodium correspond to the individual types 
of fever, as given above, but it must be noted that the fever-forms known 
as quotidian, subcontinuous, and continuous {“ comitata”) may also 
arise through the presence in the blood of different generations of the 
plasmodia of tertian or quartan fevers, so that daily a portion of the 
parasites comes to sporulation. In this way there arise quotidian forms 
of fever, which must be regarded as a double tertian infection or as a 
triple quartan. 
According to Schaudinn, the relapses that occur sometimes weeks 
and months after the original attack may be explained by the fact that 
the macrogametes, which are longer-lived, revert to schizonts by throw- 
ing off a portion of their nucleus and protoplasm. According to Plehn, 
basophile granules are found in the red blood-cells as long as the infection 
persists. They vanish when the infection comes to an end. 
The malaria occuring in northern countries corresponds in general 
to the vernal forms of Italy, while the sestivo-autumnal form is found in 
the tropics. 
Haemosporidia—that is, sporozoa Which live at the cost of the red blood- 
cells, and thereby produce diseases which are to be classed with malaria — occur 
frequently in animals. Those of birds are best known (Danilewsky, MacCallum, 
Ross, Grassi, Dionisi, Celli, and Schaudinn) and the life-cycles of the haemosporidia 
of the pigeon, owl, and skylark have been determined. Labbe distinguishes two 544 
THE ANIMAL PARASITES. 
genera in birds, Halteridium and Proteosoma (Hcemoproteus of Kruse) ; as to the 
number of undifferentiated species, nothing can be said at the present time. Celli 
obtained from the birds mentioned three well-defined species. Schaudinn assigns 
the parasites of birds designated as proteosoma to the genus plasmodium. 
Of the Mammalia, cattle in particular suffer in different countries (Southern 
States of North America, Italy, South Africa, Roumania) from malaria character- 
ized by high fever and haemoglobinuria. In the malaria of cattle known as Texas- 
fever, Smith and Kilbourne found in the red-blood cells a small, often pear-shaped, 
and paired parasite (Piroplasma bigeminum), whose pathogenic significance they 
determined through the inoculation of healthy cattle with blood containing the 
parasites. Babes found the same parasite in the epidemic haemoglobinuria of 
cattle prevalent in Roumania. The first-named observers showed that infection 
takes place through parasitic ticks (Boophilus bovis) living on the cattle, the infec- 
tion being transmitted, not by the same tick which takes up the infected blood, 
but through the generation descending from the same. This mode of infection was 
confirmed by Koch in the haemoglobinuria of cattle occurring in German East 
Africa and by Grassi in that occurring in cattle in Italy. The mode of development 
of the piroplasma in the body of the tick is still unknown; and it therefore cannot 
be decided whether the parasite should be classed with the known malaria parasites. 
Against a near relationship with the latter is the fact (Luhe) that it increases in 
the red blood-cells by repeated simple division. According to Kolle, there occurs in 
South Africa, besides Texas-fever, another malarial disease of cattle (Febris ma- 
laria formis), which is caused by an endoglobular parasite. Theiler also distinguishes 
two forms of piroplasmosis of cattle in South Africa. The piroplasma occurring 
in dogs and in horses he regards as a form distinct from Piroplasma bigeminum. 
According to observations by Nocard and Almy and Motas piroplasmosis associated 
with haemoglobinuria is not uncommon in dogs in France. According to Galli, 
Valerio, and Piana, it also occurs in Italy. 
According to Bonome and Celli, haemosporidia also cause malaria in sheep and 
lambs, according to Koch and Kassel in apes, and according to Dionisi in bats; but 
the life-history of these parasites is unknown. 
Danilewsky and Celli have described haemosporidia in the frog, and the latter 
observer determined the development of the parasite in the blood. 
Whether the malarial parasites of man can be transmitted to animals, or whether 
the malaria of animals can lead to infection of man through the medium of mos- 
quitoes, is not decided with certainty, but it appears improbable. The plasmodia of 
the bat most closely resemble those of man, yet attempts at inoculation made by 
Dionisi gave no positive results. It may therefore be assumed that malaria would 
die out in a given region, either when all susceptible anopheles were killed, or all 
infected human individuals healed or protected from mosquito bites. 
The malarial plasmodia are stained best by the Romanowski stain, which dif- 
ferentiates the nulceus. 
The view that mosquitoes were concerned in the distribution of malaria is 
old, and has obtained in Italy since Roman times. Koch found it a popular belief 
among negroes. Manson (1896) and Bignami (1896) were the first to turn their 
attention to the problem and to give hypotheses concerning the role played by mos- 
quitoes in the spread of malaria. Bignami carried out experiments along this 
line, but came to no positive result. Ross was the first (1897~98) to determine the 
cycle of development of the malarial plasmodium of birds (usually known as proteo- 
soma). According to his investigations, the parasites taken up with the blood of the 
infected bird into the intestinal canal of mosquitoes penetrate into the intestinal 
wall, and there change into cysts in which innumerable rod-shaped germs develop. 
Becoming free, these germs gain entrance into the salivary glands of the mosquitoes, 
and thence into the organism of the bird during the act of blood-sucking. Ross 
found the parasites in the blood of the infected bird in from five to nine days after 
infection. 
About the same time, Grassi found that the distribution of malaria in man cor- 
responded to the distribution of Anopheles claviger (Fabricius) (Fig. 492), and 
not to that of the common mosquito (Culex pipiens). Basing his experiments on 
this observation, Bignami succeeded in producing malaria in healthy men by means 
of the bite of anopheles. Later Grassi in cooperation with Bastianelli and Bignami, 
succeeded in determining the life cycle of the malarial parasite. It was then shown 
that several species of anopheles native in Italy (Anopheles claviger [Fabricius] or 
Anopheles maculipennis [Meigen], Anopheles superpictus, pseudopictus, bifurcatus) 
spread the malaria occurring in man, while Culex pipiens is the host of the para- 
sites of bird-malaria. THE MALARIAL PARASITE. 
545 
The cycle of development of the malarial plasmodium is as follows: Within 
the blood (of man as well as of birds) multiplication takes place first by schizogony. 
The young form of the plasmodia, represented by a small, unpigmented body,, grows 
in the red cells (Fig. 495, 1) into a larger body (2), in whose central portion pig- 
ment-granules collect. This cell-body known as schizont shows in preparation for 
schizogony an increase of nuclei (3), and then divides into a number (varying with 
the species) of spores or merozoites (4) with the abandonment of a pigmented 
residual body. The merozoites then seek a red blood-cell (1), and the cycle is 
again begun. 
In sporogony the merozoites develop into sexual individuals, macrogametes (5) 
and microgametocytes (5a). When taken up into the stomach by blood-sucking 
mosquitoes, the sexual individuals become ripe for fertilization, the macrogamete by 
throwing off the karyosome (6), the microgametocyte through the formation of 
miicrogametes (6a). Copulation then follows (7). From the copula arises the mo- 
tile ookinete (8), which in 
the wall of the mosquito’s in- 
testine becomes the oocyst, 
in which through the divi- 
sion of the nucleus the sporo- 
blasts (9) are formed, which 
in turn break up into a large 
number of sporozoites (10), 
which (11), becoming free, 
collect chiefly in the salivary 
glands, and are thence trans- 
ferred by the bite of the 
mosquito to a new host, in 
whose blood they increase 
through schizogony (1-4). 
According to the investi- 
gations of Schaudinn, the 
macrogametes and the micro- 
gametocytes of Plasmodium 
vivax may be distinguished 
from each other in the 
earliest stages of develop- 
ment in the red blood-cell, 
and also from the schizonts, 
at first through the peculiar 
structure of the nucleus and 
later through that of the 
protoplasm. In a new infec- 
tion of tertian malaria the 
differentiation of the gametes 
began after the third attack. 
The growth takes place es- 
sentially slower than in the 
case of the schizonts. The 
pigment production is more abundant, while the nucleus is larger and less dense. 
The larvae of anopheles live chiefly in slowly flowing water. The eggs of 
Anopheles claviger require about thirty days at 20°-25° C. for the development of 
the insects, and these in turn lay eggs when twenty days old. The pupae are re- 
sistant to drying, to cold, and to contamination of the water. The mosquitoes fly 
during the evening and night, but do not rise very high above the level of the earth, 
and do not go very far away from the place of development. According to Grassi, 
Bignami, and Bastianelli, the aestivo-autumnal parasites will not develop in ano- 
pheles at a temperature of 14°~15° C., and grow only slowly at 20°-29° C.; at 
30° C. they complete their entire development up to the formation of sporozoites in 
about seven days. 
The literature concerning malarial parasites is extremely rich. The results of 
the latest investigations are given in the publications of Grassi, Schaudinn, Manna- 
berg, Nuttall, Celli, Marchiafava, Bignami, and Liihe. 
Fig. 495.—Cycle of development of Proteosoma. (After 
Schaudinn and Liihe.) i, Sporozoite (or merozoite) within 
a red blood-corpuscle; 2, schizont; 3, schizont with numerous 
nuclei; 4, schizogony, formation of merozoites; 5, macro- 
gamete (female cell) arising from a merozoite; 6, fully de- 
veloped macrogamete after extrusion of the karyosome; 5a, 
microgametocyte (male cell) arising from a merozoite; 6a, 
microgametocyte surrounded by loosened microgametes 
(spermatoza) ; 7, fertilization of the macrogamete; 8, ookinete; 
9, oocysts with sporoblasts; 10, oocysts with sporozoites; 11, 
free sporozoite. 546 
THE ANIMAL PARASITES. 
Literature. 
(Hcemosporidia.) 
Barker: Fatal Cases of Malaria. Johns Hopkins Hosip. Rep., 1895. 
Celli: Le Malaria, Rome, 1899; Die Malaria, Berlin, 1900 (Lit.). 
Celli u. Marchiafava: Die Veranderung der rothen Blutkorperchen bei Malaria- 
kranken. Fortschr. d. Med., i., 1883, iii., 1885, ix., 1891; Arch. p. le Sc. 
Med., ix., 1885, xi., 1886, xii., 1888, xiv., 1890; Ueber die Parasiten der rothen 
Blutkorperchen. Internat. Beitr., Festchr. f. Virchow, iii., Berlin, 1891. 
Celli u. Santori: Die Rindermalaria in d. Campagna. Obi. f. Bakt., xxi., 1897. 
Councilman: Unters, iiber Laveran’s Organismus d. Malaria. Fortschr. d. Med., 
vi., 1888; Further Observations on the Blood in Cases of Malarial Fever. 
Med. News, i., 1889. 
Crookshank: Flagellated Protozoa in the Blood of Diseased and Apparently 
Healthy Animals. Journ. of the Roy. Microsc. Soc., Ser. ii., vol. iv., 1886. 
Ewing: Pathological Anatomy of Malarial Fever. Journ. of Exp. Med., vol. 
vi., 1902; Malarial Parasitology. Journ. of Exp. Med., vol. v. 
Laveran: Nature parasitaire des accidents de l’impaludisme, Paris, 1881; Traite 
des fievres palustres, 1884; Les hematozoaires du paludisme. Ann. de l’lnst. 
Pasteur, i., 1887; Arch. de. med. exp., i., 1889; ii., 1890; Du paludisme et de 
son hematozoaire, Paris, 1891; Traite du paludisme, Paris, 1897. 
Laveran et Blanchard: Les hematozoaires de l’homme et des animaux, Paris, 
1895. 
MacCallum: Hsematozoan Infections of Birds. Journ. of Exper. Med., iii., 1898. 
Manson: The Mosquito and Malaria. Brit. Med. Journ., ii., 1898. 
Nuttal: Die Rolle d. Mosquitos bei Verbr. d. Mai. Cbl. f. Bakt., xxv., xxvi., 
1899; xxvii., 1900 (Lit.). 
Opie: On the Hsemocytozoa of Birds. Journ. of Exp. Med., iii., 1898. 
Ross: Mosquitos and Malaria. Brit. Med. J., i., 1899; Ann. de l’lnst. Pasteur, 
1899. 
Sambon: Life History of Anopheles. Brit Med. Journ., i., 1901. 
Thayer and Hewetson: Malarial Fevers of Baltimore. Johns Hopkins Press, 
1895. 
§ 189. Of the ciliates or infusoria occurring within the human 
organism the best known and most important is the Balantidium or 
Paramaecium coli, a unicellular animal 60-70 n long, covered with short 
uniform cilia. At its anterior end it has a short peri- 
stoma (Fig. 496, a) -which opens into a short gullet. 
The body is marked with parallel stripes and encloses a 
bean-shaped chief nucleus (b) and an accessory nucleus 
and two vacuoles. Multiplication takes place by divi- 
sion into two new individuals. It develops a permanent 
form in the shape of a spherical cyst with a firm mem- 
brane. 
Balantidium coli occurs often in the colon of swine 
without causing apparent changes. In cases of chronic 
diarrhoea in man it has been found in the dejections and 
in the colon, and probably stands in causal relation to 
the intestinal catarrh. According to investigations by 
Solowjew, Askanazy, Klimenko, and others the balan- 
tidia may penetrate into the mucosa and submucosa of 
the intestine and cause ulcers. They may also wander 
Fig. 496.—Balantid- 
ium (paramaecium) 
coli, with two con- 
tractile vacuoles. 
(After Claus.) a, 
Mouth; b, nucleus; 
c, included starch 
grains; d, foreign 
body in the act _ of 
being extruded. High 
magnification. FLAT WORMS. 
547 
Other species of ciliates have been, observed in the intestine of man, Balanti- 
dium minutum (Schaudinn, 1899) and Nyktotherus faba (Schaudinn). In the 
paunch and reticulum of ruminants, in which cellulose digestion is carried on, and 
in the blind intestine of horses, infusoria are universally present and occur in 
enormous numbers, for example Isotricha prostoma, Entodinium caudatum, Ophryos- 
colex caudatus, and others. 
II. Vermes (Worms). 
A. Platyhelminthes (Flat-Worms.) 
1. Trematoda, Sucking Worms. 
§ 190. The Trematodes or sucking-worms, are flat-worms of tongue 
or leaf shape. They possess a clinging apparatus in the form of ventral 
sucking-cups of varying number, and are sometimes furnished with 
hooks or clasp-like horny projections. The intestinal canal is without an 
anus, and is usually forked. The development 
takes place either by the direct growth to 
maturity of the embryos (miracidium) hatch- 
ing from the eggs, or by alternate generation 
through the formation of germs within the 
host. The miracidium, or ciliated embryo, 
penetrates into a snail or mussel, and there 
grows into a germ-sac (sporocyst), within 
which there develops, either directly or after 
the formation of an intermediate generation of 
germ-sacs (redice), a swarming generation of 
cercarice, which are provided with rudder-like 
tails. These lose their tails and penetrate into 
a new host (mollusks, arthropods, fish, am- 
phibia), become encapsulated, and attain sex- 
ual maturity as soon as they reach the final 
host. The germ-sacs which produce cercarise 
are designated primary germ-sacs; if they first 
form redise and then cercarise, they are called 
secondary germ-sacs. 
Fig. 497.—Distoma hepaticum with male and female sexual apparatus. (After Leuckart.) 
x 3.2. 
Fig. 498.—Eggs of Distoma hepaticum. (After Leuckart.) x 200. 
Fig.. 497. 
Fig. 498. 
Distoma hepaticum, or liver-fluke, is a leaf-shaped sucking-worm 
about 28 mm. long and 12 mm. broad (Fig. 497). The cephalic end 
projects like a beak, and bears a small sucking-cup, in which the mouth 
is placed. Close behind this, on the ventral surface, is a second sucking- 
cup, and between the two lies the sexual orifice. 548 
THE ANIMAL PARASITES. 
The uterus consists of a convoluted, globular sac behind the posterior 
sucking-cup. On each side of the hinder part of the body lie the yolk- 
sacs, and between are found the testicular canals, which branch many 
times. The forked intestinal tract (not visible in Fig. 497) is repeatedly 
branched. 
The eggs (Fig. 498) are oval, 0.13 mm. long and 0.08 mm. broad. In 
water there developes an embryo, the miracidium (Fig. 499, A), with 
cellular germ-balls (a) ; with the aid of its ciliated covering the embryo 
swims about, and seeks out a new host from the family of the mollusks 
(Limn ecus minutus). On penetration into the snail the cutaneous layer is 
thrown off, and the miracidium, which possesses an intestine, an excre- 
tion-organ and a brain-ganglion, becomes changed into a sporocyst (B), 
in which the intestine and nervous system atrophy, while the cellular 
germ-balls (B, a) form a second generation of germ-sacs, the redia 
(B, b). The redise (C), which possess an intestine (C, a), produce then 
Fig. 499.—Development of the liver-fluke. (After Leuckart.) A, Miracidium with germ-balls 
(a); B, sporocyst with germ-balls (a) and redise (b); C, redia, with intestine (a) and germ- 
balls (6); D, cercaria with mouth (a), abdominal sucking-cup (b), intestine (c), and glands (d). 
within the same host the cere aria (D) from cells which are loosened 
from their germ-matrix (C, b) ; these abandon the host and with the aid 
of a rudder-like tail swim about in the water. With the loss of their 
tails they become encysted on almost any foreign body, and reach their 
final host (usually through the food), in which they attain sexual ma- 
turity. The sexually mature animal inhabits the biliary passages; more 
rarely it is found in the intestine or inferior vena cava. The liver-fluke 
is rare in man but common in cattle and sheep. The results of its invasion, 
especially when it is present in great numbers, are obstruction and ulcera- 
tive strictures of the bile-passages, formation of biliary concretions, in- 
flammation of the tissues in the neighborhood of the bile-ducts, and 
hyperplasia of the periportal connective tissue with atrophy of the glandu- 
lar tissue. The same changes are found in cattle. In sheep, following 
marked invasion of the liver, there may develop a general cachexia. 
Distoma lanceolatum is only 8-9 mm. long and 2-2.5 mm. broad, is 
lancet-shaped, and the cephalic portion is not especially marked off from 
the body (Fig. 500). 
The skin of the body is smooth. Two irregularly lobed testicles (h) 
lie close behind the ventral sucking-cup, in front of the ovary (o) and FLAT WORMS 
549 
the uterus (a), the coils of which shine through the transparent body. 
The anterior coils are black with the ripe eggs, the others are rusty' red. 
The yellowish-white yolk-sacs (d) lie in the middle of the lateral margin. 
The oval eggs are 0.04 mm. long, and while still in the uterus con- 
tain an embryo which escapes only after several weeks following the 
casting-off of the eggs. Its metamorphoses are unknown. 
Distoma lanceolatum likewise inhabits the bile-passages, but is rare 
in man. It is of frequent occurrence in sheep and cattle. When present 
in small numbers, it causes no marked changes; but large numbers may 
excite inflammation and proliferation of the periportal connective tissue. 
Distoma spathulatum (Fig. 501) is a sucking- 
worm occurring in man in Japan and China. It is 
10-14 mm. long and 2.5-4 mm. broad. The eggs are 
0.027-0.03 mm. long and 0.015-0.018 mm. broad. The 
parasite inhabits usually the bile passages and gall- 
bladder, but may gain access to the pancreatic duct 
(Katsurada), and pass into the intestine. When 
occurring in great numbers (Katsurada counted 
4,361 in one case) it causes obstruction to the out- 
flow of the bile, and often excites more or less 
severe inflammation and proliferation of connective 
tissue. 
The parasite is found also in cats and dogs 
(Katsurada). 
Distoma Westermanni (Kerbert), or Distoma 
pulmonale (Baelz) occurs in Japan, China, and 
Corea. The worm is 7.5-10 mm. long, 5-7.5 mm. 
broad, egg-shaped, with slightly flattened ventral 
surface. The oval eggs are 0.09 mm. long and 
0.056 mm. broad. The internal organization (Fig. 
502) resembles that of the other trematodes. It 
occurs in man as well as in cats and dogs (Katsu- 
rada). It is found most frequently in the lungs, 
but occurs in other organs: the pleura, brain, liver, 
intestinal wall, peritoneum, orbital cavity, eyelid, 
scrotum, etc. In each case it occupies small cavities 
surrounded by newly formed connective tissue, and 
occurs occasionally in pairs. In the lung it may be 
found in the bronchi, the walls of which show in- 
flammatory changes (Katsurada). Its presence 
in the lung may give rise to hsemoptoe and cause death. The number of 
lung-flukes may run from twenty to thirty or even higher. Healing is 
possible after death of the parasite. 
Distoma felineum or Distoma sibiricum is a flat, almost transparent 
sucking-worm, of from 8-10 mm. in length and 1.5-2.5 mm. broad, which 
is present in the bile-passages of the cat and dog, and in a few countries 
(Siberia) has been observed in man. According to Winogradow it is the 
most common parasite in Tomsk. Askanazy observed several cases in 
Konigsberg. The sources of the infection were fish eaten raw (roach, 
Lenciscus rutilus). 
The inflammatory proliferations which the different forms of distoma 
cause in the liver of man, as well as in animals, may be followed by the 
development of carcinoma. 
Fig. 500.—Distoma lan- 
ceolatum. (After Hertwig.) 
s1, Anterior sucking-cup, 
and entrance into the 
forked intestine; s", pos- 
terior sucking-cup; h, tes- 
ticles with vasa deferentia; 
c, cirrus; u, uterus; o, 
ovary; l, duct of Laurer 
and shell-gland; d, yolk- 
stalks and duct leading to 
the shell-gland; _ w, water- 
vessel; g, ganglion. x 8. 550 
THE ANIMAL PARASITES. 
In Distoma haematobium or Bilharzia hamatobia (Fig. 503) the 
two sexes are separate. The mouth and ventral cups lie close together on 
the tapering anterior extremity. In both sexes the sexual openings lie 
close behind the ventral sucking-cup. The male is 13-14 mm. long. The 
body is flat, but in its posterior portion is rolled together to form a tube 
(Fig. 503) which serves for the reception of the female. 
The female is 16-19 mm. long and nearly cylindrical. The eggs are 
an elongated oval (Fig. 504), 0.12 mm. long, and possess a terminal or 
a lateral spine. According to observations by Sonsino, no alternation of 
Fig. 501. 
Fig. 502. 
Fig. 501.—Distoma spathulatum. (After Katsurada.) a, Mouth sucking-cup; b, intestine; 
c, uterus; d, testicles; e, yolk-stalks; f, sperm-pouch; g, ovarium, x 6. 
Fig. 502.—Distoma Westermanni, flattened by pressure, in the ventral position. (After 
Katsurada.) a, at, Mouth and abdominal sucking-cup respectively; b, intestinal loops; c, testicles; 
d, ovarium; e, yolk-stalks; f, shell-gland; g, uterus; h, excretory vessel, x 7.2. 
generations occurs in the development of Distoma Hcematobium. The 
part of intermediate host is taken by small Crustacea, into which the 
ciliated embryo, swimming around in water, bores its way to become 
encapsulated in the tissues of its host. It is probable that infection may 
be transmitted through the drinking of water containing larvae. 
The worms are found in the trunk and branches of the portal vein, in 
the splenic vein, mesenteric veins, as well as in the vessels of the rectum 
and bladder; and may pass through the inferior mesenteric vein into the 
haemorrhoidal and vesical veins, the veins of the ureter and prostate, 
and by chance into the inferior vena cava, and thence into the lungs. 
Their eggs are distributed, therefore, especially throughout the mucosa 
and submucosa of the ureters, bladder, and rectum, and occasionally FLAT WORMS. 
551 
in the liver, lungs, kidneys, and prostate. While still in the urinary pas- 
sages the cylindrical embryos (miracidia) covered with fine cilia may 
develop. Kartulis found them also in the skin of the leg and foot, and 
is of the opinion that the infection may take place not only through the 
intestine, but through the skin. 
The deposit of eggs causes severe inflammations which lead to tissue- 
destruction and to proliferations of tissue, which appear in the mucous 
membranes as papillary and polypoid formations. In the bladder it may 
lead to incrustations and concretions, and to the development of fistulous 
tracts. In the liver the process leads to connective-tissue induration. 
Following the inflammatory process, development of carcinoma may take 
place in the bladder, seminal vesicles, prostate, and in the skin (Kartulis). 
Fig. 503. 
Fig. 504, 
Fig. 503.—Distoma haematobium. (After Leuckart.) Male and female, the latter lying in 
the canalis gynaecophorus of the former, x 10. 
Fig. 504.—Eggs of Distoma haematobium. (After Leuckart.) a, Egg with terminal spine; 
b, egg with lateral spine, x 150. 
The parasite is found along the entire eastern coast of Africa, and 
also in Zanzibar, Tunis, Lake Nyassa, in Beyrout, and in Sicily. It is 
most common in Egypt, where about twenty-five per cent, of the native 
population suffers from the disease. 
2. Cestoda (Tapeworms) 
§ 191. The tapeworms are flat-worms devoid of mouth or intestine, 
which increase after the method of alternate generation through the germi- 
nation of a pear-shaped primary head or scolex, and remain united to the 
latter for a longtime as a (usually) long, band-shaped colony. The single 
segments of this colony, the sexually active individuals, or proglottides, 
increase in size the more widely they become separated from their place 
of origin by the formation of new members, but outside of this are de- 
void of any distinguishing peculiarity. The pear-shaped head or scolex, 
on the other hand, is provided with from two to four suckers, and usually 
with curved claw-like hooks. With the aid of these clinging organs the 
tapeworms fasten themselves to the intestinal wall of their host, which 
appears to be invariably one of the vertebrate animals. The scohces de- 
velop from a round embryo having four to six hooks, and are found as the 
so-called “ measles ” in different organs, chiefly the parenchymatous ones, 
from which they pass by passive migration into the intestine of their 
future host. 
The tapeworms occurring as parasites in man belong to different 
families: the Tceniadce and the Bothriocephalidce. The first occur in man 
as “ measles ” or tapeworms, the latter only as tapeworms. 552 
THE ANIMAL PARASITES. 
§ 192. Taenia solium in its fully developed condition possesses a length 
of 2-3 meters. The head (Fig. 505) is the size of a small pin-head, 
spherical in form, with rather prominent sucking-cups. The crown of 
Fig. 505.—Head of Taema solium with protruding rostellum (carmine, balsam), x 50. 
Fig. 506.—Half-developed and fully matured segments. Katural size. (After Leuckart.) 
Fig. 507.—Two proglottides with uterus. (After Leuckart.) x 2. 
Fig. 505. 
Fig. 506. 
Fig. 507. 
the head is not infrequently pigmented and bears a fairly large rostellum 
with about twenty-six plump, close hooklets having short root-processes. 
Following the head there is a thread-like neck about an inch in length. 
At a certain distance from the 
head segmentation begins, the 
first segments being short, but 
their length increases with 
their distance from the head 
(Fig. 506) ; they become 
quadratic and finally longer 
than broad. The mature seg- 
ments appear about 130 cm. 
behind the head, although the 
sexual organs are fully de- 
veloped in earlier segments. 
The ripe segments (Fig. 507) 
are, when stretched out, 9-10 
mm. long, and 6-7 mm. broad, 
and have rounded corners. 
The sexual opening is situated 
laterally just behind the mid- 
dle of the segment. The uterus, which is filled with eggs, possesses seven 
to ten lateral branches separated from each other by a wide interval, and 
which break up into a varying number of boughs branching like a tree. 
Fig. 508.—Segment of Taenia solium with fullv de- 
veloped sexual apparatus. (After Sommer.) A Sur- 
Lace,.vi7w segment; B, border of next anterior seg- 
ment; C, that of next posterior segment; a, longitudinal 
excretory trunk; ai, transverse anastomosis; b, longi- 
tudinal plasma-vessel; c, testicular vesicles; d, seminal 
ducts; e, vas deferens; f, cirrus-bag with cirrus; gporus 
genitalis; h border papilla; *. vagina; k, ovarium; l 
albumin-gland; m, shell-gland, and oviduct in front of 
same; n, uterus. TAPEWORMS. 
553 
The parenchyma of the body of mature as well as of immature proglot- 
tides, or tapeworm segments (Fig. 508), is divided into two chief layers, 
the central one being designated the middle layer, the peripheral one the 
cortical layer. The middle layer contains the sexual apparatus (Fig. 508), 
c, d, e, f, g, h, i, k, l, m, n), as well as the water vascular system 
(a), an excretory apparatus, which traverses the whole tapeworm from 
the head to the last segment in the form of two canals lying in the lateral 
border of the middle layer. The canals are connected with each other at 
the posterior end of each segment (a1) and also send out numerous fine, 
subdividing branches into the body-parenchyma. 
The sexual apparatus consists of male and female sexual organs, which 
lie close together. A number of small, clear vesicles serve as testicles 
(c) they lie chiefly in the anterior portion of the middle layer. The vas 
deferens (e), which is connected with the testicles by the seminal ducts 
(d) empties into a grooved papilla situated on the lateral border (h). 
1 he coiled end (/, g) lies in a muscular bag and may be protruded through 
the sexual opening (cirrus). The 
female sexual opening lies close be- 
hind the male orifice in the same 
sexual cloaca. The vagina (i) 
leads thence to the posterior border 
of the segment. Before this is 
reached it widens into the seminal 
vesicle, and behind this into the 
fructifying canal and the so-called 
“ globular body.” The germ-pre- 
paring organs, which must be sought 
in the immature segments, consist of 
a double ovary (k) and a single 
albumin gland (/) ; these are sac- 
like or tubular organs lying in the 
posterior portion of the segment and 
communicating with the globular body. The latter is joined to the 
anteriorly located uterus (n), which at the time of sexual maturity 
forms a straight canal. When the eggs enter the uterus from the 
globular body, in which they pass their first stage of development, the 
above-mentioned lateral branches sprout and become filled with eggs. 
During this process the remaining sexual organs disappear. 
The cortical layer of the proglottides is essentially muscular in nature, 
but in addition contains a number of so-called calcareous bodies, which are 
not entirely wanting in the middle layer as well. The musculature con- 
sists of smooth fibres, which form special groups in the suckers of the 
head. The surface of the tapeworm is covered with a clear cuticle, which 
forms the hooks on the heads. 
The eggs in the ovary are thin-skinned, pale and yellow, nearly globu- 
lar cells. In the uterus they change into yellow balls having a thick, 
more or less opaque shell, covered with closely set spicules (Fig. 509, a), 
and often surrounded by a second layer, an albuminous envelope (h) 
limited by a membrane; in it there are embedded granules (primitive 
vitelline membrane). The diameter of the eggs, not including the vitel- 
line membrane, is about 0.03 mm. 
The thick-shell spheres are not undeveloped eggs, but contain an 
embryo with six hooklets. Intra-uterine development of the embryo 
therefore takes place, the ripe segments are pregnant animals. 
Fig. 509. 
Fig. 510. 
Fig. 509.—Eggs of Taenia solium, b, With 
primitive vitelline membrane; a, without 
primitive vitelline membrane. (After Leuck- 
art.) X 300. 
Fig. 510.—Cysticercus cellulosse, with fully 
developed head in situ. (After Leuckart.) 
x 4. 554 
THE ANIMAL PARASITES. 
The further development of the embryos enclosed in the brownish 
shells takes place ordinarily in a new host. Should they gain access to the 
stomach of a hog, the egg-shell is dissolved, and the embryos, thus set 
free, penetrate into the stomach or intestinal wall. Thence they pass 
either by the blood-stream or by active migration through the tissues into 
different organs. Having reached a resting-place, the embryos undergo 
various metamorphoses and become changed in two or three months into 
a cyst filled with serum (Fig. 510), the inner wall of which shoots forth 
into a bud from which there develops a new tapeworm head, scolex, as 
well as a sac enclosing the same, 
receptaculum scolicis. 
The cyst containing a tape- 
worm head is known as a “measle” 
or cysticercus cellulosae. The 
scolices, when fully developed, pos- 
sess a circle of hooklets, suckers, a 
water-vascular system and numer- 
ous calcareous bodies in their 
body-parenchyma. If they gain 
access to the human stomach, the 
cyst is dissolved, and there 
develops through the formation 
of segments from the scolex 
(Amme), a new chain of proglot- 
tides, a new Tcunia solium. 
The Tccnia solium inhabits the 
small intestine of man, and is ac- 
quired by eating uncooked pork, 
since the “ measles ” belonging to 
this parasite occur almost exclu- 
sively in the hog and in man. By 
means of its sucking-cups and its 
circlet of hooks it clings firmly to 
the mucosa of the intestine; the 
remaining portions float in the in- 
testine. Usually but a single para- 
site is present in the intestine, al- 
though several at the same time is 
not rare. Occasionally as many as 
thirty or forty have been observed 
in one individual. They excite 
irritation of the intestinal mucosa, 
colic, and reflex disturbances of the central nervous system. 
The “ measles ” occur in the tissues of the hog, sometimes singly, 
sometimes in great numbers (Fig. 511) ; individual organs, for example, 
a muscle or the heart, may be thickly studded with them. 
In man, cysticerci occur in varied tissues — the muscles, brain, eyes, 
skin, etc. In the meninges and in the brain the measle may appear in 
the form of mulberry or grape-like collection of cysts, known as cysticer- 
cus racemosus. The cysts are for the greater part sterile, though some 
of them may contain a scolex. 
The importance of the measle depends on its location, but is in gen- 
eral slight. Its presence in the brain often causes severe disturbances, but 
Fig 51I._Cysticerci of the Taenia solium> in the 
epicardium and myocardium of a hog. TAPEWORMS. 
555 
in other cases all signs of disease may be lacking. Locally it excites 
slight inflammation, which leads to thickening of the connective tissue in 
its immediate neighborhood. The cyst may retain its vitality for years. 
After the death of the scolex the cyst contracts and there is deposited 
within it a chalky mass. The hooklets are 
preserved in this mass for a long time. In- 
fection with the “ measles ” follows the in- 
troduction of eggs or proglottides into the 
stomach of man. 
Taenia mediocanellata or saginata sur- 
passes the Tania solium not only in length, 
as it measures 4-7 metres and more, but also 
in its breadth and thickness, as well as in 
size of the proglottides (Fig. 512). 
The head is devoid of rostellum and circle 
of hooklets (Fig. 513), has a flat crown and 
four large, powerful suckers, which are 
usually surrounded by a black border of 
pigment. 
The eggs resemble those of Tcenia solium. 
The fully developed pregnant uterus (Fig. 
514) has a large number of lateral branches 
which run close to each other, and instead of 
branching dendritically divide dichotomously. 
Fig. 512. 
Fig. 513. 
Fig. 514. 
Fig. 512.—Portions of a Taenia saginata. (After Leuckart.) Natural size. 
pIG. 513. Head of Taenia saginata, retracted. Black pigmentation in and between the 
suckers. Unstained glycerin preparation, x 30. 
Fig. 514.—Segment of Taenia saginata. (After Leuckart.) X J4. 
The sexual opening lies back of the middle of the lateral border. The 
segments discharged spontaneously are for the greater part empty of 
eggs. 
The “ measles ” are found usually in the muscles and the heart, more 
rarely in the other organs of cattle (Cysticercus bovis). They are some- 
what smaller than the measles found in pork. 556 
THE ANIMAL PARASITES. 
The development follows a course similar to that of Tccnia solium. 
Malformations of this tapeworm are of frequent occurrence. 
The parasite is acquired by man through eating raw beef. It lias 
not been definitely settled whether the “ measles ” of this worm occur 
in man, but some authors (Arndt, Heller) believe that such an occurrence 
does take place. 
By means of its powerful suckers the parasite is able to cling firmly 
to the intestinal wall. Stieda has observed a case in which a tsenia 15 cm. 
long had penetrated the wall of the duodenum into the pancreas, and had 
caused tissue-necrosis and haemorrhage in its neighborhood. 
Taenia cucumerina or elliptica is 15-20 cm. long, and possesses a head with 
rostellum and circle of hooklets. It is of frequent occurrence in dogs and cats, 
but rare in man. Its cysticercoid inhabits the louse and flea of the dog, more rarely 
the flea of human beings (Grassi). 
Taenia nana, a small tapeworm of from 8 to 15 mm. in length, has a head 
with four suckers and a circle of hooklets. It has been observed chiefly in Egypt 
and in Italy. B. Grassi was able to obtain several thousands of specimens from 
two Sicilians who had suffered from severe nervous disturbances. 
According to his investigations, the taenia passes its entire develop- 
ment, from the embryo on, in the same host. Visconti (Rendiconti 
R. Instituto Lombardo, xviii., 1886) found, at the autopsy of a young 
man from northern Italy, great numbers of Tccnia nana in the lower 
portion of the ileum. In Germany it has been observed in only a few 
cases (Mertens, Leichtenstern, Roder). 
Taenia diminuta (Rud.) or flavopuncta (Weinland), minima 
(Grassi) is a tapeworm, 20-60 mm. long, and has a head without 
hooklets. It is of common occurrence in rats and mice, and has been 
observed in a few cases in man. According to Grassi and Rovelli, 
the measles live in a small butterfly, as well as in beetles. 
Von Linstow has described as Taenia africana a large tapeworm 
with scolex devoid of hooklets, which he observed among the negroes 
of German East Africa. 
Besides those which also occur in man, taeniae are of frequent 
occurrence in domestic animals, both in the carnivora and in birds, 
as well as in the herbivora. 
Tccnia marginata of the dog is a tapeworm, 1-5 m. long, provided 
with a double circle of hooklets. Its cysticercus forms cysts (cysti- 
cercus tenuicollis) of varying size in and under the serous mem- 
branes of sheep, cattle, goats, and hogs. 
Tccnia serrata is found in the dog. It is 50-100 cm. long, and 
possesses a circle of hooklets. The cysticerci (cysticercus pisiformis) 
are found in rabbits and hares. 
Tccnia ccenurus is a tapeworm of the dog, 40-100 cm. long, and 
is provided with hooklets. It passes its cystic stage most frequently 
in sheep, where it seeks the central nervous system and forms cysts 
varying in size from a millet seed to that of a hen’s egg, that contain great num- 
bers of scolices. Its presence in the brain (cocnurus cerebralis) gives rise to the 
so-called “ staggers ” of sheep. 
Fig. 515.— 
Full - grown 
Taenia echino- 
coccus. (After 
Leuckart.) X 
12. 
§ 193. The Taenia echinococcus lives in the intestinal canal of the 
dog. It is 4-5 mm. long and possesses only four segments, the most 
posterior of these surpassing in length all the rest put together (Fig. 
515). 
The small hooklets have coarse root processes and are implanted on a 
rather bulging rostellum. Their number runs from about thirty to fifty. 
The cyst-worm (hydatid) alone is found in man. It results from the 
introduction of taenia eggs into the intestinal canal. 
If the embryo wanders from the intestinal canal into an organ, it 
changes into a cyst, which is not capable of active motion. It consists of ECHINOCOCCUS. 
557 
an outer lamellated, elastic cuticle (Fig. 516, a) and a parenchymatous 
layer (b) lying internal to this, consisting of granular masses and cells, 
and containing muscle-fibres and a vascular system. When the cyst has 
reached the size of a walnut (sometimes earlier), there are formed 
from the parenchymatous layer small brood-capsules (c) which produce 
a great number of scolices. The first stage of these tapeworm heads 
consists of coarsely granular protoplasmic masses (d) lying in the wall 
of the brood-capsule; these develop further and sI\ow cavities (e) com- 
municating with the cavity of the brood-capsule, and later become dif- 
ferentiated into a tapeworm head (/) furnished with a circle of hooklets. 
The head (h), which now protrudes into the lumen of the brood-capsule, 
(g, h) is about 0.3 mm. long, possesses a rostellum with small, plump 
hooklets, four suckers, a water-vascular system, and numerous chalky 
Fig. si6.—Wall of an echinococcus-cyst containing brood-capsules and scolices (alcohol, 
carmine), a, Chitinous membrane; b, parenchymatous layer with vesicular cells; c, brood-cap- 
sules; d, e, f, g, h, scolices in different stages of development, x ioo. 
bodies‘in it's parenchyma. Frequently the anterior part of the body is 
telescoped into the posterior (g). 
In many cases the echinococcus cyst remains single. Its only change 
consists in enlargement to the size of an orange or fist, through the 
formation of new brood-capsules and heads. The surrounding tissue 
forms a capsule, in which the cuticular cyst lies. The cavity of the cyst 
is filled with clear fluid, which does not coagulate on boiling or on the 
addition of acids, and contains none or but little albumen, but does 
contain sodium chloride, calcium oxalate, triple phosphates, uric acid, 
sugar (in the liver), and often cholesterin. The brood-capsules are al- 
ways situated on the inner surface, if not mechanically dislodged; and 
are visible through the transparent parenchyma as small white points. 
Occasionally the cyst remains sterile. 
In many cases daughter-cysts (Fig. 517, c) are formed. Their de- 
velopment proceeds in the depth of the cuticle independently of the 
real parenchymatous layer. Between two lamellae of the cuticle there 
arises a collection of granules, which surround themselves with a cuticle, 
and thereby become the centre of a new set of layers. As the number 558 
THE ANIMAL PARASITES. 
of layers increases, the cavity grows larger and the contents become clear. 
If the daughter-cysts grow they bulge out the wall of the mother-cyst 
like a hernial sac, until it finally gives way and liberates its contents. 
If they now pass outward by the side of the parent-cyst, they obtain from 
the parenchyma in which they lie an external capsule of connective tissue, 
and then produce brood capsules in the same manner as the primary cysts 
arising from the six-hooked embryos. 
An echinococcus with exogenous proliferation is called echinococcus 
granulosus, or sometimes echinococcus veterinorum from the fact 
that it is of frequent occurrence among domestic animals. 
Fig. 517.—Echinococcus hydatidosus. a, Surface of liver; h, indurated connective tissue; 
c, daughter-cysts within a parent-cyst, which has been opened by an incision; d, adhesions. 
Three-fifths natural size. 
A second compound form of echinococcus is the echinococcus hydati- 
dosus. It is characterized by the presence of inner daughter-cysts (Fig. 
517, c). According to statements by Naunyn, and confirmed by Leuckart, 
the scoliees and brood-capsules undergo cystic metamorphosis, and so 
become changed into daughter-cysts which occasionally produce grand- 
daughter cysts. Through the formation of numerous daughter-cysts the 
chief cyst may attain large size. 
Infection of man follows the ingestion of the eggs of the taenia which 
occurs in dogs. The cysts are most often found in the liver, but the 
echinococcus occasionally occurs in the lungs, spleen, kidneys, intestine, 
in a bone or in the heart. With the exception of the disturbance from 
pressure and of the local inflammation which it causes (the latter leading 
to the formation of a connective-tissue capsule in many organs) the cyst 
produces no harmful effects. It often dies on attaining a certain size ECHINOCOCCUS. 
559 
(that of a walnut to an apple), the fluid is absorbed, the cyst contracts, 
and there remains in it fatty, cheesy detritus, which often calcifies. The 
hooklets are preserved for a long time. 
In other cases the echinococcus becomes larger, particularly when 
endogenous or exogenous daughter-cysts develop. It may become dan- 
gerous through size alone. Severe inflammations are occasionally pro- 
duced, particularly after trauma, or after rupture of the cyst into' one 
of the body cavities. Rupture into a blood vessel may occur and lead to 
the metastasis of cysts and embolic blocking of vessels. In more favorable 
cases rupture may take place externally or into the intestines. 
The spontaneous spread of brood-capsules and scolices in the same 
host, as well as the experimental transplantation of the same into another 
host, may lead to the formation of new cysts. 
The form known as echinococcus alveolaris or multilocularis pre- 
Fig. 518.—Transverse section of an Echinococcus multilocularis. a, Alveolar echinococcus tissue; 
b, liver tissue; c, cavity produced by softening; d, fresh nodules. Natural size. 
sents itself as a hard tumor, situated usually in the liver, rarely in other 
organs (brain, spleen, adrenal), and possesses an alveolar structure 
(Fig. 518), in that a firm, dense connective-tissue mass encloses numer- 
ous cavities. Its contents are translucent and gelatinous, or consist of 
fluid and a gelatinous substance. The cavities are spherical or irregular 
in shape. Usually, through softening and disintegration of the paren- 
chyma, ulcerative cavities (c) are formed. In other places the tissue is 
fibrocaseous, necrotic or calcified, or impregnated with bile. At times 
caseation of the proliferating tissue is the most prominent feature of the 
process; at other times the alveolar structure. When the development 
of the colonies has progressed further, there appear in the tissue gray and 
yellowish nodules (d) in which cavities containing colloid plugs (chitin- 
cysts and coils) are developed. The exquisite alveolar structure gave rise 
to the now abandoned theory that this form of echinococcus is an alveolar, 
colloid-containing tumor of the liver. Virchow first recognized the true 560 
THE ANIMAL PARASITES. 
nature of the condition, and demonstrated that the so-called colloid masses 
were echinococcus cysts. 
According to the investigations of Melnikow-Raswedenkow the alve- 
olar echinococcus is to be regarded as a different species, which increases 
in the tissue of the host in a peculiar manner, suggesting the mode of 
development of the Trematodes; and in many 
cases spreads by hsematogenous and lympho- 
genous metastases from the primary focus of 
development to other organs (lymph-nodes, 
lungs, brain). 
Should the alveolar echinococcus occurring 
in any organ, for example, in the liver, en- 
croach on neighboring tissues, there are found 
in the latter finely granular multinucleated 
protoplasmic structures surrounded by granu- 
lation tissue. Later, small chitinous cysts de- 
velop or a folded membrane studded with 
granular masses, while the granulation tissue 
becomes changed into fibrous connective tissue. 
The majority of the cysts remain sterile. 
Scolices develop only in a few. Ovoid granu- 
lar structures with a thin membrane may be 
formed, and are regarded by Melnikow as em- 
bryos. The chitinous membranes which lie in 
the granulation tissue are often surrounded by 
giant-cells. 
The life-history of the alveolar echino- 
coccus outside the parenchyma of the organ 
is unknown; feeding to dogs has given no 
positive results. It appears that the embryos 
and scolices are not capable of 
development in the intestine of 
the dog. 
The ordinary echinococcus is 
widely distributed, though not 
common. It is of most frequent 
occurrence in Iceland, where the 
inhabitants live in close associa- 
tion with dogs. The alveolar 
echinococcus has been observed 
chiefly in Switzerland, South 
Germany, Austria, and in Russia. 
§ 194. Bothriocephalus latus 
or pithead is the most formidable 
tapeworm of man, measuring 5-8 
metres in length, and consisting 
of three to four thousand short 
but broad segments (Fig. 519), which are broadest in the middle region 
and narrower at the end. The length of the largest segment is about 3.5 
mm., the breadth about 10-12 mm. 
The head (Fig. 520) has a long oval or club shape, is about 2.5 mm. 
long and 1 mm. broad. It is somewhat flattened, possesses on each mar- 
grin a slit-like depression and is mounted on a filiform neck. 
Fig. SI9. 
Fig. 520. 
Fig. 519.—Bothriocephalus latus. (After Leuck- 
art.) Natural size. 
Fig. 520.—Plead of Bothriocephalus latus of 
Bremser. (After Heller.) Enlarged. TAPEWORMS. 
561 
The body is thin and flat like a ribbon, with the exception of the central 
parts of the segments, which project somewhat outward. At this spot the 
uterus is found, in the shape of a single canal, which forms a number of 
coils (Fig. 521, m). When the eggs collect here in great numbers the 
lateral coils of the uterus arrange-themselves in folds, so that a remarkable 
rosette-like appearance is produced. The sexual openings lie in the 
middle line of the ventral surface, near the anterior border of the seg- 
ment, the female orifice (o) being close behind the male opening (/). 
The ovary (g) is a double organ which lies in the.middle layer; the 
yolk-chambers (h), on the other hand, are located in the cortical layer. 
Fig. 521.—Median portion of a proglottis of Bothriocephalus latus, seen from the dorsal 
surface. The cortical layer of the segment has been removed except a border on each side, and 
the middle layer thus exposed. (After Sommer.) a, Lateral vessels; b, testicular vesicles; c, 
testicular canaliculi; d, seminal ducts; e, posterior, f, anterior hollow-muscle apparatus (cirrus- 
sac of vas deferens); g, ovary; h, yolk-chambers lying in the cortical area; i, collecting-duct of 
yolk-stalk, branches of which lead ventrally to the yolk-chambers; k, shell-gland; l, beginning of 
the uterus; m, loop of uterus filled with eggs, the orifice of uterus opening on the anterior 
surface; n, vagina; o, vaginal opening, x 35. 
The shell-gland (k) lies behind the collecting-tube (i) of the yolk- 
chambers. The testicles consist of clear vesicles (b) which lie in the 
lateral portions of the middle layer, and communicate by means of fine 
canals (c) with the vas deferens (d), which terminates in the cirrus- 
sac (e, /). 
The eggs (Fig. 522) are oval, and about 0.07 mm. long and 0.045 mm. 
broad. They are surrounded by a thin, brown shell, the anterior pole of 
which forms a sharply outlined cap-like cover. 
The Bothriocephalus latus occurs chiefly in Switzerland, in the north- 
eastern parts of Europe, in Holland and in Japan, and lives, as does the 
Taenia, in the small intestine of man. According to Bollinger it is rather fre- 
quent in Munich. The first stage of development of the eggs takes place in 
water. After the lapse of months there develops an embryo (Oncos- 
phcera) armed with six hooklets and covered with cilise (Fig. 523). This 562 
THE ANIMAL PARASITES. 
develops, in some intermediate host as yet unknown, into a measle (Piero- 
cercoid), which, according to the investigations of Braun in the Russian 
Baltic provinces,, seeks out as second intermediate host the pike or tad- 
pole, and develops in the muscle or internal organs of these animals 
into a sexless tapeworm. According to Grassi and Parona, the measle 
of Bothriocephalus latus in Italy occurs in the pike and in the river-perch. 
In Japan it is found most frequently in the Onchorhynchus Perry (Ijima, 
Leuckart). Zschokke found it in the Lake of Geneva in the following 
forms of fish: Lota vulgaris, Perea fluviatilis, Salmo umbla, Esox lucius, 
Frutta vulgaris and Trutta lacustris. It is found most often in the tad- 
pole (Lota vulgaris) and perch (Perea fluviatilis). Should the measle 
gain entrance, through ingestion of the 
fish mentioned, into the intestinal canal of 
man, it again attains sexual maturity. Ac- 
cording to Braun and Parona the measles 
may also be brought to development in 
both dogs and cats. The presence of 
Bothriocephalus in the intestine gives rise 
to a gradually in- 
creasing anaemia, 
which resembles per- 
nicious anaemia. The 
diminution of the red 
blood-cells and of the 
haemoglobin content 
of the blood is prob- 
ably due to the fact 
that, after the death 
of the tapeworm, 
poisonous products arise having an injurious action on the blood-corpuscles 
Fig. 522.—Eggs of Bothriocephaltis latus, the one at the 
right having been emptied of its yolk-contents. (After Leuck- 
art.) 
Fig. 523.—Free embryo of Bothriocephalus latus with ciliated 
envelope. (After Leuckart.) 
Fig. 522. 
Fig. 523. 
Bothriocephalus cordatus (Leuckart) is a tapeworm, of 80-115 cm. long, 
and has a heart-shaped head, whose sucking-grooves are flattened. The breadth 
of the ripe segments is about 7-8 mm.; the length, about 3~4 mm. In Greenland and 
Iceland it is a frequent parasite of the dog, seal, and walrus, and is found occa- 
sionally in man. The measles likewise occur in fishes. 
Bothriocephalus Mansoni (Cobbold) or liguloides (Leuckart) is the measle 
(plerocercoid) of a tapeworm which has been observed a few times (Manson, 
Ijima, Murata) in the body-tissues and in the descending urinary passages or in the 
urine. Its origin is not known. 
Bothriocephalus felis, which occurs in cats, is similar to Bothriocephalus latus. 
Bothriocephalus latus occurs also in dogs. In the United States this worm is 
found occasionally in individuals who have come from various infected regions of 
Europe. In the mining regions of Northern Michigan it has been found a number 
of times in Finns. 
B. Nemathelminthes (Round Worms). 
§ 195. All the round worms which occur as parasites belong to the 
Nematoda. They possess a slender, cylindrical, elongated, at times fili- 
form body without segments or appendages. The cuticle is thick and 
elastic. The mouth opening is found at one extremity, and is provided 
sometimes with soft and sometimes with horn-like lips. The elongated 
intestine, together with the pharynx and chyle-stomach, extends through ROUND-WORMS 
563 
the entire body-cavity (Fig. 524) and 
opens on the ventral surface a short 
distance from the posterior extremity, 
■which is usually awl-shaped. The sex- 
ual organs and their openings are also 
found on the ventral surface. The fe- 
male sexual orifice is located at about 
the middle of the body, less frequently 
near the anterior or posterior extrem- 
ity (Fig. 524, A, a). In the male the 
sexual opening and the anus are to- 
gether (B, c). The chitinous covering 
of the lower gut forms in the male the 
means of clinging during the act of 
copulation. The males are usually 
smaller than the females. The develop- 
ment is direct, and the metamorphoses 
are not striking. The nematodes occur- 
ring in man are in part harmless para- 
sites of the intestine, and in part danger- 
ous, sometimes even fatal. 
§ 196. Ascaris lumbricoides, the 
common round-worm (Fig. 524) is a 
light-brown or reddish, cylindrical 
worm with tapering ends. The female 
(A) is 25-40 cm. long, the male (B) is 
much smaller, and the posterior extrem- 
ity of the latter is bent in the form of a 
hook and provided with two spicules 
(c) or chitin processes. 
The mouth (b) is surrounded by 
three muscular lips bearing fine teeth. 
The female sexual opening (A, a) lies 
anterior to the middle of the body. 
The eggs which the mature female 
carries in enormous number possess in 
their fully developed condition a double 
shell (Fig. 525) and around this an 
albuminous envelope. They are about 
50—70 fx in length. The worm inhabits 
the intestinal tract, most frequently the 
small intestine. It is the most common 
parasite of man, and is frequently found 
in great numbers. When mature fe- 
males are present the faeces contain the 
eggs in abundance. These are resistant 
to external influences, for example to 
drying and freezing. 
The eggs require no intermediate 
host (Lutz, Leukart, Grassi, Epstein). 
Man is infected by the ingestion of eggs 
which have been expelled from the 
bowel and have matured in the faeces. 
Fig. $24. 
Fig. 525. 
▼ Fig. 524.—Ascaris lumbricoides. 
(After Peris.) A, Female; B, male. 
Natural size. At a is the female 
sexual orifice; c, the two spicules of the 
male; b, the (enlarged) cephalic end with 
the three lips. 
Fig. 525.—Egg of Ascaris lumbricoides, 
with shell and albuminous covering. 
(After Leuckart.) x 300. 564 
THE ANIMAL PARASITES. 
According to feeding-experiments which Epstein carried out on human be- 
ings with eggs which had been cultivated in damp faeces for a long 
time, the round-worm attains its maturity in from ten to twelve weeks 
after the ingestion of the eggs. At this time the male is 13-15 cm. long, 
and the female from 20-30 cm. Their presence in the intestine may not 
cause any noticeable disturbance. When present in large numbers they 
sometimes, especially in children, cause intestinal catarrh, vomiting, 
nervous disturbances and convulsions. Occasionally the worm crawls 
into normal and pathological openings in the wall of the intestinal canal, 
and in this way causes trouble. Thus, when it crawls into the ductus 
choledochus, it may produce bile-stasis. If it penetrates an ulcer into 
the peritoneal cavity or into a hernia sac, it may excite inflammation of 
the tissues concerned. According to Leuckart it may penetrate the un- 
injured intestinal wall. It is frequently passed with the stools, but at 
times per os in vomiting. From the pharynx it may wander into the 
larynx. 
According to Crowell, the dangers of ascariasis are apt to be under-estimated. 
The worms may cause symptoms and even death through toxic, reflex and mechani- 
cal effects either in the larval stage, or while adult in the intestine, or in the course 
of migration to other parts of the body. The number of worms in the intestine 
varies from one or two to hundreds, occasionally producing symptoms of intes- 
tinal obstruction. Collections of worms in the sigmoid may cause palpable masses 
simulating tumor growth and the abdomen has actually been opened under this 
misconception. The worm is often found in the peritoneal cavity as a result of 
escape through any available exit, or by direct passage through the intestinal wall 
by separation of its fibers which, coming together again, leave no trace of perfora- 
tion. Sometimes the worm escapes through the umbilicus or from fistulous tracts 
in the groin or urethra. In countries where the parasite abounds, the worm not 
infrequently opens repaired wounds of the intestine with the production of fatal 
peritonitis. Migration of the ascaris into the common bile duct, gall-bladder, 
intrahepatic and pancreatic ducts is common. In this way severe infections of these 
passages arise. It may also invade the accessory nasal sinuses, the antrum of High- 
more, the lachrymal duct, Eustachian tube, larynx and trachea. The reproduction 
of ascariasis in animals and in man is often associated with the occurrence of 
broncho-pneumonia due to the presence of larva; in the respiratory passages. 
Crowell suggests that, in certain tropical countries, broncho-pneumonia in infants 
and children may not uncommonly be due to the same cause. Clinical observations 
and the therapeutic effects of vermifuges unite to incriminate the ascaris as the 
cause of all sorts of toxic and nervous phenomena — fevers, nausea, flatulence, 
abdominal pains, convulsions, tetany, symptoms of chorea, hysteria and epilepsy, 
psychic disturbances, symptoms simulating meningitis, and many other disorders of 
similar nature. The disturbances of the central nervous system are attributable to 
chronic poisoning by volatile aldehydes of fatty acids, Flury having found these and 
other pharmacologically active substances both in the body and in the excretions of 
pig-ascaris. In this climate, ascaris is not uncommon. At Bellevue Hospital we 
meet with the worm in the intestine in about 5 per cent, of all autopsies, particu- 
larly in Europeans. In the Philippine Islands, on the contrary, infestation with 
ascaris was demonstrated by Willets in 62.3 per cent, of nearly 20,000 persons. 
(Crowell, American Journal of Medical Sciences, 1920; Flury, Arch. f. exp. Path. 
U. Pharm., 1912; Willets, Philippine Journal of Science, Section B, 1911.) 
In domestic animals ascarides are of frequent occurrence. Ascaris lumbri- 
coides is found in swine (Ascaris suilla) and in cattle (Ascaris vituli). Ascaris 
megalocephala, a round worm whose female is 18_37 cm. long, is a common para- 
site of the horse and donkey. Ascaris mystax, whose female reaches a length of 
12 cm., is found frequently in dogs and cats, and has also been observed in man. 
Various species, designated as Heterakis, occur in birds. Heterakis maculosa, the 
round worm of pigeons, may cause the death of the pigeon when occurring in large 
numbers in its intestine. PINWORM. 
565 
§ 197. Oxyuris vermicularis, awl-tail, pinworm, or threadworm is a 
small round worms (Fig. 526), the female being about 10 mm. long (a, b) 
and pointed at the caudal extremity like an 
awl, while the male is about 4 mm. long (c) 
with a blunt posterior end, the anus being 
provided with a spiculum. 
The eggs (Fig. 527, a), which the body 
of the female often contains in great num- 
bers, are 50 fx long and 24 [x broad, have a 
flat and a curved surface, and a shell which 
is covered by a thin albuminous layer. 
Oxyuris vermicularis inhabits the large in- 
testine and the lower portion of the small 
intestine. According to Zenker and Fleller 
only the impregnated mature females are 
found in the large intestine, the young indi- 
viduals and the males remain in the small 
intestine. They occur frequently in larger or 
smaller numbers. At night they often 
wander from the rectum over the anal region, 
and may enter the vagina; they excite itching 
of the affected parts. In the pelvic peri- 
toneum encapsulated worms or eggs have 
been observed a number of times. It has not 
been determined whether they can penetrate 
the intestinal wall (Vuillemin). Wagener 
found dead and calcified worms in the sub- 
mucosa of the intestine. 
For the development of the eggs (Fig. 
527, a-e), it is necessary after their expul- 
sion with the faeces that they again be taken 
into the stomach of man or beast. It is prob- 
able that the original host may again infect 
himself with oxyuris, for example, the eggs becoming attached to his 
finger during the act of scratching may later get into his mouth. 
Fig. 526.—Oxyuris vertnicularis. 
a, Sexually mature female; b, female 
full of eggs; c, male. (After Heller.) 
x 10. 
Fig. 527.—Eggs of Oxyuris yermicularis in different stages of development. (After Zenker 
and Heller.) a, b, c, Segmentation of yolk; d, tadpole-shaped embryo; e, worm-shaped embryo, 
x 250. 
The eggs are resistant to drying, and in this condition may be widely 
scattered. 566 
THE ANIMAL PARASITES. 
Oxyuris is a common inhabitant of the appendix and sometimes gives rise to 
grave symptoms. Brumpt, in Paris, found pin worms in the appendix in 3.5 per 
cent, of normal cases and in 40 per cent, of all cases of appendicitis. Hoepfl, in 
Germany, demonstrated them in the appendix in 21 per cent, of all cases of appen- 
Fig. 529. 
Fig. 530. 
Fig. 528. 
Fig. 528.—Male of Anchylostoma duodenale. (After Schulthess.) a, Head witn mouth- 
capsule; b, oesophagus; c, intestine; d, anal-glands; e, cervical glands; f, skin; g, muscle-layer; 
h, porus excretorius; i, three-lobed bursa; k, ribs of the bursa; l, testicular canal; m, seminal 
vesicle; n, ejaculatory duct; o, groove of latter; p, penis; q, penis sheath, x 18. 
Fig. 529.—Cephalic end of Anchylostoma duodenale. (After Schulthess.) a, Mouth- 
capsule; b, teeth of ventral border; c, teeth of dorsal border; d, mouth cavity; e, skin pro- 
tuberance on ventral side of head; f, muscular layer; g, dorsal groove; h, oesophagus, x 100. 
Fig. 530.—Eggs of Anchylostoma duodenale. (After Perroncito and Schulthess.) a-d, 
Different stages of segmentation; e, f, eggs with embryos, x 200. ANCHYLOSTOMA DUODENALE. 
567 
dicitis. In London, Still found oxyuris in 19 per cent, of all normal childrens’ 
appendices examined at autopsy. In this country, Cecil and Bulkley found oxyuris 
in 13 per cent, of 129 cases of appendicitis in children. The oxyuris burrows into 
the submucosal tissues and its invasion is usually accompanied by extravasation of 
blood and sometimes by the formation of haemorrhagic ulcers of the mucosa. A 
characteristic feature of the lesions is absence of inflammatory reaction about 
them, except in those cases where there is secondary bacterial infection. In some 
instances the process may heal spontaneously. (Journal Experimental Medicine, 
1912.) 
§ 198. Anchylostoma duodenale (Dochmius duodenalis, or Stron- 
gylus duodenalis, Uncinaria duodenalis, Uncinaria Americana [Stiles'], 
Hook-worm, is a small worm belonging to the family of Strongylides, 
which inhabits the upper part of the small intestine (Fig. 528). The 
cylindrical body of the female is 5—18 mm. long, that of the male 6—10 
mm. The cephalic end (Fig. 529) is curved toward the dorsal surface, 
and possesses a bellied mouth-capsule (d). It is almost completely 
divided dorsally, and the cleft is covered by two chitinous lamellae. On 
the ventral border there are four incurving teeth (b), on the dorsal 
border two teeth which are perpendicularly placed (c), all being held 
together by chitinous bands. 
The male is provided at its caudal extremity with a threefold bursa 
(Fig. 528, i) and two thin, fishbone-like spicules (/>). In the female 
the posterior end is pointed, and bears an awl-shaped spine; the vulva 
lies posterior to the body centre. The oval eggs (Fig. 530) are 44-67 fx 
long, 23—40 yu. broad. They undergo the first stages of cleavage in the 
human intestine (a-d), develop further in muddy water (e, /), and may 
then, if brought into the human intestinal tract, develop into sexually 
mature animals. With its teeth the worm works its way into the mucous 
membrane as far as the submucosa, and sucks itself full of blood. Its 
point of attack is distinguishable later by a small ecchymosis in the middle 
of which there is a white spot with a central perforation. Occasionally 
there are found in the intestinal mucosa small cavities filled with blood, 
in each of which there lies a coiled-up worm. The parasites, when 
present in large numbers, cause continuous and serious loss of blood, 
which may lead to severe forms of anaemia (Egyptian chlorosis), but they 
are not infrequently found in individuals who present no symptoms of 
disease. The parasite is common in the tropics, also in Japan. Accord- 
ing to Griesinger and Bilharz about one-quarter of the native Egyptians 
suffer from this disease. The parasite was often observed in the work- 
men engaged in the Saint Gotthard tunnel. According to Menche and 
Leichtenstern the brickfields of the Rhine provinces are to a great extent 
infected with anchylostoma (brick-burner’s anaemia). 
In 1903 the worm was distributed to an extraordinary degree through- 
out the mines of the district of Dortmund, so that in the autumn of that 
year over seventeen hundred individuals infected with the worm were 
found. 
The infection takes place chiefly through larvae ingested with the 
drinking-water and food. According to the investigations of Looss and 
Schaudinn, the larvae may penetrate through the skin into the veins, 
thence are carried into the lungs, whence they wander through the 
bronchi, trachea, and larynx and into the intestinal tract. In experiments 
made on apes the larvae may be found in the intestine within -twenty-four 
hours. 568 
THE ANIMAL PARASITES. 
According to Stiles (1902), the hookworm disease of the American continent is 
due to a species distinct from that found in Europe. He distinguishes them as the 
Old-World hookworm and the New-World hookworm (Necator americanus or 
Uncinaria americana). The latter form is prevalent throughout the Southern 
United States as far north as the Potomac River, and in the West Indies, and has 
also been found in Italy, Africa, China, and the Philippines. It is a cylindrical 
worm 7“11 m.m. long, with a dorsal and ventral pair of lips, a prominent dorso- 
median buccal tooth, and four buccal lancets. In the male the dorsal ray of the 
bursa divides at the base and each branch possesses two tips. In the female the 
vulva is in the anterior half of the body. The eggs have more sharply rounded poles 
than those of the Old-World worm. It is estimated that about ninety per cent of 
the rural population of Porto Rico is infected with this parasite, and in some parts 
of Florida a similar degree of infection is reported. According to Stiles, the piney- 
wood and sandy-soil portions of the South are especially regions of infection. In 
these regions “ ground itch ” is of common occurrence, and is believed to be due to 
the penetration into the skin of the larvae of the hookworm. Among the most strik- 
ing symptoms of the American infection are anaemia, perverted appetite (“clay- 
eaters”), pain and tenderness in the epigastrium, delayed puberty, mental lassitude, 
etc. The “cotton-mill anaemia” of the South is due to a moderate degree of hook- 
worm infection. The economic importance of uncinariasis in America is great. It 
is estimated that thirty per cent of all deaths in Porto Rico are the result of hook- 
worm infection. According to Stiles, this infection is chiefly responsible for the 
inferior mental and physical condition of the poorer classes of whites in certain 
parts of the Southern States. 
Eustrongylus gigas, a palisade-worm of red color, whose female reaches 
a length of 1 metre, is a rare parasite, which has been observed a few times in the 
kidney-pelvis of man. It occurs frequently in dogs. It possesses a mouth-opening 
with six papillae; the male has on its posterior extremity a bursa with a single 
spiculum. The eggs are oval, 0.06 mm. long, and provided with a rough albumin- 
ous capsule. 
Strongylus longevaginatus, a thread-like, white worm, 26 mm. long, was 
once observed in the lung of a boy. 
In the domestic animals Strongylides occur in greater numbers than in man, 
and are in part inhabitants of the intestine, and in part of the lungs (Muller, “ Die 
Nematoden der Saugerthierlungen,” Deut. Zeitschr. f. Thiermed., xv., 1886). 
Dochmius trigonocephalus and Dochmius stenocephalus occur in the intestine 
of dogs, and give rise to anaemia similar to that produced by the Anchylostoma in 
man. 
Strongylus armatus is a common parasite of the horse, which enters the intes- 
tinal tract as an embryo, bores into the intestinal wall (Olt), thence into the liver, 
by way of the portal vein, and into the lungs and organs of the major circulation. 
Following this migration, it may develop in diverse organs and cause the formation 
of fibrous nodules, which become calcified after the death of the parasite enclosed 
in them. In the intestinal wall it may develop after direct migration or after 
embolic lodgment in the part, and leads to the formation of cavities, from which 
it again breaks through into the intestinal lumen. In the mesenteric arteries it 
attains sexual maturity, and causes thrombosis and the formation of aneurisms. 
The male of the mature worm is 20~30 mm. long; the.female, 20-55 mm. 
Strongylus tetracanthus, which inhabits the large intestine of the horse, causes 
haemorrhagic enteritis when present in large numbers. 
Strongylus paradoxus is an extremely common parasite of the lungs of hogs. 
Strongylus capillaris, Str. c'ommutatus, and Str. filaria are frequent parasites of the 
lungs of goats and sheep, and different species may be present in the same lung at 
one time (Schlegel, “Die durch Strong, capillaris verursachte Lungenwurmseuche 
der Ziege,” Arch. f. wiss. Thierheil., 25 Bd., 1899). The latter causes in sheep 
bronchitis and nodular proliferating pulmonary inflammations; through the swal- 
lowing of many embryos inflammations of the intestine may be produced. 
Strongylus rufescens and Str. paradoxus, Nematoidium ovis pulmonalis (Lyd- 
tin), or Pseudalius ovis pulmonalis (Koch) are also inhabitants of the lungs of 
sheep, the last-named causing pseudotuberculosis. Str. commutatus and Str. pusil- 
lus occur in the lungs of the hare and rabbit; Str. syngamus and bronchialus in the 
trachea of birds; and excite inflammations.. Str. micrurus (Strose, “ Bau von 
Strongylus micrurus,” Deut. Zeitschr. f. Thiermed., xviii., 1892) occurs in cows 
and calves, in arterial aneurisms as well as in the respiratory passages. 
Strongylus pusillus causes in cats a pulmonary disease resembling tuberculosis 
(Jeanmaire, “Ueber die hist. Verand. der Lunge bei der verminosen Pneumonie ANGUILLULA INTESTINALIS. 
569 
der Katze und des Hasen,” Inaug.-Diss., Freiburg, 1900). Syngamus trachealis 
(Klee, “Der ge paarte Luftrohrenwurm des Gafliigels,” Deut. Thierarzt. Wochen- 
schr., 1899) is a dangerous parasite of birds, particularly of pheasants, in the 
trachea of which it appears in great numbers, and attaches itself to the mucous 
membrane. It is easily recognized by its red color. Similar to the last-named is 
Syngamus bronchialis, which has been observed a few times in geese and ducks. 
Literature. 
(Anchylostoma and Strongylus.) 
Looss: Lebansgesc'hichte d. Anchylostomum. Cbl. f. Bakt., xx., 1896, xxi., 
1897, xxiv., 1898; Eniwanderung des Ankylostoma von der Haut aus. C. f. 
B., xxix., 1901, u. Orig. xxxiii., 1903. 
Stiles: Prevalence and Geographic Distribution of Hookworm Disease (Unci- 
nariasis or Anchylostomiasis) in the United States. Bull, of Hyg. Lab., Pub. 
Health and Marine-Hospital Service of the United States, 1903; Osier’s 
Modern Medicine, vol. i. 
Ward: Nematoda. Ref. Hdb. of Med. Sc., 2d ed., vol. vi. 
Fig. 531.—Anguillula intestinalis. 
(After Braun.) 
Fig. 532.—Female of Anguillula stercoralis, 
with eggs and embryos. (After Perroncito.) 
X 85. 
§ 199. Anguillula intestinalis (Fig. 531) is a worm of 2.25 mm. 
length, which is found in the intestine, particularly in the tropics, and in 
Italy, and has been occasionally observed in Switzerland, Germany, Bel- 
gium, and Holland (probably transported from Italy), under similar 570 
THE ANIMAL PARASITES. 
conditions as the Anchylostoma duodenale. According to the observa- 
tions of Leuckart, Golgi, Grassi, Leichtenstern, Zinn and others, the 
Anguillula intestinalis is a hermaphrodite, the eggs of which develop 
even in the intestine to embryos of 0.2 mm. in length; and, in the presence 
in the intestine of numerous parent-worms, are found in the faeces in 
great numbers. In the stools they become changed in about twelve hours 
into filaria-like larvae, which, when gaining entrance into the human 
intestine, again grow into parasitic anguillulae, which are in turn able to 
produce eggs capable of development. In addition there also occurs 
development with an intermediate sexual generation, a heterogony. 
In the event of sexual develop- 
ment the embryos grow outside the 
body in about three days into sex- 
ually mature animals (female 1.2 
mm. long, male 0.88 mm.) which 
are known as Anguillula or Rhab- 
ditis stercoralis (Fig. 532), and 
were formerly regarded as a sepa- 
rate species. The embryos of the 
separate sexual individuals develop 
into filaria-like larvae, which, enter- 
ing the intestine of man, again grow 
into parasitic anguillulae. 
According to Leichtenstern and 
Zinn the filaria-like larvae of direct 
development are more resistant than 
those of the sexual: The sexual 
mode of multiplication occurs par- 
ticularly in the anguillula, coming 
from the tropics, while in the in- 
digenous form (brick-laborers of 
Germany, Belgium, Holland) direct 
metamorphosis predominates. Leich- 
tenstern explained this by the as- 
sumption that the tropical anguillula, 
after transportation into a temperate 
zone, adapts itself to the less favor- 
able climatic conditions of the latter 
in such manner that the anguillula 
of the temperate zone favors the 
simpler mode of development which 
is the more independent of the 
climate — namely, the direct transformation of the embryo into the 
filaria-shaped larvae, which in turn grow directly into parasitic anguillulae. 
According to the statements of various authors Anguillula stercoralis, 
when present in large numbers, causes diarrhoea. According to Normand, 
Grassi, Golgi, Leichtenstern, and others, the worms are found chiefly in 
the upper parts of the small intestine. According to Leichtenstern and 
Askanazy the mature animals and the larvae penetrate not only into the 
crypts of Lieberkiihn, but also into their epithelium and into the con- 
nective tissue of the mucosa, and in cases may break through the 
muscularis mucosae. The mother animals lay their eggs in the intestinal 
crypts. The embryos when hatched wander out into the intestine. 
Fig. 533. 
Fig. 534- 
Fig. 533.—Tricocephalus dispar. (After 
Kiichenmeister and Ziirn.) A, Male; B, caudal 
end of female; a, cephalic end; b, anterior 
portion of body with oesophagus; c, stomach; 
d, intestine; e, cloaca; f, seminal duct; g, penis; 
l, bell-shaped penis-sheath, with end of penis; 
m, intestine of the female; n, anus; o, uterus; 
p, vaginal opening, x 9. 
Fig. 534.—Egg of Tricocephalus dispar. (Af- 
ter Hellar.) x 315. TRICHINAE. 
571 
Literature. 
(Anguillula Stercoralis and Intestinalis.) 
Thayer: On the Occurrence of Strongyloides Intestinalis in the United States. 
Journ. of Exp. Med., 1901. 
§ 200. Tricocephalus dispar (Trichuris, trichuria), the whipworm, 
is a common and relatively harmless parasite, though according to 
Askanazy it sucks blood from the intestinal mucosa. It inhabits the 
caecum and the neighboring portions of the intestine. It is found also in 
domestic animals. The male and female are about 4—5 cm. in length 
(Fig. 533). The anterior body-half (a, b) is thin, thread-like; the 
posterior, which bears the sexual organs (/, g, l, o, p), is much thicker, 
in the female (B) cylindrical, in the male (A) rolled up and provided 
with a spiculum (g). 
The eggs (Fig. 534) are an elongated oval, 50 /x long, and possess 
a thick brown shell, which shows at both poles a peg-shaped, glassy 
swelling. 
The first stage of development of the embryos takes place in water 
and moist earth. It advances slowly, even in summer lasting four to five 
months, and in the colder months of the year much longer. The eggs are 
resistant to cold and drying. (For the literature see Huber, “ Bibliogra- 
phic der klin. Helminthologie,” Miinchen, 1893, p. 213; Askanazy, 
“ Der Peitschenwurm,” Deut. Arch. f. klin. Med., 57 Bd., 1896; Heine, 
“Anatomie d. Tricocephalus,” Cbl. f. Bakt, xxviii, 1900). 
§ 201. Trichina spiralis occurs in two forms — the trichina of the 
intestine and the trichina of the muscles. 
The intestinal trichina (Fig. 535) is the sexually mature form, and 
is a small, white, hair-like worm scarcely visible to the naked eye. The 
female (A) is 3 mm. long, the male (B) is much smaller. The posterior 
part of the body is elongated in both sexes, and in the male (B) is pro- 
vided on the dorsal half with two conical terminal pegs, which are 
directed toward the belly and are separated from each other by four 
knob-like papillae. Instead of a spiculum the muscular cloaca is pro- 
truded outward during copulation. 
The intestinal canal begins with a muscular mouth, and this, becoming 
wider, passes into the oesophagus, which throughout its length is sur- 
rounded by the so-called cell-body — that is, by rows of large cells. The 
stomach, which follows the oesophagus, is a flask-shaped dilatation of the 
intestine, and is lined with finely granular cells. The stomach passes 
without essential change of structure into the intestine, which in the 
male unites with the seminal duct at the posterior end to form the cloaca. 
The testicles consist of a pouch, which begins near the caudal end as 
a blind sac, proceeds as far forward as the cell-bodies, and bending there, 
passes over into the seminal duct. 
The sexual organs of the female (A) consist of a single ovary, a 
uterus and a vagina, which opens externally at the junction of the first 
and second quarters. The ovary likewise forms a pouch lying close to 
the posterior end of the body, in which the round eggs develop. The 
pouch passes anteriorly into the sac-shaped uterus. 
The eggs develop in the uterus into embryos which are set free at 
birth. 572 
THE ANIMAL PARASITES. 
The muscle-trichina (Fig. 536) is a worm 0.7-1 mm. in length, 
w'hich lives in the muscles of the body. It is usually rolled into a spiral 
and lies in a capsule, which occasionally contains 
lime-salts. Between the coils of the worm there 
is a finely granular mass. 
A single capsule may contain three to five 
trichinae. 
If a piece of muscle containing living trichinae 
is taken into the stomach of a host — for example, 
man — the capsule is dissolved and the trichinae 
are set free. In the intestinal canal they attain 
sexual maturity within two and a half days, when 
copulation takes place. On the seventh day after 
the ingestion of muscle trichinae, the birth of em- 
broyos begins, and continues some time, even for 
weeks. A single female trichina may bear from 
one thousand to thirteen hundred young. Ac- 
cording to Pagenstecher, Chatin, Cerfontaine, and 
Askanazy, the female trichinae penetrate into the 
intestinal villi and deposit the embryos in the chyle- 
vessels, whence their migration begins. To what 
extent they are swept along passively by the lymph, 
or to what extent active migration is concerned in 
their spreading, is difficult to determine. When 
arriving in the muscles they penetrate the primitive 
fibres, cause the adjacent contents of the fibre to 
degenerate, and grow in about fourteen days to 
fully developed trichinae. In the neighborhood of 
the trichinae there occurs proliferation of muscle- 
nuclei. At first the muscle-trichinae are enclosed 
only by the sarcolemma, which appears thickened 
and hyaline about them. Later there occurs in the 
neighborhood inflammatory proliferation of granu- 
lation tissue which leads to the production of con- 
nective tissue on the outside of the sarcolemma 
and penetrates even within the sarcolemma tube, 
the muscle-nuclei being destroyed. Fat-cells may 
appear later in the connective tissue of the cap- 
sule, the development of the latter being especially 
marked at the poles. \ 
The intestinal trichinae have a limited life of 
from five to eight weeks. The muscle-trichinae, on 
the other hand, may live for long, possibly an un- 
limited time — that is, until death of the affected 
individual; at any rate for years, although, accord- 
ing to Ehrhardt, a few may die before encapsula- 
tion. After some time there frequently occurs de- 
position of lime-salts in the capsule, especially at 
the poles, causing it to appear glistening-white by 
reflected light, and cloudy and dark by transmitted 
light. In rare cases the trichinae after dying be- 
come calcified. 
Trichinae have been observed, besides in man, 
Fig. 535.—Sexually mature 
trichinae. A, Female; B, 
male. (After Leuckart.) 
X 120. TRICHINAE. 
573 
in the hog, cat, dog, rat, mouse, marmot, polecat, fox, marten, badger, 
hedgehog, and raccoon. Through feeding of trichinous meat muscle- 
trichinae may be developed in rabbits, guinea-pigs, sheep, dogs, etc. Man 
becomes infected through eating uncooked pork. The invasion of trichinae 
produces various phenomena in man. The introduction of trichinous 
meat into the intestine is followed by the symptoms of intestinal catarrh. 
With the invasion of the muscles there are produced pain, swelling, 
oedema, paralysis, and not infrequently fever. In the blood there occurs 
marked increase of eosin- 
ophile cells (Opie, 
Schleip). The symptoms 
are most severe in the 
fourth and fifth weeks. 
Death not infrequently 
results. The intensity 
and severity of the symp- 
toms depend on the num- 
ber of worms wandering 
into the muscles. 
The trichinae are found 
most abundantly in the 
diaphragm, tongue, inter- 
costal muscles, the mus- 
cles of the neck and 
larynx, the lumbar mus- 
cles, and are scattered 
most sparsely in the dis- 
tant muscles of the extremities. They are usually most numerous about 
the insertions of tendons. 
Fig. 536.—Encapsulated muscle trichinae. (After Leuck- 
art.) x 60. 
According to Frothingham (Jour, of Med. Res., 1906), the trichina embryos 
are found in the sinuses of the mesenteric lymph-nodes and in the liver sinusoids, 
showing that they enter the lymph-stream and are distributed by the circulating 
blood. Trichina embryos are found in the areas of haemorrhage occurring in the 
lungs. Local destruction of tissue may take place in the liver, pancreas, brain, and 
heart as a result of the parasite leaving the blood-vessel. The capsule of the ency- 
sted trichinae is formed of connective tissue which surrounds the whole of the 
invaded fibre. 
Staiibli, in 1905, recovered embryos from the heart’s blood of infected guinea- 
pigs by laking a small quantity of blood with 3 per cent acetic acid, certifugalizing, 
and examining the sediment. This method has since been successfully employed 
by Herrick and Janeway in human infection. In view of the fact that examination 
of the faeces is practically always fruitless and since consent for the removal of a 
portion of muscle for histological examination is not always to be obtained, this 
method of diagnosis is of particular value. Staiibli, Verhandlung des Kongress f. 
klin. Med., Wiesbaden, 1905; Herrick and Janeway, Archives Internal Medicine, 
1909.) 
Literature. 
(Trichina Spiralis; Trichinosis.) 
Chatin: La tricfhine et la trichinose, Paris, 1883. 
Ehrhardt: Muskelveranderungen bei Trichinose. Beitr. v. Ziegler, xx., 1896. 
Opie: Relation of Cells with Eosinophile Granulation to Infection with Trich. 
spir. Am. J. of the Med. Sc., 1904. 
Stiles: Trichinosis in Germany. Bull. 30, U. S. Bureau of Animal Indus., 1901. 
Williams: The Frequency of Trichinosis in the United States. Jour, of Med. 
Res., 1901. 574 
THE ANIMAL PARASITES. 
§ 202. Filaria or Dracunculus medinensis, the 
Guinea-worm (Fig. 537), is a thin, thread-like fe- 
male worm from 60 to 100 cm. in length. The males 
(observed by Charles) which were attached to fe- 
male filariae, were only 4 cm. long. The anterior 
extremity is rounded off, while the posterior tapers 
into a pointed tail which is curved toward the belly. 
The external covering consists of a firm cuticle, 
which at the cephalic end is thickened in the form 
of a shield. The intestinal canal is narrow and has 
no anus. The uterus, filled with young, takes up 
nearly the whole of the body-cavity. The embryos, 
which are set free by bursting of the mother-worm, 
have a firm cuticle and an awl-shaped tail. As inter- 
mediate host, the embryos seek out small crustaceae, 
in which they are probably taken into the stomach of 
man with drinking water. In Africa and Asia the 
worm is of frequent occurrence. It developes in the 
skin to sexual maturity and causes abscesses of the 
affected region. It is usually found on the lower 
extremities, especially in the region of the heels. 
Filaria sanguinis hominis is the name given to 
larva (Fig. 538) that occur 
in the blood and lymph of 
man, and are about 0.35 mm. 
in length. The sexually mat- 
ure worm is filiform, the male 
about 8 cm. long and the female 
15 cm. It is called Filaria Ban- 
crofti after its discoverer. The 
worm inhabits the lymph-vessels, 
particularly those of the scrotum 
and lower extremities, and may be 
present in large numbers. It 
causes lymph-stasis and inflamma- 
tions which lead to swelling of the 
lymph-nodes and to elephantiasis- 
like thickening of the tissue, asso- 
ciated with oedema and lymphan- 
giectasis. Purulent inflammation, 
lymph-abscesses, buboes, chylous 
hydrocele, and chylous ascites may 
appear in consequence of its 
presence. 
From the lymphatics of the 
limbs and scrotum the eggs and 
embryos (0.35 mm. long ) (Fig. 
538) pass into parts of the 
lymphatic system and into the 
blood, giving rise to haematuria, 
chyluria, and chylous diarrhoea. 
According to Manson and Scheube 
the filariae are present in blood 
Fig. 537. 
Fig. 538. 
Fig. 537.—Filaria sive Dracunculus medinensis. 
(After Leuckart.) Natural size 
Fig. 538.—Embryo of Filaria Bancrofti, _known 
as Filaria sanguinis hominis. (After Lewis.) X 
400. FILARIA. 
575 
taken from the skin only during the night; von Linstow explains this phe- 
nomenon as due to the fact that during sleep the peripheral vessels 
become dilated, and so permit the entrance of the filarise, while the capil- 
laries, being narrower during the day, do not permit such entrance. The 
hsematuria is the result of the collection of embryos in the blood-vessels 
of the urinary tract. The chyluria and the chylous diarrhoea, on the other 
hand, are due to obstruction by the parasites of the thoracic duct, thus 
causing lymph-stasis which extends to the lymphatics of the bladder and 
intestine and there occasions the escape of lymph. According to 
Scheube rupture of the lymphatics is attended by rupture of blood- 
vessels, so that blood becomes mixed with the lymph. The embryos may 
pass out through the urine. 
The distribution of the embryos is, according to Manson, accomplished 
by means of mosquitoes, which take up the parasite during the act of 
blood-sucking. In the mosquitoes they pass through a second stage of 
Fig. 539-—Female itch-mite, ventral surface, 
x 40. 
development and are then (James) after two or three weeks ready for 
the infection of a new host. Manson formerly held the opinion that they 
entered the water, and in a free condition were taken up in the water into 
the intestinal tract. The investigations of James, Low, Grassi, and Noe, 
who followed their development and migration in the body of mosquitoes, 
make it probable that they are transmitted to a new host through the bite 
of the mosquito. 
The Filaria sanguinis occurs most commonly in the tropics (Brazil, 
Egypt, Algiers, Madagascar, Zanzibar, Soudan, South China, Calcutta, 
Bahai. Guadeloupe), sometimes in the Southern States. 
Of the Acanthocephala, nematode-like worms having no intestine, and 
possessing at the anterior end a retractile proboscis set with hooklets, the 
most important is the Echinorhyncus qiqas. The male is 10-15 cm. long, 
and the female 30—50. It occurs chiefly in the intestine of the pig, and 
penetrates into the intestinal wall. According to Lindemann, it occurs 
occasionally in man. The rose chafer and the May beetle serve as inter- 
mediate hosts. 576 
THE ANIMAL PARASITES. 
Mackenzie estimated the number of filaria-embryos present in the total bulk of 
the blood of a case of hsematochyluria studied by him at from thirty-six to forty 
millions. The patient died from empyema; during the disease the filarise died. 
In domestic animals numerous filaria-species occur and inhabit different parts 
of the body. Filaria papillosa is a common parasite of the horse, donkey, and 
cattle; it lives in the serous cavities and reaches a length of from 5—18 cm. Filaria 
hcematica, a worm 3-13 cm. long, inhabits the right heart and the pulmonary artery 
Fig. 540.—Scabies (alcohol, carmine), a, Horny layer of the epidermis, perforated by 
numerous burrows of the itch-mite; b, mucous layer, and papillary body, the latter greatly en- 
larged and infiltrated with cells; c, cutis infiltrated with cells; d, section through a fully de- 
veloped itch-mite; e, eggs and embryos of different sizes; f, fseces. x 20. 
of the dog, and in this situation gives off its embryos to the blood-stream. It occurs 
particularly in America, China, and India. Filaria hcemorrhagica or multipapillosa 
causes a nodular cutaneous affection in the horse and donkey. 
Literature. 
{Filaria.') 
Blanchard: Filaria loa. Arch, de parasitol., ii., 1899. 
Charles: History of the Male of Filaria Medinensis. Scient. Mem. Med. Office 
Army of India, vii., Calcutta, 1892. 
James: On the Metamorphosis of Filaria sanguinis in Mosquitoes. Brit. Med. 
Journ., ii., 1900. 
Kaseworm u. Steinbriick: Nematoden bei Haustieren. Ergebn. d. a. P., viii., 
1904 (Lit.). 
Lothrop and Pratt: Two Cases of Filariasis. Amer. Journ. of Med. Sc., cxx., 
1900 (Lit.). 
Low: Filaria nocturna in culex. Brit. Med. Journ., i., 1900. 
Mackenzie, St.; Transactions of the Pathological Society of London, 1892. 
Manson: The Filaria Sanguinis, London, 1883; The Filaria Sanguinis Hominis 
Major and Minor, Two New Species of Hsematozoa. Lancet, 1891; ref., 
Cbl. f. allg. Path., ii., 1891. 
Sonsino: The Life-history of Filaria Bancrofti. Brit. Med. Journ., i., 1900. MITES. 
5 77 
III. Arthropoda. 
i. Arachnida. 
§ 203. The parasites included among the Arachnida are chiefly 
epizoa, which either temporarily or permanently inhabit the skin. Only 
one species — Pentastoma — occurs in the larval form in the tissues. 
The most common parasites of this group belong to the Mites (Acarina). 
The pentastoma belongs to the family of tongue-worms (Pentastomidce or 
Linguatulidce). 
(1) Acarus scabei or Sarcoptes hominis, the itch-mite, is the size 
of a pinhead with a turtle-shaped body, provided on the ventral surface 
Fig. 543. 
Fig. 54j 
Fig. 542. 
Fig. 544- 
Fig 541.—Leptus autumnalis. (After Kiichenmeister and Ziirn.) 
Fig. 542.—Acarus folliculorum hominis. (After Peris.) x 300. 
Fig. 543.—Ixodes ricinus, sucked half full of blood, x 2. 
Fig 544.—Cephalic end of Pentastoma denticulatum. (After Peris.) x 40, 
both anteriorly and posteriorly with two pairs of legs, each of which is 
furnished with bristles (Fig. 539). The anterior pairs of legs extend 
out into pedicled clinging-discs. The same arrangement is found in the 
posterior two pairs in the male, while in the female both of the posterior 
pairs end in long bristles. Several bristles are also found along the 
border of the posterior portion of the body, while the back is studded 
with tooth-like knobs. The head is round and likewise set with bristles. 
The female is nearly double the size of the male. 
The mite lives in the epidermis (Fig. 540, a, d), in which it forms 
burrows, some of which are 10 cm. long. 
In the burrows the female (d) lays the eggs, which develop in situ 
into the young itch-mites (e), which penetrate still deeper into the epi- 578 
THE ANIMAL PARASITES. 
dermis, and after repeated sheddings of their skins grow into sexually 
mature animals. The skin responds to the irritation produced by the 
presence of the mites by increased production of epithelial cells (a) and 
inflammation (c). The latter is further increased through the scratching 
of the spots which itch in consequence of the invasion. 
2. Leptus autumnalis, the harvest-mite (Fig. 541) is the red- 
colored larva of a variety of Tromhididce, which lives on grasses and 
bushes and on grain, and when occasion offers alights on the skin of man, 
where it penetrates the epithelium and causes itching and inflammation. 
3. Demodex or Acarus folliculorum hominis (Fig. 542) occurs 
either singly or in numbers in the hair-follicles of the face, as well as in 
the ducts of the sebaceous and Meibomian glands. Flausche found the 
demodex on the eyelashes in seventy-nine per cent., and Joers in sixty- 
four per cent, of the cases examined. Children under one year of age 
were free. The female is 0.4 mm. long, the male 0.3 mm. The eggs are 
deposited on the shaft of the hair or on any other portion of tissue, and 
develop after two sheddings into sexually mature animals which are 
found in the entrances to the hair-follicles and sebaceous glands, with 
their heads directed inward. The assumption that the demodex causes 
inflammation (acne, blepharitis acarica) is not supported (Joers, 
Hausche), since in spite of its presence in the great majority of cases 
signs of inflammation are wanting. 
It has on its anterior ventral surface (Fig. 542) four pairs of short 
thick feet. The head possesses a snout and two feelers. 
4. Ixodes ricinus, the wood-jack or wood-tick (Fig. 543), is a 
fairly large yellowish-brown member of the Arachnida belonging to the 
ticks. It has a black head provided with a sucking apparatus, and a dis- 
tensible leathery body. It is of common occurrence on grass and bushes, 
and sometimes alights on man or beast. By means of its sucking appa- 
ratus it draws blood from the skin and swells to a remarkable extent. 
5. Pentastoma denticulatum is the larva of Pentastoma taenoides, 
a lancet-shaped animal belonging to the tongue-worms or Pentastomidce. 
It inhabits the nasal, frontal, and maxillary cavities of various animals, 
especially of the dog, rarely of man (Laudon) and occasions inflam- 
mations. The female of the mature animal is 50—80 mm. long, and 
anteriorly from 8-10 mm. broad; the male is 16—22 mm. long, and 
anteriorly from 3-4 mm. broad. The body consists of eighty-seven to 
ninety segments, the most anterior of which bear lateral segment- 
appendages, the pairs of limbs. The eggs, which are produced in great 
numbers, are oval. The larva is 4—5 mm. long, 1.5 mm. broad, plump, 
flattened, and inhabits chiefly the liver, lung, or spleen, or more rarely the 
other organs of man and the herbivora. It occurs in the form of a small 
nodule encapsulated in connective tissue. The body consists of about 
fifty ring-shaped segments which are provided at the borders with spines 
(Fig. 544), and the cephalic end is provided with four hook-shaped feet. 
The eggs are taken in from the external world through the intestinal 
tract. The parasites set free in the intestine wander by means of a boring 
apparatus through the mesentery into the mesenteric lymph-nodes, or 
penetrate directly into blood-vessels, and are carried to the liver or even 
to the lumgs, where after shedding they develop into the encysted larvae. 
The larvae may in their wanderings gain access to the nasal cavity of their 
host, and develop into mature animals, although the further development 
usually takes place only after their reception into a new host. MITES. 
579 
According to the published reports of Tanaka a small red mite occurs in great 
numbers in different parts of Japan during midsummer, and clinging firmly to the 
skin of man causes the so-called Kedani-disease, which is characterized by inflamma- 
tion of the skin and lymph-nodes, with high fever, and often ends fatally. It is 
probable that these symptoms are due to secondary infections (proteus and strepto- 
cocci) in the bites of the mite. Argus reflexus, a tick, causes by its bite not only 
local inflammation, but nausea, diarrhoea, cardiac palpitation, asthma, etc., through 
a poison derived from its salivary glands. It is found also in pigeons. 
in domestic animals living mites occur frequently as parasites of the skin, 
and represent different species of various families (Sarcoptides, Dermatocoptes, 
Dermatophages, and Acarides). 
Sarcoptes hominis, the burrow-mite or itch-mite of man, is also found in horses 
and Neapolitan sheep. In addition still other different species of sarcoptes may be 
distinguished . as parasites of the domestic animals—for example, Sarcoptes 
squatniferus in dogs, hogs, sheep and goats, and Sarcoptes minor in cats and 
rabbits. 
Fig. 545. 
Fig. 546. 
Fig. 545.—Male of Dermatophagus communis seen from the ventral side. (After Putz.) x 50. 
Fig. 546.—Male of Dermatocoptes communis, seen from the ventral side. (After Putz.) x 50. 
Dermatophagus, the devouring-mite (Fig. 545), with a broad head, occurs in 
different animals, and different species may be distinguished. It lives on the cells 
of the epidermis and causes desquamation of tnc skin. 
Dermatocoptes, the sucking-mite (Fig. 546), with long narrow head, takes 
blood and lymph from the skin and causes inflammation. Dermatocoptes communis 
occurs in horses, cattle, and sheep. 
Dermatocoptes cuniculi is a parasite of the rabbit’s ear, and causes the ear-scab 
which usually occurs on the inner side of the auricle. 
Symbiotes equi of Gerlach is a mite which occurs chiefly on the feet of the 
heavy English and Scotch horses, and causes a moist dermatitis, often incorrectly 
called malanders. 
Dermanyssus avium is a long, red, blood-sucking mite, about 1 mm. long, and 
is often found on birds. 
Dermatoryctes mutans causes the foot-itch of chickens whereby the skin ac- 
quires a mortar-like scabby covering. 
A cams folliculorum or Demodex folliculorum, the mite of the hair-follicles, 
occurs most frequently in the dog or cat, more rarely in the hog, cattle, and the 
goat. In the dog it causes the formation of scales, falling out of the hair, and a 
pustular eruption. 
Demodex phylloides causes in swine nodular inflammations and ulcers particu- 
larly on the snout, neck, breasts and flanks, and the inner surface of the thighs. 
The purulent foci contain great numbers of the mites. The mite may develop also 
on cattle. 580 
THE ANIMAL PARASITES. 
Various species of Ixodes of the tick family occur on dogs, cattle, and sheep; 
Argas reflexus occurs on pigeons; and other forms of ticks occur on the domestic 
animals. 
Leptus autumnalis occurs also on dogs and chickens. 
Pentastoniata occur also in cattle, sheep, and goats, and in certain regions are 
very common in the first-named. 
2. Insecta. 
§ 204. The parasites belonging to the class of Insecta are for the 
greater part epizoa. In part they are but transient inhabitants of the skin, 
deriving from it their nourishment; in part they are permanent inhabi- 
tants and utilize the skin structures for the deposit of their eggs. Of the 
numerous species belonging to this class the following may be mentioned: 
(1) Pediculus capitis, the head-louse (Fig. 547), inhabits the hairy 
portions of the head, and derives its nourishment (i.e., blood) from the 
skin, by means of its feeding apparatus. Its eggs (nits) are barrel- 
Fig. 547.—Female of Pediculus capitis, seen from the ventral surface. (Ktichenmeister and 
Zurn.) X 13. 
Fig. 548.—Male of Pediculus pubis, seen from the ventral surface. (Kuchenmeister and 
Zurn.) x 13. 
Fig. 549.—Female of Pediculus vestimentorum, seen from the ventral surface. (Kiichen- 
meisten and Zurn.) x 9. 
Fig. 547. 
Fig. 548. 
Fig. 549- 
shaped and white, and are attached to the hairs by means of a chitinous 
shell. The embryo hatches in about eight days. In consequence of the 
scratching induced by the itching there often arise inflammations of the 
skin, in particular eczemas, which are often severe. 
(2) Pediculus pubis (Phthirius inguinalis), the felt or crab-louse 
(Fig. 548), inhabits the hairy parts of the trunk and extremities. Its 
habits of life are the same as those of Pediculus capitis. 
(3) Pediculus vestimentorum, the clothing or body-louse (Fig. 
549), lives in the wearing apparel, and lays its eggs in the same. It gets 
on man to obtain its nourishment. 
(4) Cimex lectularius, the bedbug, dwells in beds, floors, closets, etc. 
During the night it gets on man to suck blood. It causes wheals in the 
skin. 
(5) Pulex irritans, the common flea, also draws blood from the skin. 
At the point where it has sucked there is found a little punctate haemor- 
rhage. Occasionally it causes wheals and swellings. It lays its eggs in 
the cracks of floors, in sawdust, etc. MOSQUITOES; FLIES. 
581 
(6) Pulex penetrans (Sarcopsylla penetrans), the sand flea, occurs 
in South Africa in the sand. The female lays her eggs in the skin 
thereby causing intense inflammation. 
(7) Mosquitoes provided with stinging and sucking apparatus 
(Culicidce and Tipulidce), horse-flies (Tabanidce), and flies (Stomox- 
yidce) draw blood frequently from the skin of man. Various flies 
(CEstridce, biting bot-flies, Muscidce or blow-flies) occasionally lay their 
eggs in the skin, in ulcers or wounds, or in the accessible body-cavities, in 
consequence of which the maggots developing cause local destruction of 
tissue and inflammation (myiasis). Under certain conditions their larvae 
(for example, that of Anthomia canicularis, Fig. 550) may get into the 
Fig. 550. 
Fig. 551. 
Fig. 552. 
Fig. 553. 
Fig. 550.—Larva of Anthomia canicularis. (After Braun.) About X 6. 
Fig. 551.—Larva of Musca vomitoria. (After Braun.) About X 6. 
Fig. 552.—Larva of Lucilia macellaria. (After Braun.) About x 6. 
F!G. 553.—Larva of Dermatobia cyaniventris. (After Blanchard.) About X 6, 
intestinal tract with the food and there undergo further development 
(myiasis intestinalis). This is especially likely to occur when abnormal 
conditions which interfere with digestion are present in the stomach and 
intestine. The eggs of the Muscidce (in Europe usually of Sarcophila 
wohlfarti and Masca vomitoria [Fig. 551], in America of Compsomyia 
or Lucilia macellaria [Fig. 552], and Musca anthropophaga), when laid 
on the mucous membranes or in wounds, hatch after a few hours, and 
cause destruction of the neighboring soft parts through their efforts to 
obtain nourishment. In the auditory canal, nose, and antrum of High- 
more the bones may be laid bare (myiasis mucosa). In the course of 
about a week the larvae leave the ulcers and pass into the pupa stage in 
the earth. The CEstridce (in Europe, Hypoderma bovis and Hypoderma 
diana; in America, Dermatobia cyaniventris [Fig. 553] or Cuterebra 
noxialis) lay their eggs on wounds or in the intact skin. The larvae, 
hatching soon, penetrate into the cutis by means of their hooklets, and 
after several sheddings grow in from one to six months into larger larvae 
about 2 cm. long. They cause, particularly in their later stages, painful 
swellings of the neighboring tissue (myiasis cestrosa). 582 
THE ANIMAL PARASITES. 
Parasites belonging to the Muscidce and Oestridce play a more important role in 
the case of the domestic animals than in man; and the larvae of the species of 
Oestrus in particular occur as parasites in animals. For example, the larvae of 
Gastrophilus equi (Fig. 554), Cast, pecorum and Cast, hcemorrhoidalis inhabit the 
stomach and adjacent portions of the intestinal tract of the horse, where they com- 
plete their development up to the pupa- 
stage, when they leave the animal. 
Oestrus ovis lays its larvae in the 
nasal cavities of sheep, whence they may 
wander, under certain conditions, into 
the frontal, nasal, and maxillary cavities, 
or even into the cranial cavity, and ex- 
cite inflammation. 
Hypoderma or Oestrus bovis, the 
biting fly, or bot-fly, lays its eggs on the 
skin of cattle. The larva bores into the 
skin and enters the spinal canal of cattle, 
completing here its development up to 
the pupa-stage, at which time it leaves 
the animal. According to Schneidemiihl, 
the larvae do not always enter through 
the skin, but are often taken in with the 
food, whereupon they penetrate through 
the wall of the oesophagus toward the 
skin and spinal canal. The latter follows 
from the fact that they are found in the 
wall of the oesophagus from October to January, and under the skin, on the other 
hand, from January to April. In the skin they cause the so-called “fly-boils.” 
Sarcophila wohlfarti (Sarcophaga magnified) lays its larvae on the skin of horses, 
sheep, cattle, dogs, a»d geese. Lucilia macellaria lays its eggs between the hind legs 
of lambs suffering with diarrhoea. The larvae seek the thick-wooled portions of the 
root of the tail and the lumbar region and bore into the skin. 
Fig. 554.—Gastrophilus eaui. (After Brauer.) 
a, Male; b, larva. GENERAL INDEX. 
Abdomen, congenital fissure of, 405 
Abrachius, 409 
Abscess 
chronic, 279 
definition of, 258, 276 
Acanthocephala, 575 
Acardius, 417 
Acarus folliculorum hominis, 578 
scabei, 577 
Achorion Schonleini, 521 
Achromatopsia, 38 
Acid-fast bacilli, 474 
Acrania, 400 
Acromegaly, 63 
status lymphaticus and, 68 
Actinomyces, 505 
Actinomycosis, 505 
Addison’s disease, 65 
status lymphaticus and, 68 
Adenocarcinoma, 366 
Adenocystoma, 349 
Adenoma, 344 
Adenomyoma, 313 
Adenosarcoma, 372 
Adhesions, formation of, 272 
Adipositas, 147 
Adiposis dolorosa, 296 
2Egagropilae, 180 
Agglutination, diagnostic use of, 94 
Agglutinative thrombi, 111 
Agglutinins, 94 
Aggressins, 29 
Agnathia, 404 
Albinism, 200 
Albinos, 200 
Alexins, 78, 79 
Algor mortis, 130 
Alkaloids, cadaveric, 23 
Alveolar echinococcus cysts, 559 
Amelus, 409 
Amoebae, 525 
Amphimixis, 43 
Amyelia, 396 
Amyloid 
experimental production of, 168 
incidence of, 166 
occurrence of, 166 
origin of, 169 
stains for, 165 
Amyloid degeneration, 164 
Amyloid infiltrations, 170 
Anabiosis, 7 
Anaemia, 100 
anchylostoma duodenale in, 657 
and bothriocephalus latus, 562 
Anaemia, blood-sucking worms in, 32 
“ cotton-mill,” 568 
local, 102, 105 
Anaesthetic leprosy, 499 
Anaphylaxis, 95 
Anaplasia, 363 
Anasarca, 120 
Anchylostoma duodenale, 567 
Androgynes, 413 
Anencephalus, 401 
Aneurism, cirsoid, 309 
Angioma, 303 
arteriale racemosum, 309 
hepatic, 306 
lymphaticum, 309 
Angioneurotic oedema, 121 
Anguillula intestinalis, 569 
Anhydraemia, 100 
Anthrax, 452 
Antibodies 
bactericidal, 80, 82 
globulicidal, 80 
Antitoxins, 80, 82, 83, 95 
Anus, malformations of, 408 
Apparent death, 131 
Appendix, oxyuris in, 566 
Aprosopia, 403 
Arachnida. 577 
Argyria, 18, 199 
Arrhinencephalus, 401 
Arsphenamine, untoward effects of, 17 
Arterioliths, 115 
Arthropodes, 32, 577 
Ascariasis, dangers of, 564 
Ascaris lumbricoides, 563 
Asiatic cholera. 511 
Aspergillus, 518 
mycoses, 520 
Asphyxia, 3 
Atmospheric pressure, effects of sudden 
lowering, 10 
Atrophy, 5, 141 
active, 143 
degenerative, 143 
disuse, 144 
neuropathic, 144 
nutritional, 144 
of fat tissue, 147 
passive, 143 
pressure, 144 
senile, 143 
simple, 143 
Autointoxication, 46 
application of term, 58 
eclampsia as a form of, 58 584 
GENERAL INDEX. 
Autointoxication, mode of origin, 56 
varieties of, 57 
Autolytic degeneration, 146 
Avian tuberculosis, 487 
Bacillary dysentery, 459 
Bacilli, 449 
acid-fast, 474 
encapsulated, 463 
pathogenic, 451 
saprophytic, 450 
Bacillus 
aerogenes capsulatus, 462 
amthracis, 451 
botulinus, 450 
coli communis, 458 
comma, of cholera, 511 
diphtherise, 464 
Ducrey’s (chancroid), 468 
dysenterise, 459 
enteritidis, 459 
Friedliinder’s, 462 
influenzae, 463 
leprae, 497 
mallei, 502 
mucosus capsulatus, 462 
pestis, 466 
phlegmones emphysematosae, 462 
pneumoniae, 462 
prodigiosus, 451 
proteus vulgaris, 451 
pseudo-diphtheriae, 466 
pyocyaneus, 451, 460 
subtilis, 451 
tetani, 460 
tuberculosis, 468 
typhi abdominalis, 456 
Bacillus of 
anthrax, 451 
blue-pus, 451, 460 
bubonic plague, 466 
chancroid, 468 
cholera, 511 
diphtheria, 464 
dysentery, 459 
glanders, 502 
influenza, 463 
leprosy, 497 
malignant oedema, 461 
rhinoscleroma, 503 
tetanus, 460 
tuberculosis, 468 
typhoid fever, 456 
Bacteria 
action on tissues, 429 
and chemical conditions, 425 
and double infections, 429 
and temperature conditions, 425 
and transformations of nutrient ma- 
terial, 427 
avenues of entrance into body, 25 
cocci, forms of, 432 
development of, 424 
diplococcus intracellularis menin- 
gitidis, 442 
fission-fungi, morphology and bi- 
ology of, 423 
Bacteria, general considerations, 423 
general effects, 26 
gonococcus, 446 
identification and growth of, 430 
infection by, 22 
influence on animal organism, 431 
intoxication by, 25 
local effects, 25 
method of increase, 24, 27 
method of spread, 24, 26 
micrococcus of gonorrhoea, 446 
micrococcus pyogenes, 444 
pneumococcus, 440 
polymorphous, 449 
products of, 25, 428 
relation to infection, 23 
saprophytic, 450 
schizomycetes, infection by, 428 
secondary infection by, 429 
staphylococcus pyogenes albus and 
citreus, 446 
staphylococcus pyogenes aureus, 444 
streptococcus pyogenes, 434 
transmission to foetus, 27 
variation in virulence of, 429 
Bacterisemia, 26 
Bacterial proteins, 24, 29 
Bacterial toxins, 23 
Balantidium coli, 546 
“ Barber’s itch,” 522 
Bedbug, 580 
Bedsore, 138 
Beggiatoa, 499 
Beri-beri, 15 
Bezoar stones, 180 
Bilharzia hsematobia, 550 
Biliary calculi, 180 
Blastomycetes, 515, 519 
Blastomycosis, 30, 519 
Blood 
coagulation of, 106 
platelets, 109 
regeneration of, 226 
stagnation of, 118 
Blood-poisons, 18 
Blood-pressure, 97 
Blood-vessels, regeneration of, 220 
Boil, Delhi, 533 
Bone, regeneration of, 225 
Bone-marrow, Martland’s tumor of, 328 
Bothriocephalus 
cordatus, 562 
fells, 562 
latus, 560 
Mansoni, 562 
Botulismus, 15, 450 
Bovine tuberculosis, 487 
Brachygnathia, 404 
Branchial cysts, 404 
Bronchial calculi, 180 
Bubonic plague, 466 
Burns, 6 
Cachectic oedema, 123 
Cachexia, 4 
suprarenal, 65 
thyreopriva, 61 GENERAL INDEX. 
585 
Circulation, disturbances of, 97 
collateral development of, 106 
in inflammation, 243 
Cirsoid aneurism, 309 
Cladothrix, 449 
Cladothrix asteroides, 510 
Clinical signs of inflammation, 242 
Cloudy swelling, 144 
Club-foot, 410 
Coal-dust, pigmentation by, 198 
Coagulation necrosis, 134 
Cocci, 432 
diplococcus intracellularis menin- 
gitidis, 442 
diplococcus pneumoniae, 440 
gonococcus, 446 
micrococcus of gonorrhoea, 446 
micrococcus pyogenes, 444 
pneumococcus, 440 
staphylococcus albus and citreus, 446 
staphylococcus aureus, 444 
streptococcus lanceolatus, 440 
streptococcus pyogenes, 434 
Coccidia, 534 
reproduction of, 537 
Coccidioidal granuloma, 30, 519 
Coccidium oviforme, 535 
Colds, 6 
Collateral circulation, development of, 
106 
Colliquation necrosis, 136 
Colloid, 160, 162 
Comma bacillus, 511 
Commotio cerebri, 13 
Concretions, 179 
amyloid, 164 
calcification of, 174, 177 
corpora amylacea, 170 
hyaline, 162 
Concussion 
effects of, 12 
sequelae of, 12 
Congenital syphilis, 495 
Congestion, hypostatic, 105 
Conglutination, 112 
Connective-tissue, regeneration of, 222 
Contagion, direct, 22 
Copraemia, 57 
Cornification, 163 , 
Corpora amylacea, 170 
Corpulence, 36 
Craniopagus, 419 
Craniorachischisis, 400 
Crenothrix, 449 
Cretinism, 62 
Croupous inflammation, 252 
Cruor, 107 
Cutaneous horns, 204 
Cyanosis, 98 
Cyclopia, 401 
Cystadenoma, 349 
multiple, of kidneys, 352 
Cysticercus cellulosae, 554 
Cystocarcinoma, 352, 374 
Cystoma 
adenocystoma, 349, 352 
papillary, 343 
Cachexia, tumor, 291 
Caisson disease, 10 
Calcification, 174 
ossification and, 177 
Calculi, 179 
urinary, 182 
Calmette’s reaction, 477 
Carcinoma, cancer, 352 
adenocarcinoma, 366 
chorioncarcinoma, 370, 379 
coccidia in, 535, 538 
conditions favoring, 353 
durum, 368 
gelatinous, 370 
gigantocellulare, 371 
hyaline spherules in, 163 
infiltrative growth of, 355 
metastasis of, 356, 376 
mucoid, 370 
parasites, as possible cause of, 354 
retrograde changes in, 356 
sarcocarcinoma, 372 
scirrhous, 368 
secondary changes in, 370 
simplex, 367 
tubular, 367 
Carcinomatosis, 378 
Cardiopathy, idiopathic, 63 
Carotinsemia, 199 
Cartilage, regeneration of, 225 
Caseous necrosis, 135 
Castration, effects of, 66 
Catarrhal inflammation, 252 
Cell-division, 
atypical. 216 
mechanism of, 214 
Cephalocele, 401 
Cephalothoracopagus, 419 
Cercomonas, 527 
Cerebral concussion, 13 
Cestodes, 551 
Chancre, 491 
Chancroid, bacillus of, 468 
Cheilo-gnatho-palatoschisis, 403 
Chemotaxis, 77, 254 
Chemotropismus, 77 
“Chicken-fat” clots, 107 
Chilblains, 6 
Chills, 71 
Chlorosis, Egyptian, 567 
Choking, 3 
Cholfemia, 57 
Cholera, 511 
Cholesteatoma, 344, 381 
Cholesterin, 155 
Chondroma, 297 
Chondrosarcoma, 299 
Chordoma, 300 
Chorion-carcinoma, 363, 370, 379 
Chorio-epithelioma. 363, 370, 379 
and teratoma, 388 
Chromafifine cells, 65 
Chronic inflammation, 276 
Chyluria, 128 
Ciliates, 546 
Cimex lectularius, 580 
Circulation 586 
GENERAL INDEX. 
Cysts, 201 
branchial, 404 
echinococcus, 556 
ectodermal, 381 
teratoid, 380 
Cytolysins, 93 
Cytotoxins, 93 
Darier’s disease, 538 
Deaf-mutism, 38 
Death, 130 
apparent, 131 
Decubitus, 138 
Degeneration, 144 
amyloid, 164 
autolytic, 146 
fatty, 146, 151, 152, 154 
hyaline, 171 
hydropic, 146 
lardaceous, 164 
mucous, 158 
Zenker’s, 163 
Degenerative atrophies, 143 
“ Delhi boil,” 533 
Demodex, 578 
Dercum’s syndrome, 296 
Dermatitis, blastomycetic, 519 
Dermoid cysts, 381, 384 
Dermoids, 381, 384 
Desmoid, 292 
Diabetes mellitus, 59 
and acromegaly, 64 
changes in Islands of Langerhans 
in, 60 
experimental production of, 60 
Diapedesis, 125 
Diathesis, 126 
Dicephalus, 418 
Diphtheria, 465 
Diphtheritic inflammation, 260 
Diplococcus 
intracellularis meningitidis, 442 
pneumoniae, 440 
Diprosopus, 418 
Dipygus, 419 
Disease 
Addison’s. 65 
caisson, 10 
Darier’s, 538 
due to disturbances of internal 
secretions, 59 
Graves’, 63 
hookworm, 567 
hypersusceptibility to, 33, 34, 35 
immunity to, 33 
inheritance of pathological qualities, 
39 
Hodgkin’s, 326 
Nagana, 531 
Paget’s, 538 
secondary, 54 
trophoneurotic, 56 
tsetse-fly, 531 
Distoma 
felinum, 549 
haematobium, 550 
hepaticum, 547 
Distoma, lanceolatum, 548 
pulmonale, 549 
sibiricum, 549 
spathulatum, 549 
Westermanni, 549 
'Disuse atrophy, 144 
Diverticulum, Meckel’s, 406 
Dochmius duodenalis, 567 
Dourine, 532 
Dracunculus medinensis, 574 
Drill-bone, 302 
Dropsy, 120 
Ducrey’s bacillus (chancroid), 468 
Dwarfism, 36 
Dyschromatopsia, 38 
Dysentery 
amoebic, 525 
bacillus of, 459 
Ecc-hondroses, 299 
Echinococcus cysts, 556 
Eclampsia, 58 
Ectodermal cysts, 381 
Ectopia 
cordis, 405 
of urinary bladder, 405 
Eczema marginatum, 522 
Egyptian chlorosis, 567 
Ehrlich’s side-chain theory, 91 
Elastic fibres, regeneration of, 224 
Electric discharges, 11 
Elephantiasis, 203, 411 
Emboli, secondary changes in, 116 
Embolism, 47 
air, 52 
fat, 50 
paradoxical, 48 
Embolus, 47 
fate of. 51 
straddling, 51 
Embryoma, Wilms’, 372, 385 
Emphysema, traumatic, 52 
Emphysematous gangrene, 137 
Empyema, 258 
Encephalocele, 401 
Enchondroma, 297 
Endothelioma. 329, 334 
Endotoxins, 24, 28 
Entozoa, 31 
Enzymes, 28 
Epidemic, 21 
Epidermoids, 381 
Epinephrin, 66 
Epithelial pearls, 365 
Epithelial tumors, 283, 341 
Epithelioma, 364 
chorion, 363, 370 
contagiosum, 535 
papillary, 342 
Epithelium, regeneration of, 218 
Epispadias, 407 
Epizoa, 31 
Ergot, effects of, 18 
Erysipelas, 435 
Erythrasma, 523 
Eunuchoidism, 67 
Eurotium, 518 GENERAL INDEX. 
587 
Eustrongylus gigas, 568 
Exencephalus, 401 
Exophthalmic goitre, 63 
Exostoses, 300 
multiple, 303 
External genitals, development of, 415 
Extremities, duplication of, 411 
Extrophy, 406 
Exudates, 244 
absorption of, 262 
catarrhal, 252 
croupous, 253 
distribution of, 247 
fate of, 249 
fibrinopundent, 258 
fibrinous, 254 
fluid, 245 
haemorrhagic, 255 
purulent, 257 
serofibrinous, 252 
seropurulent, 258 
Exudation, inflammatory, 244 
mechanism of, 246 
Eye, regeneration of, 233 
False hermaphrodism, 413 
Fat-cells, embryonal, 297 
Fat deposit, 146 
Fat stains, 147 
Fats 
animal, 150 
body, nature of, 155 
food,151 
from albumin, 151 
from carbohydrates, 151 
glandular, 150 
granule-cells, 151 
synthesis of, 151 
Fatty degeneration, 146, 151 
transportation of fat in, 152, 154 
Favus, 521 
Fever, 69 
significance of, 84 
Fever, Gamba, 532 
Fever, malarial, 539 
development of parasite, 545 
in animals, 543 
mosquitoes in, 544 
Fever, relapsing, 514, 528 
Fever, typhus 
parasites in, 539 
Fibrin, in inflammatory exudates, 254 
Fibrin thrombi, 111 
Fibrinopurulent inflammation, 258 
Fibroma, 291 
intracanalicular, 348 
multiple, of skin, 319 
Fibromyoma, 312 
Fibrosarcoma, 321 
Filaria, 574 
Fission-fungi, 423 
Fissura 
abdominalis, 405 
genitalis, 406 
sterni, 405 
vesicae urinariae, 406 
Fistulous tracts, 258 
Flagellates, 527 
Flat-worms, 547 
Fleas, 580 
Flies, 581 
Foetus 
papyraceus, 416 
transmission of bacteria to, 27 
transmission of tuberculosis to, 484 
Food and water, effects of total depriva- 
tion of, 4 
Foreign-body gianit-cells, 267 
Formative cells, 223 
Freckles, 310 
Friedlander’s bacillus, 462 
Frolich’s syndrome, 296 
Fungus of favus, 521 
Gall-stones, 180 
Gamba-fever, 532 
Gangrene, 137 
Gas-phlegmon, 462 
Gastroschisis, 405 
Gelatinous carcinoma, 370 
Genitalia 
development of, 414 
malformation of, 406 
Germinal acquisition, 44 
Germinal transmission, 44 
Giant-cell carcinoma, 371 
Giant-cells, 217 
foreign-body, 267 
in tuberculosis, 471 
syncitial, 218 
Giant-growth, partial, 411 
Giantism, 36, 203 
acromegalic, 64 
Glanders, 502 
Glioma, 316 
Globular thrombi, 114 
Glycogen,156 
Glycosuria, 59 
Goitre, exophthalmic, 63 
histological changes in, 63 
iodine content in, 62 
Gonococcus, 446 
Gonorrhoea, 447 
Gout, 36, 178 
Granular degeneration, 144 
Granulation-tissue, 265 
tuberculous, 478 
Granuloma, infective, 279 
actinomycosis, 505 
blastomycosis, 30, 519 
coccidiosis, 30, 519 
glanders, 502 
leprosy, 498 
rhinoscleroma, 503 
syphilis, 490 
tuberculosis, 468 
Gravel, 182 
Graves’ disease, 63 
“ Ground itch,” 568 
Gummata, 493 
Gynaecomastia, 412 
Hemangioma 
cavernosum, 305 588 
GENERAL INDEX. 
Haemangioma, hypertrophicum, 308 
simplex, 303 
Haemangiosarcoma, 333 
Haematogenous infection, 26 
Haematogenous pigments, 188 
haematoidin, 189 
haemosiderin, 190 
Haemochromatosis, 188, 191 
Haemofuchsin, 187 
Haemoglobinaemia, 191 
Haemolysins, action of, 93 
Haemophilia, 126 
Haemorrhage, 123 
diabrosin, 125 
diapedesin, 125 
rhexin, 125 
Haemorrhagic inflammation, 255 
Haemosporidia of malaria, 539 
Hair-fungi, 509 
Haptins, 29, 93 
Haptophorous group, 29 
Harvest-mite, 578 
Healing, 262 
of carcinoma, 373 
of wounds, 269 
Heart 
action of, 97 
effect of poisons on, 21 
impaired action. 98 
increased action, 100 
Heart, diseases of, 97 
hypertrophy, 99, 102 
valvular lesions, 99 
Heart-muscle, regeneration of, 229 
Heat-stroke, 5 
Height of body, average, 206 
Hemicrania, 400 
Hereditary syphilis, 495 
Hermaphrodism, 412 
types of, 413 
Hernia 
cerebri, 401 
umbilical, 405 
Herpes tonsurans, 521 
Herxheimer’s reaction, 18 
High-tension currents, effects of, 11 
Histoid tumors, 282 
Hodgkin’s disease, 326 
Hook-worm, 568 
Horns, cutaneous, 204 
Hunterian chancre, 491 
Hyalin 
concretions, 162 
epithelial, 161 
nature of, 173 
spherules in cancer, 163 
Hyaline degeneration, 171 
Hyaline products, 173 
Hyaline thrombi, 111, 114 
Hydrencephalocele, 401 
Hydromeningocele, 398 
Hydromyelocele, 398 
Hydropic degeneration, 146 
Hydrops, 120 
Hyperaemia, 98 
active, 103 
local. 1P2 
Hyperaemia, passive, 103 
Hyperkeratosis, 163 
Hypermas'tia, 412 
Hyperplasia 
definition of, 203 
of adipose tissue, 147 
Hypersusceptibility to disease, 33 
age, and, 34, 35 
variations in, 34 
Hyperthelia, 412 
Hyperthyreosis. 63 
Hyperthyroidism, 63 
Hypertrichosis, 204 
Hypertrophy, 5 
compensatory, 213, 220 
definition of, 203 
varieties of, 206 
Hyphomycetes, 514 
Hypochondria, 14 
Hypospadias, 407 
Hypostasis 
livores, 105 
postmortem, 105 
Hysteria, 14 
Ichthyosis, 204 
Ichthyotoxin, 16 
Icterus, 195 
haematogenous, 196 
haemolytic, 197 
hepatogenous, 196 
of new-born, 198 
Idiosyncrasy, 33 
Immunity, 33. 74 
acquired, 85 
artificial, 85 
natural, 75 
Immunization 
active, 86 
passive, 86 
Induced thrombi, 113 
Infarcts, 123, 126 
anaemic, 126 
embolic, 127 
haemorrhagic, 126 
uric acid, 182 
Infection 
baoterial, 22 
climate and, 23 
cryptogenic, 27, 438 
definition of, 21 
entrance of bacteria in, 25 
epidemic, 21 
general effects of. 25 
haematogenous, 27 
intrauterine, postconceptional, 44 
local effects of, 25 
lymphogenous, 27 
metastasis in, 26 
method of spread, 21 
mixed, 27 
parasitic. 22 
production of poisons in, 23, 28 
relation of bacteria to, 23 
relation of moulds to, 29 
secondary, 27 
spread of bacteria in, 24 GENERAL INDEX. 
589 
Infection, status lymphaticus and, 68 
streptococcus, 434 
transmission by insects, 32 
wound, 34 
Infiltrations, 129 
amyloid, 170 
haemorrhagic, 123 
hydropic, 144 
(Edematous, 119 
of lymph, 128 
Inflammation, 242 
arrangement of fibrin in, 252 
by continuity, 243 
catarrhal, 252 
causes of, 242 
chronic, 276 
clinical signs of, 242 
coagulation in, 250 
croupous, 252 
designations of, 251 
diphtheritic, 260 
disturbances of circulation in, 243 
ectogenous, 243 
effusions in, 250 
emigration of white cells in, 244 
escape of fluid in, 245 
excretory, 243 
fibrinopurulent, 258 
haematogenous, 243 
metastatic, 243 
nature of changes in, 245 
necrotic, 259 
parenchymatous, 250 
purulent, 257 
removal of cause in, 263 
serofibrinous, 252 
seropurulent, 258 
streptococcal, 434 
superficial, 250 
tissue infiltrates in, 247 
tissue lesions in. 243 
tissue proliferation in, 245, 263, 264 
tuberculous, 477 
Inflammatory oedema, 123 
Influenza, 464 
Infusoria, 546 
Inheritance of pathological qualities, 39 
Insects, 580 
conveying infection, 32 
Insolation, 6 
Internal genitals, development of, 414 
Internal secretions, diseases due to dis- 
turbances of, 59 
Interstitial inflammation, 250 
Intestinal trichina, 571 
Intestinal tuberculosis, 469 
Intoxication, 46 
effects of, 14 
general, 26 
intestinal, 25 
tissue changes in, 280 
Iodothyrin, 62 
Irradiation, experimental, 8 
Ischaemia, 105 
Ischiopagus. 418 
Islands of Langerhans in diabetes, 60 
Itch-mite, 577 
Ixodes ricinus, 578 
Jaundice, 195 
haematogenous, 196 
haemolytic, 197 
hepatogenous, 196 
of new-born, 198 
Kakke, 15 
Kala-azar, 532 
Karyokinesis,. 
atypical, 216 
mechanism of, 214 
Karyomitosis 
atypical, 216 
mechanism of, 214 
Keloid, 293 
Keratin, 163 
Keratohyalin, 163 
Kidneys, polycystic, 352 
Kinetoses, 14 
Lamblia intestinalis, 527 
Laminated thrombi, 110 
Lardaceous clots, 107 
Lardaceous degeneration, 164 
Lardaceous spleen, 164 
Lead, effects of, 18 
Leiomyoma, 312 
Leischman-'Donovan bodies, 533 
Lentigines, 310 
Leontiasis ossea, 204 
Lepra mutilans, 499 
Leprosy 
facies in, 498 
forms of, 499 
geography of, 500 
of nerves, 499 
of skin, 498 
tissue changes in, 498 
white, of Jews, 201 
Leptus autumnalis, 578 
Leucocytic thrombi, 111 
Leucocytosis, definition of, 227 
Leucoderma, 200 
Leucopathia 
acquisita, 200 
congenita, 200 
Leukaemia, varieties of, 227 
Lightning-stroke, 11 
Lipochrome, 186 
Lipoma, 295 
Lipomatosis, 147 
varieties of, 296 
Liquefaction necrosis, 136 
Liquefaction of tissues, non-bacterial, 
259 
Lithopaedion, 395 
Liver-flukes, 547 
Luxations, congenital, 410 
Lymphangioma, 303 
Lymph angiosarcoma. 329 
Lymphangoitis, 26, 27 
Lymph nodes, as filters, 78 
Lynwhoeenous infection, 26 
Lymmhorrhaeia. 1?8 
Lymphosarcoma, 323. 325 590 
GENERAL INDEX. 
Macrocheilia, 310 
Macroglossia, 310 
Madura foot, 510 
Malaria, pigments in, 194 
Malarial fever, 539 
development of parasite, 545 
in animals, 543 
mosquitoes in, 544 
Malformations, congenital, 390 
different forms of, 394 
due to excessive growth or multi- 
plication, 411 
experimental production of, 392 
of abdominal cavity, 405 
of cranium, 400 
of external genitalia and anus, 406 
of extremities, 408 
of face and neck, 402 
■of thoracic cavity, 405 
of vertebral canal, 396 
rachischisis, 396 
spina bifida, 397 
Malignant oedema, 461 
Marasmus, 4 
Martland’s tumor of bone-marrow, 328 
“ Measles,” 554 
Meat-poisoning, 450, 459 
Meckel’s diverticulum, 406 
Medullary sarcoma, 321 
Meischer’s sacs, 537 
Melanin, 185 
Melanoma, benign, 310 
Melanosarcoma, 335 
Melanosis, of viscera, 187 
Melasma suprarenale, 65 
Meningocele, 401 
Meningoencephalocele, 401 
Metamorphosis, viscous, 112 
Metaplasia, 237 
Metastasis, 47 
in actinomycosis, 509 
in tuberculosis, 482 
of benign tumors, 291 
of bile pigment, 52 
of carcinoma, 356, 376 
of dust, 48 
of fat droplets, 50 
of iron-containing derivatives, 52 
of parasites, 51 
of parenchyma-cells, 49 
■of pigment-granules, 53 
of silver particles, 52 
of tumor cells, 51, 288, 291, 356, 376 
results of, 50 
retrograde, 48, 376 
Miasma, 22 
Microcephalus, 401 
Micrococcus 
of gonorrhoea, 446 
pyogenes, 444 
Micromelus, 409 
Microsporon 
furfur, 523 
minutissium, 523 
Milk-spots, 273 
Mites, 577, 579 
Mixed thrombi, 110 
Moist gangrene, 137 
Moles 
non-pigmented, 311 
pigmented, 310, 336 
Monobrachius, 409 
Monsters, 390 
double, 415 
single, 394 
Mosquitoes, 581 
in malaria, 544 
Moulds, 515 
pathogenic, 29 
Mucins, 159 
Mucoid carcinoma, 370 
Mucor, 518 
Mucous degeneration, 158 
Mucous membrane, cancer of, 360 
Multilocular echinococcus cysts, 559 
Multiple myeloma, 327 
Mummification, 137 
Muscle, regeneration of, 227, 229 
Muscle trichina, 572 
Mycetoma, 510 
Mycoses, aspergillus, 520 
Myelin, 155 
Myelocystocele, 398 
Myelocystomeningocele, 398 
Myeloma, multiple, 327 
Myelomeningocele, 397 
Myofibroma, 312 
Myoma 
a denomyoma, 313 
laevicellulare, 312 
malignant transformation of, 314 
striocellulare, 315 
Myosarcoma, 314 
Myositis ossificans, 302 
Myxoedema, 62 
Myxoma, 294 
Myxosarcoma, 294 
vascular, 304 
Naval stones, 180 
Necrosis, 131 
caseous, 135 
causes of, 132 
coagulation, 134 
colliquation, 136 
course of, 134 
histology of, 132 
results of, 134 
Necrotic inflammation, 259 
Necrotic tissue, replacement of, 275 
Nemathelminthes, 562 
Nematodes, 562 
Nervous system 
effect of poisons on, 21 
regeneration of, 229 
syphilis of, 495 
Neurasthenia, 14 
Neuroblastoma, 318 
Neurofibroma, 319 
Neuroglioma ganglionaire, 316 
Neuroma 
amputation, 318 
true, 321 
Neuropathic atrophy, 144 GENERAL INDEX. 
591 
Neuroses, traumatic, 13 
Nitroso-indol reaction, 514 
Nutritional atrophy, 144 
Obesity, 147 
Obturating thrombus, 113 
Ochronosis, 187 
Odontoma, 300 
CEdema 
ex vacuo, 123 
malignant, 461 
varieties of, 121 
CEstrus, 582 
Oidiomycosis, 30, 519 
O'idium albicans, 518 
Omphalocele, 405 
Opsonic index, 80 
Opsonins, 80 
Organs, supernumerary, 411 
Ossifying myositis, 302 
Osteoarthropathy, pulmonary, 209 
Osteoma, 300 
Osteomyelitis, chronic haemorrhagic 
(Barrie), 328 
Osteophyte, 300 
Osteosarcoma, 338 
Over-work, results of, 5 
Oxygen, effects of deprivation or dimi- 
nution in supply of, 3 
Oxyuris vermicularis, 565 
Paget’s disease, 538 
Pandemic influenza, 464 
Papillary cystoma, 343 
Papillary epithelioma, 342 
Parakeratoses, 163 
Paralysis, pseudohypertrophic muscular, 
149 
Paramsecium coli, 546 
Parasites, 31, 32 
animal, 525 
as possible cause of cancer, 354, 357 
ectogenous, 31 
endogenous, 31 
Parasitic arthropoda, 32 
Parasitic diseases, 22, 31, 32 
Parasitic protozoa, 31, 32 
Parasitic worms, 31 
Paratyphoid fever, 458 
Parenchymatous degeneration, 144 
Parenchymatous inflammation, 250 
Parietal thrombi, 113 
Passive atrophy, 143 
Pearl disease, 487 
Pediculi, 580 
Pellagra, 15, 30 
Pentastoma denticulatum, 578 
Perithelioma, 333 
Perniones, 6 
Perobrachius, 409 
Perodactylism, 410 
Peromelus, 409 
Petrifaction, 174 
“ Petrified Child,” 395 
Phagocytosis, 74, 77, 78 
Phimosis, 407 
Phlebohths, 115 
Phlegmon, 258, 438 
gas, 259, 462 
Phloridzin diabetes, 60 
Phocomelus, 409 
Pigment, absence of, 200 
Pigments, pathological, 185 
autochthonous, 185 
exogenous, 198 
in chronic arsenic poisoning, 194 
in malaria, 194 
Pin-worms, 565 
Pirquet’s reaction, 477 
Pithead, 560 
Pityriasis versicolor, 521 
Placental transmission, 44 
Plague, bubonic, 466 
Plasmodium malarias, 539 
Platyhelminthes, 547 
Plethora, 100 
Pneumococcus, 440 
Pneumotoxin, 443 
Poisons, poisoning 
action on heart, 21 
action on nervous system, 21 
animal, 15 
arsenic, pigmentation by, 194 
bacterial, 15 
blood-poisons, 18 
caustics, 17 
classification of, 15 
definition of, 14 
enterogenous, 46 
ergotism, 18 
gaseous, 17 
histogenous, 46 
in infection, 23, 28 
meat-poisoning, 450, 459 
method of action, 16 
mineral, 15 
poisonous eels, 16 
poisonous fish, 15 
poisonous mussels, 16 
ptomaines, 23 
snake-venom, 16, 18 
vegetable, 15 
Polvblasts, 267 
Polycystic kidneys, 352 
Precipitin reaction, 94 
Precipitins, 93 
Predisposition to disease, 33 
racial differences in, 36 
relationship of sexes, 36 
Pressure-atrophy, 144 
Primary thrombi, 113 
Proliferation of cells, causes of, 213 
Prosoposchisis, 403 
Proteins, bacterial, 24, 29 
Protozoa 
parasitic, 31, 32 
pathogenic, 525 
Psammoma, 339 
Pseudohermaphrodismus, 413 
Pseudohypertrophic muscular paralysis, 
149 
Pseudoleuksemia, 327 
Pseudotvberculosis, 489 
cladothrichica, 510 592 
GENERAL INDEX. 
Psorospermosis, 538 
Psychoneurosis, 13 
Ptomaines, 23 
Pulex irritans, 580 
Pulse, disturbances of, 99 
Puriform thrombi, 115 
Purulent infiltration, 258 
Purulent inflammation, 257 
Putrid gangrene, 137 
Pyaemia, 26, 27 
Pygopagus, 418 
Rachipagus, 420 
Rachischisis, 396 
Radioactivity, 9 
Rag-sorters’ disease, 454 
Ray-fungus, 505 
Rays 
Becquerel, effects of, 9 
effect of ultra-violet on bacteria, 7 
effect on viriola-lesions, 7 
Roentgen, effects of, 8 
therapeutic use of ultra-violet, 7 
ultra-violet, 7 
violet, 7 
Recurrence of carcinoma, 379 
Red thrombi, 110 
Regeneration of tissues, 209 
in inflammation, 263 
of blood, 226 
of blood-vessels, 220 
of bone and cartilage, 225 
of connective-tissue, 222 
of elastic fibres, 224 
of epithelium, 218 
of eye, 233 
of heart-muscle, 229 
of muscle, 227, 229 
of nerve elements, 229 
Regenerative capacity of tissues, 212 
Relapsing fever, 514, 528 
Repair, 262 
Rhabdomyoma, 315 
Rhinoscleroma, 503 
Rhizopoda, 525 
Rider’s bone, 302 
“ Ringworm,” 522 
Rodent ulcer, 356 
Round worms, 562 
Sago spleen, 164 
Saprophytic bacilli, 450 
Saprophytic moulds, 516 
Sarcocarcinoma, 321 
Sarcoma, 321 
adenosarcoma, 372 
chondrosarcoma, 299 
definition of, 321 
fibrosarcoma, 321 
giant-cell, 325 
haemangiosarcoma, 333 
hyaline formations in, 340 
intercellular substance in, 321 
large round-cell, 324 
lymphangiosarcoma, 329 
lymphosarcoma, 323, 325 
medullary, 321 
Sarcoma, melanosarcoma, 335 
myosarcoma, 314 
myxosarcoma, 294 
osteosarcoma, 338 
small round-cell, 322 
spindle-cell, 324 
Sarcoptes hominis, 577 
Sarcosporidia, 537 
Scarlet-fever bodies, 539 
Scirrhous carcinoma, 368 
Schistoprosopia, 403 
Schizomycetes, 423 
infection by, 428 
Sclerosis, 172 
Scrofula, 486 
Segmentation, direct and indirect, 214 
Senile atrophy, 143 
Senile gangrene, 138 
Sepsis, 26 
Septicaemia, 26 
Septicopyaemia, 26, 27 
Sera 
bactericidal, 95 
healing, 86 
protective, 86 
Serofibrinous inflammation, 252 
Seropurulent inflammation, 258 
Shock 
erethistic, 13 
torpid, 13 
Simple atrophy, 143 
Situs inversus viscerum, 410 
Skin, cancer of, 358 
Sleeping-sickness, 532 
Snake-venom, 16, 18 
Solitary tubercles, 479 
Sphacelus, 137 
Spina bifida, 397 
Spirillae, 511 
Spirillum 
of Asiatic cholera, 511 
of Finkler and Prior, 514 
of Metschnikoff, 514 
of relapsing fever, 514 
tyrogenum, 514 
Spirochaete 
life-history of, 529 
obermeieri, 527 
pallida, 490 
Splanchnomegaly, 64 
Splenomegaly, tropical, 532 
Sporozoa, 534 
Squamous-cell carcinoma, 364 
Staphylococcus 
pyogenes alibus and citreus, 446 
pyogenes aureus, 444 
Stasis, 118 
Status lymphaticus, 67 
Sternum, congenital fissure of, 405 
“ Stone child,” 395 
Streptococci, pathogenic, 434 
poisons produced by, 439 
varieties of, 439 
Streptococcus infection, 434 
Streptococcus 
lanceolatus. 440 
pyogenes, 434 GENERAL INDEX. 
593 
Streptothrix, 449 
Strongylides, 567 
Sucking-worms, 547 
Suffocation, 3 
Sunstroke, 6 
Superficial inflammation, 250 
Supernumerary organs, 411 
bones and muscles, 412 
breasts, 412 
fingers, 411 
Suprarenal capsules, 65 
Surra, 532 
Sympus, 409 
Syncephalus, 419 
Syncope, 13 
Syndrome 
Dercum’s, 296 
Frolich’s, 296 
Synophthalmus, 401 
Syphilides, 492 
Syphilis, 490 
chancre in, 491 
gummata in, 493 
hereditary, 495 
initial sclerosis of, 491 
of nervous system, 495 
spirochseta pallida in, 490 
syphilides in, 492 
ulcers in, 494 
visceral, 493 
Syphilomata, 493 
Tactile irritability, 77 
Taenia, 552 
Africana, 556 
cucumerina, 556 
diminuta, 556 
echinococcus, 556 
in domestic animals, 556 
mediocanellata, 555 
nana, 556 
saginata, 555 
solium, 552 
Tape-worms, 551 
Tattooing, 48, 198 
Temperatures, effects of, 5 
Tendinous spots, 273 
Teratoid cysts, 380, 388 
Teratoid tumors, 283, 380 
Teratoma, 380, 384, 388 
bigerminal, 420 
Testicle, teratoma of, 386 
Tetanus, 460 
Thoracogastroschisis, 405 
Thoracopagus, 420 
Thoracoschisis, 405 
Thread-fungi, 521 
Thread-worms, 565 
Thrombi, 110 
calcification of, 115 
formation of, 111 
organization of, 115 
puriform, 115 
softening of, 115 
varieties of, 110, 113 
Thrombosis, 108 
disturbances of circulation in, 112 
Thrombosis, of heart, 113 
Thrush, 517 
Thyroid gland 
hypersecretion of, 63 
in acromegaly, 64 
in cretinism, 62 
in Graves’ disease, 63 
in idiopathic cardiopathy, 63 
in myxoedema, 62 
secretion of, 62 
Thyroiodine, 62 
Toxalbumins, 23, 28 
Toximemia, 26 
Toxins, 23, 28 
Toxons, 29 
Toxophore group, 29 
Transplantation of tissues, 234 
Trematodes, 547 
Trichina spiralis, 571 
embryos in blood, 573 
Trichomonas, 527 
Trichomycetes, 509 
Trichophyton tonsurans, 522 
Trichuris, 571 
Tricocephalus dispar, 571 
“ Tropical sore,” 533 
Tropical splenomegaly, 532 
True hermaphrodism, 413 
Trypanosoma, 530 
life-history of, 532 
Trypanosomiasis, 532 
Tsetse-fly disease, 531 
Tubercle bacillus, 468 
Tubercles, development of, 470 
Tuberculin, 88, 475 
Tuberculosis, 468 
as a local disease, 477 
avian, 487 
bacillus of, 468 
bovine, 487 
Calmette’s reaction in, 477 
caseation in. 473 
catarrhal inflammations in, 487 
cryptogenic infection in, 477 
formation of tubercles in, 470 
fungous granulations in, 478 
giant-cells in, 471 
granulation-tissue in, 478 
hsematogenous, 482 
in cold-blooded animals, 489 
infection through intestine, 486 
infectious nature of, 474 
intestinal, 469 
lymphogenous, 481 
method of infection, 469 
of animals. 487 
Pirquet’s reaction in, 477 
pseudo, 489 
secondary infections in, 484 
solitary tubercles in, 278 
termination of, 479 
transmission of, 470, 483 
transmission to foetus, 484 
Tumors, 281 
adenocarcinoma, 366 
adenocystoma, 349, 352 
adenoma, 344 594 
GENERAL INDEX. 
Tumors, adenosarcoma, 372 
angioma, 303 
benign, 291 
cachexia in, 291 
carcinoma, 352 
causes of, 285 
cholesteatoma, 344, 381 
chondroma, 297 
chordoma, 300 
chorioepithelioma, 363, 370, 379 
chorion-carcinoma, 370, 379 
cure of, 290 
cystadenoma, 349 
cystocarcinoma, 352, 374 
cystoma, 343 
desmoid, 292 
enchondroma, 297 
endothelioma, 329, 334 
epithelial, 283, 341 
epithelioma, 342, 364 
fibroma, 291, 319, 348 
glioma, 316 
grouping of, 212 
growth of, 287 
haemangioma, 303, 305, 308 
haemangiosarcoma, 333 
histoid, 282 
hyaline changes in, 340 
keloid, 293 
lipoma, 295 
lymphangioma, 303 
lymphangiosarcoma, 329 
lymphosarcoma, 323, 325 
Martland’s, of bone marrow, 328 
melanoma, benign, 310 
melanosarcoma, 335 
metastasis of, 288 
myeloma, multiple, 327 
myoma, 312 
myxoma, 294 
neuroblastoma, 318 
neurofibroma, 319 
neuroglioma ganglionaire, 316 
neuroma, amputation, 318 
odontoma, 300 
of connective-tissue origin, 291 
osteoma, 300 
osteosarcoma, 338 
pearl, 344 
perithelioma, 333 
psammoma, 339 
retrogressive changes in, 290 
rhabdomyoma, 315 
sarcocarcinoma, 372 
sarcoma, 321 
teratoid, 283, 380 
teratoma, 380, 384, 388, 420 
theories of, 286 
usefulness of, 284 
Wilms’, 372, 385 
Twin monsters, varieties of, 416, 418 
Typhoid carriers, 457 
Typhoid fever 
Typhoid fever, bacillus of, 456 
Widal reaction in, 458 
Typhus fever, parasites in, 539 
Ulcers, 258 
chronic, 279 
rodent, 356 
syphilitic, 494 
tropical, 533 
Umbilical hernia, 405 
Uncinaria, 567 
Uraemia, 57 
Urethra, malformation of, 407 
Uric acid infarct, 182 
Urinary-bladder 
congenital fissure of, 406 
ectopia, 405 
Urinary calculi, 182 
Uterus, muscle tumors of, 313 
Vaccines, 89 
Valvular polypi, 114 
Valvular thrombi, 113 
Variola and vaccinia, 539 
Vascular resistance, increase in, 101 
Venous pulsation, 99 
Vermes, 547 
Vibrio 
cholera, 511 
of Metsehnikoff, 514 
Vibrion septique, 461 
Viscera, transposition of, 410 
Visceral syphilis, 493 
Vitiligo, 200 
Weight of internal organs, average, 
206 
Welch’s bacillus, 462 
Whipworm, 571 
Whooping-cough, bacillus in, 464 
Widal’s reaction, 83 
Wilms’ embryoma, 372, 385 
“ Wolf’s jaw,” 403 # 
Wood-jack, wood-tick, 578 
Worms, parasitic, 31, 547 
awl-tail, 565 
blood-sucking, 31, 547 
flat, 547 
hook,568 
pin, 565 
production of anaemia by, 32 
round, 562 
tape, 551 
thread, 565 
whip, 571 
Wounds, healing of, 269 
Xanthochromia, 194 
Yeasts, 515 
Zenker’s degeneration, 163 
Zymase, 28